Scientific Method / Science & Exploration

Is our genome a straitjacket or a comfy sweater?

We can't know how significant epigenetics is until scientists define it.

NEW YORK CITY, NY—Back in December, the geneticist Mary Claire King warned that, when it comes to epigenetics, "we have a semantic problem that's becoming a philosophical problem—and on the verge of becoming a dangerous political one." She meant that scientists themselves were being a bit sloppy with defining epigenetics, the process by which long-term biological changes can occur without changes in the underlying DNA. This sloppiness is now leading to public confusion about what exactly is involved in epigenetics and how it might affect human health and behavior. In the absence of clear ideas, non-scientists are grasping at any meaning they find convenient and using that to draw grand conclusions about human nature.

Unfortunately, nearly every aspect of this confusion was on display at a panel called "The Social Impact of Epigenetics," part of this past weekend's World Science Festival in New York. The panel started with grand declarations about how Lamarck might have been on to something about the inheritance of acquired characteristics. But before it was over, one panelist was saying that we only have a single clear example of this in mammals, and it involves coat color in mice.

What is epigenetics anyway?

We partly described epigenetics when we covered a recent example that suggested it may influence human metabolism. But it's worth going over in a bit more detail. In short, epigenetics involves stable changes in gene activity that don't involve changes in the DNA.

Almost all human cells share an identical collection of DNA. The difference between cells comes down to which genes they activate and how strongly they activate them. Some of these differences in gene activity are transient as cells respond to their environmental conditions. Others are more permanent, so that once a cell adopts a neural or blood identity it maintains that identity. It's these more permanent changes that are often referred to as epigenetic since they get passed on to a cell's daughters when it divides.

The differences in gene activity are mediated by a combination of proteins that stick to the DNA, and some of these stick to specific sequences. For example, there's a protein called REST that binds a sequence near many genes involved in nerve functions and shuts them off in any cell that isn't a neuron. Other proteins called histones stick to DNA more generally, helping package it up so that it fits inside a cell. Histones can be chemically modified in ways that make the nearby genes either more or less active.

One source of confusion is that both the transient and more permanent responses often involve the same proteins and histones. Because of this, some people (including Jim Watson) have argued that none of this should be considered epigenetics—it's all just gene regulation. In contrast, some people on the panel were saying that even the transient changes constitute epigenetic activity and that epigenetic markings change almost daily (although the panel was hardly unanimous on this).

Daily changes in epigenetic programs probably sound new and exciting. But if things are defined this broadly, then epigenetics is not as exciting as it seems. It's just another way of saying that gene activity changes in response to the environment, which was already firmly established.

Epigenetics across generations

As noted above, these sorts of epigenetic changes only apply when a cell divides; they don't generally get inherited by a fertilized egg. In fact, part of the process of producing sperm and eggs involves wiping out most of this information in its entirety. But there is a form of epigenetic inheritance that can survive this. Some specific DNA sequences can be chemically modified by having an extra carbon added to one of the bases in a process called methylation. Methylation often survives through the production of sperm and eggs and on through fertilization—and in some cases through much of the life of the organism. In contrast to the modifications that can change daily, methylation only seems to change very slowly over the course of an organism's lifespan.

If methylation in the sperm and eggs can be altered in response to environmental conditions, then it's possible for a parent's environment to influence gene expression in their children. There is clear evidence that this sort of epigenetic inheritance goes on in plants and some insects. But, when it comes to humans, the only evidence we have so far is suggestive. When the panel was asked about cases that went beyond a maternal influence on one generation of offspring, biologist Randy Jirtle said there's only a single well-demonstrated case in mammals and it involves coat coloration in mice.

So even though epigenetic inheritance may end up being significant, it's hardly an earth-shattering change in our understanding of human heredity. In fact, there was nothing that came up during the discussion that justified mentioning Lamarck's name.

Scientific sloppiness and public confusion

The person who did mention Lamarck, moderator Bill Blakemore, probably should have known better. At one point during the program, he admitted that when talking to scientists about the topic he never came across the same definition twice. That sort of confusion was present throughout the discussion, as different scientists lumped everything from transient changes in gene expression to trans-generational inheritance under the "epigenetics" umbrella without bothering to clarify what it was they were talking about.

All of this, of course, would just be an obscure academic debate if people weren't trying to infer something about human nature from the existence of epigenetics. The title of the panel itself, "The Social Impact of Epigenetics," implies that the discovery of human epigenetics will have an impact on how we run our society. Lone Frank, a European journalist on the panel, was explicit about how epigenetics changed her perspective. She called genetic determinism, the idea that your genes dictate who you are, a "straightjacket." For her, the chance that epigenetics meant that the genes could be overridden made the genome seem more like a "comfy sweater."

This was an attitude similar to the one the President of the European Research Council expressed in Stockholm. In general, people seem to be hopeful that epigenetics can explain some persistent social issues without forcing us to accept that these issues are all in our genes and there's nothing we can do. Given how little we know about human epigenetics, hope seems very premature.

In any case, the rest of the panel was there to put a brake on things. Jean-Pierre Issa pointed out that some genes are deterministic and many others will increase risks no matter what epigenetic inheritance does to them. At best, in his view, epigenetics will only shift things like disease risks a few percentage points; it won't completely reset your biology. And when it comes to human health, you could make a larger impact simply by following basic health advice: eat well, exercise, and avoid smoking. (Naturally, someone on the panel suggested these good habits could change your epigenetic status.)

Could our understanding of epigenetics create or solve societal issues? Absolutely. Some aspects of cancer seem to involve epigenetic changes, and epigenetics may explain why some childhood traumas cause changes that persist into adulthood. But the same could be said of plain old vanilla genetics. In the same way, the thorny questions considered by the panel—do we have a right to epigenetic privacy? Should we do something about those we find are epigenetically at risk of violence? These are things genetics itself has forced us to look at previously (and we didn't always come up with satisfying answers then).

But right now, all of that speculation is extremely premature. Scientists themselves are still arguing over what is and is not an epigenetic change. They're still struggling to provide conclusive evidence about how significant it is in humans. Until we have a clearer picture of that, asking what its impact on society might be isn't likely to generate any informative answers.

Listing image by crayonbeam

Expand full story

You must to comment.

You May Also Like