The Human Genome Project: Brave new world of scientific understanding or false dawn?Issue: 139
Posted: 5 July 13
This year marks the anniversaries of two key events in science. Sixty years ago Jim Watson and Francis Crick revealed their famous “double helix” model of the structure of DNA, the “molecule of life”. And ten years ago saw the completion of the Human Genome Project, the international mission to decode all the DNA information in our genomes. So how important are these two events and how do they affect the way that socialists view the natural and social worlds? To answer these questions I will begin by going back to the birth of evolutionary theory and genetics in the 19th century, before going on to explore how these areas of biology have developed in modern times.
First though, I will lay out a few ground rules that I believe are essential to any Marxist discussion about science. One is to reaffirm science’s claim to be objective. Marx claimed that “if the essence and appearance of things directly coincided, all science would be superfluous”.1 I take this to mean that the primary aim of science is to glimpse this inner essence. But since this essence is often concealed, we can only learn such truths indirectly. This led Lenin to say that “human knowledge does not follow a straight line, but endlessly approximates a series of circles, a spiral”.2 To uncover the essence of reality, scientists put forward theories and then use experiment or observation to see if these match up to reality. But of course theories will also be influenced by the society in which they arise. This means that even the most penetrating scientific insights into the nature of reality can be distorted by the social prism through which individual scientists view the world around them. Picking apart what is real and objective about scientific discovery, as opposed to what is merely a social prejudice of the age, is thus a challenge to anyone seeking to construct a radical critique of science, but it is what I will be trying to do in the remainder of this article.
A meddling monk
Marx and Engels saw Darwin’s theory of evolution by natural selection as “containing the basis in natural history for our view”. By providing a mechanism for evolutionary change, Darwin’s theory, popularised in The Origin of Species in 1859,3 showed that there was no need to appeal to a supernatural creator to explain the origins of human behaviour and society—instead this was purely a product of the natural world. Natural selection required that populations of species varied in their size, shape and capabilities, and that new environmental pressures acted upon these variants to ensure the “survival of the fittest”. Importantly, against the idea that nature is always “red in tooth and claw”, Darwin pointed out that survival is equally relevant for a plant on the edge of a desert struggling in a drought, as for two dogs battling for scraps in a famine.4 In addition, there would need to be some way for survivors to pass on their attributes to their offspring, who would then represent a more significant proportion of the population. Through selection over generations, the variants that survived best in the new environment would come to predominate. Eventually this could lead to the birth of a new species.
In fact, Darwin was not the only person who had this crucial insight. Alfred Wallace was, unlike Darwin, a self-made man who had to work for a living, and also a socialist, but he reached the same conclusions about natural selection through a remarkably similar route. First, he experienced the same crucial exposure to an extraordinary variety of species and their variants in the natural world during his travels around what is now Indonesia, as Darwin had on his The Voyage of the Beagle. Secondly, he was drawn to the idea of a struggle for existence after reading Thomas Malthus’s An Essay on the Principle of Population. Writing to Darwin to tell him about his idea, Wallace unwittingly prompted the former to finally go public with his insights. But Wallace was unwilling to apply natural selection to the origin of human consciousness, unlike Darwin in his The Descent of Man, published in 1871. Thus Darwin, the bourgeois gentleman, proved more of a scientific revolutionary than Wallace, the socialist. Instead the latter ended up appealing to supernatural mechanisms to explain humanity’s unique mental attributes.5
While Darwin pioneered the application of evolutionary theory to human society, it was Engels who first correctly identified the sequence of events that led from apes to sentient humans in The Part Played by Labour in the Transition from Ape to Man, written in 1876 but only published after his death, in 1895.6 Engels argued that humanity arose through our ape ancestors first walking upright, then using tools cooperatively to act upon the natural world, which triggered a development in the growth of the brain and the birth of language. This allowed production and use of more sophisticated tools, which in turn led to more brain and language development in a positive feedback loop. In contrast, Darwin incorrectly assumed that it must have been the development of a bigger brain that preceded these other changes.
One major problem with the theory of natural selection as expounded by Darwin was that it lacked a proper explanation for how new characteristics could be passed down to offspring such that those more appropriate for survival in a new environment would come to predominate. Human offspring, like animals or plants, were known to share many characteristics with their parents, whether in looks, abilities or temperament, but this was thought to occur through mixing of the two parents’ blood, an idea underlying the phrase “blood relations”. However, this mechanism posed problems for Darwin’s theory, for such mixing would dilute out any new characteristics that arose. This was a problem that plagued Darwin up to his death.
Ironically, the problem of inheritance had, unknown to Darwin, been solved in his lifetime. For anyone who thinks that religious belief and scientific achievement are incompatible, it is worth remembering that the founder of genetics was a monk. Gregor Mendel’s experiments on inheritance in pea plants at St Thomas’s Abbey, Brno, now in the Czech Republic, first showed that characteristics such as height, colour and shape are passed down to offspring according to precise mathematical rules. For so-called human monogenetic diseases like cystic fibrosis, we still use these rules to predict the likelihood of someone inheriting them. Mendel concluded that an organism’s inherited characteristics were determined by discrete “factors”, later called genes. This was hugely important for evolutionary theory, for if inheritance was due to discrete elements, these could be passed down to offspring without their effect being diluted by mixing.
Yet despite being published in 1866, less than a decade after The Origin of Species, the importance of Mendel’s findings lay unrecognised for decades until they were rediscovered in 1900. By providing the missing link in the theory of natural selection, they helped trigger a renaissance in Darwinism that has never abated. Combined with increasing awareness of the role of mutation in generating new variants in a population, they led to a new synthesis of evolutionary theory and genetics, so-called Neo-Darwinism, that remains dominant today.
The new synthesis
Mendel’s work implied that for any particular characteristic, there are two genetic determinants, one inherited from the father, one from the mother. In so-called “dominant” situations, only one copy of a gene variant is needed to determine the characteristic, while in “recessive” situations both copies are required. Huntington’s Disease, a monogenetic disease that begins with subtle changes in mood, jerky movements and loss of coordination, and ends in psychosis and full-scale dementia, is a dominant disorder. Even if a person inherits only one faulty Huntingtin gene7 copy from a parent, they will get the disease at some point in their lives. In contrast, cystic fibrosis, most known as a disorder of the lungs, but affecting many other parts of the body, is a recessive disorder. Having only one faulty copy of the cystic fibrosis transporter (CFTR) gene is insufficient to give a person the disease. This is why Gordon Brown and Sarah Brown, both carriers of this disease, do not suffer from it themselves, despite having a son with the condition.
In fact, the majority of human characteristics and diseases, even if they show evidence of a hereditary component, do not follow these simple rules since they involve a number of different genes whose combined influence is complex. However, this has not prevented a whole industry of speculation developing about the genetic basis of human behaviour and human society that essentially treats quite complex human characteristics as if they were determined by one or a few gene variants, without providing any molecular evidence.
Richard Dawkins’s book The Selfish Gene, published in 1976,8 is one example of a type of reasoning first known as sociobiology, and more recently as evolutionary psychology, which continues to dominate popular science writing about evolution.9 A common strategy is to identify a particular human behaviour or aspect of society, be it altruism, homosexuality, women’s position in society, nationalism, or prejudice against immigrants, and explain it by reference to genetics. It is suggested that a variant of a specific gene, or small number of genes, is responsible for a particular behaviour, and that natural selection has preserved this variant in all or part of the human population. Yet although genes are mentioned a lot in such writing, what is generally absent is any attempt to relate the particular characteristics under discussion to actual molecular mechanisms.
In fact, on the occasion when a study was undertaken to link the inheritance of a complex human behaviour to simple Mendelian rules, the result was an abject failure. Thus in 1993 Dean Hamer and colleagues at the National Institutes of Health in the US claimed to have discovered a genetic basis for human homosexuality.10 Headlines worldwide proclaimed that a “gay gene” had been discovered, and a huge debate erupted in the gay community about the pros and cons for gay rights.11 Yet no actual gene had been discovered, only an apparent association between DNA in one part of the genome and male homosexuality in some families. Subsequently, others failed to replicate Hamer’s work, and it now seems likely that the original findings were an artefact based on flawed statistical analysis and underestimation of the prevalence of homosexuality in society.12
Yet there is no doubt that the writings of Dawkins, and those who have followed him along the sociobiology route, continue to have a lot of resonance. For instance, Wired for Culture by Mark Pagel, published in 2012, extrapolates in a single page from self-sacrifice in amoeboid slime moulds to what he calls a “helping gene” that codes “for an emotion that disposes people to be friendly”.13 This all sounds quite nice except this helping gene’s influence apparently only extends to people of the same nation; to other national groups it turns into the “jingoism” or “xenophobia” gene. Pagel ends his discussion thus: “Next time you feel that warm nationalistic pride at the sound of your national anthem or the news of one of your country’s soldiers’ valour, think of the amoebae!”14 Pagel, by the way, is a Fellow of the Royal Society, and described on his book’s cover as “the world’s leading expert on human development”.
So why have such viewpoints become so acceptable, without good mechanistic evidence to back them up? One reason may be the pervasiveness of the ideology of bourgeois individualism within capitalism. This states that any complex system is best viewed as the sum of its individual components. It is this that underlies Margaret Thatcher’s notorious claim that “there is no such thing as society”, only individuals and their families. Applied to nature, this ideology informs the practice of “reductionism”. This is the belief that a system is best understood by dissecting it into component parts and studying these individually. Now, as a tool to understand the natural world, there is no doubt reductionism can have great power. My colleagues and I used this method to identify the mechanism whereby a sperm kick-starts an egg to develop into an embryo. By stripping this process down to its bare essentials, we were able to identify the gene responsible for regulating this process and show that this is mutated in certain infertile men.15
Such examples abound in modern medical research and show the power of a gene-centred approach for understanding the mechanistic basis of many physiological processes in the body. But those who appeal to genetics to explain scares over immigration, or the tendency for women to be excluded from the top jobs in society, or even why most men do not iron, never delve into real biological mechanisms; instead the “gene” takes on an almost mythical property of being responsible for practically everything in society, although generally with a reactionary bent. With this in mind, it is time we turned to the actual molecular basis of genes.
Molecule of life
Despite Mendel’s pioneering work, almost a century would elapse before genes were shown to be made of deoxyribonucleic acid, or DNA. This substance was first discovered by Friedrich Miescher at Basle University in 1869, who called it “nuclein”, since it was only present in the central “nucleus” of the cell. Subsequently the nucleus was shown to contain chromosomes, which divide into two at each cell division and are distributed equally to each daughter cell, strongly implicating them as agents of inheritance.16 Since DNA was a primary component of chromosomes, and indeed was only found in these bodies, this should have been a clue that it was the “molecule of life”. Yet this conclusion was resisted for many years, since DNA did not appear to have a complex enough structure for such a role. Instead proteins, which are in chromosomes, but also everywhere else in the cell, were assumed to be the molecules responsible for transmitting characteristics from one generation to the next.
There were good reasons for this assumption. Proteins are sometimes called the “building blocks” of life, and indeed they play a crucial structural role, both outside the cell, strengthening bones and ligaments, and also within it, in the so-called “cytoskeleton”. But proteins also catalyse the cell’s chemical reactions, compose its molecular motors, and transport nutrients and chemicals across its membranes. Proteins are ideally suited to these multiple roles, since they come in all shapes and sizes, a property based upon them consisting of long chains of units called amino acids, which come in 20 different varieties. The different combination of amino acids in each protein gives it its own character. Thus collagen is a long thin protein within our bones that is proportionally stronger than steel, while haemoglobin is a soluble, globular protein that carries oxygen within red blood cells and releases it where required in the body.
In contrast, DNA initially seemed the dullest of molecules. It too occurs as a chain of units, but an immensely long one compared to the discrete protein chains. Its units are called nucleotides, of which there are only four, distinguished by a part of the nucleotide known as a base, which can be either adenine, cytosine, guanine or thymine, usually abbreviated to A, C, G and T. Since at first there seemed no reason to believe that nucleotides were in anything other than a random order, and as the bases seemed chemically similar, it was hard to imagine this apparently inert molecule fulfilling any role in chromosomes other than a structural one.
However, the objective world often asserts its presence in scientific investigations, despite scientists’ best intentions. When in 1928 Fred Griffith at the British Ministry of Health, discovered that bacteria can exchange inherited characteristics in their version of sex, this pointed to a way to test which molecule was responsible for such inheritance.17 Still, it was only in 1944 that Oswald Avery and colleagues at the Rockefeller University in New York carried out such a test. Using radioactive isotopes to label different molecules in bacteria, Avery reasoned that it should be possible to identify the molecule of inheritance by its radioactively labelled form being transferred during bacterial sex. Starting with proteins as the most obvious choice, Avery hit a blank. However, when he and his team labelled DNA, this was transferred to the recipient bacterium. Though Avery’s findings should have led to universal acceptance of DNA as the molecule of inheritance, most biologists were sceptical. To understand how DNA could encapsulate the complexity of life, a new approach was required, one that focused on structure.
The double helix
On Saturday 28 February 1953 Jim Watson and Francis Crick identified the famous double helical structure of DNA. Having finally solved the structure that morning in their lab at Cambridge University, they retired to the nearby Eagle pub where, according to Watson, Crick told everyone who would listen that they had “solved the secret of life”.18 We now know, thanks to Watson’s The Double Helix, his own frank, scurrilous and shockingly sexist account of events published in 1968, that a crucial factor in the discovery was the glimpse that he was given of Rosalind Franklin’s unpublished X-ray diffraction experimental data.19
X-ray diffraction involves shining X-rays at a crystal of a molecule, and from the pattern of scattering of the X-rays, the position of atoms in the molecule can be determined. First used by William and Lawrence Bragg to determine the structure of common salt in 1912, its application to complex molecules was pioneered by J D Bernal, also a prominent socialist of his time.20 It was his methods that laid the foundation for Franklin’s DNA studies, and those of Max Perutz, who used them to determine the first 3D structure of a protein, haemoglobin, in 1959, in the same Cambridge lab where Watson and Crick worked.
Watson was allowed to see Franklin’s data by Maurice Wilkins, who was supposed to be working with Franklin at King’s College London on DNA structure, but who shared her data with Watson without her knowledge. Quite how much this owed to a clash of personalities as opposed to the sexism of the time is a discussion in itself, but Watson’s own attitude towards Franklin is just one example of the prejudice and marginalisation she faced as a woman scientist. And Franklin’s death of cancer at the age of 38 in 1958, possibly from exposure to the X-rays she used for her analysis, meant that she never knew the full facts about the extent of her contribution, or received proper official recognition for this in her lifetime, as did Watson, Crick and Wilkins when they received the Nobel Prize in 1962.21
Despite the dubious means by which Watson and Crick obtained one of their crucial insights, we should not underestimate their contribution. While their model building approach fed upon experimental findings gained through others’ hard graft, it also had a power of its own that was only belatedly recognised by Franklin and Wilkins. Most excitingly, the structure of DNA that Watson and Crick solved in such a manner clearly spelled out its function through its form. Or as Watson put it: “Anything that simple, that elegant, just had to be right”.22
So what were the features of the proposed structure that made Watson and Crick so sure they had succeeded in their quest? Firstly, DNA had to replicate itself at each cell division. The double helical structure showed clearly how this could occur, so much so that in Watson and Crick’s initial paper in Nature, they said: “It has not escaped our notice that the structure immediately suggests a possible copying mechanism for the genetic material”.23 What they had shown was that the four nucleotide bases project inside the double helix, and that A on one strand of the helix always pairs with T, and G always pairs with C. Thus each strand is always complementary to the other. In a follow-up paper, they proposed that during cell division the two strands split apart and a totally new strand assembles alongside each, so that one double helix becomes two.24
The second important property of DNA’s structure, for it to fulfil its role as the hereditary material, was that it must encapsulate the complexity of life. This was a trickier problem to solve but clues were already emerging from other sources. In 1952 another scientist at the Cambridge lab, Fred Sanger, found a way to read the sequence of amino acids in the two protein chains that made up the hormone insulin.25 Up to then specific proteins were known to have different proportions of the 20 amino acids, but it was not clear whether the amino acids in any particular protein were arranged randomly, or in a specific order. Sanger’s work showed quite conclusively that the latter was the case.
At this point a totally new way of looking at inheritance began to emerge. If DNA was a linear chain of four different nucleotides distinguished by their bases, and proteins were linear chains of amino acids arranged in a specific order, was it possible that the two were connected? A possible solution to this problem came not from a biologist, but from a theoretical physicist, George Gamow, of George Washington University in Washington DC.26 A refugee from Stalin’s Russia, Gamow had already made important contributions to our understanding of how the universe formed. Now learning about Watson and Crick’s discovery, he became fascinated with the way in which DNA fulfilled its role. He proposed a radical new way of looking at inheritance, namely that DNA passed on the information to make an organism by acting as a linear code.
The DNA code
The idea that DNA is a carrier of information is now so commonplace that it is easy to forget how novel the idea of life as a code was when first proposed. Up to then life’s complexity was viewed primarily as a product of the distinctive shapes and sizes of different proteins. But what if all those distinctive 3D molecules were merely manifestations of a linear code present in DNA? Gamow suggested that DNA acted as a direct template for protein production, with three nucleotides coding for one amino acid. With 64 possible ways of combining the four different nucleotides into such a triplet, there would be plenty of capacity for such a code to cover the 20 amino acids.
There was, however, a problem with Gamow’s proposal, for while DNA resides in the nucleus, proteins are produced outside it, in the remainder of the cell called the cytoplasm. There thus had to be an intermediary. This was subsequently shown to be the chemical cousin of DNA, ribonucleic acid or RNA, and specifically a particular type called messenger RNA. This is effectively a replica of the DNA composing any particular gene, which is copied from DNA in the nucleus and then travels into the cytoplasm where it becomes the template for protein production. While Gamow had the initial idea for a triplet code, many painstaking and often ingenious experiments were required to work out which nucleotide triplet coded for which amino acid. Since all 64 triplets are used, the code is “degenerate”, in that each amino acid generally has more than one triplet coding for it. Other triplets mark where the protein chain starts and stops.27
The discovery of the code made it clear how the species variants required for natural selection arise in the first place. Mutations are changes in the DNA sequence of a gene that can alter the properties of the resulting protein. While usually such changes will be detrimental to the organism in which they arise, more rarely they can be beneficial. Sometimes a mutation can be both detrimental and beneficial depending on the environmental context. Cystic fibrosis is highly detrimental but those who carry the CFTR mutation are more resistant to the cholera toxin. One explanation for the high proportion of carriers of cystic fibrosis in Europe is because in the past being a carrier meant one was more likely to survive a cholera epidemic.28
Having shown how life reproduced itself, molecular biologists began to thirst for the means to genetically manipulate life. This led from the 1950s onwards to the discovery of naturally occurring catalytic proteins—enzymes—that would become the genetic engineer’s toolkit. This included DNA polymerase, which replicates DNA; restriction enzymes that cut DNA at specific nucleotide sequences; and DNA ligase that joins such pieces back together.29 There was still no way to easily read the nucleotide sequence of DNA, but Fred Sanger solved this problem in 1977. Having already gained one Nobel Prize in 1958 for devising a way to read the amino acid sequence of proteins, he was now awarded a second one in 1980 for doing the same for DNA.30
Implications for sociobiology
Crick expressed the idea that life is primarily a one-way flow of information from DNA to RNA to protein, in what he called the “central dogma of molecular biology”. He later claimed to have not realised “dogma” meant a belief that cannot be doubted, and that he had really meant a “grand hypothesis”. Whatever his intent, his claim for the primacy of DNA was almost certainly aimed at the biochemists who for the first half of the 20th century had provided the dominant view of cellular processes. Watson and Crick and the scientists who flocked to their banner after the discovery of the double helix needed to undermine the old order that they were seeking to overthrow. Biochemists saw the cell as a network of interacting chemical reactions, all of it regulated by those ubiquitous proteins. So what better way to distinguish the new science of molecular biology from biochemistry than by asserting that, however varied and complicated the actions of proteins are within the cell, ultimately they are merely slaves of the code within DNA.
The central dogma has some troubling implications for the almost mystical view of the gene found in sociobiology and evolutionary psychology. As long as genes were undiscovered “factors”, one could ascribe whatever properties one wanted to them, whether it be the link with diseases like cystic fibrosis, or why men are less likely to do the ironing. But if genes’ role is to make proteins, this poses major problems for sociobiology. Thus Dawkins’s view as expressed in The Selfish Gene is that natural selection acts upon individual genes, or rather gene variants. Yet it is hard to see how this could work given that the selective process only assesses the capability of an organism to reproduce. The only way it could act upon the gene variant would be if that variant manifested its actions so directly upon the appearance, physical capabilities, or behaviour of the organism, that these actions could be selected for or against. Moreover, the gene variant would need to have so prominent an effect that this could be distinguished from all the other genes that affect these various properties of the organism.
For a monogenetic disease like cystic fibrosis, there is a reasonably clear link between the CFTR gene defect and the effect this has upon affected people. Lack of the CFTR protein, a transporter of chloride ions, leads to an imbalance in certain bodily tissues that leads them to malfunction. Though primarily affecting the lungs, where a build-up of thick, sticky mucus leads to an inability to breath and serious lung infections, cystic fibrosis also affects the pancreas, liver, intestines and reproductive organs. Yet while a single gene defect causes the disease, there is a huge variation in its effect upon the individual. Thus, while some sufferers die in their teens from lung failure, others only realise they have two faulty CFTR gene copies when they present at the infertility clinic, having no other obvious symptoms of the disease. This feature is called the “penetrance” of a disease. To some extent it is due to different mutations in a gene having differing effects on the resulting protein. But it is also related to the effects of other genes in an individual, and to the unique environmental influences that individuals are subjected to in their lifetimes, all of which can either counteract, or enhance, the effects of a particular gene variant. Thus sometimes the very same gene mutation leads to severe symptoms in one person, but has no effect in another.31
Now if this is the case for monogenetic diseases, how much more true must it be for complex human characteristics? Thus, when sociobiologists propose that homosexuality is coded by a single gene, or men are genetically predisposed to dislike ironing, or patriotism is genetic, it is not at all clear how a single altered protein could act in such a way, unless there were somehow specific cell types in the brain that carried out specific complex behaviours, each controlled by a different gene. Such brain “modularity” has been championed by evolutionary psychologists; yet human brain imaging studies show that complex behaviours activate regions across the whole brain, not tiny sub-regions.32 And the discovery by the Human Genome Project that humans have just over 20,000 genes, hardly more than a fruitfly, rather than the 100,000 some expected, demolishes the idea of a different gene responsible for each human behaviour.
A much more plausible explanation is that different human behaviours are all manifestations of being a species with a unique ability to act upon the world via rapidly evolving tools and technologies, self-consciousness and awareness, and the development of specific societies, while remaining biological beings whose behaviour is affected by the chemical and physiological responses occurring within our bodies, which may differ between individuals. While this point of view suggests that there is almost certainly no “gay gene”, it does leave open the possibility that subtle genetic differences between individuals may affect their sexuality.33 As for men’s willingness to do the ironing, rather than looking for a gene to explain this, a much simpler explanation is the sexist relations we still live under that grew up on the back of class society.34 And patriotism is nurtured by imperialist rivalries under capitalism, not a “xenophobia gene”.
The information paradox
Crick’s central dogma proposes a one-way flow of information from DNA to RNA to proteins, which then regulate the processes occurring in the cell and organism. We have seen how this poses problems for sociobiology, but might the central dogma itself be partially an ideological construct that reflects the society in which it arose? A lot depends on one’s definition of information. On the one hand, it seems clear that DNA stores information based on the accumulated experience of an organism over evolutionary time. If you or I could somehow retrace our ancestors, via their DNA genomes, at some point or other we would end up with some kind of single-celled bacterium. That is why we share 50 percent of our DNA sequence with a banana. In that sense, we are cousins of sorts to every other species on the planet.
But there are other ways of looking at the information flow in life. What Crick’s proposal ignores is that the DNA code can only be translated into the myriad different proteins that populate our cells and body via other proteins. Thus one could argue it is equally valid to see information flowing from proteins back to DNA. How important this flow can be was shown by Dolly the cloned sheep. The genetic information to generate Dolly came from the nucleus of the udder cell of another sheep. There the DNA only supplies the information to produce a very limited subset of proteins—those involved in milk production, storage of fat, and the other things that breast cells do. The development of specialised cells such those in the breast was thought to be irreversible. But Dolly showed that in special circumstances—in this case by introducing an udder cell nucleus into an egg with its own nucleus removed—this process can be reversed. Instead of being limited to supplying the information to make a single specialised cell type, the former udder cell DNA became capable of producing a whole new organism.35
So how did such a reversal come about? In effect, when the udder cell DNA was implanted into the enucleated egg, it became exposed to regulatory proteins that affect which genes are turned on or off, in a way that completely changed its capacity to code for the biochemical activities of life. Thus the passive potential of a DNA genome to hold information can be distinguished from the active ability of that information to be used to code for life’s processes, the latter being regulated by proteins. Such proteins are called activator or repressor proteins and they directly affect whether a gene is stimulated or inhibited, respectively, to code for messenger RNA. Such proteins were first identified by François Jacob and Jacques Monod in 1961, in bacteria, gaining the Nobel Prize for both men in 1965.36 Similar regulatory proteins exist in more complex organisms, including humans. Different cell types contain different combinations of such regulatory proteins, which explains why an udder cell produces quite different proteins from a liver, heart, or brain cell. DNA also comes wrapped in special proteins called histones, which limit the access of the activator and repressor proteins to the genes, but whose presence can be modified via “remodelling” proteins. This two-way flow of information between DNA and proteins is turning out to be highly important for gene regulation at the level of the whole genome.
A complex genome
The Human Genome Project (HGP), the international effort to both map the position of all the genes within our genome and obtain the sequence of its 3.3 billion nucleotides, was officially completed on 14 April 2003. It cost approximately $3 billion, making it the most expensive biology project in history. At its completion Sir John Sulston, of the Sanger Centre near Cambridge, who led the project in Britain, predicted that “we are going to hold in our hands the set of instructions to make a human being”.37 And Lord Sainsbury, British science minister at the time, said: “We now have the possibility of achieving all we ever hoped for from medicine”.38
Yet ten years later there is a debate about the value of the HGP. In particular, radical critics Hilary and Steven Rose have said that the project has been a “failure”, because the promised insights into the molecular nature of human disorders ranging from cancer to schizophrenia have failed to materialise.39 They have also pointed to the amount of money that has gone into the project, money which they argue has been diverted from other biomedical science projects. So do the genome discoveries represent a brave new world of scientific understanding or a false dawn? My own view is that while many claims made for the HGP were based on fundamentally flawed ideas, the project itself was far from valueless, and I will now explain why.
First, there is a danger in assessing the HGP purely in terms of the claims originally made about it. I have already argued that the way the DNA code works should undermine the mystification of the gene that we see in sociobiology. Unfortunately, the ideology of bourgeois individualism that sociobiology is based upon also influences geneticists whose findings ought to point to a quite different conclusion. Yet scientific projects can still reveal key insights, despite being guided by ideologies that may be false or distorting. Thus I would argue that the HGP has led to major new insights into how genes work, generated new technologies to study these questions, given us a better sense of what distinguishes individuals at the genetic level, and helped us understand how this relates to the differences between human beings, both in their susceptibility to disease, and also in other characteristics.
Secondly, one criticism made of the HGP was that if its primary aim was to identify gene variants linked to disease, it would have been better to have focused specifically on such variants, rather than mapping and sequencing the whole genome. There was a certain logic to such a criticism, given that at the outset of the HGP only a small proportion of our genomes appeared to be even devoted to protein coding genes, with the rest being classified as “junk” DNA. And indeed the HGP revealed that only a startling 2 percent of the human genome codes for proteins. So why bother sequencing the other 98 percent if it really is junk? For me, this sort of stance betrays a narrowness of vision about the possibilities open within scientific investigation. Thus, although science is often supposed to be primarily about confirming hypotheses, some of the most far-reaching insights are made when the opposite of what is expected is found, for this forces a reassessment of the nature of the objective reality that hypotheses are after all supposed to be probing in the first place.
In fact, a particularly exciting recent development has been the discovery that a substantial proportion of “junk” DNA may in fact have important functions. This discovery was made by the Encyclopedia of DNA elements (ENCODE) project, another “big science” project costing around $300 million. Its initial findings were published in August 2012, and some major surprises were in store. The first was that the non-coding DNA seemed awash with signs of biochemical activity. Thus Ewan Birney of the European Laboratory of Molecular Biology near Cambridge, who coordinated the analysis, has claimed that as many as 4 million genetic switches present in the non-coding DNA may affect which genes are turned on or off, yet these are often far distant from the genes they control.40
Interestingly, these long-range interactions best make sense in 3D. We are used to thinking of a chromosome as a linear chain of DNA nucleotides, but in the living nucleus it forms a complex 3D structure. Genetic switches distant from the gene they control work by binding activator or repressor proteins, then looping around to influence gene activity from a distance. The importance of this aspect of the genome is such that Job Dekker of Massachusetts University has recently claimed that “nothing in the genome makes sense, except in 3D”.41 Intriguingly, such long-range interactions also seem very dynamic, being different in a heart cell compared to a brain cell, which may further explain how although all cells share the same genome, the activity of particular genes in different cell types varies enormously.
Another important ENCODE finding is that previous links between susceptibility to certain diseases and changes in the DNA, in regions of the genome that had no obvious relationship to specific genes, now appear closely to overlap with the genetic switches identified by the project. Thus links have been identified for genetic switches that are only turned on in cells of the immune system, and the auto-immune disorder of the bowel, Crohn’s disease.42
While there is currently a debate going on about the true significance of the ENCODE findings,43 potentially they pose an important challenge to the concept of a gene as an isolated, discrete entity. Instead they point to a genome that may be a much more complex and connected entity than previously thought. A major issue now to consider is what implications this has for human characteristics and human disease.
The individual genome
A central claim made for the HGP was that it would lead to major insights into the molecular basis of disease. Thus Daniel Koshland, editor of Science, declared that the basis for “illnesses such as manic depression, Alzheimer’s, schizophrenia and heart disease” would all be unravelled, with new drug treatments for these conditions sure to follow.44 However, Steven Rose has recently argued that such claims have been exposed as a fallacy. Thus, for him, “the argument was that there were maybe three or four or ten different genes for each condition, and that we would identify these using ‘biobanks’ of DNA samples from large portions of the population”.45 Instead a much greater number of genes associated with such conditions has been found, with 120 variants linked to schizophrenia alone. He and Hilary Rose believe this has undermined the whole effort to find the genetic links to complex disorders.
Personally I am more positive about the potential value of these screening approaches. Certainly I would agree with the Roses about the fallacy of expecting to find one or a small number of genes determining these complex conditions. As discussed earlier, the very fact that genes code for proteins, many of which will be involved in regulating complex physiological processes, made it extremely unlikely that anything so broad as heart disease, diabetes or many mental disorders would be caused by a small number of gene variants, not to speak of the great influence that different environments have upon such disorders. Nevertheless, I think there is a danger of being too dismissive about the possibility of identifying important molecular links to complex disorders at an individual level.
For instance, recent studies of cancer show that while the genetic profile of a disease in the general population may be highly complex, this does not mean that valuable insights cannot be obtained about specific genetic changes that have led to that disease in the individual. Thus a recent study showed that breast cancer in 100 women was associated with more than 70 different combinations of mutations.46 Yet in each individual only one or a few such mutations were identified, meaning that specific genes might be used to define the pathology of the cancer in that individual, and drug treatments targeted against such genes. Analysis such as this involves sequencing the whole genome of an individual’s cancer cells and comparing it to that of their normal cells. Such analysis is becoming increasingly feasible as DNA sequencing costs continue to fall dramatically. Thus, whilst the original HGP cost $3 billion, technological advances mean that the latest estimate for a whole human genome sequence was only around £6,000, with this expected soon to fall to less than a few hundred pounds.
What does this mean for the diagnosis of other disorders? A certain amount may depend on the disease. Cancer is unusual in that while certain gene variants can predispose people to particular types of cancers, the disease is a multi-step process whereby subsequent mutations occur in the developing cancer cells that activate “oncogenes” or inactivate “tumour-suppressor” genes. And it is these changes, rather than the initial genetic predisposition, that may be best targeted by anti-cancer drugs in the future.
Disorders such as heart disease and diabetes are almost certainly complex because the heart and circulatory system, or the secretion of insulin and response to this hormone, both involve multiple cell types and chemical messengers, and are also influenced by other factors such as diet, stress, etc. But I would not find it surprising for specific genetic differences to underlie a tendency towards such conditions, within particular individuals. We already know that single gene defects can lead to extreme cases of heart disease or diabetes. As such, I do not think it implausible that a personalised approach to identifying specific genetic susceptibilities to more subtle versions of these disorders might lead in the future to individually tailored treatments.
Making such molecular links to mental disorders like schizophrenia may be more problematic. Notably, two individuals can be diagnosed as schizophrenic on the basis of completely different, and non-overlapping, sets of symptoms. And the fact that schizophrenia rates are much higher in British Afro-Caribbeans, not just compared to other Britons, but also to people in the Caribbean, suggests that social factors, such as racism, affect the likelihood of someone succumbing to schizophrenia, and/or being diagnosed as schizophrenic.47 But while ignoring the social aspect of schizophrenia is mistaken, an equal error would be to underestimate the pathophysiological aspects of the condition, and treat it merely as “a perfectly rational adjustment to an insane world”.48 In fact I see no contradiction in seeing schizophrenia as both affected by social triggers and influenced by genetic differences. Sir John Bell of Oxford University has recently argued about schizophrenia: “Everybody who has got it has got a different disease, but the mutations that produce the disease occur somewhere in those pathways associated with the development of the nervous system”.49 As such, identifying the specific components of such pathways in particular individuals might both reveal clues about the specific nature of their condition and point to potential drug treatments.
Of course, overly focusing on the genetic determinants for complex conditions such as heart disease, diabetes or mental disorders could lead to an under-emphasis on the social factors that may underlie such conditions, be it an unhealthy diet, lack of exercise or the growing level of psychological stress caused by a system in crisis. In addition, if genetic determinants for particular diseases were identified in specific individuals, there could be potential problems regarding the confidentiality of this information and the possibility of its misuse. This could lead not to better treatments but to a scapegoating of the individual with severe implications in a privatised, insurance-funded healthcare system such as the one that exists in the US and which neoliberals in both the ConDem coalition and the Labour Party would like to introduce in Britain. This brings me to the general question of the links between modern genetics and capitalism.
Genes and capitalism
For Hilary and Steven Rose, the “big science” that the HGP represents is “dominated by industrial sized labs, giant pharma companies and government money”, as opposed to the “small scale research” that was the previous main model for genetics. Moreover, the Roses see in this move to larger-scale enterprises a disturbing shift in the motives of the scientists who carry out genetic research. Thus, according to them, “doing the most ambitious, the most sophisticated research is no longer tied up with achievement; it’s implicated very profoundly with money.” This means that now “scientists don’t share; they spin out companies of which they are the chief executives.” Moreover the Roses see this as a key reason for the hype surrounding the HGP, with a primary problem being scientists “playing business at business’s game”.50
I have mixed feelings about these claims. In considering the money spent on the HGP, there are definitely concerns among many biomedical scientists, myself included, that big data-gathering projects are in danger of sucking funds from the sort of hypothesis-driven science that has led to major insights in the past, but which is now being starved of cash as austerity bites. Yet it is important to remember that although $3 billion seemed like a lot for a science project, that figure was well and truly dwarfed by the vast sums recently spent on bailing out the banks, or funding the wars in Iraq and Afghanistan, which run into trillions of dollars. Thus both the HGP and more focused research projects could easily be funded if science were valued as a higher priority than propping up bankers’ bonuses or raining down death and destruction on the Middle East. As such, there is a danger of scientists fighting over crumbs when we should really be combining to lobby for proper science funding for both big and small projects.
Secondly, I am not convinced that most biologists are primarily motivated by the profit motive rather than an interest in understanding how nature works. Perhaps I move in different scientific circles than the Roses, but my main impression from interacting with geneticists, both in Britain and internationally, including those who worked on the HGP, is of biologists passionate about what they do, but increasingly forced to beg for an ever-decreasing amount of public funds. Scientists do increasingly have to refer-in their funding applications, to “impact” and “translatability”. But although there will be exceptions, I imagine most British university biologists, not only struggling to raise funds for their research, but also hit by a pay-freeze that has now extended for some years, would laugh outright at the idea that they represent some new entrepreneurial class. We should also be careful about over-stating the dominance of free market values in science. It is worth remembering how key figures in the HGP, such as Sir John Sulston, fought to ensure that the findings of the project were kept freely accessible to all, in contrast to the private project led by Craig Venter, which wanted to privatise these findings.51
Thirdly, there is a danger in over-emphasising the idea that the HGP represents some major shift towards a privatised version of science. For all the big business values that the Roses allude to, the HGP and ENCODE remain overwhelmingly publicly-funded projects. Equally, it is not true that genetics in the past has been some pure scientific pursuit, unsullied by association with big business. Thus, as early as the 1930s, the Rockefeller Foundation, a legacy of “robber baron” John D Rockefeller, was supplying key funds to molecular biology labs.52 These included Wilkins’s and Franklin’s lab at King’s College London, and the Cambridge lab where Watson and Crick worked. Importantly, public funding initiatives matched this willingness to fund fundamental research.53 In this sense, it could be argued that it is not so much the HGP and ENCODE that represent a break with the past, but the current funding trend that requires all biomedical research to have immediate, translational aims, at the expense of science that studies fundamental biological mechanisms that may only in the future lead to new medicines.
These points aside, I would nevertheless agree with the Roses about the importance of the profit motive within biomedical science, for the simple reason that this is the dominant motive within capitalism as a whole. But there is a danger in simply seeing capitalism as a reactionary force. In the Communist Manifesto Marx and Engels highlighted two aspects to capitalism. Thus it is a system that “cannot exist without constantly revolutionising the instruments of production, and thereby the relations of production, and with them the whole relations of society”. As such, it has “accomplished wonders far surpassing Egyptian pyramids, Roman aqueducts, and Gothic cathedrals”. Indeed, those wonders now include the achievements of modern medicine: vaccines, antibiotics, anaesthetics and painkillers, keyhole and laser surgery, just to name a few. And in the future we can already see glimpses of new medical interventions based not only on genome analysis, but also on advances in stem cell technology.
Of course, Marx and Engels also drew attention in the Communist Manifesto to another side of capitalism, its creation of its potential future gravedigger—the working class—but also its tendency towards crisis. I would argue that it is only by appreciating this double-edged character of capitalism that we can understand the biomedical possibilities being unleashed by the system we live under, but also how much it is selling us short in terms of what might be achieved in a very different sort of society that was not driven by profit.
Therefore, against criticisms of the money being spent on “big science” projects, one could point to a much bigger problem being the lack of adequate investment in science. Thus funding by the research councils has been slashed as the crisis bites, while the pharmaceutical industry has been closing plants and sacking research staff. In addition, the current obsession with “translational” research can itself be seen as a reflection of the crisis in capitalism, with its prioritising of immediate application over identifying fundamental underlying mechanisms. This means that the basic science investigations that are now needed to make sense of the functional implications of the HGP and ENCODE findings are being hampered by lack of funds.
But it is not only basic scientific research that is being inhibited by the crisis of the capitalist system. If the possibility of a personalised approach to medicine based on assessments of individual genomes is ever to be realised in practice, an obvious next step would be to commit serious funds to enable the whole genome sequencing of every individual who wished to participate, as well as the means to act upon such information in a meaningful way. Of course, such a plan would raise a whole series of ethical issues, about the confidentiality of such information, as well as the psychological implications of an individual gaining access to this type of information. Yet even John Bell, an individual who has been at the forefront of trumpeting the possibilities opened up by the HGP, has had to admit that the infrastructure in the NHS for dealing with the new genomic information is hopelessly inadequate.54
As such, there is a danger that as the price of sequencing a whole genome decreases even further, ordinary people may have the possibility of accessing such information, but without the means of interpreting it, with potentially serious ethical implications. And while the rich may be able to use such information as part of an informed personal healthcare plan, this will be denied to the majority. As such, I believe there is an important debate to be had on the left about the pros and cons of using personal genome information, but as part of a systematic, publicly funded NHS initiative, that could deliver personalised medicine to all, for free.
The fusion of evolutionary theory and genetics has been a powerful tool that continues to reveal major insights about life. However, there is a contradiction between the common view of genes, as isolated entities with a mind of their own, and the reality of how the DNA code actually works. I have argued that despite being based on many false assumptions, the Human Genome Project has nevertheless been a highly important step forward in our understanding of what it means to be human. However, the reductionist mind-set that still dominates biology under capitalism is in danger of getting in the way of true insights into the complexity of life. Moreover, the current crisis in capitalism means that we are danger of squandering the very real medical and social possibilities that the genetics revolution has unleashed. As such, the quest for a truly personalised molecular medicine is necessarily tied to the struggle for a society run on the principle “from each according to their ability, to each according to their needs”.
1: Marx, 1981, p956.
2: Lenin, 1981, pp357-361.
3: Darwin first laid out his theory in a paper at a meeting of the Linnean Society in London on 1 July 1858, alongside one by Alfred Wallace (see below).
4: Darwin, 1859, p62.
5: Parrington, 2009.
6: Engels, 1975.
7: Named after Huntington’s disease, this in turn being named after George Huntington, who characterised the disease in 1872.
8: Dawkins, 2006.
9: Critiques include Rose and others, 1990, and Rose and Rose, 2001.
10: Hamer and others, 1993.
11: Parrington and Brown, 1993.
12: Rice and others, 1999.
13: Pagel, 2012, p81.
14: Pagel, 2012, p82.
15: Parrington, 2002b.
16: Walther Flemming and Oskar Hertwig discovered chromosomes, and that they contain DNA, respectively. See Aldridge, 2003.
17: Watson, 2004, pp37-38.
18: Watson, 2012, pp209.
19: Watson, 2012, pp180.
20: Brown, 2007.
21: Maddox, 2003; for a different version of events see Wilkins, 2005.
22: Watson, 2004, pp52.
23: Watson and Crick, 1953a.
24: Watson and Crick, 1953b.
25: Stretton, 2002.
26: Watson, 2004, pp64-67.
27: Gamow’s original proposal utilised a complicated overlapping scheme that would have meant that there was no degeneracy in the code. In fact the reality is a lot messier, further indirect confirmation that life is not designed, but evolved through blind chance.
28: That certain disease mutations confer benefits upon carriers was first proposed by
JBS Haldane, geneticist and socialist.
29: The discoveries took place at the height of 1970s US radicalism. Jon Beckwith, the first person to isolate a gene, upon receiving the Eli Lilly Award in Microbiology, announced that he would give the $1,000 prize money to the Black Panther Party.
30: Sanger is also a life-long peace campaigner and signed a letter to New Scientist deploring the election of BNP councillor Derek Beackon in Tower Hamlets in 1993. Maurice Wilkins was another signatory. See Gay and others, 1994.
31: Lobo, 2008.
32: Rose and Rose, 2001.
33: Sexual preference may be affected by differences in the hormones and nerve circuitry that underlie human sexuality, as well as by individual life experience. But clearly social values are major determinants of sexuality, as shown by the very different definitions of what has been considered normal or acceptable in different historical periods and parts of the world.
34: McGregor, 2011.
35: Parrington, 2002a.
36: These studies were actually begun by Monod before the Second World War and continued even as he fought for the French Resistance.
37: Quoted in Rose and Rose, 2012.
38: Rose and Rose, 2012.
39: Rose and Rose, 2012.
40: Whipple and Parrington, 2012.
41: Yong, 2012.
42: Whipple and Parrington, 2012.
43: McKie, 2013.
44: Koshland, 1989.
45: Rose and Rose, 2012.
46: Stephens and others, 2012.
47: Sugarman and Craufurd, 1994.
48: Laing, 1969.
49: Boseley, 2012.
50: Rose and Rose, 2012.
51: Sulston and Parrington, 2002.
52: Abir-Am, 2001.
53: Thus Perutz’s decades-long quest to determine the 3D structure of proteins received funding from the Medical Research Council, despite being seen as highly risky and unlikely to bring any direct benefit to medicine for a very long time. See Watson, 2012, pp37.
54: Boseley, 2012.
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