By CRG staff - interview with Jonathan Beckwith

Jonathan Beckwith, PhD, is a professor of Microbiology and Molecular Genetics at Harvard Medical School.


GeneWatch: Do you see a trend in the amount of research oriented toward finding a genetic basis for human behaviors?

Jonathan Beckwith: At this particular moment, yes. It seems to go in waves. What surprises me is that the wave seems to be peaking again right now, at a time when, at least in terms of using all the new genetic technologies, there is an increasing question about the utility of what's being done.

GW: Do you have any idea why that is?

JB: I think a component of it is that people outside of the field of contemporary research in genetics are getting into it. I think certain groups of psychologists have always been interested in genetics, but now it's also people in other fields, like political science.

GW: It seems like, at least up until recently, twin studies have been critical for a lot of behavioral genetics. Do you see that as a cause for concern?

JB: Yes, I've always thought it's an area of concern. The history of twin studies has gone through these ups and downs: they've been considered very important at points, then people have found problems with them, and then people in the field have come back and claimed to have overcome the problems. Twin studies are generally done by people who are not actually in the field of genetics, but are usually in psychology departments; and I think today, geneticists who are looking for genes associated with behaviors have relied on the finding of high heritabilities for certain traits from the twin studies, even though I don't think they have looked at them carefully enough to realize all the problems of twin studies.

I think that comes out very strongly in a current favorite topic among geneticists, the "missing heritability." The point is that people are looking for genes that are associated with certain behavioral conditions, or to mark chromosomal regions that are associated with those conditions, encouraged by the claimed high heritability  obtained in twin studies. But when they find genes or regions of chromosomes that they think contribute to behaviors, their contribution to the heritability of the traits is much less than that predicted by the twin studies. So there's this supposed puzzle: what's happened to the missing heritability?

GW: Of course, supposing it's missing is supposing it was there in the first place, based on the twin studies.

JB: Exactly.

GW: Are there any genes in particular that get a lot of attention in behavioral genetics?

JB: Certain genes are favored for explaining all sorts of things, like the Monoamine oxidase A (MAO-A) gene and the dopamine receptor gene. There's a whole list of behaviors for MAO-A, but the ones that get particular attention are aggression, and it's come to be called "the warrior gene."

GW: Is that similar to the "criminal gene?"

JB: Oh, yes-it goes back a long way. It started in the '90s. The very first paper that got a lot of attention and was discussed in the media as a "criminal gene" was a study of one family, where a number of the men had a mutation in a gene that completely knocked out its function. The study found an association with "antisocial behavior." That was picked up by the media to be called a "criminal gene," and even the senior author on the paper publicly stated, at least at a scientific meeting, that it was ridiculous to call it that.

Then, in the early 2000s, there was a group that presented a more subtle analysis, basically on some very common polymorphisms of the MAO-A gene, two of which are present in a significant part of the population. They found, by various measures, increased "antisocial activity," but only when the subjects had been subjected to child abuse. The problem is that a number of people have tried to replicate this, and a good portion of them have not been able to; it's not clear why.

It is argued that the reason the MAO-A and dopamine receptor genes have been focused on is that they are well-studied genes involved in brain function. Because this is one of the few genes that there were very early studies on, a lot of people who are studying various behavioral traits look at those candidate genes to begin with. However, since there are so many people looking at those particular genes to associate them with a behavior, inevitably some people are going to find a correlation just by statistical chance. That may explain why many of these findings cannot be replicated.

GW: Do you think that if someone is going into the study set on finding heritability that it can ever be a sort of self-fulfilling prophecy? If by going in to a study looking for something, could that make you more likely to find it (or think you've found it)?

JB: I think it may be, and if enough people are looking for the same thing, eventually some people are going to find it-but then it's not replicated, which goes into the long history of this field. I particularly think that's a problem because of people coming in from other fields who haven't been through the experiences of the last 20 or 30 years of research in genetics, and who are unaware of all the criteria that are necessary to really define things. That is, some of the work is just simply of very poor quality, not correcting for all the things that geneticists learned to correct for after a lot of false alarms.

Back in the '80s and '90s, there were a whole set of reports about single genes for homosexuality, schizophrenia, manic depression, risk-taking, happiness, etc. Those reports turned out to be wrong or have not been replicated. At that point, geneticists were very unsophisticated about statistics. They were using inappropriate statistical approaches and made other incorrect assumptions that required continuing revisions of the criteria needed in order to draw conclusions. When people used more appropriate approaches, if they found any genes or chromosomal regions correlated with such traits, they found, at best, large numbers (sometimes hundreds) of genes (rather than a single gene).  Even then, all of these genetic variants were still only contributing a small percentage of the variation in expression of that particular trait.

GW: Why do you think there has been an influx of people from fields outside of genetics conducting studies to find a genetic basis for certain behaviors?

JB: Maybe they start with the belief that genetics is very important in these behaviors; but also, like a lot of other fields, people have moved into genetics because there's so much money available. There are people from the social and political sciences who are getting grants from the National Institutes of Health and National Science Foundation to do science which ignores the lessons learned from previous failed attempts to find genes for complex human traits.

GW: Do you have any sense of why the NIH would be putting money into finding a genetic basis for things, even if it doesn't seem, in a lot of cases, any more successful than finding environmental influences?

JB: Well, that's what NIH does, mainly. And of course there's just been a very big push for genetics recently. Now with the National Human Genome Research Institute, it's a major segment of what the NIH is doing, and a lot of promises have been made about what's going to come out of it. But I don't particularly know why they and the National Science Foundation are funding studies that deal with genes for moral judgment or voting habits, for example.

GW: Right-it's hard to see the utility of figuring out whether or not there's a genetic basis for whether or not people vote. Do you have a sense of what the political scientists and other people studying those things-"genopolitics"-are hoping to get out of it?

JB: I'm not sure ... certain people in genetics see this field taking over, more and more, in the way in which E. O. Wilson, when he came out with his book Sociobiology in the 1970s, made the argument that sociobiology was going to subsume many other disciplines.

GW: After reading about certain claims linking a behavior to a genetic basis, the question I always find myself asking is: If something as complex as whether or not we show up to vote can be explained largely by our genes, what behaviors can't?

JB: First of all, I just have to say, that particular paper is one of the worst, I think. It's a surprisingly bad paper-at least to somebody who has been in the field or watching it carefully for the last twenty years or more.

What you asked reminds me of a conference I went to many years ago about behavior and genetics which was mainly based on twin studies in those days. The meeting was attended by both critics and practitioners in the field. One of the people got up, a quite well known geneticist who had been doing twin studies for ages, and he talked about the studies they were conducting on various behavioral issues, using identical twins and so on. And he said, "We realized we needed a control in this study of something that wasn't genetic. So we decided to ask about people's religious attitudes as a control," since that wouldn't be genetic. Instead, he said: "We found that was genetic too!"

That was the most bizarre thing. It's kind of an elemental scientific problem-you can't just change your control into an actual subject that you've proven something with-but he wasn't joking. He's published on that, in fact.

GW: Do you think this is sometimes a symptom of people coming into the field of behavioral genetics from outside of genetics-this idea of not just problematic study design, but going out and presenting those results without waiting to see if they are replicable?

JB: It's not really the same thing. I would say that, more than other fields, people come in with preconceived notions. And I don't think they were thinking about science, in terms of what it means to be doing science, the way that people in other fields were.

For example, one of my favorite beefs about the identical twin studies is a major assumption behind these studies, the equal environment assumption. That was unchallenged-it was a hidden assumption, I don't think they even felt they had to state it-that is, that if you looked at fraternal twins and identical twins, since they were born at the same time and grew up in their families and the world at the same time, that the two types of twins essentially share the same environment to the same degree. From someone outside the field, it's an obvious question whether that's true or not, but that was an unchallenged assumption until maybe 30 years ago, although twin studies have been going on since the early part of the 20th century. It was only then that they decided they had to do something to test those assumptions-which I don't think they did very well-and then they published a bunch of studies saying, "Well, we've proven the equal environment assumption is correct, therefore it's not an issue."

GW: How has the equal environment assumption been tested?

JB: What they did when they tried to test the assumption, once it had been challenged, was pretty simple, I thought. If it was a genes and intelligence study, they would go and count the number of books in the house of the twins, for example. Supposedly, one is asking the question: What are the influences that determine intelligence? If you don't know what they are, it's not clear exactly what you should be looking for, and just looking at a few things-the parents and their education, or the number of books in the house-isn't necessarily telling you much, because you don't know if you're looking at the right things.

GW: Another question that seems to sometimes be missing after a gene for something has apparently been identified is: What is the mechanism? In the political participation study, it's not surprising that although they claimed to identify a genetic basis, they didn't have an explanation for why those genes would influence whether or not someone votes. Is that a reason to raise an eyebrow?

JB: I think because of the false alarms, people have to be very careful. Before jumping into dramatic conclusions about what it means, they have to know more about the function of the gene.

I'll give you an example. A researcher, actually someone associated with our department, was doing studies on mice. I think they knocked out a gene in the mice, and they found that the mice no longer nurtured their progeny. It actually was a big story, at least in the local papers, that "the gene for nurturing" had been found. But it turned out that this gene was a major regulator of a huge number of different processes, and without it the mouse was just not a healthy mouse in general-so it's hardly a "gene for nurturing."

That kind of criticism can certainly come up when people are looking at a gene and see an effect on a behavior and don't even know what the gene does, how many processes in the body are affected and where in the body the gene is expressed. Such correlations are simply not very meaningful without much deeper study and the reporting of them is extraordinarily premature.  

GW: I guess when you start hearing things like "the gene for nurturing," the researchers might not have had that in mind or might not have expressed it that way-is it often the case that other people, at least in the media, are sort of taking the idea and running with it?

JB: I would say that most of the time, when the media presents these findings in a dramatic way, there are at least hints from the scientists themselves that it should be taken that way. That's not always the case, though-sometimes scientists who produce the work become quite dismayed at its interpretation by the media.

The MAO-A "criminal gene" study I mentioned before is an example. I spoke to one of the researchers afterwards, and the publicity was so horrendous to her ... for example, there was a Newsweek article that discussed the finding of this gene, called it a "criminal gene," and had a picture of Arabs and Israelis fighting. It got really blown out of proportion, and she was really very upset. She actually said she would never work on that subject matter again.

And the senior person on that study did make a statement about how it shouldn't be called the "criminal gene" or the "aggression gene." For these rueful scientists, some of this might have been avoided if the education of the scientist could prepare us to be more sensitive to the social implications of our work. On the other hand, I think there are many other instances where it's very clear what the intent of the authors is, if not in their publication, then in their press conferences or public statements.            

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