We Are Not Hard-Wired

[quoted]Development is the missing link between genotype and phenotype, a place too often occupied by metaphors in the past … But a strong emphasis on the genome means that environmental influence is systematically ignored. If you begin with DNA and view development as “hard-wired,” you overlook the flexible phenotype and the causes of its variation that are the mainsprings of adaptive evolution. (Mary Jane West-Eberhard, 2003: 89-90)[/quoted]Every so often, it’s important to reflect on how we think about the ways that nature and nurture collide to impact our biology. The alliteration of the two terms – nature and nurture – has given the phrase some staying power. In 1874, Charles Darwin’s cousin, Francis Galton, referred to the two as “a convenient jingle of words.” Before him, William Shakespeare described the character Caliban in The Tempest as "A devil, a born devil, on whose nature / Nurture can never stick.” Most of us would probably say that both nature and nurture count for something, though we may shift our thinking, depending on the trait in question: blood type, sexual orientation, height, temperament, etc.Different thinkers have fallen somewhere along a continuum, from hardline hereditarians at one end, to “blank-slatists” at the other. On the nurture side, the Buddhist monk Thích Nhất Hạnh once said: “When you plant lettuce, if it does not grow well, you don’t blame the lettuce. You look for reasons it is not doing well. It may need fertilizer, or more water, or less sun. You never blame the lettuce.” Of course, he was not just speaking about lettuce; this was a metaphor on the importance of compassion and nurturing people in their development. By comparison, current U.S. President Donald Trump frequently has emphasized the role of heredity in his personal life, claiming that genes have played a primary role in his “drive for success,” “health, stamina and strength,” intelligence, leadership, and even a possible genetic gift for real estate development. Neither Nhất Hạnh nor Trump is a scientist, but for our purposes they stand as exemplars of the ways that people sometimes think about nature and nurture.Yet scientists can fall into this trap too. James Watson, one of the co-discoverers of DNA, once famously said that "We used to think our fate was in our stars. Now we know, in large measure, our fate is in our genes." In his 2002 book The Triple Helix, Richard Lewontin told the story of the molecular biologist and Nobel laureate Sydney Brenner, who – while speaking at a conference – predicted that one day we would be able to “compute” an organism. All we would need are two things: the organism’s full genome and computers that were powerful enough to be up to the task.The idea is seductive. Genes are sometimes seen as self-sufficient molecules, almost existing in a vacuum, which contain all the information necessary to code for proteins. From there, it’s not a very big logical leap to think that if you had the genome, you could enter the code into a computer, hit “run,” and then watch some digitized version of the organism unfold.In fact, scientists have been doing something much like this for the tiny roundworm C. elegans with the project OpenWorm. Yet even for a relatively simple organism such as this, with only about a thousand cells in total, there are reasons to be cautious. As The Economist cautioned in its write-up of OpenWorm: “Attempting to simulate everything faithfully would bring even a supercomputer to its knees.” However, this isn’t due solely to the limits of computing power (what if we had a super-duper computer!?). Rather, it’s a matter of how the question is framed.To go back to Brenner, I don’t know what else he said that day, so it isn’t fair to caricature the rest of his comments as quite so reductionist. If asked, I think he would acknowledge that if we play the scenario out, we are immediately confronted by the fact that there is no vacuum. All organisms must reside somewhere, or – more realistically – many somewheres over a lifetime. And, whatever the genome is, environmental circumstances can have profound influences on phenotypes.“The Environment”[quoted]There are more things in heaven and earth, Horatio, than are dreamt of in your database.[/quoted]Here is a straightforward example. Barry Bogin and Ines Varela Silva found that ethnic Maya children residing in Los Angeles and Florida were, on average, 11.5 centimeters (4.5 inches) taller than those who lived in Guatemala (Bogin et al 2002). This was one of the largest population shifts in height ever recorded in that short a period of time (for those in the US, most of their parents had migrated only within the last 20 years). In fact, the heights of Maya children in the US were not significantly different from American reference data, even though they had once been perceived as pygmies and genetically “short.”

Changing growth patterns in Maya children, from Bogin et al 2002. Z-scores nearer to zero are approaching the average US child.

On the other hand, body build (the proportion of total height that was due to leg length) did not change much. Some studies have in fact found that average body proportions can change in a generation or two, such as in the case of Japan where legs got relatively longer over time (Tanner et al 1982), but there are reasons that this pattern is inconsistent across studies. Phenotypes are not necessarily set in stone, though some may be more responsive to change than others depending on the age of exposure, and degree of severity, to different environmental variables.What accounts for the difference in height in the Maya? We can dismiss the idea of a selective migration effect – that the tallest decided to migrate to the US, while shorter people remained in Guatemala. That possibility is unlikely, as most entered the US following indiscriminate forced displacement during a bloody, decade-long civil war. Another strike against that explanation is that heights of US Maya were even closer to US reference values in 2000 than they were in 1992, indicating a gradual shift in growth patterns. Instead, the authors suggested that the differences were likely due to factors such as nutrition, health care, and the quality of drinking water in the US compared to Guatemala. This is consistent with other studies that show growth patterns in many populations have changed over time (Bogin 1999; Steckel and Rose 2002).Certainly, genes are an important source of variation in traits like height, but this is complex, with many genes involved. One of the first genes to be consistently associated with variations in height across populations (the UK, Sweden and Finland), as well as in adults and children, was reported in 2007 (Weedon et al 2007). However, the effects were modest. Having one copy of a particular allele was roughly equal to an additional 0.4 cm in adult stature, accounting for only about 0.3% of the total variation observed.What accounts for the rest? There must be other genes involved, but across the globe, several studies have found correlations between many environmental variables – large and small – with how a fetus, infant, or child physically develops. This is true not only for height, but for things like adiposity and overall health. Here are a few environmental variables that have been correlated with somatic development:

• altitude (Greska 1990)
• seasonality (Little et al 1993)
• chemical pollutants (Schell et al 2012)
• maternal exposure to airport noise during pregnancy (Schell 1981)
• religious food restrictions such as during Ramadan (Reiches et al 2014)
• socioeconomic status (Leatherman et al 1995)
• neighborhood wealth (Drewnowski et al 2007)
• homelessness/ availability of shelter (Smith & Richards 2008)
• whether a child lives with family or in a group home (Nelson 2016)
• number of siblings (Ochiai et al 2012)
• infectious diseases (Moore et al 2001)
• maternal nutrition during pregnancy (Barker 1998)
• maternal smoking during pregnancy (von Kries et al 2002)
• maternal nutrition as a child (Stein et al 2004)
• whether one’s mother was a twin or triplet (if you’re a marmoset; Rutherford et al 2014)
• grandmother’s exposure to famine (Stein and Lumey 2000)
• psychological stress (Gohlke et al 2004)
• our gut microbiota (Turnbaugh et al 2006)
• amount of sleep during childhood (Taveras et al 2014)
• whether a premature infant was physically held or massaged (Field et al 1986)
• prenatal exposure to a nearby landmine explosion (Camacho 2008)
• physical activity levels (Cardoso and Garcia 2009)
• political instability and war (Clarkin 2012; Devakumar et al 2014)
• cultural beliefs about food and household distribution of resources (Dettwyler 1993)

This is just a partial list; a complete one is probably an exercise in futility. One of my professors in graduate school, Gary James, liked to say that “the best model of reality is reality itself.” What he meant was that we can never account for all of the variables that influence our biology. We can pick out a few major ones, but it’s beyond our capacity to model everything, even for a simple organism like C. elegans. This doesn’t mean we can’t know anything; otherwise what’s the point? In fact, we know a great deal about growth and development. It’s just a reminder about the complexity of organisms, and how many moving pieces there are.Seamless and Inseparable[quoted]What is inherited is DNA. Everything else is developed. – James Tanner, “Foetus Into Man” (1990 :119)[/quoted]As nearly everyone would acknowledge, BOTH genetics and environment are essential, as the two are inextricably intertwined. There is no organism without a genome; but there is also no such thing as an organism without an environment.This also puts a serious damper on the idea of “computing” organisms based solely on genomes, at least not in any absolute sense. If you had the complete genome of an extinct mammoth, and could somehow find it a suitable place to gestate and then find someone to care for it until maturity, you’d get something we would identify as a mammoth, rather than, say, a jellyfish. But to fully account for its individual biology – what kind of mammoth or jellyfish would we get – we would need much more than the genome. We would also need a crystal ball to predict all future environmental variables the organism would ever encounter.Speaking of jellyfish, if you grow one in on a space shuttle in orbit, you will still get a jellyfish. But without being exposed to gravity in the early stages of its life, even for a few days, there is a decent chance that they will move abnormally once they’ve returned to earth (Spangenberg et al 1994). Of course, most jellyfish will never experience life in space, but the point is that being able to navigate something even as basic as gravity does not come automatically, but may require exposure to it.We’re then forced to confront the reality that the effects of the environment on development are not merely noise interfering with the “true” nature of the organism. They are integral. It makes sense that jellyfish genomes should “expect” gravity because, before space travel, it had never been otherwise in the billions of years of life on earth. In other words, genomes are sculpted by natural selection to navigate probable environments, but there is always some degree of unpredictability. The same is true for us. As the developmental psychologist Michael Tomasello once said: “Fish are born expecting water, and humans are born expecting culture.” Our cultures and social environments certainly can vary widely, and we are then bathed in them.An illustration of this “environment-as-noise” perspective comes from the language deprivation experiments of the Holy Roman Emperor Frederick II. In the 13^th century, Frederick wished to discover how infants might speak if they weren’t exposed to spoken language. Essentially, he wanted to know if there was some default human language that would arise spontaneously in an infant, even without external interference. He hypothesized that it might be Hebrew, Arabic, Latin, or Greek, or perhaps whatever the language of the infants’ parents happened to be. Why not suggest Hausa? Or Vietnamese? Even emperors’ hypotheses are partly products of their environments. No ethical review board would acquiesce to such a study today, but Frederick had foster-mothers bathe and nurse the infants. However, they were not allowed to speak to them, lest they be influenced.Details from Frederick’s experiment are scarce, though it appears it had a tragic ending. The Franciscan friar Salimbene wrote that Frederick “laboured in vain, for the children could not live without clappings of the hands, and gestures, and gladness of countenance, and blandishments." Had the infants survived their deprivation, we can be sure that they wouldn’t have spoken any fully fledged language at all. There is no default human language that arises spontaneously. While the capacity for language may be innate, there is a critical (or optimal) window for language exposure in order for us to become proficient (Werker and Tees 2005).The idea that we are “hard-wired” for language or for other aspects of our biology and behavior should be viewed with some skepticism. Biological anthropologist Barbara J. King argued that the hard-wired concept is fuzzy and not very well defined, especially when applied to humans. Does it mean something is inexorable, the inevitable product of our genes, or is it more like an inclination? Still, the term remains popular, which likely has an effect on the way we think about nature and nurture. A quick Google search reveals that people have suggested that we may be hard-wired for: religion, war, beauty, social connection, compassion, racism, even doodling. It’s pretty clear that some of these are contradictory. If we are hard-wired for them, then they certainly cannot come out all at once. After all, doodling might not be your top priority during a war. If we are predisposed to any of the above, this at least suggests that circumstances matter when they are expressed. And, being able to respond to circumstances is part and parcel of being an organism, as we’ll see in Part 2.ReferencesBarker DJP. 1998. 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