We don't know that mounting such a strong challenge to the idea that genes are predominantly what make us who we are was the editors' intention, but the subtitle suggests that, and in our view, that's certainly what they have done. Indeed, we can't help noting that this is an unintended but eloquent counterpoint to Nicholas Wade's view of life, in which everything including the kitchen sink is genetic (or at least we assume he'd say this, since sinks are designed by Eurasians who are because of natural selection genetically of superior inventiveness).
|Cover of Science, Aug 15, 2014|
Lane et al. write about "Parenting from before conception". Infant health, they write, seems to be particularly influenced by conditions during 'fertilization and the first zygotic divisions, [when] the embryo is sensitive to signals from the mother's reproductive tract.'
The oviductal fluid surrounding the embryo varies according to maternal nutritional, metabolic, and inflammatory parameters, providing a microcosm that reflects the outside world. In responding to these environmental cues, the embryo exerts a high degree of developmental plasticity and can, within a discrete range, modulate its metabolism, gene expression, and rate of cell division. In this way, the maternal tract and the embryo collaborate to generate a developmental trajectory adapted to suit the anticipated external environment, to maximize survival and fitness of the organism. But if the resulting phenotype is a poor match for conditions after birth, or if adaptation constrains capacity to withstand later challenges, offspring are at risk.Further,
Maternal diet at conception has a major impact on the developmental program. Reduced protein content for just the first 3 days of embryogenesis retards cell proliferation and skews the balance of cell lineage differentiation in the blastocyst. The effect of nutritional disturbance at conception persists through implantation and influences placental development and nutrient transfer capacity, then after birth, the neonate gains weight more rapidly, developing higher systolic blood pressure and elevated anxiety.Some of the effect is epigenetic, that is, modifications to the DNA structure that affect gene expression. And some of the effect is, Lane et al. write, on oocyte mitochondria. These organelles, "powerhouses of the cell", support blastocyst formation. Their location and activity levels are known to respond to the mother's nutritional status, and ultimately affect the health of the child, as well as affecting gene expression in the brain, among other things. Epigenetic effects on sperm, influenced by environmental conditions, also can affect the developing embryo. But it's the "epi" in epigenetic that tells the tale: it's not the genetic (DNA sequence) variants that cause the trait difference, but variation in the use of the same sequence.
Many of the essays in this issue use the word 'plasticity', meaning that developing embryos are able to respond to various and varying environmental conditions. If conditions are too extreme, of course, the embryo can't survive, but in general, how an embryo responds to immediate conditions may have lifelong effects. From the review by Rilling and Young ("The biology of mammalian parenting and its effect on offspring social development"):
Parenting... shapes the neural development of the infant social brain. Recent work suggests that many of the principles governing parental behavior and its effect on infant development are conserved from rodent to humans.That parenting has a strong effect on the infant's physiology, and that the effects of parent/child interactions have evolved to be strong is not a surprise, of course, given that parenting in mammals is essential for the survival of the offspring. And plasticity, or adaptability, is a fundamental principle of life. We have referred to this as 'facultativeness' in the past. Organisms that are able to adapt to changing environments -- within survivable limits -- are much better equipped to survive and evolve. Indeed, the final piece in this special section on parenting is titled "The evolution of flexible parenting." Parenting behaviors among many species are well-documented to respond to environmental changes. Put another way, it is not being genomically hard-wired that is most adaptable in these ways.
So, with all these examples of the interdigitation of nature and nurture, can we declare the death of genetic determinism? Well, no. Genetic determinism is alive and well, thanks in large part to Mendel and the resulting expectation that there are genes for traits that are out there to be found. But in many ways, we've become prisoners of Mendel -- while many genes have been found to be associated with disease, we know very well that most traits are polygenic, and/or due to gene-environment interaction and we've know this for a century. So the idea that the effect of parenting might transcend genes shouldn't be surprising. And the idea that there might be factors that we haven't predicted that affect traits such as diseases or how brains work shouldn't be surprising, either.
The BBC recently aired an excellent 25-part program called "Plants: From Roots to Riches" about the history of Kew Gardens, and because the gardens have been so central to botany for so long, about the history of botany in general. The series is still accessible online, and well worth a listen. I bring this up because a story told on one of the episodes struck me as a very apropos lesson about causation. A "Great Storm" hit the UK in 1987. This was a hurricane that did tremendous damage, including killing millions of trees, 700 at Kew alone.
Before the storm, arborists had been concerned about a 200 year old tree at the Gardens, the Turner Oak. It was clearly not well; leaves were stunted, growth was slow, but it wasn't clear what was wrong with it. During the storm, the tree was uprooted completely and tossed into the air, but as luck would have it, it came back to earth right in the hole its exodus had created. The arborists decided it didn't need as much attention as many other trees in the gardens after the storm, though, so they left it until they were finished tending to others. This was three years later, at which time they discovered that the tree was thriving, growing again, and looking healthier than it had in decades.
|Quercus x turneri at Kew Gardens; Royal Botanic Gardens|
Why? The arborists eventually realized that all the foot traffic at the Gardens had compacted the soil to the extent that the roots, and thus the tree, were suffering. It turns out that the soil around a tree must be aerated if the tree is to thrive.
I love this serendipitous discovery. A tree was ailing, no one knew why, until an unexpected event uncovered the explanation, and it turned out to be something that no one had thought to consider. Many of the discoveries reported in the August 15 issue of Science strike me as of the same ilk. Scientists have been looking for genes 'for' diabetes, taste, mental illness, obesity, and so on for decades now, and the explanation for these conditions may be instead events that happen even before conception, where it never occurred to anyone to look before.
There are numerous other examples; a few years ago it was reported that age at death (for late-life, not infant mortality) is affected by the month in which someone is born. The authors, for some reason, did not follow up this potentially very important finding. Maybe the effect is due to seasonal foods consumed by the mother during what turn out to be the riskier months of conception--if so, should there be lifelong evidence, if we but looked for it, of accelerated disease prodromes like obesity, hypertension and the like.
Perhaps the Turner Oak effect should be a thing -- it might encourage investigators to explicitly look for the unexpected. What causes asthma? Could it be disposable diapers? Who knows? Broccoli has never been blamed for anything -- maybe it's time for broccoli to be implicated in some disease. The problem is that we don't think to look because we all 'know' that broccoli is good for us.
Some ideas are kooky, but when it turns out that some kooky ideas really do seem to explain cause and effect, it means we shouldn't always be looking in the same place for our answers (the drunk under the lamppost phenomenon). The cause and effect relationships described in the parenting issue of Science involve some unexpected environmental effects on gene expression -- epigenetic effects of various kinds -- and plasticity, meaning that cross-talk between genes and environment creates a give-and-take that can't be called genes or environment alone. We don't know that these are final answers, but we know that we should expand our range of expected possibilities.
Perhaps the Turner Oak effect should guide more of our thinking in science.