During pregnancy the mother's hormonal communication systems are coming under joint control of both the mother and the fetus. The fetus secretes a number of hormones into the mother's body to achieve various effects, particularly increasing the nutrient levels of the maternal blood. In the early stages of human pregnancy, the embryo embeds itself in the uterine wall and taps into the maternal blood system, releasing hormones into maternal blood that can influence the mother's physiology, blood sugar levels, and blood pressure. The higher the levels of sugar and fats in maternal blood, the more nutrients the fetus can obtain. Typically, hormones are molecules produced in tiny amounts that have big effects, at least when communication occurs within a single body and there is no conflict between sender and receiver. However, in pregnancy, one individual (the fetus) signals to another (the mother) and there is potential for conflict. Natural selection favors increased production of the hormones by offspring to get a bigger effect, while at the same time it favors maternal receiving systems that become more and more resistant to manipulation. There is thus potential for an evolutionary escalation that sometimes results in placental hormones being produced in absolutely massive amounts. It's estimated that about a gram a day of human placental lactogen is secreted into the maternal blood stream, and yet it has relatively minor effects.

I think this observation, that placental hormones tend to be produced in very large amounts, is the best evidence for the existence of maternal-fetal conflict. The fetus secretes these hormones into the mother's body in an attempt to persuade the mother to do something that she might not necessarily want to do. Think of placental hormones as the equivalent of the junk mail that you get in your mail box. These messages are trying to persuade you to do something. They're relatively cheap to produce so they're distributed in vast quantities but have relatively minor effects. They must work sometimes, but it's very different from the sort of intimate whisper you might get between two individuals who have common interests.

The most successful application of my ideas on imprinting has been to the study of growth during pregnancy, and the prediction that paternally derived genes are selected to produce larger placentas that extract more resources from mothers. But the basic idea of the theory applies to any interactions among relatives that are what I call asymmetric kin; that is, relatives on the maternal side of the family but not on the paternal side, or vice versa. I suspect that genomic imprinting is going to be relevant to understanding the evolution of social interactions. There's also evidence now that imprinting is implicated in some forms of autism. There are a number of imprinted genes that are known to be imprinted in the brain, and I'm interested in exploring those ideas.

The most exciting empirical work that's been done to test my ideas came out of Shirley Tilghman's lab before she became President of Princeton. Hers was one of the first labs to describe an imprinted gene. Paul Vrana, a postdoc of Tilghman's, looked at crosses between two species of mice, one of which had a very high rate of partner change—multiple fathers within a litter—whereas the other was a so-called monogamous mouse, where a single father fathered all the offspring in a litter and the female had about an 80 percent chance of staying with the father to produce the next litter. The researcher predicted that the conflict between maternal and paternal genomes would be more intense in the mouse with multiple paternity than in the monogamous mouse, and in fact, when you cross them you get a dramatic difference in birth weight.

If the father came from the species with multiple paternity, there had been intense selection on paternal genomes to extract more resources from mothers. This paternal genome would be matched against a maternal genome that had not been strongly selected to resist paternal demands. In this direction of the cross, offspring were larger than normal, whereas in the reciprocal cross where the paternal genome came from the monogamous species and the maternal genome from the polyandrous species, offspring were smaller than normal. Paul Vrana was able to show that this difference was largely due to imprinted genes in these two species. This suggests that divergence of imprinted genes may contribute to the speciation process, and in particular that changes in social systems and mating systems can cause changes in the expression of imprint. These can then contribute to reproductive isolation between sister species.

The second bit of work is being done in, of all places, a liver oncology lab at the Duke University Medical Center that is studying genomic imprinting. Out of curiosity, Randy Jirtle and Keith Killian looked at marsupials and then at the platypus—an egg-laying mammal—to see where imprinting arose. They found that imprinting is absent in the platypus, at least for the genes they looked at, but was present in marsupials. Thus, imprinting appears to have arisen more or less coincident with the origin of live birth, before the common ancestor of marsupials and placental mammals. There are some exciting areas of research of that kind.