On neurodivergence as a general phenomenon

In this article, I return to the idea of “neurodivergence” and one form of it I had not discussed earlier. Since every human being is different genetically, molecularly, neurologically from a hypothetical strictly average human – even so called “identical twins” are not literally identical, genetically or neurally --we are all in some way or some degree “neurodivergent”. However, some differences are significant and tend to repeat and create the categories that are usually designated as neurodivergent types. In a previous piece I examined one form in detail, ASD.

Unlike such psychological conditions as Tourette’s syndrome, obsessive compulsive disorder (OCD), dyslexia, simple schizophrenia, paranoid schizophrenia, malignant narcissism, both ASD and ADHD are distinguished by their wide ranges, often blurring into conditions that overlap with more typical cognitive and behavioral personalities. It is that range that gives them special interest -- and special difficulty.

At what point can one say that there is a genuine problem as distinct from simply an interesting difference, one that may even constitute a form of giftedness in some cases? For ASD, that ability might be found in the condition of “Asberger’s syndrome”1, long a subset of the condition, where the affected individual often has great analytical capability, far above the average. For ADHD individuals, the special ability in many cases may be “hyper-focus”, the ability to concentrate very effectively on certain tasks that have special interest for the individual. However, even for such positive features, the trait is not always a benefit but sometimes a problem. (Gifted ASD individuals may suffer further isolation because of their unusual intelligence and people with “hyper focus” may be more subject to addictions.)

On getting to grips with ADHD

What exactly is ADHD? Unfortunately, the question is easier to ask than to answer, even today. Its defining symptoms are an inability to pay normal attention and, often, accompanying that symptom, hyperactivity and/or impulsive behaviors. Its current name only goes back about 40 years though its first description was by a doctor in 1775. By the early 19^th century, with compulsory education in the still new United States becoming more common, children with attention or hyperactivity problems were becoming more obvious in school settings.

Attention to it grew further during the 19^th and 20^th centuries and by the 1960s it was recognized as a wide-spread condition needing care. It was initially called “attention deficit disorder” but the “hyperactivity” component was added to the name in 1987 and that symptom remains a part of the term even though not all individuals diagnosed as having the disorder show hyperactivity.2

Despite its long history, nearly everything about ADHD has been somewhat controversial. These features include: 1) its precise diagnosis, 2) the number of symptoms that are regarded as defining it, 3) whether it really is a biological condition or a cultural/social artefact, 4) if it has biological underpinnings (which is the consensus), the extent and nature of the responsible genetic differences, 5) its somewhat different nature in males versus females, 6) its relative frequencies in different cultures and between males and females, 7) how much or how frequently it declines from childhood to adulthood, 8) the degree to which some of the detected brain differences between people with ADHD and those who do not have it reflect the condition itself or the effects of the medications especially when the latter have begun in childhood, and more.

All these ambiguities make it difficult to write about ADHD with complete clarity and certainty. One thing I think is definite, however, is that it is a real condition, albeit with a lot of variability. It is biologically-based but influenced by various physical and social variables, affecting its severity. It should also be seen as a developmental disorder which means that the stage of its development in any individual is often relevant to its treatment.

A suitable starting point is its incidence in the general population. Although the reported frequency of ADHD cases in recent decades has been rising, perhaps due to more intensive testing and discovery, the frequency in children in the US is deemed to be about 5% while that in adults is often given as 2.5%. Thus it is more frequent in children and some fraction of affected children seem to “grow out of it” as they reach adulthood.

It is also apparently more common in boys than girls, with the ratio in the US given as about 2.5:1.0. However, the higher frequency in males may partly reflect the hyper-activity component, which is either genuinely more common in boys or more culturally acceptable in them. Young girls with ADHD seem to feature more frequently inattentiveness, which may be easier to miss in a classroom setting.

Though the statistics are probably best for the US of all countries that collect these data, the available figures indicate it to be a worldwide phenomenon and on roughly this scale. With a total human population of about 8 billion people and frequencies estimated between 2.5 and 5%, this would come to between 20 and 40 million people, a not inconsiderable number. Yet, even those figures are probably an underestimate of those affected since nearly every individual with ADHD has several close relatives and friends, many of whom are indirectly affected by the way the condition plays out in the affected individual. These effects are often in social interactions or work situations and frequently involve academic or work problems. Hence, it is probably not overstating the problem to say that perhaps between 100 and 200 million people worldwide are either directly or indirectly affected by ADHD. This undoubtedly has an economic dimension as well, as every widespread psychiatric condition does, though I have not found estimates of the economic losses traceable to ADHD.

It should also be emphasized that there are many successful people who have ADHD. Having it is not a professional death sentence. However, it is probably safe to say that nearly all of these individuals have had to devise some kinds of work-arounds for their situation.

On the genetic and biological foundations of ADHD

The idea that ADHD is a biologically-based condition, not just a cultural or social artifact, is attested by the fact that it has a high “heritability”. That means that a large proportion of the effects are connected to one’s genetic inheritance. People with ADHD are disproportionately likely to either be the offspring of people who have it or to be the parents of children with it. The heritability is usually given as .7 to .8, which is too high to be the result of shared family influences.

In effect, there must be a high genetic predisposition to developing ADHD. In principle, that usually means that there are one or two genes that have large effects or lots of genes whose individual variants have small effects that add up. Earlier 20^th century genetic work revealed little but did not find genes associated with large effects. Much larger recent studies confirm that and indicate that typically many genes are involved. I have argued earlier that many conditions with an underlying genetic basis involve such cumulative effects of genetic variants that collectively “nudge” a condition in a particular direction.

I think that the developing ADHD story points in the same direction. One needs to go beyond such generalities and find out which specific brain neural processes are involved and then how the specific genetic variants that predispose toward ADHD actually do so. We are still quite ignorant but certain things are clearer. The most important general conclusion is that ADHD is not one condition but several kinds, perhaps three distinct “biotypes” .

That is, at one level, not a surprise since different individuals show differing degrees of inattentiveness, hyperactivity and impulsivity. Furthermore, the known neurobiology of the neural states involved in these properties indicate the involvement of different brain regions and different predominant neurotransmitters. Yet a detailed recent study, carried out in China and involving 1154 participants, about half of them children with ADHD and the other half controls (children of similar ages without it) has both confirmed that conclusion and considerably extended the findings.3

These findings, in turn, predict that the genetic complexity underlying ADHD will become somewhat simplified. The three “biotypes” would be expected to be somewhat different in the genes implicated. Those differences, in turn, may point the ways toward different therapies for the different kinds of ADHD. Some treatments may involve new drugs but others might involve other approaches. One line of evidence indicates that the dopamine “reward” system in people with ADHD is defective. If one is not getting a dopamine “hit” at the right time, some of the motivation for doing something can disappear. However, much evidence suggests that this is only one aspect of ADHD.

It is clear that various other biological or external factors influence the course and/or severity of ADHD for different cases. For example, low birth weight is now known to be a serious risk factor, and exposure to alcohol and nicotine in utero highly probable risk factors. Also, home environment and parental understanding and support are important. Parents who are unaware of ADHD are not going to be understanding and supportive when their children experience problems typical of it, and that lack of emotional back-up is most likely to make it much harder to deal with it by the affected individuals.

Gender effects

In this set of factors, one that has simultaneously been known all along and at the same time, largely ignored, is gender. As noted above, male children are more likely to experience ADHD and females less so. Yet, just as gender is not strictly a binary state – no matter how much some people want it to be so – gender as experienced is also not a static one. In particular, females undergo their monthly reproductive cycles and this entails strong hormonal fluctuations. The fluctuation of oestrogen may be particular important for young girls or women who have a genetic predisposition to ADHD.

Indeed, more cases are coming to light of women who only became aware that they had ADHD because of abnormal changes in their moods or cognition during their monthly cycles or as they approached the onset of menopause (so called “perimenopause”). Other studies indicate that administered progesterone can help with these problems but especially if the progesterone dose had been preceded by additional oestrogen.4

Outlook

The nature and treatment of ADHD remain real challenges for medical science. However, in the 250 years since it was first recognized, there has been substantial progress, particularly notably in the last decade or so. I expect to return to some more of the new findings, in particular in connection with how ADHD relates to other aspects of human psychology and neurodivergence. These questions relate to fundamental questions about how the human brain works as an integrated whole and thus to basic ones about human experience generally.

The initial rise of “the gene”

Certain words or terms are central to given scientific fields. For example, “atom” and “molecule” are essential to chemistry while “matter”, “energy”, “quantum” and “space-time” are crucial to physics. Similarly, “gene” has been a key term in genetics. Indeed, it was proposed only three years after the field itself was named. Its significance in 20^th century thought is indicated by the title of a book by the noted scholar Evelyn Fox Keller, The Century of the Gene (2002). In it, she argued that however important the word had been, it had begun to lose its clarity and usefulness. In this piece, I extend her argument. This might seem initially a mere semantic issue but it is more than that. It is central to how geneticists think about heredity and how organisms work.

First, before entering into the difficulties, a brief historical overview is appropriate. In the 20^thcentury, the “gene” went from being a completely unknown, mysterious entity to one with a completely clear meaning in the early 1960s. The next half-century, however, saw the concept evolve into such a state of complexity and diversity that it now eludes a simple definition.

The science of genetics was named in 1906 by the English biologist, William Bateson (1861-1926). It was based on the Greek word genesis, meaning “origin” and the field was dedicated to solving how living things originated and reproduced themselves faithfully, generation after generation . Three years later, the word “gene” was proposed by a Danish scientist, Wilhelm Johanssen (1857-1927), to denote the fundamental “unit of heredity”. Some word was needed to embody this idea and “gene” fit perfectly. What a gene actually was, in physical or chemical terms, however, was completely unclear. By then, it was believed that heredity was carried on the long strings of material in the nucleus known as “chromosomes”, and after Johansson’s coinage it was inferred that the genes, whatever they were, were located on the chromosomes. Johansson was content to regard them as dimensionless points, without knowing their material nature, but of course people wanted to know more.

A decade later, means that seem relatively crude today but which worked showed how specific genes affecting particular traits could be located at specific locations on particular chromosomes. Genes could still be treated as mysterious, dimensionless points but now, at least, they were known to have ascertainable, individual locations.

By the late 1930s/early 1940s, there was evidence that genes were not points but very small linear segments of chromosomes. This had been shown for only a few genes at this point but it seemed safe to generalize that all genes were such segments and growing evidence soon supported that. The gene had thus acquired its first physical dimension, length.

The gene acquires form and function: the mystery dissolves

By the early 1950s, the “gene” had become fully three dimensional: it was a segment of a long thin molecule named deoxyribose nucleic acid or DNA. In animals and plants, the chromosomes consist by weight of approximately equal amounts of DNA and protein but it is the DNA that carries the hereditary information, while the proteins can be regarded as the packaging. (Of course, that packaging role is complex and the proteins there do more than just coat the DNA but we can leave those aspects aside.) DNA is a double-stranded molecule in which the two strands wrap around each other as helices (like a spiral staircase), and one strand can be copied, from one end of the gene to the other, into a related molecule, termed “messenger” ribonucleic acid, RNA or mRNA. This had been established by 1960.

The mRNA’s sequence of units (nucleotides) is “translated” or “decoded” into a sequence of linked amino acids, to create a proteinaceous molecule, a so called polypeptide chain. It is the proteins of the cells, each composed of one or more polypeptide chains, that do the work of the cell, such as hemoglobin in the red blood cells carrying oxygen, insulin regulating the uptake of sugars from our food, digestive enzymes in our stomach breaking down our food, the proteins in our muscles that let them work as muscles, and so on.

The details of how genes specify protein chains are complex but the general picture is simple: a segment of DNA specifies an mRNA molecule which then specifies proteins. The mechanism is shown in the figure below, with some of the details given in the legend.1

Figure: (Left) One strand of the double-helical DNA is copied in the nucleus to give a mRNA, which leaves the cell’s nucleus and is “translated” into a protein chain in the colloidal cytoplasm that surrounds the nucleus. (Right) The mRNA is “read” three nucleotides at a time, each such triplet corresponding to one of the 20 amino acids, which are the basic units of proteins (Figure by Sarah Kennedy, from Darwin’s Chronic Illness, by Hayman and Wilkins, coming out soon.)

That was the understanding achieved by 1963 and the solution to the puzzle of the nature of the gene was (rightly) seen as a scientific triumph. It was wonderfully appealing in its simplicity. The chemical information in the gene was mirrored closely in, indeed was “co-linear” with, the sequence of the chemical units, the amino acids, in the protein. Since it was soon known which amino acid was specified by any “triplet” of nucleotides, one could deduce the basic structure of the protein from the nucleotide sequence of the mRNA or the gene itself. The implication was: know the genes and you will know the proteins and if you know something about the proteins, you can often figure out what they do in the cell. These ideas were to have tremendous impact in the selling of the genome projects in the 1980s and 1990s – the efforts to sequence all the DNA in the genome – to the funding agencies by the scientists who wanted to do this work.

There was just one catch, which only became apparent in retrospect. The picture of gene-polypeptide colinearity was derived from work on a bacterium, Escherichia coli, or E. coli, a normal, non-pathogenic bacterial resident of our gut, and on a few of the DNA viruses that infect E. coli. It was assumed that genes in far more complex organisms would be the same. After all, with such an elegant, comparatively simple mechanism, why shouldn’t Nature use it in all organisms? This assumption was summarized in the adage “What is true for E. coli is true for the elephant”, from one of the great 20^th century molecular biologists, Jacques Monod. Of course, E. coli differs from elephants in many obvious ways but Monod was referring to basic genetic mechanisms.

Genes acquire more dimensions and become mysterious again

For about 15 years, there were few reasons to question this assumption. Animals and plants have much bigger cells than bacteria and also a lot more DNA but it was assumed that this simply reflected far more genes in animals and plants. E. coli was believed to have about 4000 genes while humans were estimated to have maybe 100, 000 genes. Were humans to have E. coli-sized genes, this would still leave humans with much more DNA in each of their cells than they seemed to need. This was viewed as a detail that would be sorted out.

However, in 1977, something was discovered that was immediately seen to be a potentially major complication. First, certain genes in an animal virus, were found to be not co-linear with their proteins but had large segments of their DNA sequence that, after being copied into their mRNA transcripts, were then cut out and the protein-specifying segments tied (or “spliced”) together. This was soon found to be not unique to a few viral genes but generally true of the genes of animals and plants. In effect, genes were much larger than they seemed to need to be and there was no simple colinearity between the nucleotides in a gene and its resulting encoded protein. The dispensible parts that were cut out were called “introns” and the protein-coding segments “exons”. Evidently, in animals and plants and many of their viruses, genes exist “in pieces”.

No one had predicted “genes-in-pieces” and no one could understand what purpose it might serve or its possible evolutionary origins. (We might return to these issues in a separate article in this newsletter.) Things soon got more complicated, however, annoyingly so for those who like simplicity (as most scientists do, a desire embodied in the idea of “Occam’s Razor”). One of these complications concerned the exons, the parts of the gene saved from the initial cutting out of the introns from the original RNA transcript: they were found not always to be the same. The cutting out process, termed splicing, could and would often produce final transcripts that omitted some exons! This “alternative splicing” meant that the same gene could produce variant proteins and often did in different cell or tissue types. Evidently, an idea from classical genetics of the 1940s, “one gene-one protein” (that each gene specifies one and only one protein chain) was false. One gene could be the source of multiple, though related, proteins: different spliced transcripts could be found in different cell types and did different things. Soon ways to predict the protein sequence from the DNA sequence were found but the safest way to deduce much of the essential (protein-coding) part of the gene was from its product. This was now the reverse of the situation in the 1960s when one could predict the protein directly from the sequence, using the known rules of the “genetic code”.

Over the next four decades, further complications piled up. I will not give a full catalog here but will mention two. First, it was found that sometimes splicing would happen between transcripts from different positions on the chromosomes. This was not an error but a “programmed” event. This was termed “trans-splicing” (as opposed to the normal splicing, which happened in segments close together on the chromosome, thus “in cis”.) It too violated an old idea, namely that a given gene had one and only one chromosomal location.

Furthermore, simple three dimensionality of genes was no longer accurate; more “dimensions” to define specific genes were needed. One was time, the fourth dimension, since genes were turned on and off at specific times in development and others were the cell types in which the specific protein chains were produced, since the splicing patterns were a function of those cell types. The gene had become a multi-dimensional entity though few people then, or even now, talked about it that way.2

A second phenomenon was just as applecart-upsetting, and emerged from many discoveries starting in the 1990s. The gene had been confidently defined as a segment of DNA that specified a mRNA that encoded a polypeptide chain. The only exceptions known in the 1960s were the genes that specified the two kinds of RNA components that are essential for the protein-synthesizing process, (translation), namely the genes for transfer RNAs and ribosomes. (See the figure and the references in note 1.) As the evidence accumulated, it became clear that there are many DNA sequences that are copied into RNAs that do something else, often that new function being to regulate the synthesis of mRNAs from conventional genes. These transcripts are now classified as “non-coding RNAs” (ncRNAs). The number of the genes that specify these non-traditional RNAs is in the thousands; by one estimate there are about 8000 in the human genome. The number of conventional, protein coding genes in our genome is now known to be on the order of only 21,000, hence the number specifying the ncRNAs is clearly substantial, undermining the concept of the gene as simply a protein-coding device.

Perhaps you shrug and are thinking, “well, life is always more complicated than we imagine and these are just another set of complications”. I believe, however, that the intellectual challenge is more wide-ranging than that. For a large part of the 20^th century, for most biologists, it was assumed that “the genes” held the essential clues to what living things on Earth were and in the mid-1960s, it seemed basically simple. With the rules of protein coding, one could go back and forth between DNA and protein sequence. Now, one needs so much extra information to define specific genes and what they are and do. The world of the gene has become mind-bendingly complex.34

The future of genetics?

In effect, many genes of interest are effectively embedded in a cloud of overlapping sequences. The bold, confident claims of the 1980s and 1990s to justify the expense of the genome projects, namely that determining the sequences of genomes would open up “the Book of Life”, have been discredited. Of course, the genome projects have produced a huge amount of invaluable information and have had a transformative effect in the practice of biology. But DNA sequences are not the sole key to understanding living things and, as we know now, never could have been. As Evelyn Fox Keller argued, the “century of the gene” was the 20^th century and biology is now in a new era. One may regret the lost simplicities but it will be more productive to see the present in genetics as a new set of challenges that present an opportunity for new understanding.

On the surfacing of a 76 year old memory

Memory is a marvelous thing. It can suddenly bring up something long forgotten that suddenly gives it new relevance. Here, I retrace a memory from 76 years ago that recently resurfaced and how it connected for me two things that initially seem quite unrelated, a war that ended nearly ¾ of a century ago and the biodiversity crisis today.

For Americans of my generation (I am now 81) everyone remembers where they were and what they were doing when they heard that John F. Kennedy had been assassinated in November, 1983. Likewise many people in this cohort and even younger remember when they watched television in July, 1969 to see the first images of men walking on the moon. There are no prizes for such memories. But a memory I highlight here concerns my finding out about the outbreak of the Korean war, an event that will seem quite distant and obscure for most people today.

It was June, 1950 and I was still very young. I had walked into my parents’ bedroom and my mother was still in bed with the Sunday edition of The New York Times spread out there. She had been reading it and looked up from it and said – more to herself than to me – “They’ve just started another war.” I remember looking at her face and then at what she was reading. It was the book review section of the Times and I had enough reading ability then to see that the front page was about some German author and his new book. German literature was her thing (she would later become a distinguished German translator) but there was no obvious connection there to a new war.

My then young brain probably did not have the concept of “preoccupation”. Only later did I realize she must have been reading one thing (the book review) but was still preoccupied about the new war. This was when I first learned that there was a country called Korea and that a war had just started there.

I then largely forgot about the war – I was not really reading the papers then – but I remember three years later finding out that the war had ended. I was on holiday at Lake George in upper New York State with my mother and brother and saw a newspaper headline that gave me the news. I knew little about war but was glad to learn it had ended. In fact, formally it had not. An armistice had been signed but the war has never been officially declared “over”. Most Americans do not know this but the Korean War remains the ultimate Forever War, still technically on though thankfully not in an active state with people dying from it.

On the DMZ and biodiversity

What triggered this trip down memory lane? It was reading an article recently, from about a year ago, about Korea. Specifically, it was about the buffer region set up roughly along the 38^th parallel, the old boundary between the two halves of Korea. It marks the separation between North and South Korea and is called the Demilitarized Zone or the “DMZ”.- It runs 160 miles (about 250 km) across the Korean peninsula and is 2.5 miles (about 4 km) wide. It is thus about 400 square miles in extent (640 square kilometers), thus about 2/3 the size of an average American national park but much thinner.

Its purpose is to provide space between the militaries of the two Koreas. Initially it was a barren No-Mans-Land like the very narrow open space between east and west Berlin that existed between 1961 and 1989, but much narrower. The latter had been set up by the East Germans as a deliberate open space kill zone for anyone who had the temerity to try to defect from East Germany. It never hosted much natural life. In contrast, the much broader Korean DMZ today is a de facto nature reserve filled with living things that have made their homes there. It includes forests, wetlands toward the east, and a mountainous region toward the west.

Initially the DMZ was a barren moonscape-like war zone but now it is home to an estimated 6000 species, both animals and plants, including 100 of the 273 endangered species found in Korea. The mountainous west hosts, amongst other mammals, Siberian musk deer, yellow-throated martens, and Asiatic black bears. The DMZ is also a stopping place for several migratory bird species including the beautiful white-naped crane. As the article says, the DMZ is an “accidental ecological paradise”.1

Along with the so called Civilian Control Zone, a strip that runs along the south side of the DMZ, this region is equivalent to only about 10% of the total area of South Korea. However, it is a unique and invaluable part of the peninsula as a nature reserve. What accounts for its success?

It is not truly “demilitarized”. In fact, both sides of the DMZ are amongst some of the most heavily armed regions on the planet. That alone helps explain why so few people attempt to defect from North Korea’s poverty and repression by attempting to cross the DMZ. Even if someone made it that far, they would not get a warm welcome on the other side. The South Korean army treats would-be defectors from the North with grave suspicion.

The even stronger form of deterrence is that the whole DMZ is heavily mined. Hence, the existence of this ecological paradise in the middle of the Korean peninsula owes its idyllic state to the fact that it is potentially a deadly area for anyone who ventured on to it. (I have not been able to find out what the consequences of the mining for the wildlife are. Presumably most of the animals are not heavy enough to set off the mines and probably those that could do so are mostly in the mountainous area which I assume is more lightly mined. Anyone who knows about this is invited to put a note in the comments.)

How do we put these divergent facts together? On the one hand, the Korean War was a disaster for the hundreds of thousands of those (Koreans, Chinese, Americans) who were killed or wounded in it and for their relatives. On the other, the blooming of the DMZ as a natural paradise is a delightful positive development we should be grateful for. Yet, the fact that the DMZ owes its success to its being surrounded by the machinery of death and underlain by mines is an irony that cannot be banished.

On Nature’s resilience to war and volcanoes

Still, the DMZ is telling us something invaluable, that Nature has tremendous regenerative powers. The same thing was seen in the moonscape that resulted from the devastation of the sudden explosion of Mt St Helens in 1980. It destroyed over a 100 square miles around it, leaving a barren landscape of ash and rock. Yet, soon, the lowland areas that had been devastated had begun to re-vegetate themselves.2

In short, Nature has much resilience. We tend to think of resilience as a personal characteristic, a psychological one. Some people really do bounce back from problems and hard times far better than others. They have a propensity to do so that others do not.

However, resilience is a biological property too. Recovering quickly from an illness or a wound is a sign of that. Again, individuals vary in how quickly they do this. The fact that younger animals generally have quicker recovery times than older ones also tells us that biological recovery processes are involved. (A positive attitude can speed the process but does not seem to be the whole answer.) We are learning more about these mechanisms that ensure resilience at both the molecular and cellular levels. At the molecular level, it is often the case that two or more gene activities reinforce each other in this way. And often, for illnesses or wounds, the more cells that participate, the faster the recovery. Again, being younger often helps precisely because more cells can be mustered for the recovery process.

It makes sense that even at the level of ecosystems, there must also be recovery systems. What is unknown is how quickly they will operate. That speed – or lack thereof – must be a function of how great the damage is and how many and how robust the recovery systems are. The examples of the DMZ and Mt St Helens suggest that they can operate fast.

On the “30 x 30” proposal

This insight is at the heart of a proposal that was made in 2022. It is being worked on cooperatively by a number of major conservation organizations. The shorthand designation for this is the “30 by 30” proposal. This refers to the goal of restoring to health 30% of the land and marine ecosystems on Earth by 2030. We are now halfway from the year in which the proposal was first set out to the target date 2030. Without being excessively gloomy, one can predict that this goal will not have been met by then.3

Does that mean that it will not have been worth trying? Of course not. First of all, having goals encourage efforts and there is some evidence of progress having been made for some ecosystems, both terrestrial and marine. Both the goals and the efforts concentrate thinking and attention that help make these things happen.

Second, both the positive results in ecosystem restoration and the shortfalls will almost certainly stimulate further thinking. With luck, this will translate into new approaches to restore our planet to ecological health. This will include better descriptions of what is needed for different ecosystems and what further steps are required to ensure their future.

Thus the process involved in the 30 x 30 proposal should be seen as a step involving the further development of ideas about what we want and need for ourselves (the human species) and the animals and plants with whom we share the planet. That intellectual quest has been going on since the start of the Industrial Revolution in the late 18^th century. While the riches, wonders, and comforts that that revolution could deliver were appreciated by thoughtful people from its beginnings, its dangers were also understood by a small but growing number. This produced a lagging but real public awareness of those dangers and the need to protect the natural world, which progressed in stages, perhaps most visibly in the US.

The first stage was probably the setting up of the first natural parks in the United States in the 1870s. A second stage, a century later, was the conservation movement of the early 1970s, which featured Earth Day and the passing of the Endangered Species Act. The latter was immensely important yet missed an emphasis of the importance of saving whole ecosystems. The 30 x 30 proposal, made about 50 years later, is aimed to make up that gap.

There is a lot at stake here. Ultimately, the issue is about saving our planet as a livable one. Not least it involves strengthening our agricultural systems to deliver the food we need. This requires, of course, avoiding nuclear wars and reining in climate change but, no less, repairing and restoring so many of the ecosystems of our world.

To answer the question in the title, “Does the DMZ point the way to saving biodiversity?”, my personal answer is: I hope not. We have to learn how to preserve nature without the machinery of death all around it and underlying its soil. Yet it demonstrates an invaluable lesson: leave large chunks of Nature alone, and she will provide much of the restoration that is so badly needed.

Diseases of civilization: how should we view them?

This essay is about the disease of obesity and some developments in its treatment. I will discuss a new class of drugs that has tremendous potential not just for treating obesity but a large number of quite different medical problems as well.

I have referred to obesity as a “disease”. This connotes a long-lasting dysfunctional state of the body that has a root cause. Thinking about it that way, one has to wonder what that root cause might be. (Labelling it only as a “condition” does not.) For any disease, one should ask: is it due solely to an external agent, e.g. an infectious bacterium or virus, or to an internal one, usually a genetic variant? Or is it due to some combination of external and internal risk factors?

That last possibility, a combination of causes, encompasses some of the diseases that have the biggest impact on society. At the same time, society helps to create or at least exacerbate many of them. One might call them “diseases of civilization”.

There are two reasons why the distinction between diseases of civilization and other kinds is important. First, if one wants to eliminate or reduce the incidence of a disease, one must first understand its causes; doing so helps one devise preventative measures. Second, if social customs foster certain diseases, then sufferers should not be assigned sole blame for having them. If society has some responsibility for them, it has a duty to respond with compassion and practical help.

Let us make this less abstract by naming a few diseases of civilization. Lung cancer and emphysema are two, since the overwhelming proportion are a consequence of smoking, a cultural artifact. Although smoking tobacco was an invention of certain Native American peoples, they apparently used it only for special ceremonial occasions and, apparently, did not suffer a health burden from it (though of course there are no statistics on this.) In contrast, today, smoking is a daily habit for many people around the world and certainly increases the frequency of these diseases.

Another disease of civilization is adult-onset diabetes, or diabetes type 2. (Juvenile diabetes or diabetes type 1 is not such a disease; it has a genetic cause, and appears in children and teenagers.) We know that diabetes type 2 is promoted by Western–style diets. As those eating habits have spread around the world, the incidence of cases of diabetes 2 has ballooned. The relationship between eating a Western style diet and developing diabetes 2 is increasingly well understood.1

A fourth disease of civilization is obesity – the focus here. The evidence that our civilization promotes obesity is very strong, particularly in the United States where the statistics are particularly good though obesity is now increasingly a world-wide problem.

Obesity as a growing problem

“Obesity”, please note, is not just a qualitative descriptor term, like “being thin” but has a precise numerical indicator, the so called BMI (body mass index). It is the weight of the individual (in kilograms) divided by the square of their height (in meters). A BMI of below 25 is considered a good value, while values between 25 and 29.9 correlate with being overweight, and those over 30 are judged to indicate obesity.2

Between 1960 and 1980 in the US, when the increase in cases of obesity became apparent, the incidence of obesity was about 13-15%. By 2020, the incidence of obesity, as measured by BMI, was 42% and overweight individuals constituted a further 33% of the American population. In other words, approximately 75% of the American population is judged to be at least overweight, with more than half of this group considered to exhibit obesity.

This is important. Leaving aside all considerations of appearance and the social consequences (which for many individuals is not a trivial matter), there are major health problems associated with, and to some degree, triggered by obesity (see below). These health concerns are not limited to this group but increase with BMI in the overweight group. Furthermore, once one is overweight, there is an increased risk of becoming truly obese.

The most obvious indicator that obesity potentiates health problems is the mortality statistics: people who are greatly overweight tend to die sooner and the more serious the weight problem, the more likely one is to do so. The known health problems associated with obesity include all the major organ systems – heart, guts, kidneys, lungs – while the conditions that obesity predisposes one to include cardiac problems, kidney diseases, sleeping difficulties, muscle and bone weaknesses, gall bladder problems, and, not least, cancers. A blanket condition that many people with high BMIs experience is known as “metabolic syndrome”. This burden of disease that comes with obesity not only causes greater suffering but creates a large economic burden for society.3

It would not be an exaggeration to refer to the obesity epidemic, given the way the problem has grown in Western societies, and increasingly in less wealthy countries in the Global South. What, if anything, can be done about it?

Some failed approaches

There have been two distinct approaches taken over the last 50-60 years. The first is what may be termed “life-style changes” and the second is new drug therapies. If either set of approaches had had much success, this should be evident in a reduction in frequency of people classified as suffering from obesity. This has not happened.

The approaches involving changes-in-life-style have focused on 1) better diets, with reduced calorie intake, more vegetable fiber, fewer carbohydrates, and the like and 2) more exercise. Both strategies are perfectly sensible, in terms of what we understand about healthy living and reduction of weight. These approaches tend to produce marginal reductions in weight/fat mass or temporary larger reductions that are soon erased as body weight tends to increase again. Obesity seems to be one of those suboptimal body states that once entered are hard to leave, a so called “allostatic state”.

Similarly, pharmaceutical (that is drug-based) approaches to obesity-reduction, for decades, involved no long-lasting success stories. Each drug had a rationale behind it that seemed promising but none that really worked. Again, there might be relatively slight reductions in weight but none that achieved major reductions in fat mass or over-all body weight. These attempts comprise a long story of failure, essentially. This is not unusual in drug development. Each drug typically has a highly specific and limited target, matching its chemical specificity. In addition, many, when used, have side-effects if used repeatedly or in too high a dosage. In addition, they frequently lose efficacy over time because the body often builds up resistance to them.

Is the tide turning with GLP-1-like drugs?

Until about 2010, the anti-obesity drugs seemed to be going down this disappointing road. And then, something unexpected happened. A drug developed as a potential treatment for type 2 diabetes proved to have unexpected benefits in reducing weight in obese individuals. The substance was a short proteinaceous molecule, a polypeptide of 31-32 component amino acids, whose sequence resembled another polypeptide termed “glucagon”. Glucagon had the function of increasing glucose release from cells into the blood stream. In contrast, the new molecule, of which there were soon shown to be two forms, in contrast promoted the opposite action, taking glucose out of the blood with the help of the hormone insulin. The two peptides were named “glucagon-like peptide-1” or GLP-1 and “glucagon-like peptide-2” or GLP-2. GLP-1 is the one that has been the focus of most work and is the one we will concentrate on here.

Since diabetes type 2 is the condition of inadequate sugar uptake from the blood, due to an inadequacy in the action of insulin, it seemed possible that GLP-1 or slightly modified polypeptides could aid the action of insulin and be of therapeutic aid in diabetes. The early results were positive though not a cure for this form of diabetes.

The pleasing surprise was that injection of the early drug forms of GLP-1 were found to initiate a significant decrease in weight in people with obesity. This was easy to determine since many of the individuals being treated for diabetes type 2 were also obese and suffered from metabolic syndrome. New forms of GLP-1 (each of which has a proper chemical name and a brand name, making for some confusion) were also found to have these benefits, several superior to the original form. Like insulin, they had to be injected on a daily or weekly basis but as the decade of the 2010s went on, they were found to have fewer side effects in the majority of patients. In 2014, these therapies were approved by the FDA to be marketed in the USA for obesity reduction.4

How do they work? There are still many unknowns but briefly, they seem to operate chiefly through the special receptor molecule they bind to on cells. Such molecular facilitators are said to be “agonists”. That binding increases insulin production, reduces glucagon, and slows gastric emptying. The first two increase the efficacy of glucose metabolism while reducing excess glucose in the blood. The slowing down of emptying of the stomach during digestion of food, however, antagonizes the wish to eat: with a fuller stomach for a longer period, one simply craves less food. In addition, there appear to be direct effects of these drugs on certain neurons in the brain that regulate appetite with the result that there are fewer neural signals stimulating eating. People taking these drugs report that their previously constant thinking about food had stopped.

All of this is remarkable and encouraging enough but there is more. Specifically, there is a growing body of evidence that they have direct ameliorative effects on a host of other conditions. These include: cardiovascular disease, liver diseases, several kidney conditions, and various immune system disorders where low level inflammation is a part of the problem. The GLP-1 drugs seem to have efficacy in damping down inflammatory responses. This last fact may relate to findings that they may be useful in treating various neurodegenerative diseases, including Parkinson’s disease. In short, these drugs may be opening up a whole new world of possible therapies.5

A phrase that popped into my head, while reading about these possible therapeutic benefits, was: “a man for all seasons”. This was the title of a play written in the 1960s and then turned into a great movie, of the same title, in 1966. It was about Thomas More (1478-1535), a major figure of 16^th century England. He was an influential political advisor to King Henry VIII but also a writer, philosopher, humanist, theologian and diplomat. His book “Utopia” invented the concept of the perfect society and the word describing it. He was someone of tremendous versatility and talents, indeed “a man for all seasons”.

Could the GLP-1-based drugs turn out to be “a drug family for all seasons”, that is many disease conditions? Of course, there are problems ahead – costs and access included – and many questions remain, concerning their mechanism, range of efficacy, the matter of side-effects in those who do experience them (frequently nausea). (One advance is that they are now increasingly available as pills.) Also, because they seem to be effective against many diseases, there is something like a non-controlled wave of experimentation, without the security of clinical test trials. This may become a problem for testing drug efficacy in the years ahead.6 Still, in a world seemingly awash in problems, these drugs may prove to be an important part of the answer to a major disease of civilization. This subject is important and we will return to it.

Thinking about The Selfish Gene today

About three months ago, I wrote an essay on two mid-20^th century books about genetics that had had major impacts on how people thought about the subject. One was What is Life? by the physics Nobel laureate Erwin Schrodinger, published in 1944; the second was The Selfish Gene by Richard Dawkins, published initially in 1976. As my article developed, I ended up primarily discussing the Schrodinger book. Here, I try to correct that imbalance with a fuller critique of The Selfish Gene. In that first article, I criticized it slightly for its heavy stress on the ability of genes and genetic differences to determine properties of organisms (while, of course, I recognized the foundational role of genes). Here, my criticisms go a bit deeper.

Of course, if one gives criticism, one should be prepared to receive it. I am happy to do so. I welcome criticisms and corrections from readers; please make them in the Comments section. The criticisms I offer here are my own and not published previously though some similar ones have been made by others. And I am fully aware that the book has had some very prominent supporters. In a subsequent edition, Dawkins included extracts of some very positive book reviews from three prominent evolutionary geneticists, John Maynard Smith, Peter Medawar, and William D. Hamilton. For prestigious supporters, you cannot do better than that trio. Thus, I am consciously entering a mild dissent from the opinions of a formidable group. My comments on the book are based on the version published 40 years after the first.1

On “genes” versus “alleles”

My critique begins with a comment on one particular word in the title. Many people would guess that that word is “selfish”. Indeed, I will discuss that but not immediately. The word I focus on is “gene”. Dawkins is clearly talking about versions of particular genes that have some claimed advantage over others. Such different gene forms are termed “genetic variants” and if such a variant becomes established in a population such that it is passed from parents to offspring, it is known as an “allele”. That word makes an appearance just once in the book and only near the end.

This might seem like semantic hair-splitting but I do not think so. Talking about “selfish genes” when you are really focusing on variant forms of a gene seriously distorts meaning. All members of a given species, whether it is a fruit fly, sperm whale, or daffodil, essentially all have the same gene set – the percentage of exceptions is very small – but not the identical set of alleles. It is the allelic differences that contribute mightily to what makes every human being different from any other, or that near absence in the case of identical twins, the near-identity of alleles that makes them essentially the same physically. Of course, other things, such as nutritional status and other environmental conditions, contribute to differences but we do not differ in our basic set of genes.2

Yet a possible alternative title, The Selfish Allele, does not have nearly the same ring, does it? I suspect that commercial considerations came into this choice of term. I will come back to this point.

“Replicators” versus “vehicles”

My second criticism of The Selfish Gene is of the basic premise that is foundational to the book. That is Dawkins’ hierarchical distinction between genes as the primary movers in biological entities and the rest of the organism. He describes genes as “replicators” and contrasts them with the organism as a whole (excluding the genes). He terms the organism as the “vehicle” for the genes, or less technically as a “survival machine” or even a “lumbering robot”. In this view, the living organism is the servant of its genes. This is not some casual usage; Dawkins repeatedly emphasizes that the genes, as replicators, are the directors of the whole show. This is as genetically deterministic as one can get.

Though the biological history behind his story is not essential to his argument, he makes it clear that he thinks that this is the way it was from the beginnings of life on Earth: first, there were the replicators (the genes) and then everything else in the evolution of life followed. Of course, no one knows how living things got started on this planet and it is not actually important for his argument, but he feels it is this way today and was from the beginning, over 3.5 billion years ago.

This, to me, is a problem because it is such a simplification; it amounts to a gross distortion of biology and evolution itself. The genes are segments of DNA and DNA by itself is an inert macromolecule. The effects of a gene are the result of a long stream of events, involving many molecules, that convert a sequence of base pairs into a chemical activity that actually does something (in cells and in the organism). In other words, “replicators” do not have some magical in-built properties that allow them to act directly. Nor did they ever have such wondrous abilities. There is a genuine “which came first – the chicken or the egg?” problem here and simply asserting that, “of course, it was the chickens (or the eggs)” does not solve it. It merely asks the reader to join a game of let’s pretend we have the answer.

It also does something else: it hides the whole interest of the evolutionary changes that take place in actual organisms that then become the substrate(s) for further changes. In this way, Dawkins’ version takes the place of an earlier version of “let’s pretend”: let’s pretend that we understand evolution by reducing it to changes in “gene” (actually, allele) frequencies. This view came on the scene in the 1930s and ‘40s and at the time it was actually a great advance over a lot of loose, imprecise talk. Yet, at the same time, for the geneticists, it effectively banished organisms to being mere epiphenomena, whose biological properties were of distinctly secondary interest. And they mostly remain so for the first eight chapters of The Selfish Gene and much of the remaining five.

How informative is game theory?

What about organismal behaviors in the Dawkins’ view? Dawkins trained as a zoologist and animal behaviors are his special interest and love. Here, they get a lot more attention than biological development though, in my opinion, in a somewhat lopsided view. That view is the perspective of game theory. It views the genesis and maintenance of different behaviors from the standpoint of “how will or might this behavior of mine facilitate the transmission of my genes?”. This is introduced and discussed in chapter 10, “You scratch my back, I’ll ride on yours”. To me, this has interest and worth but I find it very incomplete. While I agree with Dawkins completely that pure “altruism” can be discounted as a direct and prime motivating force in animal (not to mention plant) evolution, there is, to my eye, a complete discounting of the value of many interactions between individuals (including plants!) that can be broadly termed “social” that have real value in promoting the survival of the individuals involved.

Many of the game theoretic situations given here can indeed be put within a selfish gene framework but one that is highly artificial. For instance, they omit any form of oral communication that frequently affects or triggers interactions between individuals, certainly mammals and birds. Dawkins shows these behaviors to be roughly explicable within his framework. However, consistency with a model is far from proof that the particular model was the real explanation or that that model has much relevance to what happens in the super-diverse biological world we exist in.

In the final chapter, chapter 13, “The long reach of the gene”, we come back more explicitly to physical biological reality, including the first open admission that genes do nothing directly but only through their effects. And then the author almost immediately skips away from this insight into talking about how genes within organisms affect indirectly the activities of organisms that shape the environment. In this chapter, at last, we are asked to confront how the selfish DNA paradigm might actually work in accounting for the actual activities of organisms in shaping their environments.

This chapter is fun and I enjoyed it but will not try to explain it in detail here. Its aim is to show how the genes influence behaviors that shape the physical environment of the organism, which then affects its life. This is the reference to the “long reach of the gene” or the extended phenotype. Not stressed is that most genes are intermediary actors in creating the phenotype during development. Hence, most genetic changes altering the phenotype (appearance of the trait) do so indirectly and not as a shaping condition. The idea of genes “for” particular traits is a fallacy, which Dawkins indulges in a lot. It goes back to the early 20^th century and was already dying out when The Selfish Gene was published though it was the human genome project that killed it.

How you assign “agency” matters

It is the aspect of “agency”, however, that is at the heart of my criticisms of this book. “Agency” refers to the ability of individuals to shape their own lives. Organisms have plenty of it even though the overwhelming majority undoubtedly have no human-level consciousness of it. Every response by an organism to an external stimulus shows agency and it often determines whether an organism lives or dies. The genes of an organism may well set up its potentiality to respond but those responses are produced by the organism. Ironically, or at least to my eyes, this book assigns agency to the genes, however metaphorically, but more or less takes it away from the individual organism, which actually has it.

Another idea that is virtually absent from this book is “population thinking”. This is the concept that evolution works on the actual differences amongst individuals in a population. In a sense it is obvious but it is often not mentioned and Darwin was the first major figure to give it emphasis. Dawkins’ examples of evolved properties all involve either strong advantages or disadvantages favoring either life or death. In reality, small differences that shift probabilities of outcomes are the most important. These add up over long periods of time in populations. Darwin certainly believed so and the three great population geneticists of the early 20^th century (R.A. Fisher, J.B.S. Haldane and Sewall Wright) evidently took their task as establishing this, in different ways, as one of their major challenges in restoring Darwinism to favor in biology after a long period of neglect.3

Yet, with such criticisms, I am verging on committing the most common sin of book reviewers: criticizing the author for not writing the book that the reviewer wanted. Did Dawkins succeed in writing the book that he wanted to create? Judging from his Preface to the first edition, initially published in 1976, hence a half century ago, I would say “yes”. He evinces pleasure at what he had achieved and indeed it was an instant success in terms of attention and sales. He says that he wrote it for three kinds of reader: interested laypersons, experts, and students. Again, by the ways one can judge such things, I would say that he succeeded on all three counts. The names of notable people who read chapters or helped in other ways is impressive. My guess, however, is that it may have had its most important success in inspiring students; perhaps hundreds were influenced by it in their choice of fields. If so, that was a tremendous contribution to biological science.

Yet the 1976 edition did not contain his final thoughts on this subject, as judged by later editions. In the second edition, published in 1989, he added more material – on the “extended phenotype”, game theory and I suspect a key chapter on “memes” (an idea that he did not originate but put on the map.) My guess is that, judging from his comments in the 40^th year edition, he did meet his major goal of producing a thought-provoking, informative look at how evolution works for a very wide readership. By that criterion, The Selfish Gene is a fine achievement and in its boosting of interest in genetics and evolution, a real service to the community and the world.

On choosing a good metaphor

Still, I would like to take a minute to look at the phenomenon of the success of this book. I think that a part of that success lay in the title, which is a metaphor. Metaphors are inherently somewhat tricky, as will be no surprise to anyone. By their nature, they are inexact. If they were exact statements, they would be identities and identities are boring. Similes are less exact than metaphors but perhaps even more boring than identities. Metaphors have the potential for being exciting: they announce some essence of identity while suggesting interesting differences at the same time.

Richard Dawkins wanted to write about genes and make them interesting. He tells us that he gave a lot of thought to the title. He needed a good metaphor and considered several, including “the immortal gene” before choosing ”the selfish gene”. I suggest that the appeal of the title was partly because it was, in its own way, transgressive. It wanted to convey that genes weren’t goody-two shoes (promoting the good of the species, ha!, ridiculous!) but could be as rough and tough as anybody. This was a good thing; that quality was the actual evolutionary motor behind which gene forms succeeded and which didn’t. Remember, this was the mid-1970s and already the Zeitgeist was changing from the Beatles “All You Need is Love” to the tougher, more Rolling Stones vibe of “Ain’t Got No Satisfaction”. I would say that The Selfish Gene as a title fitted right in with those times. An author has not the right, even the duty, to pick a title that will grab attention and thus draw in readers.

Of course, once you have chosen a title, you need to stick with it and, if need be, defend it. Richard Dawkins had to do that, even as the sales of his book vindicated his choice. Had I been commenting at the time, I would have been one of those carping, “no, no, you mean selfish allele, not gene” but now think I would have been wrong to do so.

Nevertheless, I have to say that despite the success and value of The Selfish Gene, I still have some caveats. Beyond the criticisms given above there is the feeling that it leaves out so much that is interesting that has become known since 1976. In particular, there is no mention of how eukaryotic cells evolved. This involved non-Darwinian processes as central features, hence has that kind of interest, and lay the groundwork for animal and plant evolution, which has so transformed our world. Nor does the book mention anything about the discoveries, in the last decades of the 20^th century, of how animals develop and evolve, which to me is fascinating stuff. Nor is there a hint of the nature of the diverse genetic processes that create new gene activities.

Looking forward

Yet, such comments again come perilously close to criticizing a book for not being the book that the critic wanted. And that, as I acknowledge, is an unjust criticism. Perhaps, in the end, all I want to say is that I hope that someone writes a popular book with the power and verve of The Selfish Gene but with more attention to these exciting things about evolution that are not in this one.

On snobbery in scientists and its blind spots

Snobbery is not an attitude typically associated with scientists but many scientists, being human, express it from time to time. This can involve a judgement not just on the worth of certain non-science subjects but on certain scientific fields. It is based on the feeling that their brand of science is vastly superior to the one they are commenting on.

My guess is that if there is one field of biology that suffers from such a derogatory judgment more than any other, it is taxonomy. Taxonomy is the science in which a particular living organism is classified as a member of a particular “species”, the natural category that living things are divided into. Without getting into the weeds of precisely what is meant by “species”, let us take this as an achievable goal. Taxonomy is I believe the oldest sub-field of biology, going back to Aristotle (388 to 322 BCE), though it did not receive its name until 1813. Aristotelian taxonomy preceded the second oldest field, human gross anatomy, by about four centuries, which began with another prominent Greek thinker, Galen (129-216 CE). All the other branches of biology (such as plant science, cell biology, physiology, marine biology, neurobiology, genetics, molecular biology) are far more recent fields of research, stemming from the 19^th and 20^th centuries.

Yet, the snootiness sometimes displayed toward taxonomy is not because it is old but because it is often regarded as having little intellectual depth. The putdown phrase attributed to Ernst Rutherford, the Nobel Prize-winning early 20^th century physicist who produced the first modern ideas about the structure of the atom, is that taxonomy is the equivalent of “stamp collecting”. (Indeed, he seemed to think that all of biology was at that level but we can assume that he knew little about biology.) Francis Crick, another Nobel Laureate in Physics, would several decades later, use the same putdown and he certainly extended it to much of biology although his Nobel Prize was in “Medicine & Physiology”, two branches of biology. (As someone who is a biologist and who had a lot of pleasure collecting stamps as a boy, I feel that this is grossly unfair both to biology and to stamp-collecting.)

On why taxonomy still matters

Like most forms of snobbery, such attitudes are based on a combination of ignorance and arrogance. To be a good taxonomist requires extensive knowledge of the groups of organisms you are studying, a great deal of patience, and a willingness to make judgements, often when those are difficult, and defend them. It is a different skill set than that involved in physics but “different” does not mean ”inferior”.

Furthermore, the deductions in taxonomic research are often essential for understanding the actual composition of particular ecosystems in specific regions. In turn, those conclusions are often essential for making intelligent decisions about how those regions can be best protected. Thus, in contrast to stamp collecting – whose goal is limited to the enjoyment of the individual collector – taxonomy is vital to preserving our world.

These thoughts were prompted by reading an article from a few months ago in The Guardian, about a taxonomist named Art Borkent who studies species of midges, the small kind of fly also known as “gnats”, of which there are about 6000 known species, of which he has studied and named over 300.1

A word about how he studies them is needed. Classical taxonomy is dependent on its sister discipline, anatomy. Anatomy, however, is typically divided into two parts, macroscopic or “gross” anatomy and microscopical anatomy. The former one can study in larger organisms with either the naked eye or magnifying glasses. For the anatomy of small organisms, one has to approach them with microscopes. For Borkent, who does much of his classifying based on the detailed morphology (shapes) of midge hearts and guts, his approach has to be primarily microscopical. In fact, he has to know them outside and in.

He has specialized in the kind of midges that bite. Before one can think, “who cares about biting midges?”, let us point out that certain plants are dependent for their pollination on them, including the cocoa tree, our source of chocolate. If all biting midges -- which also bite many other mammals (not just us), reptiles, even fish, and other insects -- were suddenly to disappear, chocolate might soon follow. Thus, even midges, a tiny animal (whose adults are typically an 1/8^th of an inch long) can have large roles in their ecosystem. The fact that many insects are in precipitous declines in various insect populations around the world, many of which in turn are required to pollinate vital plants and perform other ecological functions, should be of concern to anyone who wants to see a livable future for our species and our world.

Taxonomy for the study of animals and plants is in deep trouble

Yet the focus of the Guardian article is not Borkent’s work on midges specifically but on how his kind of expertise may be dying out. This thought is highlighted in the subheading: “Art Borkent has spent much of his life documenting endangered species. Only recently did it occur to him that he may have become one himself. “ (My article’s title obviously comes from that subheading.) It refers to the fact that he is just about the only person left who knows his group of organisms as well as he does. One close colleague in his sub-field has been disabled by dementia, a second has retired. When Borkent finally stops his work for whatever reason – which fortunately may not be for many years, since at 72, he is still in excellent health – the biting midges may become an “orphaned” (unstudied) taxonomic group. Yet, worldwide, there may be tens of thousands of species of them that are essentially unknown.

This situation is, of course, not unique to the study of midges. Taxonomy as a whole is in trouble: scientific research depends on grants of money primarily from public sources, and these are drying up, particularly research grants for taxonomic work. This is happening although this research is understood to be vital for biodiversity and conservation work.

Even more importantly, it draws fewer and fewer young scientists to work on it. Taxonomy seems like a “sleepy” field, not a “sexy” or “cool” one, and that can drive people away. Furthermore, a financially starved field, whatever its intrinsic appeal, will struggle to draw in young recruits. Young scientists are the life-blood of science. When they disappear from a field, for whatever reason, that field may not be doomed but it will suffer terrible harm that may take decades to repair. Taxonomy may be facing that kind of future. It does not deserve to.

About two decades ago, the prospects looked different, thanks to the advent of a new technique. This was the invention of DNA “bar coding”. It involves taking a segment of mitochondrial DNA, chopping it up into pieces and spreading them out in a gel and viewing them with UV light. The fragmentation uses a group of enzymes called restriction enzymes, each of which cuts at a specific short DNA sequence, with the result that the fragments, when spread out, make a characteristic pattern, analogous to a bar code as seen on products in supermarkets. Presto! One could isolate and test this DNA sequence from two individual animals or plants that looked to the eye like members of the same species and, from the results, judge whether they probably were or not. In general, members of the same species have much less variation in the bar-code sequence than members of separate species. This method is not without its ambiguities and shortcomings but it has unquestionably been an advance.2

Often, morphology does not provide a reliable guide to species’ difference or identity between two individual animals or plants. In contrast, DNA barcoding can do this and with high reliability. However, it cannot tell you much or anything about whether there are significant biological or ecological differences between two different species or not. For that, one needs people to study them, both their morphology and their activities in the wild. Taxonomists and other kinds of biologists are needed for those studies. Thus, taxonomy has not been put on the scrap heap by DNA barcoding. The latter is an invaluable assist to taxonomy, not a replacement.

Beyond the world of animals and plants: the taxonomy of microbial species

So far, I have been talking about the importance of taxonomy for classifying animals and plants. However, such complex, multicellular organisms are just a fraction of the kinds of living things that inhabit our planet. The number of identified species of animals and plants is on the order of two million or so but the real number may be far greater than that, particularly in the number of insect species in the various forests of the world. However, whatever the number of animal and plant species, the probably far more numerous kinds of organism are bacterial and viral species, which impact the lives of animals and plants in innumerable ways.

How many kinds are there? Asking this returns us to thinking about taxonomy but with the added difficulty that bacteria and viruses do not have anatomy as we think of it. That is true at the visible level (eyes and magnifying glasses) and the microscopic; there is some morphology but not much that is good for classifying purposes at the species level. For that discrimination, one has to rely either on metabolic or biochemical differences, primarily, or DNA sequence level differences (as in the DNA bar code studies though without mitochondrial DNA since microbes do not have mitochondria). The difficulties are formidable as is that of trying to evaluate whether over-all diversity of microbial species is decreasing – like that, almost certainly, of plants and animals world-wide -- or staying the same or even increasing, all of which are conceivable.3

Microbiomes and their lessons

Despite all these problems of assessing microbial diversity in general, there are special reasons for studying it in certain specific circumstances, where the informational pay-off is bound to be large. One of these is the gut microbiome, namely the diverse microbial community that resides in the human gut. That system extends from the mouth through the esophagus to the stomach to the small intestine and from there to the large intestine and, finally, to the anal area. This extensive microbial community was first discovered in the early 2000s and it was deeply surprising, at first simply from the numbers of different species inferred – initially about 400, vastly more than expected, now over 2000 known – and the first findings that there were significant correlations between certain changes in microbiome constitution and certain health problems. At first it was not clear whether these correlations involved cause-effect relationships leading either from microbes to humans, or the reverse, or simply consequences, where the bacterial change was simply an effect of the health problem.

As the studies have accumulated over more than two decades, however, it has become clear that the microbiome does not just reflect changes in diet and health but often plays a major part in promoting health or contributing to the problem. That the direction of the cause-effect arrow goes from bacterium to human has been shown in many studies by transplanting certain suspected bacterial species to the human gut and then seeing that the physical or psychological effect often ensued. This has not happened in all cases but many.

One problem, however, has been not knowing how general the effects might be. Most of the studies on people (there have also been animal studies) have involved people from North America or Europe, namely people from the rich, industrialized countries. Can conclusions from studies on such populations be justifiably generalized to human populations around the world? Slightly more than a decade ago, two post-doctoral fellows at MIT in Cambridge, MA decided to find out by starting to sample microbiomes from people around the world, principally from intestinal bacterial species but also from other body parts that have rich microbiomes, e.g. mouths, vaginas. The two researchers, Mathide Poyet and Mathieu Groussin, are now a husband-and wife team working at the University of Kiel in Germany and they have produced a fascinating, rich body of research findings. Their collection of human microbiomes from around the world is called the Global Microbiome Conservancy.4

This work is worth a BioBuzz article on its own and I plan to write one but I will give a big conclusion from it here: there is vastly more diversity of microbiomes than was initially expected. This variety reflects not just differences between those in healthy and ill people with different conditions but amongst healthy people from different parts of the world. In other words, whether your microbiome works for your good health or against it is largely a matter of context, whether you come from a rural or urban environment, and of course what your diet is, and more. (That “more” may include some genetic differentiation amongst diverse human populations.) What I emphasize here is not the specific findings but the value of taxonomy in classifying the members of the different biomes. That classification is done initially on the basis of DNA sequences but once the identity is established, then investigators can begin to investigate why particular bacterial species are associated with particular health or other conditions. That latter work is still in its early stages and may well require decades. Yet one general conclusion that I think is beginning to emerge is that, in general (as fits with the earlier studies involving people from richer Western countries) more diverse microbiomes correlate with healthier human beings. Furthermore, in general, people living in more industrialized countries, with less fiber-rich diets and more processed foods, have less diverse microbiomes and somewhat less healthy people. If these tentative conclusions hold up, this large study will have already more than justified its existence and costs.

I will close, however, with a further thought. While stand-alone taxonomy projects, like the earlier one discussed here, about biting midges, may seem hard to fight for in the current financial climate, that of the Global Microbiome Conservancy would not. Yet the latter’s success, resting on taxonomic findings on complex biological communities, illustrates the potential value of taxonomy. Perhaps its success will strengthen support for the work of more traditional taxonomists like Art Borkent. It would be ironic, but pleasing, if microbial communities which used to be the hardest to study taxonomically, helped come to the rescue of the taxonomic studies of organisms that used to be the bread-and-butter of taxonomy.

Ruminating about the implications of the 4^th of July

About three months ago, I decided to write occasional articles in this series that would be reflections on the larger implications of various topics. In the past few days, I found myself reflecting on the significance of the Declaration of Independence and the 250^th anniversary of the founding of the United States in 1776, celebrated on Saturday. Specifically I came to focus on a key, but unspoken assumption, behind the Declaration of Independence and how it relates to the purpose of this newsletter, the need for people to understand more about biology.

A connection between the founding of the US and the subject of “scientific literacy” might seem quite a stretch. I will explain my thought but that will require backing up and giving a bit of history.

Some historical background

The 4^th of July holiday commemorates, as everyone knows, the coming together of a group of notable men from what were then the 13 British North American colonies south of Canada to sign a public statement about why they were rejecting rule by the British crown. In early July of 1776, they had been in a state of low-level rebellion against Great Britain for more than a year but without much coordination or a master plan for the war or a clear idea of what might come afterwards. It was felt by many of these prominent colonists that a statement of purpose was badly needed. It was needed to tell the British what the aims of the colonists were but, no less, to explain to the citizens of the thirteen colonies what the whole effort was about and why it was needed. Thus the document we know of as the Declaration of Independence, first drafted by one of these men, a Virginian named Thomas Jefferson, then only 33 years old, was approved and soon publicized throughout the colonies.

It is a peculiar document and had to be since nothing quite like it had ever been written before. It grounds the reason for the rebellion in a highly idealistic statement about the nature of humanity and what human societies should aim to be. In its most famous phrase, the one that gives the document its universality, it says that “All men are created equal“. Furthermore, it adds that they are all entitled to “life, liberty and the pursuit of happiness“. The Declaration then went on to describe a bill of charges against the British king for having done many things that infringed those rights.

Much ink has been spilled detailing the hypocrisy of the signers, in particular the fact that they could not have literally meant “all men“ since a large fraction were slave owners, who did not immediately set their slaves free. Nor did they ask their wives to co-sign, Hence, “men“ meant men, not human beings, which would have included women. Clearly, the signers were thinking of men like themselves: white, wealthy, upper middle-class. But let us leave such complications aside.

The document ended with the declaration that the colonies were hereby leaving the kingdom of Great Britain. It did not, howeveer, contain a clear statement of what would come next for the colonies. Thus, it was not a plan of government. After all the colonies were fighting a rebellion and it would have been premature to try to design a new government. That would come later with the Constitutional Convention in 1789.

A critical implication of the Declaration

Yet there was a hint of what kind of government would be needed. If the British government exemplified what could go wrong under a king, perhaps a different kind of government was needed. One that did not hinder people from pursuing “life, liberty and the pursuit of happiness.“ Evidently, one could not automatically trust a king to provide that protection. One needed a wider group of people and some form of collective decision making to ensure a greater degree of fairness and justice. That was not stated but was a critical implication.

The Declaration is widely lauded for ploughing new ground in political philosophy and rightly so. Nevertheless, in one sense, it was simply widening the application of a principle that had been established earlier in Britain. That principle was respect for the rights of those being governed. It had first been established by the signing of the Magna Carta in England in 1215, setting out the rights of the feudal lords with respect to the English king. It was followed in the formation of national parliaments in England, Scotland, France and several other countries. (One already existed in Iceland.) The so called Glorious Revolution in England in 1688 further reduced the power of the English king and elevated the rights of the people represented in Parliament.

What the Declaration did was to claim that all the people, not just aristocrats or land owners, should have their rights and views respected by the government. How could that be achieved unless the people could let their views be known? Just as important, how could the rulers – the king, his advisors, the parliament – trust the views of the people to be sensible? Could the government be certain that the people were able to give sound advice on how they should be governed?.

To make sensible decisions about how a government should run, people need to think critically about proposed policies. That is a different skill set than needed for doing one’s normal work. One needs to be able to read and to reason about new things. In effect, one requires new information and the ability to evaluate it.

In short, if one is going to have a democracy, you need an educated people; citizenship requires an educated citizenry. I am sure this was not something the signers of the Declaration were thinking about much in 1776 nor perhaps were the men who assembled thirteen years later at the convention that drew up the Constitution. But by the early 19th century, it was widely recognized in the new country. If one were to going to have a democracy, one needed a people who could think about larger issues. That required systems for their education.

To return to the beginning of this article: What does this have to do with “scientific literacy“ and, more specifically, knowing and understanding some biology? Probably very little in the early days of the Republic. The word “biology“ was not coined until 1802 and “science“ in its modern sense not until the 1840s. Hence, the average citizen of the US or indeed of any country did not need to know much about biology or science in general in the late 18th century.

On the importance of scientific literacy today

Things are different today. Scientific findings are embedded in virtually everything we do and engage with, from our modes of cooking to using our phones and computers to many of the things we do simply for enjoyment. The knowledge of the underlying science need not be deep but some understanding is helpful. I would argue, however, that we especially need to engage with a lot more biology than we do for our mechanical-electrical devices. For everything connected with our diets and health, understanding the basic facts of the relevant biology is immensely useful. Even for many things we take for granted and rarely think about, such as sleeping, it is good to know something about the basic biology. It is, I would add, even enriching, to understand such things. The biology of sleep is an example. It is interesting in itself and helps one understand why we need it and how to get enough.

There is, however, a reason beyond decisions in our personal lives that makes understanding of biology so important. We are biological beings and that is relevant to everything in our lives, not just our basic individual needs, but our environments and social interactions. Virtually every political decision and every public policy that affects us does so, in part at least, through our biology. The effects may not be just physical but often also psychological, since our psyschology is part of our biological make-up. Our moods are effected by our bodily state and vice versa.

The implication of those thoughts is that in thinking about political actions proposed by the government, we should evaluate them in part by their expected effects on us as living creatures. For that we need to understand more biology. That does not mean having vast knowledge of biology but enough to make at least preliminary critical judgments about new facts that concern our biology. Once we know some biology, we can often draw more reliable conclusions as to how proposed policies are likely to affect us. Those effects may involve our environments, the medications we take (or do not), our diets and nutritional states and many other things .

The political implications

Knowing more biology and science generally also allows us to evaluate better our top political leaders. A politician who declares that climate change is a hoax or that approved vaccines are dangerous should be viewed with real scepticism. Not only are such people more likely to create harmful policies on those topics but, in making such claims, they indicate that they probably lack sufficient critical ability to make good decisions about anything.

Thus, good citizenship is more demanding than it was at the time of the Declaration of Independence. However, it also has the potential to be more rewarding because it requires a deeper understanding of our world– and that is always satisfying.

The signers of the Declaration not only set a higher standard for government but for us, the people. Whatever their conscious intentions and personal blind-spots, the Declaraion was a massive vote of confidence in the ability of humanity to look after itself. We should welcome both the compliment implicit in that confidence but also the responsibility it lay upon us to make intelligent decisions affecting ourselves and our posterity. The reference to “all men“ extends both the compliment and the duty far beyond Americans to humanity as a whole.

On defining what “theory of mind” means

We humans are clearly highly social animals. We like being together and interacting with one another, and much of our lives is bound up with those social interactions. Indeed, as a social animal, we are undoubtedly the GOAT (“greatest of all time”). That is because we have language and speech, which give us a precise form of oral communication. It is unparalleled amongst other animals and is vital to our social interactions.

Yet while language is essential for so much of our sociality, it is hardly sufficient. It is made possible by a hidden characteristic: all of us, or at least the great majority, fully understand that each of us has their our individual mentalities, which is the source of our outward behaviours, especially our social behaviours. This understanding, that others have their own mentalities, has been called “a theory of mind” or ToM. Human beings are quintessentially a species with “theory of mind”. (Synonyms for this term include: “mentalizing”, “mind-reading” and “folk psychology”.)

If this concept, or at least this formulation, is new to you, your reaction, after a moment, might be: could it be any other way? How could we interact with other people without realising that they too must have a personality and inner life that shapes those interactions?

There is, however, an alternative possibility. This is that we are genetically “programmed” to react in standard ways, though often in a series of reactions, to each typical situation. For instance, if I know you and pass you on the street I will smile at you and you might then smile at me and/or one or both of us may say “hello” and wish each other a good day. Or, another time, if I accidentally step on your toe and you get angry, you would see from my expression and exclamation that I had not meant to do this and will feel less angry and (probably) accept my apology. However, do such actions automatically indicate an inner life? Would a space alien observing such interactions from a distance automatically conclude we had ToM or would they just see us as automatons undergoing complex sequences of programmed reactions? The second answer might be the one that occurs to them first, especially if they had little emotional content in their own lives.

The automaton view of behaviour seems to be well illustrated by the intricate social activities of the social insects, namely ants, bees, wasps, termites. These are fascinating animals with amazing behavioural repertoires but, until recently, no one had argued that they saw each other as individuals with their own minds. Yet new information suggests that bees are sensitive to each other’s emotional states and modify their behaviors accordingly. If further work supports this, we are edging up to the inference that bees see and respond to each other as individuals, i.e. that they have something like ToM.

On human language as a guarantor that we humans have ToM

The reason that we can be sure that we humans are not biological automatons is that we have language and can tell each other about our feelings and motivations. We can describe them rather precisely and in so doing share our mentalities. The point is not that language ensures that we always do this accurately – we do not always understand the roots of our own feelings or why we reacted with action A, not B, on one occasion when the day before, in a comparable situation, we did B and not A – but that we feel that we have an interior life which is shaped by our individual mentality. Our words and life histories reinforce this conclusion all the time.

But what about non-human animals who lack language?

But that is us, humans. What about other animals such as our fellow mammals and even birds? In principle, the behaviours of these animals, including their social interactions could be complex action-reaction sequences that they perform without understanding what they are doing. Examples might be birds guarding nests or monkeys engaging in grooming or any of the other typical myriad behaviours of these more complex animals. This idea of animals-as-automatons has a long history in Western thought.1 It goes back to the mathematician and philosopher René Descartes (1596-1650), who posited that the human soul simply inhabited the human body but was wholly distinct from and unaffected by it. Complementary to that thought, and in line with his religious beliefs, he denied that animals have souls of any sort and saw them as utterly different, indeed as “machines” and their behaviours an automatic outcome of their material nature (which, of course, was completely unknown at the time).2

That view of animals may have faded somewhat as Cartesian ideas lost some of their prominence in philosophy over the following century but returned in the 20^th century in the guise of “behaviourism” in psychology, which tried to obliterate the idea of mentality altogether. Its founding father, the psychologist B.F. Skinner (1904-1990) maintained that the Mind was something that was forever beyond scientific investigation and that what science should concern itself only with things that could be measured. For him, this was behaviour. In Skinner’s view, one could do experiments and measurements on the behaviours of animals but no conclusions about mentalities could ever be reached. He thought that the idea of mind was an unsupported fiction that deserved no attention. (Needless to say, he had no patience for the ideas of Sigmund Freud, who had led an earlier 20tjh century revolution in psychology.) Skinner’s ideas were very influential for several decades.

This whole issue – do animals have a “theory of mind”? – came alive in 1978, with the publication of a paper by two primatologists, David Premack and Guy Woodruff. It was titled “Does the chimpanzee have a theory of mind?” The paper introduced both the term and the idea, via a review of some behavioural experiments, to the field of psychology. They worked with tame chimpanzees and their experiments involved chimps viewing humans who faced one problem or another. The experiments involved giving their chimps behavioural choices that revealed whether they understood a dilemma the humans were experiencing. In effect, the tests were designed to show whether or not the chimps could put themselves in the shoes of the humans, that is imagine their thinking. There was one kind of situation where the chimps could not do that but the results for the most part were positive. Hence, the authors gave a firm “yes” to the question posed in their title while arguing that the chimpanzee theory of mind might be simpler than that of humans.

The choice of chimpanzees for this work deserves a comment. First, it was always going to be the animal of choice for David Premack and his wife Ann, his chief co-worker, since they were trained as primatologists and worked with chimpanzees. In addition, chimpanzees had long been recognized as humans’ nearest animal relative, hence the most likely to show either the same or closely-related mental qualities to ours, if any animal had them. Furthermore, it had been known, since the work of the pioneering psychologist Wolfgang Kohler in the 1920s, that chimpanzees had lively intelligence and could solve various problems put to them by experimenters, including using various tools to help them, where the animals had not been trained to use them but were using their native intelligence to figure out a new situation.

Furthermore, in testing chimpanzees for a previously unassessed ability, you could hope to learn something about the evolutionary roots of that quality in humans. If you confirmed that the chimps had that ability, you could tentatively conclude that it had probably been present in the common ancestor of chimps and humans. That primate ancestor was estimated to have lived about six million years ago, when the human and chimpanzee lines of descent had separated. Hence, any mental capacity shared by chimps and humans today could be judged to be at least that old. In contrast, if the experiment produced a negative result, one would tentatively conclude that it had arisen in the human lineage specifically after the evolutionary split from chimps.

The results of the first experiments on chimps were positive and thus indicated that ToM in primates was probably at least six million years old, though it could have been even older in the primate lineage. Scattered earlier observations on monkeys, however, were interpreted to mean that these primates did not have ToM, hence that mental ability might have arisen no earlier than six million years ago.

The Premack and Woodruff work on ToM had been preceded and in part inspired by various studies on how human children develop their own ideas of the mentality of others. This was work carried out by Jean Piaget and others interested in child development. The results indicated that in human infants, of one to two years, there is already the capacity for understanding that someone else’s perspective can be different from their own. However, the chimp study in 1978 was the first comparative and experimental study on non-human primates and set off much new work on this topic, both in chimpanzees and later in monkeys and, still later, other animals.

This remains, of course, a controversial area and, as in any approach to states of mind, one inherently difficult if not impossible to resolve definitively. Hence, it is not surprising that there have been a diversity of results and interpretations, some supporting ToM in other animals, others disputing it. On balance, however, the consensus is that chimpanzees, at least, have theory of mind though not as sophisticated as that of humans. Some more recent work on monkeys, particularly marmosets and rhesus monkeys, also suggest that these primates have ToM, at least for their conspecifics.

However, what about still more different animals, such as dogs and intelligent birds such as crows and parrots? Dogs are a particularly important test case because they are so much our creatures, having been first domesticated between 20,000 and 30, 000 years ago.

For much of this period, dogs have lived not just in close physical proximity to us but been so enmeshed in our lives. For an animal in such constant contact with humans, there would be a huge advantage in their having a theory of mind for their humans. And ask any dog lover whether their dog has some sense of them as an individual and the response is likely to be astonishment that you could ask: “why my dog loves me and my family and shows no such feeling for anyone else!” But that is anecdotal evidence. Perhaps dogs are simply clever manipulators of their humans, to get food, affection, etc. Are they just treating us as food-delivering automatons for whom the right buttons must be pushed? Reassuringly, some brain scanning work confirms that dog brains do not work this way and that their emotions are engaged when interacting with their owners specifically.3

At present, one must conclude that the issue of whether non-human animals have ToM is still not settled, with much controversy still surrounding the question. The answer depends upon: a) one’s definitions (e.g. what exactly “theory” means); b) what are the criteria for ToM? (The more stringent the criteria, the more frequently different animals will be ruled out), and c) of course, the quality of the experiments and how one evaluates the results.4 Yet, there is certainly much more evidence today in favour of the idea that some animals have ToM than when the work began nearly 50 years ago.5

I have no credentials in this field but I would like to offer a tentative opinion; I suggest it only as something to consider. The problem is, in part, that the question is posed as a binary: do non-human animals have ToM or not? But what if there are degrees of understanding that the other person/creature has their own mentality and of the kinds of thinking they can do? A non-human animal almost certainly will not have the depth, breadth or range of understanding in interacting with a conspecific or human that a human has but they might have some inkling of the other’s mentality. This is what Premack and Woodruff concluded about chimpanzees, that chimps had a theory of mind but that it was not as good as ours. Furthermore, isn’t this what one would expect in evolutionary terms: that the capacity for theory of mind that we humans have could not have emerged out of nowhere in our lineage but must have had precursor states in our ancestors, perhaps the earliest long ago in our early mammalian ancestors?

Let me leave the reader with an image and a question. The image is of two sibling lion cubs having a play fight, as lion cubs will. This is play right from the start of a session and neither gets hurt though it looks pretty rough at times, with teeth occasionally bared. Does not each cub at some level know that the other is engaging in non-threatening, non-dangerous activity? And doesn’t that feeling amount to knowledge of the other’s mental state during this activity? Perhaps that knowledge is too basic to be called an idea let alone a “theory” but it does amount to some understanding of the mentality of the other. Might it not be the case that all complex social interactions in mammals and other vertebrates involve at least a primitive sense that the other participants have their own degree of agency and their own mentalities?

After all, the history of animal behaviour studies over the last 60 years or so has in part been a story of one claim after another of human uniqueness being undermined by demonstrations that those properties can be found in other animals. We will return to that history in subsequent articles but, for the moment, I will only suggest that ToM might be following a similar trajectory, a trait believed initially to be unique to humans (or only shared with their nearest relatives) to something more diffuse in character than the human version but far more widely shared in the world of animals.

Recommended Reading

1. Premack, D., Woodruff, G. (1978). Does the chimpanzee have a theory of mind? Behaviour and Brain Sciences 4: 515.526.

2. Baron-Cohen, S. (1999). Evolution of a theory of mind? In The Descent of Mind: psychological perspectives on hominid evolution. Eds. M. Corballis, S. Lea. Oxford: Oxford University Press.

3. Berns, G. (2013). How Dogs Love Us: a neuroscientist and his adopted dog decode the canine brain. Boston: Houghton Mifflin Harcourt.

4. Berns, G. (2017). What It’s Like to Be a Dog: and other adventures in animal neuroscience. New York: Basic Books.

5. Call, J., Tomasello, M. (2008). Does the chimpanzee have a theory of mind? 30 years later. Trends in Cognitive Sciences 12: 187-192.

6. Call, J. (2001). Chimpanzee social cognition. Trends in Cognitive Sciences 5: 388-393.

On “scientific suicide”

The phrase “scientific suicide” in the title might not be immediately clear. Does it refer to a suicide done “scientifically” (whatever that might mean)? Does it indicate science done so badly that it terminates careers? Or does it denote the actions of a larger entity that inexorably damages or terminates scientific work? In this article, I will be talking about scientific suicide on the largest possible scale, the national one. Perhaps, however, “suicide” is the wrong word. Perhaps “grievous self-harm” is more accurate. In none of what I describe did a country deliberately set out to kill its ability to do science. Yet “scientific suicide” is a more vivid term and expresses the seriousness of the situation better.

Spoiler alert: the short answer to the question in the title is that there are three main ways in which nations commit scientific suicide. They are: 1) reducing or eliminating the participation in science of any large group of people, 2) taking away the money for research, and 3) doing both. In this article, I want to look at three examples that illustrate these routes. Two are in the past: Nazi Germany in the 1930s and Russia in the 1990s. The third is the United States and what it is doing to itself right now.

The three situations differ greatly but a common theme emerges: scientific systems that had taken decades to build can be destroyed within months or a year or two and the damage can be irreparable. The two historical examples (Germany and Russia) show how slow and incomplete the recovery can be while the current example, the US, is still going through the destructive phase, hence we cannot say when a recovery might begin or how long it would need. However, the historical precedents and simple logic indicate that the diminishment of US science will be marked and long-term. This account will not be detailed in its numbers and statistics but in its general outlines it is correct.

Germany, 1933-1935

Let’s start with Nazi Germany, the simplest to describe. The destruction of German science started with a clear ideological idea: that Jews were harmful to German society and therefore that any Jews in high positions should be removed from them. The National Socialist-dominated government came to power in Germany on January 30, 1930 and immediately started propagandizing against Jews. On April 7, it issued an edict requiring the sacking of all Jewish professors from university positions and this was promptly carried out by the universities. The effects upon teaching and research were immediate, and affected all departments, not just science faculties though the latter were particularly hard hit.

This might seem more accurately described as a governmental action rather that of a country as a whole. Yet there was overwhelmingly compliance by the universities and departments in Germany and many academics supported the new law. Behind that widespread complicity lay wide-spread anti-Semitism, fear of the consequences of non-compliance, and, of course, opportunism since this expulsion of Jewish scientists opened up new positions for people remaining.

It was of course not portrayed by the government as a destructive act but as an improvement, an act of purification as it were. Hitler spoke of eliminating “Jewish science” and it was clear that he had certain Jewish scientists in mind, in particular Albert Einstein. Whether he actually believed that the kind of science a person does actually reflects their ethnic origins is unknown. There is no evidence that he understood much about science but it is clear that his particular animus was against scientists who were of Jewish origin; this was not bigotry against a certain religion, Judaism, but against an ethnicity. Those fired included many whose family had converted to one or another branch of Christianity. Altogether, it is estimated that around 2500 Jewish scientists, about 20% of the scientific workforce in Germany, lost their jobs. The vast majority chose to emigrate, not to stay in Germany and look for other work there.1

Behind such numbers lie as many individual stories. One particularly interesting account is by a biologist who was not Jewish but who had Jewish friends in a German village in Bavaria during his childhood in the 1930s and early 1940s. This was the late Ulrich Grossbach and he witnessed their forced departure without fully understanding what was happening to them but was deeply disturbed by it. (I learned the story directly from him.) His account was of a geneticist named Ernst Caspari (1909-1988), who was Jewish by descent though his parents and he were practicing Protestants. As a graduate student in the 1930s, he made one of the seminal discoveries about what genes do – namely, that many genes specify enzymes – that led to the definitive later work in this area. He was not forced out of German science in 1933, with the initial wave of firings of Jewish scientists, but in 1935 after publishing that important work. He first went into exile in Turkey, then a few years later to the United States, where he had a decades-long distinguished academic career. In the end, Caspari’s story was thus a lucky one but Grossbach’s account makes clear how stressful the beginnings of the Nazi period were for German scientists.2

Though one cannot quantitate the damage done to German science by this expulsion of Jewish scientists, historians generally agree that it seriously harmed it, especially in physics. A current estimate of the number of scientists, mostly Jewish, who emigrated in the 1930s, in response to Nazism is 2500. That exodus included seven Nobel laureates and 20 scientists who would win a Nobel Prize later. This brain drain almost certainly contributed to the fact that Germany lost the race to develop the atomic bomb. Indeed, the Manhattan Project was initiated by the Roosevelt administration in 1942 in response to a plea by two Jewish immigrant scientists, namely Einstein himself and Leo Szilard.

The immediate damage to German science was probably not apparent in the early 1940s but it was clear after the war. Of course, the defeat in the war itself massively set back German science. Hence, it is impossible to estimate what proportion of the diminishment of German science was due to the forced emigration of Jewish scientists in the 1930s. What is certain is that what was Germany’s loss, due to its own actions, became a gain for other countries, especially Britain and the U.S., which gained the majority of the Jewish scientists who had fled Germany.

In the 1960s, when I was working for my degree in genetics, I was aware of four of them as major figures in my field. Three were men (Caspari, Curt Stern, and Richard Goldschmidt) and one a woman (Salome Gluecksohn-Waelsch) whom I had the honor of getting to know three decades later when she was in her 80s. Before the war, the U.S. had not been in the first rank of nations scientifically but after the war, it was, without question, the leading country in science.3

Russia, early 1990s

The second case of national scientific suicide concerns Russia, after the end of the Soviet Union in 1991. Maybe this is best seen as an accidental consequence rather than the result of a deliberate policy, as occurred in Nazi Germany.

I first learned about it on a two week trip to Russia in 2007. The purpose of that trip was to commission interesting articles for my journal, BioEssays, a broad-ranging biology review journal. This trip involved talking with many Russian scientists. Again and again, the decade of the 1990s came up as a traumatic experience. Basically, during most of that decade, until the very end when there was the beginning of an upturn, Russia was bankrupt. There was neither money for the work itself nor for salaries. People were struggling simply to survive and where possible to keep their programs going on a shoestring. Apparently, the financial disaster began with the lifting of price controls, which had been a feature of the Soviet years, and suddenly, everything became very expensive. In addition, all the banks involved with printing rubles did so with little restraint. (This happened not just in Russia but in all the other former Soviet republics.) The result, predictably, was hyper-inflation.

Altogether, about 1.4 million people left scientific research in Russia during this period, with estimates of 80,000 to 100,000 scientists emigrating. This was obviously a catastrophic blow to Russian science.

The whole traumatic experience began to ease soon after Vladimir Putin came into power in 1999. He made several changes that stabilized the currency and strengthened the foundations of the economy. (This is when Russia started becoming a petrostate, dependent for its survival on its oil reserves.) Many of the scientists I talked with gave Putin credit for creating the conditions that allowed some sort of normal life in Russia to resume after the catastrophic Yeltsin years but I was struck by how little warmth and approval many of them had for him. Some even referred to him as a dictator and did so without fear, which would have been impossible during the Soviet years (and quite possibly again today as Putin has tightened his control on Russian society).

Hence, by 2007, science in Russia was reviving somewhat. People had salaries that they could live on and there was now money for research (though still far less than in Europe or North America.) But one kind of damage had persisted. There was a missing generation in Russian science, those who had been in their mid-20s to mid-30s during the 1990s – this tends to be the period in life when one is at one’s most creative – but who, seeing the situation, had fled abroad (to Europe, North America, Australia). This not only created a major hole in the scientific work force but had removed the very people whom young scientists in the noughties (British slang for 2000-2009) needed as mentors. During my visit, many people stressed to me what a serious problem this was.

It is now nearly 20 years since that visit in 2007 and I do not know what the situation in Russian science is today, though I suspect it is worse. The war in Ukraine has drained both people – about 2500 Russian scientists have emigrated – and the war must be draining resources for science. What I took away from the experience of my visit was a new appreciation of the importance of the continuity of human resources in science. If you want a healthy national scientific environment, you cannot delete a generation. Doing so creates a deep wound that is very difficult, perhaps impossible, to heal.

The United States: 2025-??

My third example of national self-harm in science is the United States now. If you visit the US today and talk to scientists, as I have just recently, things do not look that different at first. College campuses and institutes look largely the same, many labs are busy, life goes on. But if you probe a little deeper, or just read the top science magazines, one realizes that there is some kind of general crisis in American science today. It is hard to quantitate the damage done so far and impossible to estimate the long-term effects but it is helpful to keep the distinction in between the immediate damage and the knock-on long term harms that will follow the present damage. The latter are certain to be huge but hard to estimate now.

There will be books written about this period in American science and any short summary now will be grossly incomplete and quite probably distorted relative to later evaluations. However, the source of the problem is clear: the animus of the Trump administration to scientific research and perhaps the idea of science itself. The first Trump administration showed some signs of this hostility but in the second one, the attitudes are more obvious and the attacks more virulent. It is not just the views of Trump himself but a whole cadre of people who serve under him who were almost certainly picked in part for their rejection of science or, at least, for their rejection of certain ideas. The most obvious of these is Robert F. Kennedy, Jr., the Secretary of Health and Human Services, who is famous for his rejection of vaccines (despite the mountains of evidence in their favor). He is often described as now the most important man in American science. Unfortunately, he is not a scientist and clearly knows little biological science. The dangers that he poses to American scientific research and to the health of America and, indeed, the world, cannot even be estimated today but are probably huge.

I think that the pitchfork attack on science in the USA has at least four prongs. First, and most obviously, there is the cutting back of specific programs and their funding. These range from space research projects, sometimes decades in the planning and creation, to all kinds of disease research projects and biodiversity programs and climate change research. Second, there have been the attacks on and often the firing of many prominent scientists whose views were seen as out of register with the Trump administration goals. Third, there has been a tightening of the rules around allowing non-US citizen scientists to come work in the US. Since young scientists, many from outside the US, are often at the heart of scientific research, this crack down on young scientists from other countries may be the most damaging. Finally, there is the open attack on specific ideas, in particular those about the efficacy of vaccines and the reality of climate change.

The attack on funding of so many programs, totaling many billions of dollars, was the most dramatic and promised the most immediate damage in early 2025. However, the courts have increasingly weighed in and reversed a lot of these cuts. Also, enough Republicans in Congress, responsive to constituents who benefit from many of these programs have restored many of the funds, giving evidence of a certain resilience in the system. Still, it appears that thousands of research programs have been ended or severely curtailed. Also, the Trump administration is still talking about massive further cuts to NIH and the NSF.

Nevertheless, at present, I would emphasize the loss of human scientific resources as probably the most serious aspect of the attack on science. This has multiple forms, in particular the discouragement of young foreign scientists from obtaining work in the US, noted above. However, a worsening of the climate for scientific work is also affecting young native born Americans. There has not yet been a massive exodus of these scientists to Europe, Canada, Australia and other places but I cannot remember a time when so many were thinking and talking about it. Ultimately, the health of science depends on its human resources and the current threat to that element in American scientific research is big..4

Outlook

Of course, these four factors are connected and reinforce each other, which makes the potential reversal of the whole situation anytime soon hard to imagine. The diminution of American science today is still not close to what Germany did to itself in the 1930s or what happened to Russia in the 1990s but the undisputed pre-eminence of American science since the end of WWII is at some level, already gone. The reason is that confidence in the future of American science is already gone. As noted earlier, destruction of a civilizational state is much quicker and easier than building it up in the first place. Similarly, recovery from a period of extensive damage may be very slow even if new financial resources begin to flow in. That slowness reflects the fact that it takes both time and continued effort to restore the full human resources. Large numbers of people have to believe in the future of science for them to commit to it. I suspect that it will take decades to repair the damage that has been done in the past year and a half and, of course, it is not guaranteed that such repair will take pace.

We will return to this topic later. Stay tuned.

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On expecting unforeseen disasters

As readers of this newsletter may suspect, I give some thought to titles of my articles. A good title draws people in to read the piece; dull titles do the opposite. There are two criteria for a good title for any non-fiction essay. First, it should indicate the subject of the piece. to sort likely readers from those not interested in that subject. Second, a good title can hook the interest of the reader, promising something informative. Of course, an appealing title obliges the author to deliver a good piece, not a boring one.

I hope that my title, “The pandemic next time”, has caught your interest. In 2026, everyone over 12 years old knows what pandemics are, since we all went through one between 2020 and 2022/23, and will have a sense of their importance for human societies. Furthermore, many older readers will catch the reference in the title to a book first published in 1963. That book was by the gifted Afro-American writer James Baldwin and was titled The Fire Next Time. It was about how anti-black racism had poisoned American society for centuries, for whites as well as black people. It was meant to serve as a warning for America that racism, if not attended to, would continue to be a major problem for the society.

A pandemic disease, especially one that has not yet taken place, is clearly a different kind of problem from racism, a persistent long-standing condition, not an event . However, once one accepts that the extent and severity of a pandemic will be influenced by the character of the societies it races through, the difference diminishes. If various factors can influence how bad or long a pandemic is, then steps can be taken in advance to ameliorate those effects. In his book. Baldwin did not lay out a program for reducing racism but his warning was prescient. His book was published just as the civil rights movement in America had begun to gather strength. By the late ‘60s, there was a small wave of urban riots by black Americans, who increasingly saw that increased accessibility to the vote in the South had done little or nothing to address the problems of black people in the North. Martin Luther King, Jr. had emphasized this point for several years in his public statements. The fire next time had arrived by 1968.

As for a new pandemic, should we, having just recovered from COVID-19, be thinking about it now? Most public health experts think so. It is hugely probable that there will be another and probably within the next few decades. Please remember that we have had two in the last 40+ years. First, there was the AIDS pandemic of the late 1980s, then COVID-19. There had also been a couple of near-misses, in particular, the Ebola outbreak in Africa more than a decade ago, which was handled and curtailed with some very fast and intelligent management. Then there was SARS-1, in the early 2000s, involving a virus related to that causing COVID-19. The existence of two big pandemics in about 40 years should alert us to the strong possibility of another pandemic . Will we be ready for it?

On the favorable conditions for new pandemics

The conditions favoring pandemics are already in place. Let us note them. The essential ones are: dense human populations, frequent animal-human interactions, and animal and human contact between distant regions. These have been a feature of human civilizations for more than a millennium but especially so in more recent times.

A pandemic occurs when the disease agent begins to be rapidly transferred from human to human across large distances. A highly infectious agent, bacterial or viral, and close proximity of people to each other – from small groups such as families to much larger social units, such as towns or cities – is usually enough to produce this condition. Before this stage, however, there is often a long prior stage in which the infectious agent circulates in one or more animal species, often without marked pathogenicity though sometimes causing illness or death of the animals. This relatively “silent” period ends when the infectious agent is transferred to humans, causes visible illness, and is readily infectious. This process of movement from wild animals to humans is termed “spillover” or, to use the technical term, “zoonosis”. 1

It is believed for instance, on several grounds, that the AIDS virus, HIV, initially circulated at low levels, probably in a somewhat less pathogenic variant in wild chimpanzees in Africa for perhaps more than a century before it spilled over into humans, probably through the ingestion of chimpanzee meat from infected chimpanzees, so called “bushmeat”.2

However, wild animals are not the only source of pathogens with human pandemic potential. Domesticated animals, which exist in far greater numbers than any wild animal species, can also be a major reservoir, and source of, such pathogens. It is believed that SARS-1, which never went beyond epidemic status to become a pandemic, came from infected chickens.

A big factor in the spread of pandemic pathogens, once humans have been infected, is modern air travel. The rapid spread of the COVID-19 virus from China to Europe and North America in late 2019-early 20202 almost certainly involved air travellers who had picked up the virus but were asymptomatic at the time of their flights. Since many pathogens have an incubation period that can last days during which they do not cause visible symptoms, the dangers of infected travellers can never be entirely eliminated.

In an ever more crowded world, of bothpeople and domestic animals, and probably of increased contacts between wild animals and people, the factors that lay the groundwork for a pandemic, are, if anything, increasing.

Reasons for both hope and pessimism

What can be done to reduce either the chances of a new pandemic starting or, at least, the force of its impact? Should the world treat such events as inevitable, the equivalent of an Act of God, as viewed in earlier times, against which we are powerless? Fortunately, the answer is a firm “no”. Measures that could make a big difference can and should be taken. What is unclear is whether they will be taken soon enough and how efficacious they will prove to be.

One action that might help, in principle, would be identifying likely viruses that might be involved. A problem is the sheer numbers of different viruses that exist that might have some pathogenic potential and with some ability to spread from animals to humans. One estimate that I have seen of the numbers of kinds of viruses present in mammals and birds that may have that potential is on the order of 2 million. Of course, the a priori expectation is that a large proportion of these viruses are well-adapted to their hosts. This might make them less likely to infect humans. That is some consolation but not much. Sometimes a non- or weakly zoonotic virus is just one or two mutations away from being more strongly pathogenic to humans.

Fortunately, much is known about many viruses and the factors that influence their zoonotic capacity. Clearly, if any of those with high spillover potential are identified in samples taken from infected persons in a new infectious outbreak, and if the identification is made early, often things can be done both to treat the patients and to limit the spread to new people. Even if the virus is new to biological science, most such would be clearly related in their RNA or DNA sequence to previously identified viruses – being in the same virus “family” – about whose disease potential something is already known. Sometimes this includes information on treatment and how to reduce the spread of such viruses. That relatedness might in turn provide clues as to how to proceed.

An informative analysis of this kind was published in 2021 in a top American journal, the Proceedings of the National Academy of Sciences. It scored a total of 887 viruses from about half a million tissue samples from approximately 75,000 wild animals, for their risk potential in terms of 31 well known risk factors. They were then ranked as to probable dangerousness from the combined assessment of these factors and put in a data base named, appropriately, Spillover. Gratifyingly for the reliability of the analysis, the top 12 viruses, rated in this way, out of the top 50, were all known to have serious zoonotic and pathogenic potential. These particularly “bad actors” included Lassa virus, the COViD-19 virus (officially designated SARS-CoV-2), Nipah virus, and rabies, for all of which there is helpful information. This data-base will undoubtedly be a big help in identifying pathogenic viruses with the potential for causing pandemics in the future.3

There is a chance, however, that we already know the viral agent of the next pandemic. This is the influenza virus known as H5N1, more commonly referred to as “bird ‘flu”. This virus has been spreading amongst wild birds for many years now. It has spread amongst many different species around the world and has killed many millions of wild birds.

Over the last three years, the virus also has been detected in domestic poultry, sometimes mild but frequently lethal to the chickens. One estimate of the number of infected chickens in the US alone is 175 million. That is less than 10% of the estimated number of domesticated chickens in the world but it is still a large number. It is now apparent that it is also spreading amongst domesticated cattle and that it can be transmitted from chickens and cattle to humans, though at a relatively low rate and most typically in a mild form. Human-to-human transmission has, so far, not been reported.

At this point, therefore, this disease does not look threatening to humanity, at least compared to the known influenza pandemics of the past, especially the most severe, that of 1918-1919, estimated to have killed 50 million people. Nevertheless, the speed of spread and the documented record of its zoonotic potential, amongst different wild birds, then amongst domesticated chickens and cattle and other animals (such as cats and raccoons) give serious grounds for concern. A letter to Science in the March 5^th issue, signed by seven experts, is titled “Prepare now for a potential H5N1 pandemic”. That letter and its warning should reduce complacency about the problem. Remember, the genetic distance between a mild infectious virus and a deadly pathogenic one can be as small as one base pair in the genome of the virus. Of course, other factors come into play as to whether a virus becomes a serious pathogen but the potential for a pandemic developing from a previously mild disease is real. Waiting until there are greatly increased numbers of very ill, or dead, humans does not seem like a particularly wise strategy.4

And, of course, the danger of a new pandemic arising unexpectedly from a new source remains real. In recent weeks, there has been news of a new deadly hantavirus infection, seemingly arising on a cruise sheep. The passengers who did not fall ill were given some degree of screening before being allowed to return home but the risk of this virus yet spreading is not zero. Perhaps more worryingly, there is a new outbreak of Ebola in Africa involving a viral strain for which there is no vaccine and the danger of its spreading is still unclear.

On possible policies of containment

Inevitably, with an issue of public health, one comes back to questions of policy to head off any new pandemic or, at least, limit its death toll. A distinct strategy is needed for each new virus but there are lots of potential containment measures known that can be chosen from.

Here, however, one comes to a fact both scary and sad. Instead of preparing to head off or at least limit the death toll from the next pandemic, the Trump administration is dismantling safeguards and, thereby, increasing the risks. The first Trump administration did something excellent in 2020, when faced with the COVID-19 pandemic. They facilitated the rapid development of vaccines, so called “Operation Warp Speed”, and thereby probably saved millions of lives.

However, a few years earlier, they had done something that went in the opposite direction. The Obama administration, in response to the Ebola epidemic, had developed a preparedness program for dealing with a future pandemic. The Trump administration never put its recommendations into effect, for reasons they never even tried to explain, and essentially cancelled it. The result was that the US was left flat-footed when COVID-19 hit in 2020. The second Trump administration is continuing along the same lines, which will undermine readiness to deal with the next pandemic and public health in general, again without anything resembling a rational explanation. These measures included: taking the US out of the WHO, ending thousands of research grants for various medical and health issues, firing the advisory board of the CDC, ending the avian ‘flu vaccination program, and more.

One can only hope that there is a return to sanity in public health measures but at the moment there is little sign of that turn-around. That is rather a grim note upon which to end this essay but I cannot think of one that is both cheerful and realistic. The pandemic next time? It may not be that far away.

Why should we believe that all organisms on Earth are linked through evolution?

According to polls in the US, about 50% of all Americans do not believe that evolution created life on Earth as we know it today, in its vast range of organisms, from bacteria to blue whales, from dandelions to cactuses. Indeed, many do not believe in evolution at all. I begin this Substack article, therefore, with two questions for you. The first is: do you believe that all living things on our planet are related through evolution? There are only three possible answers: “yes”, “no”, and “don’t know”. Let us leave aside the “no” and “don’t know” replies and focus on those of you who said “yes”. Then, here is question 2: What is your evidence? Why do you believe in evolution?

One possible answer is: the sequence of forms in the fossil record. With its succession of seemingly related forms over successively laid down rock strata over millions of years, does it not prove the general role of evolution? Actually, it does not. It indicates many, often profound, changes over time in the detailed forms (the“morphologies”) of animals and plants but it does not prove that one form ever evolved into another. It is consistent with that but does not prove it. The fossil record is best at showing extinctions, where a particular kind of animal present for a long time disappears from the fossil record and never appears again.

What it could do, in principle, but has not, is disprove evolution. One of the most brilliant 20^th century biologists, the British geneticist J.B.S. Haldane, was once asked if there was anything that could make him disbelieve in evolution. His instant reply was “A rabbit in the Ordovician”. What he meant was a rabbit’s fossil skeleton in rocks dating to the Ordovician period (485 to 444 million years ago), a time that is more than 400 million years prior to the immediate ancestors of rabbits. If such a rabbit fossil was genuine (not a planted fake) that would indeed be a fatal blow to our ideas of evolution.

What about morphologies themselves as proof of evolution? It is easy – at least once you know a lot about the different kinds of animals – to group animals by degrees of physical resemblance; that is the basis of taxonomy, the classificatory scheme of living things. For instance, lions resemble tigers much more closely than they do elephants or apes. Do not such resemblances provide strong evidence for evolution? Again, no. Those resemblances are consistent with evolution but do not prove it to be the source of changes in living things over time.

If neither the fossil record nor taxonomy supplies proof of evolution as a general shaper of life on Earth, what does? My guess is that most people would, after struggling with this question, reply to the effect of “well, the biologists who study these things have lots of evidence”. True (see last two references, below) but, clearly, that is a weak answer, an evasion. Wouldn’t you want to have a better argument than that?

Most of those who deny evolution’s power in shaping life on Earth do not totally deny the reality of evolution but concede that it can produce small changes, “microevolution” (though that word is used in a more technical sense by evolutionary biologists). The existence of antibiotic-resistant bacteria is an example of this kind of evolution. However, evolution skeptics or outright deniers balk at the possibility that the big changes in shape and form and mental traits in animals were generated by evolution. Furthermore, it is true, as many such skeptics note, that no one has ever observed any such big changes take place. So, to return to the question: is there a kind of evidence that indicates that this huge diversity was produced by evolution?

Here, I will argue that the answer is “yes” and that it comes from study of the large molecule uniquely made by living things that carries biological heredity, namely deoxyribose nucleic acid or DNA. It is the basis of heredity for all organisms on Earth except for certain viruses (whose hereditary material is the related substance, ribonucleic acid, RNA.) My claim (not original to me of course) is that the DNA molecules of living animals and plants and microbes, including viruses (except for the RNA viruses), when analyzed appropriately, provide the essential evidence for evolution.

On DNA and how it changes through time

We must avoid getting deep into the biochemical weeds but we can describe DNA sufficiently to see the gist of the argument. Briefly, DNA is a long molecule, consisting of two intertwined strands, each of which consists of a long polymer (long strings) of repeating units termed nucleotides. The two strands link up in the center via two smaller parts called “bases”, such coupled bases termed a “base pair”. Altogether, scanning down the length of the molecule, there are four kinds of base pairs, each one constituting a chemical “letter”. A DNA sequence is a sequence of these letters, where any letter can, in principle, follow any other. For our purposes, let us just label the four kinds of base pairs as A, B, C, and D.

Each “gene”, a “unit of heredity” (we will return to what this means in another article) has its unique sequence of such letters, which defines it and whose sequence gives it its ability to do its individual thing. In the mid-1970s, two scientists (Frederick Sanger in the UK and Walter Gilbert in the US) and their laboratory colleagues figured out ways to deduce the complete sequence of the base pairs, its “letters”, in a DNA molecule. By the early 2000s, this could be done for all DNAs, no matter their length. The total set of human hereditary material, its “genome”, is present in all cells of the body except red blood cells and has a total of about 3 billion nucleotides. That sequence has been known to near completeness since 2003.

If each nucleotide position can be occupied by one of the four letters, then even in a relatively small gene of, say, 1000 nucleotides, there are 4 ¹⁰⁰⁰ possible different sequences (of A, B, C, and Ds) for that gene. This is already a vast number! but the key fact is that each gene has its distinct chemical identity, written in its sequence. Furthermore, all genes must reproduce themselves very accurately, during cell divisions in the body and in sexual reproduction as one generation gives rise to the next. If they did not, heredity could not work. Hence, each copy in your cells of each gene inherited from your mother is very likely to be essentially identical to her copy, just as each gene inherited from your father is likely to be essentially identical to his copy of that gene in most cells in your body.

Yet mistakes, for instance the substitution, of a B by a D (in our simple labeling scheme) at a particular place in a particular gene, do happen though they are relatively rare. Over many generations these mistakes can build up and the versions of a gene that many people may have inherited from the same ancestor – for instance, someone in your family line two centuries previously -- will generally have more differences from the ancestor’s DNA than those inherited by their immediate offspring. Yet, and this is a key point, not all those differences really matter, many of the changes have very little to zero effect. The term for this lack of effect is “neutrality” (and we return to it shortly). The upshot is that most change in the letters of the DNA script accumulates over time and generations, without causing harm and at a fairly regular rate.

This phenomenon has been termed the “molecular clock”, because the extent of mutational change is roughly parallel to the passage of time over many generations. The changes do not occur with metronomic regularity but they build up steadily over millions of years. (Of course, changes that have a positive effect, selected changes, also build up over long times but neutral and “near neutral” changes provide most of the tickings of the so called molecular clock.)

Why the parallels between DNA change and organismal change reflect evolution

Hence, the closer two organisms are believed to be in their relatedness, the more similar in sequence their genes will be. Conversely, the more distant they are (as judged by their morphological differences) the more dissimilar their DNA molecules will be. An example: all domestic dogs are believed to have descended from wolves some 20,000 to 30,000 years ago. In contrast, as inferred from the fossil record, the line of animals that became apes separated from that which became carnivores (including dogs) 70-100 million years ago, a much longer time interval. The prediction is that the DNA sequences of the genes of all domestic dog breeds will be generally more alike than any will be to that of chimpanzees or humans, despite all the visible differences in dog breeds. That is what is found: the DNA sequence of the genes of your Labrador retriever will be much more like those of your friend’s bulldog than either will be to the DNA of sea lions or aardvarks in your local zoo.

There are complications in this story of course. The most important concerns getting the DNA sequence comparisons right: that the DNA sequences compared between different species are really the same. That means that they must do the same thing, have the same function. This can be tricky because every genome of every complicated organism contains lots of sets of sequences that are similar, sometimes very similar, but actually do somewhat different things. To be certain, you should compare the kinds of DNA sequences that change the most slowly. These are those that “encode” protein chains. It was once thought that that was the main thing that DNA does. Today, we know that, for the human genome, for instance, it is only 2 per cent of our DNA though, of course, that 2% is crucially important.

Because of the way human heredity works, with protein-encoding genes specified according to the rules of the “genetic code”, the more similar the proteins of a given gene in those species, the more similar their DNA must be. The code gives us something else. It consists of 64 groups of three bases, “triplets”, of which 61 encode amino acids, the units of proteins. In general, the least critical for specifying a particular amino acid is the third nucleotide in the triplet. This position is thus frequently neutral, hence the most likely to change at the rate of the molecular clock. Each sequenced gene, therefore, has built in neutral sites for comparison with the other positions. The former tend to undergo steadier change over long periods of evolutionary change.

Is this borne out? An example shows that it is. We believe that we humans have chimpanzees as our closest ape-relatives, if our ideas about evolution are correct. In fact, when we compare the protein coding genes of chimpanzees and humans, we find greater than 99% DNA sequence similarity in specific gene comparisons between them and us, with most of the differences in the third position of the codons. Comparable gene-by-gene comparisons between us and any other species, either other primates (gorillas or monkeys or lemurs) or other mammals or other vertebrates, reveal greater differences.

Thus, the picture of evolutionary relatedness or distance that we deduce from morphologies is mirrored in their degree of DNA sequence differences! This makes perfect sense in terms of what we know about evolution, DNA sequences. But – and this is the crucial point -- that parallel would not be expected if organisms had been created by an Intelligent Designer. Why should such an all-powerful being bother to make the DNA sequences resemble each other in rough quantitative parallel to the morphologies of the organisms? This would be micromanagement on the part of the Deity to an absurd level.

The next time an evolution skeptic or denier attempts to put you on the back foot by arguing that there is no convincing evidence for all living things on Earth being linked by evolution, try this argument on them and put them on the back foot.

Supplementary Reading

1. Zuckerkandl, E., Pauling, L. (1965). Molecules as documents of evolutionary history. J. Theor. Biol. 8: 357-366. (The first detailed statement of why there should be a molecular clock and how it can be used to study evolutionary history.)

2. Pace, N.R. (2009). Mapping the Tree of Life: Progress and Prospects. Microbiology and Molecular Biology Reviews. doi.org/10.1128mmbr. (A

   very good review of how DNA sequence information can be used to

   create a picture of Life’s evolutionary history, “the Tree of Life”.)

3. Mayr, E. (2002). What Evolution Is. Weidenfeld & Nicolson, London. (The final big statement on evolution and how it works from one of the great 20^th century biologists.)

4. Coyne, J. (2010). Why Evolution is True. Oxford University Press, New York. (A slightly later, and of course different statement from Ernst Mayr’s book, on the wealth of evidence for evolution.)

On modes of communication in animals and people

The focus of this newsletter has always been biology: the individual articles describe different subjects in it, why they are interesting, why they are important. A big theme just below the surface, however, is communication. The newsletter itself is attempted communication and a bet, with myself, that this format is a good way to convey ideas and information. Communication itself is, of course, a biological property, typical of many, many organisms. Every organism that communicates with other members of its species has its own way of doing so. Those modes include: tactility (touch), olfaction, vision, making sounds and hearing them. Within each of those modes there are often different forms that work in distinctive ways. The biology of the organism is directly relevant to how it communicates.

That includes humans. We have two unique forms of communication that no other animal on earth has: speech and writing. These are made possible by our biological properties: our oral properties (for speech), our complex brains and cognitive capacities (for both speech and writing) and our dexterous hands and figures (for writing). Of course, both capacities rest on culture and learning but those have biological foundations.

For those old enough to remember the 1960s, the name Marshall McCluhan will be familiar to most. He was a Canadian social scientist who brought awareness of how modes of communication influence not just how something was communicated but what was communicated. This was encapsulated in his aphorism: “The medium is the message.” One can dispute the degree to which this is true – is the content of the message nothing but the mode (medium) of its transmission? – yet recognize that there is a substantial truth in this. The form of communication certainly influences what is communicated and/or how well.

Anyone interested in communicating something knows this, often instantly and intuitively. Take a hypothetical example: a first-rate scientist who is also a wonderfully talented singer. He would not try to present his latest findings in the form of a song, even if he thought his singing was of higher quality than his writing. There is no way he could present in song the data of a graph or a table. A lesser point in ruling out song is that the higher its quality, the more it would distract from the actual scientific content that was the point of the exercise. Thus, the medium should be chosen in large part as to how effective it will be for the particular content you want to get across.

On speech vs writing in human communication

Our species is distinctive in having language as its main mode of communication. When language evolved and how it did so are major questions in human evolution. The ability to use language was almost certainly crucial to our ascent to the top of the primate totem poll, the most achieving primate species of them all. Our highly evolved brain was essential to this ascent but, like any evolved capacity, there were undoubtedly elements of chance (contingency) in whether and how language subsequently appeared. Having a large and complex brain was not enough. Neanderthals had larger brains than we do. Did they have language too? It is unknown. My guess is that they probably had some form of oral communication, like other primates, but probably not sophisticated, Homo sapiens-style language.

Today we have two main modes of communication via language: speech and writing. Speech presumably co-evolved with language capacity. Since Homo sapiens is believed to have first emerged as a distinctive species 300,000 thousand years ago, that is probably a good minimal estimate for the origin of human language, since it is a universal human trait, present in all people everywhere. Of course, language-capacity might be older if the Homo species we emerged from, perhaps Homo heidelbergensis, also had it. If evidence emerges for any capacity for high-level organization and cooperation for any of the early Homo species, that would probably be a good sign that they had some degree of language. (Even art-making might qualify, since it is hard to imagine early humans indulging in this in their group without explaining why they were doing this; grunts or even exclamations meaning “Nice!” would not suffice.)

But with two modes of language-communication, namely speech and writing, can one say which is more effective? Most people would probably choose writing. If speech is as old as 300,000 years, writing is much, much newer, perhaps only about 5000 to 6000 years old, judging from carbon-14 dating of some of the earliest scraps of writing that survive. This late arrival suggests that writing may have been seen then as an advance over simple speaking. (A caveat, however, is that the earliest examples of writing may have been lists of items and their numbers rather than writing as we think of it to express our thoughts and ideas.)

In any event, one survey of the preferred mode of communication when there is a disagreement between people showed that 83% of respondents thought that writing is preferable. In general, writing is a bit slower, with more careful word choice. If so, it might be more precise and therefore more accurate, hence more reliable.

A recent study: speech wins!

A recent, fairly extensive, study published in Nature Communications indicates, however, that that conclusion is probably false, that direct speaking between people is more effective, less friction-generating, than writing. The reduced friction is not irrelevant: if two people are having a friendlier interaction, they are more likely to be receptive to listening to the other’s views.1

The study involved 1500 people and 1854 conversations between pairs of people, where each conversation was over a subject where the two participants disagreed. The tests were carried out at three different US universities. The three modes of communication were: e-mails (writing), direct face-to-face conversation at a table with laptops in front of the participants but not being used (speaking) and video chats (speaking through screens and audio). The participants were then asked to rate the conversations afterwards in terms of seven parameters on a scale of 0 to 5. These were: perceived conflict, perceived humanization, perceived competence, attitude shift, perceived understanding, degree of enjoyment and degree of liking.

Needless to say, with so many participants, so many different conversations, and many different subjects, there was a spread of values for each mode of communication and each parameter. Yet the results were clear: for all seven parameters, speech won out over writing, in terms of positive outcome. Direct (in person, face-to-face speech was slightly preferable to video chatting as judged by the mean values but had closely overlapping ranges. Yet the difference between speech (in both modes) over writing was clear. There was more perceived conflict with writing than with speech but greater perceived humanization, competence and understanding with speech between the conversational partners. The biggest differences concerned distinctly more enjoyment and liking when people spoke to each other than when they wrote. These latter aspects signify the emotional component of the interaction rather than comprehension per se but, as noted above, good feeling between two people in a conversation facilitates greater receptiveness to the idea(s) of the other participant.

I was very interested in these result and pleased to see them. Part of the interest comes simply from being a writer. Obviously, I believe in the value of writing for getting across ideas but it is good to be aware of some of its potential shortcomings. On the other hand, I have also given many talks and while a talk to an audience is not the same as a conversation between two interested individuals, there is some similarity. From having listened to thousands of talks in my life, I know full well that the liveliness of a voice and the animation of their face helps to engage my interest and, if it is, I am much more likely to retain the key points of the talk and think about them. A speaker who talks in a monotone or with an inexpressive face is a turn-off; listening to one, you are far more likely to be thinking about how much longer the whole thing is going to go on or what you will be doing later.

On the relevance of human evolution

But the other element of my interest related to a book that I had written, which came out in 2017, and for which I gave a big talk in Washington, DC that year. In that talk, I had predicted that for contentious subjects, writing might be less suitable than speech. The subject of the book, and the talk, was the evolution of the human face from primate ancestors. When I began the book, my chief interest had been in the unusual physical features of the human face and how they had evolved. However, by the time I finished it in 2016, I had become fascinated by the expressive capacity of the human face, which outshines that of every other animal on earth. (That is a subjective judgment but it is backed up by lots of work involving measurements of facial expression.) The human degree of facial expressiveness is based on over 50 million years of anthropoid primate evolution, leading to the monkeys and the apes. Crucially, when we speak, there is a play of facial expressions that accompanies the spoken words and gives them emphasis.2

On facial expressions and writing vs speaking

Furthermore, while writing the book, I had participated in a couple of email exchanges with friend-colleagues that had been somewhat bruising. It was clear to me that these had involved a degree of misunderstanding, probably on both sides. I concluded that email exchanges were not a good way to sort out differences. For my talk, I ended my discussion of the evolution of the human face with a bit of practical advice of relevance to current human life. My last slide said: “More than 50 million years of anthropoid primate evolution have contributed to making our faces superb instruments for communicating our thoughts and feelings. Take advantage of that! If you want to communicate something important and/or complex to someone, do it face-to-face, not by email!”

You will understand my interest in learning about the new study, which gives weight to what had been initially only an intuitive conclusion of mine. What speech does, which emails do not, is provide what I called the “emotional subtext” to words. (Emojis attempt to provide this but do so poorly.) For anything with an emotional charge, that subtext is often as important as the overt content. Does human facial expressiveness, however, drop out given the results in the study, which emphasizes the importance of speech. No, because one’s facial expressions reflect and shape the ways the words are spoken. One can tell from just hearing someone’s tone and pace of speech whether they are relaxed or tense, friendly or irritated, and more. One of the big questions left for the readers of my book concerned the mechanisms by which facial expressions, informed by the emotions, are coordinated with the spoken words. This was not understood in 2017, when the book came out and, to my knowledge, little better today. It is relevant to the study I have reviewed here. In an age when there is so much contentious communication, let us keep on speaking directly to each other, face-to-face!

Acknowledgment: I thank Brig Klyce for bringing the study reviewed here to my attention.

On the question of brain reliability in light of of brain diversity

In a prior article, we looked at four factors that influence how each individual develops, including most especially their individual mental processes. Those cognitive processes depend crucially on a specific organ, the human brain. In this piece, I will examine just how well the human brain performs its job. As the title asks, “Can we trust the human brain?”

This question may seem odd, even perverse, but it has repeatedly been raised in history by major thinkers in the past 2500 years. Before getting into it, however, let us clarify what is meant by “trust”. Here, it refers to reliability. In particular, does our brain provide a reliable picture of the external world? If our answer is “not really”, then we are in trouble in dealing with that world. Moreover, we would have to wonder whether we can rely on the brain for anything, such as beliefs about ourselves or how we relate to our fellow humans or whether we can trust our memories. In effect, if you do not believe that your brain delivers up a reliable picture of the world, then everything is uncertain in terms of what we think we know.

In contrast to several previous articles where I posed a big question but left it unanswered, here I will give an answer. It will not be numerically precise, e.g. “we can trust our brain 57% of the time” — what would such precision mean and how could it be arrived at? — but it will be an answer.

What prompted my reflecting on this was some correspondence with fellow biologist-writer Frederick R. Prete; check out his Substack. He had written a piece on people who have some highly unusual views of their own natures, e.g. people who see themselves as being reptiles in human form. He did not dismiss such views as craziness but used them as a starting point to discuss how every human brain generally builds its picture of reality, including that of oneself. This starts with sensory data, which is processed by the brain and then combined with memories, to give interpretations of the external reality as mirrored in one’s perceptions. He illustrated this by discussing colors, which do not exist in the physical world as such but which are products of our mental processes. He then elaborated on this with the individuality of our perceptions of the taste of certain foods. 

On shared reality

Of course, one can extend this picture of diversity to virtually every other realm of human experience. We know enough about human brains to be certain that every human brain is different from every other and reconstructs (Prete prefers the word “constructs”) reality somewhat differently, sometimes dramatically so. Many of the stories given by the late Oliver Sacks explored this reality in his first book about neurological case studies. Some of these things are so strange that they almost certainly reflect some degree of pathology but the general rule is true: we each inhabit our own reality, which is created by the workings of our individual brain.1

Nevertheless, we often agree about something in the outside world and those areas of agreement become our “shared reality”. If, for instance, a friend and I are walking down a railroad track and think we hear a train in the distance and then see it (or rather, think we see it), we would almost certainly get off the track to avoid being killed. We would not have to discuss it; we would just do that. As the train rushed by, over the stretch of track where we had been standing, we would feel, again without saying anything, that we had perceived things correctly.

Thus, acknowledging that everyone constructs their own world is not to deny that there is an external reality and that, often, different people will perceive it similarly. The key point is that – as in the case of colors – outside realities are not directly perceived. Perceptions are interpretations and interpretations are subjective, subject to error and difference amongst people.

Let us illustrate this with an example. When an accident takes place that was witnessed by several people, the subsequent eye-witness reports given to the authorities often differ in their details. Of course, some of this divergence reflects different angles of view and corresponding differences in their eyes registered. But “perception” is never just a matter of sensory input; it always involves memory and interpretation and different people bring different memories and interpretations of what they have seen. The properties of different brains certainly influence what was “seen”.

Given those facts, let us return to the question: in general, how strongly can we rely upon our brain to give us (reasonably) accurate reports on the world? Many of the great philosophers thought, worried and wrote about this though they put the matter not in terms of whether the brain could be trusted to report well on the world but on the reliability of the senses. Amongst them were Plato (427-348 BC ), Descartes (1596-1650 AD), Bishop George Berkeley (1685-1753 AD) and John Locke (1632-1704). Plato, for instance, likened the normal mode of human understanding of the world to the process of watching the shadows of figures on the walls of a cave and trying to understand the beings who cast them from the play of those shadows themselves. Understandably, he did not think that one could understand much from this process.2

Biology in the last 150 years has enormously expanded our ideas on how we perceive things and navigate the world in light of those perceptions but we still cannot dismiss the early philosophers’ doubts about perceptions. The fact remains that each of us constructs their own interpretation of the world via the individual workings of one’s brain and there is no way to judge the accuracy/reliability of that construction wholly independent of one’s sensory apparatus and brain. Even when scientists are measuring things that cannot be perceived directly, they are using their own sensory apparatus to read their instruments.3

The evolutionary perspective

Despite the fact that we can never perceive “reality” as directly as we would like, I am going to suggest a perspective that I think helps get us out of the darkness of Plato’s cave into a more reassuring place.  It is an evolutionary perspective, which was necessarily absent from earlier philosophical discussions (when there was no idea of evolution) but is missing even from many discussions today.

I approach this by going back into Earth’s history to the earliest animals and their brains, to ask what those brains provided. As discussed the article below, animal life forms, as exist today, originated in the Cambrian period (540 to 489 million years ago).

Indeed, that period witnessed a remarkable outburst of new forms, a phenomenon termed “the Cambrian explosion”4. Despite that diversity, there was a fundamental division in the basic shapes of these animals. Some had radial symmetry – think of jellyfish – while the great majority had what is known as “bilateral symmetry”, with left and right sides to their body. All of the latter comprise a super-taxonomic group, termed the Bilaterians. (Butterflies, spiders, cats and dogs and we humans are all in this group.) It was in the earliest Bilaterians that the first true animal brains took shape.

The first Bilaterians were both small and soft-bodied and did not leave fossils (except for “trace fossils”, namely tracks in the mud). Soft bodied tissues, especially brains, are highly susceptible to decay after death. Hence, we have no direct evidence about what those early brains were like. But we can make a good guess as to what their main “job” was.

That function was closely tied to the workings of another part of the anatomy of these animals, their faces. The face is the site of three of the five main senses that animals typically have. These are: vision, taste and smell. (The two not localized to the face are touch and hearing.) The first Bilaterians almost certainly had some kind of face with those capabilities. The reason for being confident about this is that we know that animals need to find food and the face is essential for this task. It is the “sensory headquarters” (my phrase) of the animal, and hence, it allows them to do so. (That first food for animals was probably bacteria or protozoa-like organisms or single-celled plant cells, algae.)

However, sensory capacity to detect food is not enough. The animals must interpret that information – “this is food!” – and move toward it. That is where brains come in. However small the first Bilaterian brains were, this was their function: to interpret the sensory information about possible food and its location and to enable, through the correct neural signals to the body, the animal to move toward the food. None of this can be done without an organ, the brain, that coordinates the sensory information, interprets it, and then gives signals to the body of the animal to move toward and engulf the food with its mouth.

How well did these earliest animal brains perform their work? We cannot give this a quantitative answer but can conclude “well enough for the animals to survive and reproduce”. Had they not done so, the great evolutionary radiation of the animals that took place in the Cambrian period could not have occurred. This must also have been true at every stage of that great efflorescence of animal forms.

Furthermore, even without detailed knowledge of the brains of this welter of different animal forms and species, we can also be sure that as the animals grew bigger and more diverse and added behaviors, their brains would have acquired capacities for meeting the animals’ new needs at every point. What might some of those new capacities have been? One of them certainly was the ability to eat other animals. Shifting from a diet of bacteria and simple plant material (single cell or simple multi-cellular plants), some animal lines (or “lineages” in evolutionary jargon) became predators. To hunt, however, requires new cognitive capacities. And, if your new life-style evolves to the point of dependence on the new food source, your coordinating brain has to be good enough to cope with the new demands of this situation. You have to be able to find and consume your prey frequently enough to survive from day to day, over sufficient days (or months or years) to reproduce.

If you are prey, however, you have to develop ways to avoid being eaten. Amongst the early animals of the Cambrian, this included many lineages that developed hard calcified shells. (Be indigestible and predators will avoid you or at least spit you out!) But it also involved capacities for swimming faster or taking more rapid turns or hiding in crevices. All such body movement capabilities and behaviors would have involved a more and more sophisticated brain, to coordinate these activities. And only the animals with brains that gave sufficiently reliable performance in these respects would have survived long enough to reproduce and give descendants with similar capabilities. (There are in fact a few animals with remarkable behavioral modes who lack a centralizing brain for all of the things that they are doing, octopuses and other cephalopods, who do these things with a distributed neural system but they are a subject for a future newsletter.)

Then, later in evolution, there were all the social interactions that animals undergo, whether involving mating or far more extended and complicated behaviors of animals that live in groups. Such behaviors require a brain that can not only coordinate and organize them but monitor them as they unfold. Think of the times you navigated a complex situation of this kind very well and another time when you did it poorly. Your brain was involved in both instances, performing better or worse respectively, at each step of the interactions.

We can now bring this discussion, about brain reliability, to a close. In animals that have brains, their brain must be able to do their job well enough for the individual animal with their individual brain to survive and reproduce. That seemingly minimalist requirement actually involves quite a high standard for success, in particular for accurate reporting of the environment (both the physical and social environment) at virtually every waking moment.

That high level of brain performance was achieved by meeting constant challenges from the outside world, throughout the history of the animals over more than half a billion years. Those challenges demanded a high level of match between the external world and our internal mental world produced by our brain. Can we trust our brain to report accurately on the world? My answer is: generally yes. We would not survive long if it did a bad job.

None of this negates the fact that each of us “constructs” our own world mentally nor does it omit the fact that, in some circumstances, we do so poorly, missing sensory clues or misinterpreting others’ actions. Nor does it say that our brain always operates at its top efficiency. Clearly, our brains function sub-optimally in the first minute or so after waking from a night’s sleep or when we are tired at the end of the day and are about to fall asleep.

Summing up

Let us return to the question at the start: are our brains basically reliable? There is no denying that there is huge diversity in how people think and, guided by their own mental reconstructions of reality, behave. All of that diversity is real and important. However, it co-exists with a high level of accuracy for most people most of the time in constructing an image of the external world that must be reasonably accurate. We could not have so much shared reality if that were not the case. If our brain were a trusted colleague and we had to give them a professional evaluation, we would have to say: “well done!”.

On thinking about thinking: categories and probability

In this newsletter, my goal has been to show the relevance of biology to matters of human life. The basic premise is that understanding aspects of biology is vital to understanding many things we need to be aware of and to make informed decisions about. Most of the articles have been about specific biological subjects of interest though some have been quite broad, with larger implications. In this article, I want to deal with a topic that might initially seem so abstract as to be boring, the topic of “risk factors”. The basic concept is, however, central to so much of what we do and how we think about things. It is not inherently complicated – it concerns the probability of something happening given particular circumstances– but it is both important yet often ignored in normal life. It deserves more attention than it gets.

A basic fact about human psychology is that we human beings like things to be conceptually clean. We like grouping things in categories that are simple. Chairs are chairs, tables are tables, a weather event is either a storm or is not, men are men and women are women, every statement is either obviously true or not. Re-read that short list. Did you just go from thinking “yes, indeed” to “hmm, not sure?” I hope so: that was the intention behind it. Categories are not always as clean as we would like them to be. For instance, no serious discussion today of gender would start or end with the assertion: men are men and women are women. We know today that gender is more complicated than that and that complexity has not just personal implications for people who do fit the sharp binary but social and political dimensions.

Another aspect of human psychology in addition to our wanting clear categories: we like clean cause-effect relationships, as they play out in time. We learn to think initially, from infancy onwards, by making clear connections between one event and another. If I push a pencil off a table, it will fall to the ground. If someone puts all his wealth into a Ponzi scheme that goes bust, he will go broke. Unfortunately, many things are more ambiguous and operate with probabilistic outcomes. If I cross the street against a red light, I am more likely to get hit than if I cross when the light is green. If, however, I cross against the light with my eyes closed and hands over my ears, the odds of getting hit are still higher. This is where the idea of “risk factors” comes in.

On why risk factors are important

A risk factor arises when you are in a situation of potential danger and there is something whose involvement would increase the chances of something bad happening to you. It might be something that you have no control over or it might be something that your actions affect. The basic idea of risk is centuries old, perhaps millenia. Indeed, it is probably ancient and intuitive, possessed by all sentient animals encountering a potential danger. However, the term “risk factor” only dates to the 1960s. It has proven helpful because it directs attention to specific things that can effect outcomes. One can then think about how they do so and the seriousness of the risk. Being aware of risk factors as quantitative measures, as opposed to just thinking of something as potentially “risky”, can help one evaluate a particular situation.

In principle, there are risk factors for every potentially harmful outcome, whether financial, career advancement, health or longevity. Let us concentrate on risk factors for health, which can be initially divided into environmental and genetic. (In reality, environmental and genetic risk factors interact, not just additively but often multiplicatively or synergistically, so separating their effects as genetic or environmental is not always easy or realistic.)

An example of an environmental risk factor for health is smoking. If you are a regular smoker, and have been for many years, the statistical chances of your developing lung cancer or emphysema certainly increase. But by how much? Here, one starts encountering the complexities of the subject. The question of risk is inherently a quantitative one. If you smoke only one cigarette a week, your chances of developing lung cancer or emphysema will almost certainly be higher than that of a non-smoker but only by a relatively small amount. Perhaps the risk factor is only 1% or 2% relative to non-smokers. (I have not looked for the statistics on people who smoke only one cigarette a week, for whom there may be insufficient data.) But if you smoke one or two packs of cigarettes a day, your chances of developing lung cancer or emphysema would go up by a lot, perhaps by a factor of 10 or more. There is no single risk factor for this behavior but a large and increasing series, related to the dose.

What about other possible elements affecting the risk? Being obese is one. It is known to be a risk factor for many cancers. The details of one’s diet, apart from the sheer excess of calories, almost certainly come into play here though there is less certainty about this than the fact of obesity increasing one’s risk of cancer. Also, what about genetics? Does one’s genetic constitution play a role in one’s relative susceptibility to lung cancer or other cancers? The answer is certainly “yes” from the fact that certain genetic variants are known to increase the chances of an individual coming down with one form of cancer or another. A prime example: mutations in the genes BRCA1 and BRCA2 are known to substantially increase the chances of breast cancer in women and there are increasing data for other genes and other cancers.

The effect can very probably go the other way, where some genetic variants increase one’s resistance to particular cancers and therefore decrease the risk associated with various risk factors. Take the case of the late Helmut Schmidt, former chancellor of West Germany in the 1970s. He was a chain smoker and routinely smoked four packs of cigarettes a day. He lived to 95 and died of complications of old age, not lung cancer. Of course, this could just be exceptional good luck but I think it is far more likely that there was some special element in his genetic make-up that gave him protection against the typical cancer-inducing effects of cigarette smoke.

Which brings us to the topic of how one thinks about genetic risk factors in general. A genetic risk factor is any genetic variant – a change in one’s DNA – that affects one or more genes in your genetic make-up, your “genome”, to make you more susceptible to some harmful condition. The degree of enhanced risk, relative to someone who does not have that genetic change, can be expressed as a percentage or a fold-increase. Most simply, it can be given as a probability, ranging from 0 to 1. A genetic variant that you have that is associated with a risk factor of 0.01 can probably be ignored while if the risk factor is, for instance, 0.20 to 0.50, it should be paid attention to. The breast cancer gene risk factors are in the second category. In such situations, one would be wise to seek medical advice, such as increased frequency of testing for the condition and information about possible prophylactic procedures such as surgery, or, where possible, drug treatments, etc.

How genetic risk factors create their effects

There are three general effects created by genetic changes and all risk factors can initially be put into one of these categories. First, the change may create no effect; it is said to be “neutral”.

These have risk factors of 0; we can ignore them. Second, the change might create enhanced activity of the gene product, either greater quantities of it or a more active form of it. This is termed a “gain-of-function” variant. These exist but seem relatively rare amongst risk factors. The third category is the most common and by far the most important in affecting risk. These are so called “loss-of-function” changes, in which the change reduces the activity of a particular gene by a certain amount, either by diminishing the amount of that gene product or the efficacy of its product.

For most of the risk factors in this category, it is a partial loss, not a complete loss of activity. Crucially, the amount of loss determines how severe the particular risk factor is, that is in how much it increases the probability of the harm associated with it. Hence, a mild loss-of-function mutation in a particular gene might cause an elevated risk of a few per cent, while a total loss-of-function in the same gene might increase the risk by several fold. Hence, the degree of risk is in part a function of the specific properties of the genetic variant involved.

On the importance of context, both genetic and environmental factors

Crucially, the actual risk imparted by a particular genetic variant is influenced by many other genes in your genome and their particular variants. This general influence is called the “genetic background” and the detailed characteristics of one’s genetic background can make a huge difference in how big the risk factor is associated with a particular genetic variant. This is because genes do not act independently but as part of large networks, so called “genetic regulatory networks” or GRNs. This is a large subject and we will return to it.

Then there are the environmental effects that can influence either existing health conditions or the risk of developing them. These either increase or decrease the risk factors associated with particular genetic variants. We have already referred to obesity and diet. However, such factors also include stress (if frequent), sleeping habits, the amounts and kinds of physical exercise you get, your social interactions and their quality, and more.

Summing things up

Let us sum up the key points. It is useful to be aware of risks that one faces, either from one’s inherent biology or one’s behavior. Many of these can be identified today as known risk factors. When there is enough information, a numerical estimate of the risk factor is possible, based on many observations of many people, and a numerical value for the risk factor assigned. This is only an average estimate since every risk factor is affected by the larger context of biology and behavior. Hence, if one wants to lead a long and healthy life, then you should do the things that promote health: a good diet, enough sleep, appropriate physical exercise, have good relationships. Furthermore, if there are known genetic risk factors for particular conditions that you know you have (from genetic testing), then by all means find out if there are easy ways to mitigate their effects. Of course, there will always be unknowns and complications and there is no way to eliminate all risks to one’s health and life. No one gets out of life alive. In short, let us each do our best to lead sensible and healthy lives and if everyone did that – which includes having the right circumstances to do so, which not everyone has – the world would be a healthier and happier place. In this newsletter, we will come back to risk factors and their importance often.

It is a truism that “behaviors do not fossilize”. This is short-hand for saying that fossils provide limited information about the living creatures they derived from. While fossils of animals can tell you much about the physical structures of those animals, they would seem to reveal nothing about their behaviors.

Fossilized structures, in fact, can provide some clues to the lives of the animals. For instance, teeth show whether the animals were carnivores or herbivores – hence what they ate – while the relative length of the leg-bones can reveal whether the animals were fast runners or not (as live animals do – think of greyhounds versus dachsunds.) Yet, about complex behaviors such as social interactions, the bones of fossils are essentially silent. Fossils of the same animal in a layer of rock can indicate that these animals lived in groups but little else.

However, this general conclusion about the limits of fossil information now requires some revision. It turns out that DNA sequences in fossils, if not too degraded over time, can be a source of information about some behaviors. Furthermore, the time limits in this respect have considerably expanded in recent years. It used to be thought, based on reasonable assumptions about the chemistry of such molecules, that DNA molecules older than about 10,000 years would be too chemically degraded to be useful. However, the estimated lifetime of fossil DNA has now been extended to several hundred thousand years. This requires good preservation of the DNA in the fossils but has also benefited from better, more sensitive, DNA detection methods.

These extensions of DNA analysis from fossils have been especially informative about some aspects of human evolution, in particular the connections between the evolution of Neanderthal humans (Homo neanderthalis) and modern humans (Homo sapiens). Some recent findings have illuminated a feature of the sex lives of male Neanderthals while raising new questions.

DNA analysis of Neanderthals: The first revelations

The story of DNA analysis of fossils, particularly those of hominins (species of the human evolutionary tree) begins in the 1990s, as the human genome project was picking up speed. An early investigation was of DNA from an Egyptian mummy, several thousand years old. It was in the mid-1990s that the project to sequence Neanderthal DNA began, led by the Estonian-German scientist Svante Pääbo at a Max Planck Institute in Leipzig, Germany. In 1997, he and his group published their first findings, the DNA sequence of the Neanderthal mitochondrial DNA. The mitochondria are the small organelles found in nearly all cells of animals and plants. They are responsible for the energy budget of cells – and much more. The mitochondrial chromosome is small, being only 16,569 base pairs long, hence easy to sequence even in the 1990s.

By 2010, the whole Neanderthal genome sequence, more than 3 billion base pairs long, had been deduced and was presented to the world in a couple of landmark publications. It was a monumental achievement. Of course, that is also true of the sequencing of our (Homo sapiens) genome in the early 2000s but that effort had involved hundreds of people and many labs while the Neanderthal genome work was initially solely the work of the Pääbo lab and deservedly won him a Nobel prize a number of years later.

The critical first question concerned the differences in DNA sequence between the genomes of Neanderthals and so called modern humans. The estimated time of divergence between their lines of descent from their common ancestor Homo erectus was 500,000 to 800,000 years ago, ample time to differentiate the two genome sequences from each other. Those differences reflect random mutations that accumulate in sites and regions of the genome that are selectively “neutral” (that is, not important for influencing traits that would or might affect survival.) Those differences accumulate under the influence of the “molecular clock”. Thus, scientists who work with such data can often identify a particular relatively short DNA sequence from either species as coming from one or the other.

The early comparisons of this kind quickly revealed a startling fact: the genomes of contemporary Europeans contain about 1-2% Neanderthal DNA! Thus, there must have been some matings between these two hominin species producing hybrid individuals that grew up to be fertile adults who left later descendants. Further work revealed that the percentage of Neanderthal DNA in the human genome is even somewhat higher in present day East Asians, on the order of 3-4%. In contrast, people whose heritage is solely from sub-Saharan Africa have no or close to zero Neanderthal DNA in their genomes.

How does one make sense of these findings? The explanation is that the initial and probably most of these matings occurred between about 49,000 and 45,000 years ago when H. sapiens first came into Europe where the Neanderthals had been long established. Modern humans who branched off and migrated to Asia, becoming East Asians (Chinese, Japanese, etc.) would have then have had little further contact with Neanderthals and their Neanderthal DNA sequences would date from that earlier time.

Why only a few per cent of Neanderthal DNA in the human genomes that have any today? Initially, of course, any child gets 50% of its DNA from its mother and 50% from its father. However, if the children of cross-species matings grew up predominantly in H. sapiens groups, and their children did too, and so on, the Neanderthal DNA would decrease over the generations by about 50% each generation. Due to the processes of gene shuffling that take place every generation, different chunks of Neanderthal DNA would have been passed down in individuals; yet, given their sequence differences from modern human DNA, they would be recognizable today as Neanderthal-derived.

Taking a human generation as 20-25 years, there would have been about 2000 generations from the early matings. Even allowing for some subsequent ones, at least in Europe, there should be far less than 2% Neanderthal DNA in Europe or 3-4% in East Asia. One provisionally concludes that the Neanderthal DNA sequences that modern humans carry probably were either neutral or conferred some selective benefit. Such benefits could have been only mildly advantageous but enough to ensure survival down through the generations. Of course, any Neanderthal gene sequences that were at all biologically disadvantageous would have been weeded out by selection over time and the analysis bears that out. The reason for the higher percentage of Neanderthal DNA in East Asians vs. Europeans is unknown but presumably reflects chance factors including perhaps minor selective differences as these two branches of Homo sapiens separated and diverged somewhat from each other.

Implications: humorous and serious

These findings were startling and their implications are still being digested. One has a humorous aspect. For 150 years since the first discovery of Neanderthal skeletons, in 1856, near the Neander river in Germany (from which the name is derived), “Neanderthal” has often been used as a synonym for primitive. Indeed the reconstruction of their facial features (sloping forehead, little chin, heavy brow-ridges) often became the model for what a “primitive” human being would look like. And this became adopted as a racist trope. Yet, the DNA analysis showed that white Europeans or North Americans of European descent, who were the most likely to employ such tropes, have some Neanderthal ancestry while people from sub-Saharan Africa, against whom such thinking was frequently deployed, do not. If Neanderthal denotes primitiveness, which group today should be considered to have had more primitive ancestors?

More seriously, the findings raise the question of what we mean by the term “species”. Classically, a species is a group that is reproductively isolated from all other groups. That means either that individuals cannot mate with other such groups or if they do, they will produce either inviable offspring or infertile ones. Clearly, such barriers must not have been stringent in late human evolutionary history, if many humans today carry some Neanderthal DNA sequences in their genomes. Indeed, in the past two decades, cross-species reproduction, in animals and plants, has been found to be frequent and often the source of new species, especially in plants. The Neanderthal DNA findings lend weight to the argument that reproductive isolation between species is a late step in speciation and not the invariant barrier it has long been thought to be.

Refining the picture of Neanderthal-modern human matings with information from the X chromosome

These findings have been given a new dimension by a recent analysis concerning the sex chromosomes and specifically the X chromosome.1 All mammals, which includes of course all modern humans and all our close relatives, share most of their chromosomes, a set termed “the autosomes”, each specific kind of autosome being present in two pairs. However, males and females in every mammalian species differ in one pair of chromosomes, the sex chromosomes. Every female carries in each of her body (somatic) cells, two so called X chromosomes, while every male carries one X and a smaller chromosome termed the Y (which shares some but not all of its genes with the X).

When one compares the total amount of X chromosome gene sequence with that of the autosomes in the genomes of modern humans, one finds that Neanderthal X chromosome DNA is impoverished in amount to that of the autosomes, on average 5 fold. That is no trivial difference and demands an explanation. One possibility is that the Neanderthal X had one or more genetic differences (alleles) that created a selective disadvantage. In any line of descent from a hybrid Neanderthal-human. That could have led to a more rapid loss of the X chromosome containing that allele, especially in males, since in females such a difference could have been “covered”, that is compensated by, the normal or “wild-type” allele on the other X chromosome. The result would have been a relative enrichment of Homo sapiens X chromosome DNA in the descendants of those cross species mating events 45-49,000 years ago in Europe.

The new paper extends the story by an analysis of the well-preserved DNA of a Neanderthal female from Siberia of about 120,000 years ago. That analysis found some H. sapiens DNA, hence evidence of much earlier cross-species mating events, dating perhaps to about 250,000 years ago. This was long after the divergence of the Neanderthal and modern human lineages more than 500,000 years ago but relatively soon after H. sapiens emerged as a distinct species. The data indicate that in the genome of this female there was an enrichment of H. sapiens X chromosome DNA. This suggests that such enrichment reflected something basic about Neanderthal-H. sapiens matings, not natural selection occurring over generations.

Last thoughts

The explanation proposed by Platt et al., the authors of the new studies, is that these cross-species matings involved mostly Neanderthal men and Homo sapiens females. Recall the basic sex chromosomal difference, that men have only one X chromosome and females two. Hence, a bias in matings involving H. sapiens females would give a further enrichment of H. sapiens X chromosome DNA relative to Neanderthal X chromosome DNA.

What, in turn, does this imply? It could reflect something about mating preferences, that human females found Neanderthal men sexier or more appealing, a case of opposites attract, to a degree that Neanderthal women did not find H. sapiens men attractive. However, such mating preferences would presumably indicate some measure of cross-species cohabitation and subsequent pair bonding, which seems unlikely. Alternatively, it could indicate Neanderthal male aggression and rape of H. sapiens females, a form of Stone Age #MeToo behavior. No amount of sophisticated DNA analysis is likely to decide this. However, these studies have revealed the ability of such analysis to reveal something about intimate human behavior that would have seemed like wild science fiction even two decades ago.

My proposed solution for such intense periods is to run alternate new articles with ones that I had put online earlier. I plan to revise the previously run articles and put them in the present format. Most will have some new material, or at least slightly expanded explanations, and often some new references. Though these pieces will be modified reruns, I suspect that many will not have been previously seen by many of my readers, hence should not evoke the response “Oh, that stuff again”.

Also, since, my articles usually have references to earlier ones, I will take down the pay-wall that currently limits access to the older articles. Hence, no one will be prevented from looking at that material. I had put up the pay-wall to encourage more people to take up paid subscriberships but if anyone took out such solely to get beyond the pay-wall, please contact me and we will work out some sort of refund procedure.

My motivation in starting BioBuzz was two-fold. First and foremost, I feel that broader knowledge of biological issues is widely needed. Virtually every social, economic or political issue that you follow in the news has some biological angle. That is not an exaggeration: we humans are living creatures and our whole existence is tied up with our biological reality, from the foods we eat, the environments we inhabit, the genes we inherit, and all the things we do that give us enjoyment from playing sports to making music to love and sex or even quiet things like reading or taking a walk. As one of my fellow Substackers, Frederick Prete, has named his column, “Everything Is Biology.” Well, that may not be literally true but there is always a biological dimension to everything we do and think. A lot of those connections are quite fascinating in themselves and deserve to be known better just for their intrinsic interest. However, there are innumerable issues that bear on matters of health or the environment (or both) where greater knowledge of what is involved in the science can influence either one’s personal or political decisions. Being better informed before one makes any kind of decision is always worthwhile.

That was the main motivation for starting BioBuzz. The second one was the hope that charging a small amount to readers who can afford such a fee would help supplement the pension that I live on. So far, the paid subscribership, a generous group of 15 beautiful individuals, has remained small, hence that second goal has not been well fulfilled. However, I have decided that putting in a pay wall is not the best way to handle this. I will try to grow the total subscribership and, in doing so, (I hope) expand the number of paid ones. We shall see.

I will not be posting a new article or reposting an old one this week but will resume next week. Stay tuned. Some interesting topics are coming up. They are planned to include:

• Human sexual behavior in the Stone Age as deduced from DNA

• The interconnectedness of seemingly separate ecosystems

• Consciousness in octopuses

• Human super-agers

• Neurodivergence and ADD specifically

• The importance of cross-immunity in fending off infectious diseases

• Animal vocal communication, and alot more.

We are multitudes! as Walt Whitman once wrote

If you were asked to describe yourself in 50 or so well-chosen words, you might well list some of your personal qualities (e.g. curiosity, sociability, etc.), maybe mention your work or other interests, or perhaps note your ethnicity, nationality, or gender, as part of who you are. You would probably not, however, describe yourself as a colony of organisms or as an ecosystem. Yet, in that omission, you would be leaving out something important, which applies to each and every one of us humans as well as every animal on Earth. What do I mean?

Mentioning the word “microbiome” might make it clearer. This refers to the fact that there are lots of bacteria that live in our body, especially our gut. Yet, you probably feel they are just passengers or even free-loaders and have nothing to do with your life or individuality. If so, you might be surprised. The word “microbiome” is about 20 years old but the concept goes back a few decades more, and precursor ideas date to the early 20th century. Today, however, we have a much better idea of how our microbial guests, in the trillions, shape our health, lives and experiences, hence our personalities. In effect, each of us is a giant ecosystem of microbes, consisting of literally thousands of species, interacting with themselves and our body, affecting us in all sorts of ways.

First, consider the matter of numbers. Each adult human being contains about 40 trillion human cells. Our cells are termed “eukaryotic” cells, which have a true nucleus housing our genetic inheritance or our “genome” (in the form of 46 chromosomes). Our cells are large compared to that of bacterial microbes, each roughly 1000x the volume and weight of an average bacterial cell. In contrast, bacterial cells, lack a nucleus and have a much smaller and simpler genome. Yet our body may house as many as two to ten times the number of bacterial cells as “our” cells. Because bacterial cells are so much smaller, their combined weight is only a fraction of our total body weight, about 1.5 to 2.0 lbs.

It is the variety of these cells that is truly staggering: there are 10s of thousands of different bacterial species that treat our body as their home, with an estimate of about 40,000 in our gastrointestinal, or GI, tract alone. (Initially, twenty years ago, the early estimates were in the hundreds to low thousands, which then was startingly large but the number is now known to be much greater.) In addition, there are many, though much smaller numbers of one celled eukaryotes, including unicellular fungi, protozoa, plus a few worm-like creatures (Helminthes), that are part of our individual menagerie, not to mention countless viruses that live on these microbes. Your reaction might be essentially “yuck” but contemplate how interesting this is. What are all those microbial organisms doing in us and to us?

It is almost certainly a mistake to speak of a person’s microbiome in the singular. There is now much evidence that different regions of the body each have their own microbiome. In particular, there are distinctive ones in the mouth, the skin, and the urogenital tract. Furthermore, there is regional differentiation of microbiomes in different parts of each, for instance in the mouth and in the three different regions of the gut (stomach, small intestine, large intestine). Each such microbiome can be seen as an individual ecosystem, with its own regional differentiation. Furthermore, while people in good health often show general similarities in the specific groups of microbial organisms found in each of these areas, each person’s individual microbiomes have their own compositions and characters. The factors that greatly influence the species composition and relative frequencies in each individual include diet, age, pre-existing health conditions, possibly gender and undoubtedly genetic differences between people.

Investigating the gut microbiome

The big question remains: how do our microbiomes affect us biologically and psychologically? Much evidence now shows that the effects are numerous and often major, affecting our moods, health, sense of well-being. Conditions ranging from physical ones such as obesity, diabetes, and heart disease to psychiatric ones such as autism spectrum disorder (ASD), schizophrenia, Parkinson’s disease and clinical depression are all associated with distinct changes in the make-up of the gut microbiome and probably some of the others.

With respect to various mental conditions, it has long been known that the gut and the brain strongly influence one another, as denoted by the term the “gut-brain axis”. This was recognized by Darwin and other scientists in the 19th century, but today, given what is now known about the influence of the microbiome, it is termed the “gut-microbiome-brain” axis.1

The problem with much of the earlier evidence is that it was correlative, the findings primarily involving differences in the proportions of different major microbial groups or species associated with particular conditions, relative to people in good health. As everyone knows, correlation, whether direct (A goes up and B does too) or inverse (A goes up and B goes down), does not prove causation. Often, it may indicate indirect connections that have little relevance to the conditions one is investigating. Hence, if one really wants to disentangle cause-effect relationships between particular microbial groups, in particular the dominant bacterial ones in the gut, and particular conditions, such as diabetes or schizophrenia, one must alter the microbiome first– in terms of relative composition or absolute numbers of cells or both — and then ask if there has been a change in some aspect of the body’s functioning.

A particularly effective way of doing this, though it is rather blunderbuss, is to generate germ-free mice and ask what health deficiencies or susceptibilities they show, relative to mice with a normal microbiome content. (There are several ways of producing this condition and there are other animals in which this condition can be produced as well.) This is rather drastic and often the effects are multiple, such that one cannot see immediately which conditions relate to the absence of particular microbial species. A more insightful way to approach this is to add back either small fecal implants from healthy animals, with normal microbiomes, to see if conditions are ameliorated by these additions. Often they are. Still more precision is achieved by adding back specific “probiotics”, namely microbial groups known to be part of the standard microbiome, to the GI tracts of germ-free animals. Alleviation of a condition or greater resilience to its induction is often observed.

One way to eliminate the microbiome is to treat someone with strong antibiotics, which can kill large portions of your microbiome. This is usually done to treat some bacterial disease and the depletion of the microbiome is a side-effect of the treatment rather than an experiment aimed at exploring the role of microbiome components. Yet, such treatments frequently show that losing much of one’s gut microbiome is detrimental to one’s health, in various ways, although the elimination of the pathogen is achieved and that is beneficial.

Another aspect of the microbiome is that when the “good” bacteria are no longer present in their normal frequencies or numbers, their places are taken by bacterial species that create harmful effects. Thus, for example, it has been shown in germ-free mice that when the bacteria of the microbiome of people suffering from depression are implanted into their GI tracts, these mice show depressive-like symptoms. Such experiments indicate that there are not only positive effects produced by the normal microbiomes in healthy people but that there are undoubtedly specific good effects associated with specific kinds of bacteria and, in states of ill-health, probably specific harmful effects from microbes that are not part of the normal microbiome.

How do microbial species achieve these effects? Almost undoubtedly through metabolic products they produce and secrete into the host animal, in the specific sites in which they are growing. Depending on the metabolite, the effects can be positive or negative. One set of effects can trigger neural impulses from the gut to the brain that promote brain health. The vagus nerve, the 10th cranial nerve, seems to be particularly important in this respect, relaying “messages” between the brain and the gut. These can not only affect moods but have longer lasting effects. Certain microbial species are now suspected to specifically promote certain features of psychological health. These species are known as “psybiotics”, not just as “probiotics”. This is a large and fascinating subject and we shall return to it in a future Substack newsletter.2

Future directions

The positive effects of elements of the microbiome, it should be noted, probably go well beyond ensuring normal physiologically functioning and psychological health. Some may promote anti-cancer effects or slow ageing. This has been indicated by new findings in both humans and certain long-lived reptile species, such as tortoises and crocodiles, which often show few cancers and frequently live to be centenarians. Some of the putative anti-cancer compounds from reptile microbiomes have been identified and may well have translational potential in therapies.3

Finally, apart from clues and possible new compounds with therapeutic effects derived from microbial species, simply finding alterations in the composition of microbiomes may prove to have general value in diagnosing conditions. Thus, a recent study of autism spectrum disorder (ASD) pinpointed 31 microbial species whose alterations in the over-all gut microbiome was shown to have high diagnostic value where the psychiatric evaluation had proved uncertain. The exploration of how the microbiome impacts various neurological and psychiatric conditions and may influence treatments is a burgeoning field of study.4

Despite all the unknowns and uncertainties, the unfolding knowledge about the microbiome promises to be revolutionary in at least two ways. First, it has changed our idea of what it means to be an individual human being. Each of us is host to a vast microbial community which, if it contains the right members and in approximately the right numbers, should be seen as our collective friend, helping to promote our health. Second, the microbiome has only begun to yield its secrets as to how it helps us stay healthy. There is bound to be a set of major changes in how medicine is done as the implications of these discoveries sink in. In my opinion, it is potentially as significant as was the discovery of antibiotics or the development of vaccines.

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Introduction

If one were to ask someone to name two characteristics of plants that make them different from animals, what features would they pick? They would probably say, first, that plants don’t move and second, that plants do not eat other living things, either other plants or animals, but make their own nutrition. Some respondents might add that plants can do this using light energy via photosynthesis.

Both generalizations are true but as with virtually all big generalizations in biology, unlike physics, there are exceptions. Thus, many plants can and do move parts of themselves though usually slower than animals and most often through growth. Some, however, do so without growth; they move their leaves to track the sun to increase their capture of light while a few, like the famous Venus Flytrap, have rapid moving parts for trapping insects that they slowly digest.

As for the idea that plants nourish themselves through photosynthesis, that is true for the great majority, including primitive plants such as mosses, liverworts and ferns, as well as far more complex plants, gymnosperms (which have needles instead of leaves) and the flowering plants, the angiosperms. However, there are exceptions, plants that have largely or completely abandoned photosynthesis. This article is about them and why they are interesting.

The basics of plants that live without photosynthesis

Green plants are green because they have the light-trapping pigment chlorophyll, which to our eyes looks green. Capturing light energy allows plants to synthesize sugars, which are their main source of sustenance. This way of life is termed “autotrophy”, which means self-nourishing. In contrast, animals survive by eating other living things, plants and/or other animals. This way of life is termed “heterotrophy”.

Again, this distinction is generally valid but asymmetric in their exceptions. The only animals that are autotrophic that I am aware of are a few coral species that have photosynthesizing algae in their cells and live off the excess sugars produced by those algae. In contrast, many plants have a degree of heterotrophy, absorbing nutrients through their roots. They do this with the help of fungi, which have broken down dead plants or animals or bacteria, releasing their nutrients. This form of nutrition is termed “mycoheterotrophy” where “myco” is the Latin prefix for “fungal”.

Yet most of the plants that use mycoheterotrophy fill only part of their nutrient needs in this fashion. Most of them also employ photosynthesis. This combination of modes of nutrition is termed a “mixed” one. There are about 300,000 species of flowering plants and of these about 1/10^th or 30,000 are estimated to be partially mycoheterotrophic. The great majority of these use this form of nutrition in their early stages of development, during their germination from seeds before they have mature, chlorophyll-filled leaves. This makes biological sense. Mycoheterotrophy is a less efficient nutritional supply mechanism than photosynthesis but a small young plant has smaller energy needs than a big one.

Yet a relatively small number of plants, estimated at around 600 species, have gone further: they have given up photosynthesis as their main mode of support and live by mycoheterotrophy. They physically partner with fungi that typically live on the roots of nearby photosynthetic plants. Those fungal-photosynthetic plant associations are often mutualistic in that both partners cross-feed each other. In contrast, the association in mycoheterotrophic plants is more of a one-way street: the plants definitely benefit from the nutrients produced by the fungi but it is not clear what the fungal hosts get. Those associations would therefore essentially be parasitic rather than mutualistic, with the plant being the parasite.1

Mycoheterotrophic plants, having given up chlorophyll, have pale (non-green), often translucent, stems and no green leaves. The flowers may be pigmented though with many the flowers are white. In Japan, where much of the essential work on these plants is being carried out, they are sometimes refered to as “ghost plants”. Consistent with the fact that mycoheterotrophy is less efficient at producing energy than photosynthesis, these plants are all small, hence easy to miss in woodlands unless one is looking for them.2

On the occurrence of mycoheterotrophy in the plant kingdom

In what kinds of plants and how often has mycoheterotrophy evolved in the plant world? To look at that, we first have to understand the methods used to investigate this. For centuries, biologists classified living organisms on the basis of the degree of their visible, “morphological”, resemblances. This was the method of traditional taxonomy. The more physically similar two sets of organisms are, the closer and more recent their evolutionary connections were deemed to be.

That was for very long, however, an unproven assumption. However, in the last 50 years, it has been confirmed in innumerable cases by comparing their DNA sequences. Thus, for instance, two species of mouse from different parts of the world will show more similar DNA sequences to each other than either will, for example, to a lion or an elephant. That example concerns animals but the reasoning applies to plants as well.

In the case of mycoheterotrophic plants, DNA sequence analysis allows one to place which group the plant belongs to. Such information on the participating fungi is much less complete but in principle it can be obtained. From the information on the plants alone, one can make minimal estimates of the number of times that mycoheterotrophy has independently arisen within the plant kingdom.3

A key conclusion is that mycoheterotrophy is not distributed randomly amongst angiosperm families but has occurred preferentially in certain groups. In particular, the orchid family has at least 220 mycotrophic species – almost half the number of angiosperm species who depend heavily or exclusively on mycoheterotrophy. Furthermore, the data indicate that the condition has arisen at least 30 times independently amongst the orchids. In contrast, many angiosperm families have no mycoheterotrophic species. Evidently, there is something about the basic biology of certain plant groups, especially the orchids, that favor this characteristic.

On the evolutionary forces driving mycoheterotrophy

It must take at least two structural/physical (“phenotypic”) changes to evolve a mycoheterotrophic plant from an autotrophic one. These may rest on multiple genetic changes of additive effect. The phenotypic alterations are the evolved dependence on fungi for nutrients and the loss of chlorophyll from stems and leaves.

The growing dependence on fungi almost certainly came first and would have been triggered by an insufficiency of photosynthesis to fulfill the growth requirements of the plants. Why would there have been this failure? Mycoheterotrophic plants are found in the understory of temperate forests or tropical jungles and such locations inevitably limit the amount of light that plants can receive there. Thus, genetic changes that favored the association with fungi could have been selected for. If certain plant species were fewer mutations away from developing this ability, they would have been more likely than species that needed more genetic changes to make such a transition.

But why would plants on the road to mycoheterotrophy need to lose their chlorophyll? A truism of evolutionary biology is that structures or properties that are not needed tend to be discarded, especially if they are somewhat energy-intensive. “Use it or lose it” is a general rule in biological systems. The chloroplast, which houses the chlorophyll and the whole photosynthetic apparatus, requires energy to be maintained. As plants transition to mycoheterotrophy, becoming smaller in the process, they would have needed fewer chloroplasts. Hence, the loss of photosynthetic capability probably did not follow the acquisition of mycoheterotrophy but might have accompanied it. This, of course, is speculation but it is testable, as discussed below.

One further point about the general phenomenon: there are two kinds of interaction between fungi and the plants that form mycoheterotrophic interactions with them. The first kind are called ectomycorrhizal associations and involve fungal filaments, termed “hyphae”, going between plant cells and not penetrating their walls. The other kind are so called “arbuscular” associations in which the hyphae actually penetrate plant cells. The latter presumably supply nutrients from the fungi more efficiently. The fact that both kinds of association involve intimate contact between fungal and plant cells suggests that the fungi benefit from the associations with plant cells. That might simply involve provision of a physical substrate for the fungi but some additional physiological benefit seems probable.

Final thoughts

Broadening the view from the individual plant-fungal association, a key point is that mycoheterotrophic plants are, almost certainly, active members of whatever ecosystems they belong to. They must, at least, participate in the recycling of nutrients in those systems but this larger picture needs further investigation. Hence, in any restoration schemes of damaged ecosystems, room should be left for retaining or restoring any mycoheterotrophic plants that were part of them. That is the biodiversity-conservation angle on these unusual plants.

There may now be enough understanding of mycoheteroheterotrophic plants to begin investigating exactly how they evolve. A rough evolutionary scenario was given above and it suggests an experimental approach. It is that autotrophic plants within a plant family that developed many mycoheterotroph associations could be exposed to low light conditions, over perhaps 5 to 10 generations, in the presence of fungal species known to make such associations. If the scheme above has any validity, one might see the beginnings of fungal-plant interactions in the mycoheterotrophic direction.

This would be a long-term experiment though doable for plants that have at least one generation per year. Would it be feasible to expect change in only 5 to 10 generations? The cliché about evolution is that it is slow. Much information on many organisms at this point, however, suggests that certain evolutionary changes can be fast. This experiment could be done by making the light sufficiently low to encourage this evolutionary change – to mimic the low light conditions in forest understories -- but not so low as to kill the plants. There have been a few experimental evolution studies in plants but it would be exciting to see if it could be further extended in this particular area.

The term “medical problem” tends to conjure up either an infectious or genetic disease or the result of a physical injury. Thinking a bit more about the phrase, one might include the aftermath of attacks by animals or acts of poisoning. These last two seem quite distinct --and they are except when the animal injects poison with a bite or a sting. Such animals include certain insects and arachnids, a few sea creatures (e.g. an octopus species, a few fish such as lionfish), and above all, a wide range of poisonous snake species. It is the latter that account for the great majority of human poisonings by animals.

It is estimated that about 4 million people a year are bitten by poisonous snakes. The vast majority of snakebite cases occur in the Global South, in particular in India and many countries in sub-Saharan Africa. At least half the cases are in India but some of the African countries have a higher per capita rate of injury from snakebite than India. For most cases, access to the appropriate medical treatment is neither easy nor fast.

Of the 4 million people bitten by snakes, it is estimated that at least 120,000 of them die, and another approximately 400.000 suffer long-term harm, frequently from needed amputations of fingers or limbs. (Most snakebites are on the hands, arms, feet or legs.) As large as these figures are, they may be considerable underestimates. They are based on hospital admissions but most snakebites occur in poor rural areas and many victims do not get to a hospital at all or fast enough.1

In general, medical services in poorer countries are stretched thinner and less readily available for dealing with health problems than in richer ones. Snakebites are a special problem, however, since speed of treatment to prevent death or long-term injury is especially urgent in these cases. Some kinds of snakebite, such as cobras or mambas, can be lethal in less than half a minute; a bite of this kind is usually a death sentence. But even for less lethal bites, the time needed is still a big issue.

For slower-acting snake venoms, the worst consequences can often be avoided if effective treatment is applied within one or two hours. However, even that window of opportunity is usually far too short. Victims often have to travel many hours to reach treatment centers and then frequently have to wait hours before they receive treatment. Furthermore, hospitals and clinics often do not have sufficient anti-venom treatments. Typically, a rural clinic will have only one or two vials of anti-venom medicine while a course of treatment for just one case often requires many more, sometimes up to 10.

Clearly, there is a huge gap between the need for effective treatment of snakebite and the resources for doing so. In 2019, the World Health Organization (WHO) announced that it was aiming to have effective coverage globally by 2030. It is now 2026 and the scale of the problem today has hardly changed since 2019. Funding cutbacks for WHO, triggered by US withdrawal of funds for WHO under the Trump administration, virtually guarantee that the goal for 2030 will be missed.

What are the anti-venom treatments? There are now a number of drugs in limited amounts but the typical treatment involves serum enriched in antibodies against the snake venoms. This method was first developed in the 1890s, by which point there was some understanding of the human immune system and how it could be harnessed for treating disease. In particular, successful vaccination against a small number of viruses, especially small pox and rabies, had been achieved. In principle, immune protection against snakebite might be achievable. However, unlike vaccines for infectious diseases, which can be given weeks or months before an infection, antibodies against snakebite would have to be ready to be injected as soon as possible after a bite. Hence, sufficient antibody would be needed in advance.

Accordingly, a procedure for generating antibodies against snakebite, antivenomes, had to be developed. The method involves producing them in advance of need in animals. Specifically, anti-venoms are generated in a big domestic animal by injecting small amounts of the venom. These doses must be enough to generate a strong immune response in the form of abundant antibodies but not so much to make the animal itself ill. The animals of choice for this procedure are typically horses and sheep though camels are also used in a few countries. These are all large animals, hence capable of generating big amounts of the requisite antibodies. After a suitable interval to maximize the antibody yield, the blood is harvested and the white and red blood cells are removed, to leave antibody-enriched sera. This is then put in small vials and kept in refrigerated storage until needed.

This was procedure was first used about 130 years ago and is basically the same today. It can work well but has several problems. I give four here.

First, it is labor intensive and time consuming. Hence, it is not cheap and cannot supply a big demand, such as four million or more cases per year. In this, it illustrates, all too well, why a health problem predominantly found in poorer countries can be relatively neglected by the world as a whole. (The WHO aim to reduce the problem globally by 2030 is, at least, a sign that the problem is increasingly recognized as demanding attention.)

Secondly, snake venoms are a mix of many, often dozens, of different toxic molecules. Hence, in making anti-venom from the immune response of domestic animals, one obtains a cocktail of antibodies of different specificities. Since each toxin in the venom has to be inactivated, there must be adequate amounts of each antibody in the anti-venom mix to inactivate all the toxins. This is part of the reason why many injections of anti-venom are often needed. Also, the large volume of blood in a human body – about six liters – is relevant to the problem since the dilution factor of any injected anti-venom would be larger than if the body’s blood volume were smaller.

Thirdly, while each species of poisonous snake has its own distinctive form of venom, each of which tends to preferentially damage certain tissues and organs, the precise composition of a venom can vary between different individual snakes of the same species. Furthermore, the composition of the venom can be influenced by the particular diet of the individual snake and other factors. Thus, in contrast to vaccines against specific viruses or bacteria, the chemical match between a specific kind of snake venom and its anti-venom is less exact. The fact that this form of treatment can be very effective indicates that the degree of chemical mismatch between the venom molecules and the anti-venom antibodies is not a severe problem. (We will come back to this point later.)

Finally, and perhaps most seriously, the anti-venom antibodies, generated in animals (horses, sheep, camels) are themselves experienced by the human body as alien substances, antigens, and can generate an immune response. Because of the number and variety of these “foreign” molecules, this reaction can be a very strong one, with dramatic and very harmful effects on the physiology of the recipient. This response is termed “anaphylactic shock” and it can be lethal. Fortunately, if it occurs in a clinic or a hospital, its signs (such as sudden drops in blood pressure, breathing difficulties, stomach cramps or vomiting) are readily recognized and can be treated quickly (with the hormone epinephrine). If, however, it has occurred, that means that the anti-venom cannot be used in that patient.

Hence, it is good news that a new form of anti-venom treatment has been developed that seems to avoid this complication. The early signs are that it will work well against snakebite and with a much reduced chance of generating anaphylaxis. There are two key elements to the new approach. First, it uses much smaller antibody molecules, which means that many fewer antibody-inducing foreign protein sites, so called “epitopes”, are introduced with the injection, hence greatly reducing the chances of anaphylaxis. Second, the procedure involves mass producing an engineered form of the antibodies not in animals but in bacterial cultures. This is a great simplification and should reduce costs in producing the anti-venom.

Antibodies in mammals are generally big protein molecules, consisting of four polypeptide chains. However, only a relatively small part of the molecule is involved in binding the epitope that it is specific for. Hence, by creating smaller active antibodies that contain this critical region and not much of the rest of the molecule, one should eliminate much of the anaphylactic potential of the anti-venom antibodies.

Accordingly, discovering that two members of the camel family (alpacas and llamas) produce smaller antibodies, consisting of only two protein chains, not four, was very helpful. Furthermore, in these antibodies, only part of each chain is necessary for antigen binding and inactivation. The DNA sequence encoding this region can be purified and put into the genome of the bacterium Escherichia coli and these bacterial cells become min-factories of these anti-venom molecules. These small antibodies have been termed “nanobodies”.

The new strategy is as follows. One injects alpacas or llamas with suitable amounts of a particular snake’s venom and generates antibodies for it. One then determines the protein sequence of one of the major component antibodies and then isolates and clones its DNA sequence. The short version of the sequence encoding the nanobody is then put into the genome of the bacterial cells, which are then cultured to produce large amounts of the nanobody. It is then isolated and purified and one now has an anti-venom molecule specific for one kind of snake venom. (This is a stripped down account of the method but if it is still too technical, just note the main point: that very specific snake anti-venom antibodies can now be made that carry much less risk of generating a deadly immune response.)

This procedure was carried out for a mix of venoms from 18 African venomous snakes including the most deadly. The effectiveness of the nanobodies in neutralizing the snake venoms was tested and eight were found to be particularly effective in neutralizing the venoms of all but one of the 18 snakes. These were then combined in an anti-venom cocktail and tested. Mice were first injected with one of the snake venoms, at a lethal dose, but then five minutes later with the nanobody cocktail. The results were impressive. The animals were saved from the lethal effects of most of the venoms. Improvements are being made to deal with the rest.2

How could only eight nanobodies with specific molecular sequences protect against nearly all of the 18 venoms, each consisting of many different toxins? This almost certainly involves the property of “cross-reactivity”, the fact that an antibody developed against one specific antigen can often work, sometimes very well, against antigens that are similar in structure.

The effectiveness of these nanobodies has only been shown so far in mice and the researchers estimate that it will take another three years of research before the method can be tested in humans. Doing so will involve its own special challenges, both technical and moral. However, this work is a promising start, in addressing a problem as old as our species and which remains a big one, especially for poorer countries in the Global South.

Certain books of ideas have had an outsize impact in science. To name two of the earliest most famous, there is Newton’s magnum opus, the Principia and Charles Darwin’s The Origin of Species. Would new books of substance have comparable impact today? That is a serious question, prompted by the decline of reading generally, especially among the young. At many American universities, the teachers are giving up on assigning whole books to read; their students lack the patience for such. Furthermore, it is estimated that more than 50% of adult Americans now read typically one or zero books a year. It may not be that low in many other developed countries but the decline in book-reading is probably a general trend.

To explore how books can be important, I will look at two that were significant in the 20^th century, though I will give more attention to one. Both were about genetics but were quite different in many respects: their immediate reception, their styles, lengths, the relative standing of their authors at the time, and their aims. I want to assess what made them important and whether they still can claim significance. I welcome any comments from readers.

Spoiler alert: I am going to conclude that despite their differences, these books shared a central idea, one that shaped much thought and discourse about biological heredity in the late 20^thcentury. In my view, this idea is actually wrong! Despite that, these books were valuable. Wrong ideas in science generally can be hugely helpful in science by stimulating good work. I will conclude on a more general note, however, that books of ideas in science can and will still matter despite all the evidence – the dominance of social media, the influence of AI on writing, the decline in reading – that the importance of books is waning.

The first book I will discuss is What is Life? , written by the famous (Nobel Prize-winning physicist) Erwin Schrödinger who published it in 1944. He based it on a series of lectures he had given at his university, University College Dublin, in Ireland, the previous year. It was his sole published contribution to biology.

The second book to be discussed is The Selfish Gene, first published 50 years ago in 1976. It was written by a young British biologist, Richard Dawkins. He was not well known beforehand but his book made him famous. He has written many more books, which have been praised, but The Selish Gene remains his best known and probably most important.

Schrödinger’s What is Life? has been the subject of several evaluations over the years. The latest is a recent short book by a friend, Daniel Nicholson. Reading it was the spark for this article. My account leans heavily on his though it will not do it justice (nor of course Schrödinger’s book itself).1

Though What is Life? looks like a one-off original effort, its key ideas did not come out of nowhere. In particular, there had been a paper in 1929 by the great geneticist H.J. Muller that had influenced Schrodinger. Muller had previously discovered that X-rays can cause genetic changes (mutations). Second, there had been a further paper on X-ray mutagenesis by three scientists in the 1930s that had stimulated Schrödinger. One of the authors was the physicist Max Delbruck. Delbruck had been inspired by Niels Bohr, a great 20^th century physicist and Delbruck’s mentor. Bohr had hoped that biology might yield new insights that physics had not unearthed. To Delbruck, genes seemed a good place to search for such new physical insights.2

The nature of the genetic material in living things at the time of Schrödinger’s lectures in 1943 was unknown but was believed to be either proteins or deoxyribonucleic acid (DNA). The chromosomes in higher cells were known to be the source of biological heredity and to be composed of approximately 50% protein and 50% DNA. Most biologists and biochemists of the time would have bet on the proteins as the stuff that genes are made of because proteins seemed to have the complexity and variety that the genes must have. DNA appeared too chemically simple. The first serious evidence that the genes were made of DNA was published in 1944, from a group based at Rockefeller University in New York City.3

However, Schrödinger had given his lectures in 1943, a year before, and he was not influenced by the experimental work at Rockefeller. Indeed, there is no evidence that he was interested in the detailed chemistry of genes. He cared about the general structural properties that genes must have to enable them to specify hereditary traits and to do so stably generation after generation. The stability of genes fascinated him. He illustrated it with the so called “Hapsburg lip”, a facial trait of the ruling house of the Austro-Hungarian empire, which had been genetically transmitted in that family for centuries. (Schrödinger was Austrian himself and would have grown up being fully aware of the Hapsburgs and their peculiarities.)

Focusing on that question of stability, Schrödinger proposed that the gene was what he called an “aperiodic crystal”. The word “crystal” conveyed the idea of a suitably stable molecule while the adjective “aperiodic” was meant to convey the fact that it could have plenty of variations in its detailed structure, which would have been necessary to explain the variety of what genes do. He went on, in this short book, to postulate that this “aperiodic crystal”, whatever exactly it was, constituted a “code-script” for the development of the organism. So, here, in this small book were important ideas about what genes were physically and what they did for the organism.

The book had reasonable success in terms of sales. Schrödinger’s reputation alone might have guaranteed that but the novelty of such a great man of physics dipping his toe into the then muddy waters of biology, deemed by many people an inferior branch of scientific inquiry, almost certainly added to the appeal. What did this great man of science have to say about the obscure matter of genes?

Apart from sales, however, it was important who bought it and thought about it. This would only become apparent about 15 to 20 years later, when comments from many of the leading figures in molecular biology, several of them physicists, talked about the galvanizing effect the book had on them shortly after it was published. This included all three of the men who won the Nobel Prize in Medicine & Physiology in 1962 for their discovery of DNA structure in 1953, namely James Watson, Francis Crick and Maurice Wilkins. However, whether What is Life? was really that influential at the time of its publication for these men has been controversial. The suggestion has been that they were citing Schrödinger because he was such a great figure, who could justify their interest. To me, however, their testimonials sound sincere. All were major figures themselves by the 1960s. None would have needed to wrap themselves in Schrödinger’s prestige to justify anything they had done.

To the extent that there is a consensus on why What is Life? mattered, it is this: that it acted as a recruiting device for some of the brightest young scientists to go into the fledgling field of molecular biology and develop it. I would add one further thought to this: that the book mattered particularly because it convinced these men (and probably one woman, Rosalind Franklin, who did key work on DNA), especially given the growing evidence that DNA was the genetic material. In effect, Schrödinger’s book conveyed the idea: this is a problem that can be tackled. H. J. Muller’s 1929 genetics paper could have been read similarly, and had been by Schrödinger. However, the timing of Schrödinger’s book, his prestige, and the new evidence that DNA was the “aperiodic crystal” of his formulation, gave his book influence that Muller’s paper could not have had.

Another standard explanation of why Schrödinger’s book was important is the claim that with his talk of a “code-script”, he foreshadowed the work on deciphering the genetic code -- the way that the sequence of base pairs in the DNA can determine the structure of a polypeptide. This, however, is a misreading. When Schrödinger talked about a “code-script” he was talking about the genome as a whole, an entity that specifies the organism. He was using the term in the same way that geneticists of the 1960s and ‘70s later talked about the genome as a genetic “blueprint” or genetic “program” of the organism.

This brings us to a central conclusion of Daniel Nicolson’s book, namely that the real and ultimate significance of What is Life? is that it was the inspiration for such talk of the genome as the “genetic program”. This phrase appeared in two independent publications in 1961, one by Ernst Mayr, the great evolutionary biologist and the second by two French scientists, Francois Jacob and Jacques Monod, who in their landmark paper in 1961 explained how genes are regulated.

This idea of the “genetic program” was a highly deterministic one of how DNA sets the properties of the organism. It dominated the second half of the 20^th century. Not least, it was a major inspiration for the genome projects and its rationale, that the genome was “the Book of Life” and that knowing the whole sequence of base pairs in the DNA of the organism would reveal how the organism developed. (It was never clear to me whether this was mere propaganda to get the funding for the genome projects or whether it was sincerely believed by the people who made this claim.) If Schrödinger’s genetic determinist views helped inspire or propel this view, they were important.

This brings us to The Selfish Gene by Dawkins, published 32 years after Schrödinger’s book. It is a much bigger book but written in a more accessible style. The principal intended readership was laypersons though it certainly reached and affected biologists too. Its emphasis was on genes as “replicators” and portrayed them as effectively in charge of the organism. The language and style are quite different from Schrödinger’s but the basic premise of genetic determinism is the same. In Dawkins’ terminology, the organism is seen as a lumbering “robot” being given directions by its genes. Dawkins then describes how this framework can explain many things.

The Selfish Gene was a big success, a best-seller. It had a large impact on young scientists and may well have influenced many to become geneticists. Though in my opinion, its ideas have not aged well, it generated much interest in and enthusiasm for genetic science and evolutionary biology. Viewed from the present, when there is less enthusiasm about science – for several reasons – this has to count as a good thing.

Do either of these books warrant recognition as important today? I think so, at least if one is interested in the history of ideas. In any history of ideas in 20^th century science, both books would have an honored place. Nevertheless, I would argue that a central idea, perhaps the key idea in both, that of the all-powerful genetic “code-script” or “program”, is not true. Of course, the genome is crucial for development but there is so much back-and-forth between the genes and the rest of the cell that the process is not remotely captured by the metaphors of the “program” or “blueprint”. (For one way to look at how genetic differences contribute to development, see Should genes be seen as controllers or nudgers of biological development?)4

Finally, let us return to the question raised at the beginning: can books of ideas still matter in science? Certainly, there is much less book reading in general today than 50-100 years ago and this holds for scientists too. For a book to have impact, it must have a sufficient number of readers. Hence, fewer readers would have some effect. My guess, however, is that serious books will continue to matter. New books with new ideas and vivid writing may have fewer initial readers than in earlier times, but word of exciting new things spreads more rapidly and widely than before. Fields in science that await stimulating contemporary chroniclers on the order of Schrödinger and Dawkins include the neurosciences, cancer biology, AI studies, and cosmology, though an exciting book with new ideas in any scientific subject might ignite interest. New developments in communication may somewhat displace older modes but do not kill them. Television did not kill radio and the social media will not eliminate books. There is still much room for new exciting books in science.