The Delusions of Certainty

  Of course, forms of nature are also outside our two cartoon characters, and they themselves are natural beings, part of nature, but what the division is trying to sort out is what is inherited in people and what is made through experience and what we call the environment. In this view, the organism is in its environment but can be neatly separated from it. It is a discrete, contained entity with definable borders. In her small, brilliant book The Mirage of a Space Between Nature and Nurture (2010), the geneticist and philosopher of science Evelyn Fox Keller investigates the semantic ambiguities of the nature/nurture conflict and argues that before Charles Darwin, the opposition, as we now understand it, did not exist. It is certainly true that despite the long history of innate ideas in philosophy, the poles between what has come to be called nature and nurture took on a new appearance when Darwin’s theory of evolution hypothesized how specific traits were passed on from one generation of a species to the next. For Darwin, the stuff of heredity was not genes but submicroscopic “gemmules.” Keller identifies Sir Francis Galton as the thinker who hardened the nature/nurture distinction by isolating gemmules into bounded, stable units of biological inheritance. Indeed, he was the one who came up with the “jingle” that is still with us: nature versus nurture.

  As I will show, Darwin’s gemmules take on an even more particulate (or atomic) character for Galton than they did for Darwin, becoming more independent, but also invariant. Where Darwin held that these particles might be shaped by the experience of an organism, beginning with Galton, they were reconceived as fixed entities that were passed on from generation to generation without change. The relevance of this difference to the causal separation of nature and nurture is that although the effects of malleable (or soft) hereditary particles might be regarded as separable from the effects of “nurture” within a single generation, over the course of many generations, their influence would become hopelessly entangled with the influence of experience (or “nurture”).32

  For Galton, then, hereditary nature travels inside the body through reproduction over the generations, while nurture remains mostly outside it. It is not that the flood has no effect on our two cartoon characters who nearly drown, but rather that some internal substance of nature can explain why one character rebounds and the other sinks after the frightening experience and when, in Galton’s words, “nature and nurture compete for supremacy . . . the former proves the stronger.”33 Galton coined the word “eugenics” in 1883. His understanding of heredity led him to call for social policy to strengthen the future of the race by encouraging some people to mate and others to desist from mating in the interest of the greater good.

  The eugenics movement that grew out of Galton and continued into the twentieth century had many faces, including progressive ones. The American birth-control advocate Margaret Sanger, for example, was a staunch supporter of eugenics. The horrors of National Socialism, which came later, would taint the word forever. What I am most interested in here, however, is not the well-known political applications of these ideas but Keller’s distinction between particulate (hard) and malleable (soft) hereditary substances and how the harder, atomic characterization served as a vehicle for a definitive boundary between nature and nurture, organism and environment, and that many people like M continue to attribute these hard qualities to what turns out to be softer and less definitive than many would like to think.

  Naming and conceptualization are vital to understanding, but meanings in language are not fixed. Despite great efforts to define and isolate them in biological science, semantics are rarely controllable. The idea of the gene originated with Gregor Mendel and his research on plants in the 1860s. The word “gene” itself, however, was invented by the Danish biologist Wilhelm Johannsen in 1909, who used it to refer to “germ cells” that somehow act to determine the characteristics of an organism. He declared that the word “gene” should be completely free of any hypothesis.34 Instead, it was an abstract concept about some hereditary biological substance that traveled in time over the generations. Later, it was applied to a material reality, although the characterization of that material reality, the gene, has changed over the course of the twentieth and now twenty-first centuries due to an explosion of research in genetics.

  The sensational discovery by Watson and Crick of DNA’s structure and the double helix in 1953, which is often still described as one that uncovered “the secret of life,” became known as “the central dogma”: the sequence of bases in DNA is transcribed into RNA, which the latter translates into a sequence of amino acids of a protein. In their model, the information moved according to a linear logic. Genes were seen as potent beads on a string, agents that largely determined what the organism would turn out to be. They were variously described as the engine, program, or blueprint for the organism, a hard, active unit of heredity. This idea resonates beautifully with a long history of ideas that advanced irreducible atomic bits of nature. The central dogma is Hobbesian, both because it has a hard material reality and because it proceeds in a clear step-by-step, mechanical manner. The Master Molecule explained not just how you got your mother’s nose but a great many other traits as well. However, soon after Watson and Crick’s discovery and decades before the grand genome project was completed, the model began to look a lot more complicated, less unidirectional, less neat, less atom-like and more gemmule-like. Discovery after discovery in molecular biology created a need to alter the admittedly elegant, simple model until the central dogma became untenable.

  Genomes are now understood as systems under cell control. Without its relation to the cellular environment, the gene isn’t viable. In fact, it is inert. It is neither autonomous nor particulate.35 Some have proposed dropping the word “gene” altogether because its history has given it meanings that it simply does not have any longer. The interactions among DNA, proteins, and the development of traits (such as noses) are tremendously complex and dependent on context.36 The popular idea that the fate of our cartoon people, marching through life and its inevitable hardships, is determined by their genes, which hold context-independent information like blueprints that directly code for those strong and weak traits that make one swim and the other sink, rests on an erroneous notion of what genes are. And although molecular genetics is a highly specialized, complicated field, the basic message that genes are dependent on their cellular environment is not all that difficult to grasp.

  Why then does the myth continue? Mary Jane West-Eberhard frames the problem this way: “The idea that genes can directly code for complex structures has been one of the most remarkably persistent misconceptions in modern biology. The reason is that no substitute idea for the role of genes has been proposed that would consistently tie genes both to the visible phenotype and to selection.”37 To put it another way, the problem of genotype (the inherited genes of an organism) and phenotype (all of its many characteristics, including its behavior) is not direct and does not lend itself to a reductive, simple formula such as the central dogma. West-Eberhard argues for developmental plasticity and genetics, “the universal environmental responsiveness of organisms alongside genes,” as the path of “individual development and organic evolution.”38

  The story of how a fertilized zygote turns into a complex organism is not fully understood, but studies in epigenetics are growing. The field was named by the developmental biologist, embryologist, evolutionist, and geneticist C. H. Waddington in the early 1940s. Before the discovery of DNA’s structure, Waddington hoped to capture biological occurrences in embryology that go beyond the unit of the gene. Waddington’s interests were interdisciplinary and included poetry, philosophy, and art. He drew well, and one of his drawings of what he called “the epigenetic landscape” is particularly evocative. With its billowing folds, slopes, and plateaus, his landscape has an organic, anatomical, almost erotic quality. In a curved crevice of a mountaintop sits a ball—a cell. The landscape is undergirded by intersecting guy ropes, which are in turn attached to a series of black pegs inserted into the
ground. The pegs represent genes and the ropes their “chemical tendencies.” This visual map was meant to show that there is no simple relation between the gene and the finished organism. The ball’s path is dependent on what is happening in the terrain below. As he explained, “If any gene mutates, altering the tension in a certain set of guy ropes, the result will not depend on that gene alone, but on its interactions with all the other guys.”39

  Waddington’s landscape is a metaphor, and there are scientists who believe its utility is long past. Others have expanded on it to include later science and elucidate the still opaque relationship between genotype, the developing embryo, and phenotype.40 Since the 1990s, epigenetics has become a growing field, and now it is often described in terms more narrow than Waddington’s. Genetics is the study of heritable changes in gene activity due to changes in the DNA sequence itself, such as mutations, insertions, deletions, and translocations. Epigenetics is the study of changes in DNA function and activity that do not alter the DNA sequence itself but can affect a gene’s expression or suppression, alterations that can be inherited by succeeding generations of the organism.

  Methylation is a biochemical process through which a methyl group (CH3) is added to cytosine or adenine nucleotides, two of the four nucleotides—cytosine, guanine, thymine, and adenine—that are part of the DNA structure. What is important for this discussion is simply to understand that these studies demonstrate a new twist in the story of how cells roll down Waddington’s landscape, variations that affect the genes but are not in the genes themselves. Cytosine methylation inhibits or “silences” gene expression. Further, it seems that methylation patterns can be affected by environmental factors, such as diet, stress, and aging. Research by Michael Meaney and Moshe Szyf has linked methylation in rats to early stress in the pups. By separating pups from their mothers, depriving them of care, and by studying differences in maternal behavior—some rat mothers lick and groom their offspring much more than others—the researchers found higher incidences of methylation in stressed and “low-licked” pups than in the nonstressed, “high-licked” pups. The methylation changes were then inherited by the next generation of rats even though they were not exposed to the same “stressors.” The title of a 2005 paper by Michael Meaney tells the story: “Environmental Programming of Stress Responses Through DNA Methylation: Life at the Interface Between a Dynamic Environment and a Fixed Genome.”41

  I have never liked the word “interface,” perhaps because I find it vague. It is another word connected to computers, but it seems to mean a “common boundary” that can be applied to machines, concepts, or human beings. It is hard to picture methylation changes in the DNA of an organism related to anxiety experienced through parental neglect, for example, as a shared boundary between environment and genome, as if the two met at a border. It is much easier to borrow Waddington’s drawing for a new purpose. A shock to the landscape—a big storm, for example, that doesn’t uproot the gene pegs holding up those undulating hills and dales but rather causes one of the chemical-tendency ropes to become tangled up tightly around a peg—will alter the course of the rolling ball.

  Much work remains to be done in epigenetics, and some molecular biologists remain skeptical about Meaney’s findings and wait for more research to replicate the experiments. Rats are not people, and people cannot be subjected to the bruising experiments routinely done on laboratory creatures, but there are some studies that suggest that early trauma, for example, affects methylation and gene expression in human beings, too. More remarkable perhaps is that the long discredited idea that parents hand down characteristics acquired during their lifetimes to their children, an idea that turned the French naturalist and evolutionary theorist Jean-Baptiste Lamarck (1744–1829) into the laughingstock of science, has been resurrected in epigenetics. Although Darwin and Lamarck are often seen as champions of conflicting ideas, Darwin did not oppose Lamarck. He too believed that some acquired characteristics were heritable. As for “stress,” that word now used for all manner of afflictions, it has long been known that neglect and shocks of various kinds affect a child’s development. What no one knew was that these experiences might affect nongenetic factors that nevertheless have an influence on gene behavior and how a person’s genes are expressed, and that this could be passed on to the next generation.

  M’s idea that a psychological sense of entitlement can be directly attributed to genes is not borne out by genetic research, which is not the same as saying there is no hereditary dynamic, but rather that the road from genes to an organism’s structure is tortuous and depends on many factors, including how an animal is cared for in early life. Nevertheless the “idea” of genes as a “program” persists. The biologist François Jacob launched the metaphor in 1970: “The programme is a model borrowed from electronic computers. It equates the genetic material of an egg with the magnetic tape of a computer.”42 This equation assumes that, as in a computer, the whole logic is contained in the DNA sequence. As early as the 1950s, the geneticist Barbara McClintock uncovered evidence that genes were not a static linear message inscribed in the sequence of DNA.43 All of this is well known and has been presented repeatedly in many ways by many people doing genetic research as well as by philosophers of science.

  And yet, the computer metaphor is by no means dead among geneticists. I repeatedly run into references to hardware and software and programs when I read papers on the subject. There are people working in the field who cling to the metaphor and others who think the computer analogy has served its purpose and should be dropped. As Keller points out, most metaphors contain an inherent ambiguity that can spur research but at the same time limit it because just as the metaphor opens the scientist to new ways of seeing, it may close off other visions it could not possibly contain. Unlike Jacob’s computer tape, which moves in one direction only and is the code for the organism’s features, the ball in Waddington’s landscape can roll in several directions depending on pegs, guys, and, my addition—the weather—all of which affect how the organism will turn out. Thinking without metaphors is impossible. Try doing it. You will soon find you are trapped. They are embedded in the nature of language itself, and language, as Vico believed, is at once a cultural and bodily phenomenon. Hobbes understood language to be essential to reasoning, and reasoning was logical and mathematical. Therefore it needed to be cleansed of all tropes.

  What interests me here, however, is why certain metaphors are broadly appealing and others aren’t. I suspect many people prefer heroic, active Master Molecules, modeled on an image from computer technology, to dependent genes that can’t do anything without the cell around them, a picture that rather closely resembles our prenatal life inside our mothers. Perhaps clean, hard boundaries have a nice logical feeling and entangled interactions suggest something messier, perhaps even something less rational. One can’t help but be reminded of Princess Elisabeth noting that a vaporous body can interfere with, even erase, sound reasoning, so there must be some relation between the two. The borders, Dear Mr. Philosopher, can’t be quite as neat as you hope them to be.

  Most of us like to be known as hardheaded thinkers rather than soft-minded dreamers, and we lean toward rigor, not imprecision. As I pointed out in another essay, in science, the word “squishy” is a synonym for muddle, and lurking under the adjective is the notion of the soft and feminine.44 On the other hand, rigidity can have negative connotations and flexibility positive ones. The initial understanding of DNA, a momentous discovery, certainly, was nevertheless shaped by a desire to present the findings in a form that was precise, not blurry, and this desire is a reflection of science itself and its need to fit nature into what Kuhn called conceptual boxes.

  Brains: Hard or Soft?

  What about hardwired brains? The metaphor was imported from engineering to mean a form of brain fixity, usually genetically determined, but the meaning of the word shifts depending on how it is used. The reference is to electronic wires or cables in a machine, such as the telepho
ne, but also to the computer. In a computer, that which is hardwired is controlled by hardware, not software, and therefore cannot be changed by the user or programmer without difficulty. The contemporary term “hardwiring,” which resonates with the mechanistic thought of the seventeenth century, links the brain to a machine. The terminology is now ubiquitous, both inside science and outside it in popular culture.

  A fairly conventional scientific meaning of hardwiring appears in John Dowling’s book The Great Brain Debate: Nature or Nurture? (2004). Addressing the plastic or malleable character of the human cortex, the most recently evolved part of the brain, Dowling explains that early hints of its ability to adapt to altered circumstances arrived through experiments with people who wore optical prisms that turned their worlds literally upside down. After a few days of this confounding vision, people’s eyes adjusted and they began to see normally again. When the prisms were removed, they reverted to seeing right-side up within a few hours. Dowling cites research that demonstrates this is not true for frogs. “Thus, cold-blooded vertebrates do seem to have a much more hardwired nervous system than mammals.”45 Note that the word is used not in absolute but in relative terms, not either/or but more and less. Frogs are harder-wired than people. Of course actual brains do not have wires or anything that looks like wires in them. But then, this particular metaphor has become dead or nearly dead through frequent use.