Opinion, Berkeley Blogs

The Honeymoon Mutation

By Malcolm Potts

I have been both a practicing obstetrician and a research embryologist. The more I learn about human the evolution of human sexuality the more fascinating it becomes. In a recent study in Science magazine, Stanford scientist Rajiv McCoy and colleagues[i] found evidence of a mutation that may have become more common because in our hunter-gatherer ancestors it make the time between the first intercourse and the first pregnancy longer – in short, a mutation that made the honeymoon last longer.

When I did my research at Cambridge University I was a close friend of Bob Edwards, who received the Nobel Prize for the first test tube baby 1977. Today, about 3% of children are born as a result of in vitro fertilization. One result is that more and more is being discovered about the genetic structure of the fertilized egg in the first days of life. One of the most common abnormalities observed is an incorrect number of chromosomes, technically called aneuploidy.

Human development is not like a modern factory meticulously following a blue print.  A stunning 30% of fertilized eggs are destroyed naturally because they are abnormal, even before the woman knows she was  pregnant.  These natural, spontaneous abortions are a necessary and healing process, because if one in three babies really did survive to have a devastating abnormality, few women would wish to risk getting pregnant.

McCoy’s discovery is that chromosomal errors are more common in women who also carry a genetic mutation with the curious name polo-like kinase 4 (PLK4). PLK4  is associated with failures in the complex cellular machinery that separate the chromosomes as the eggs and sperm develop.

Evolution is not about what is good, just, or beautiful – it is about what works. And what worked for most of human history was whatever enabled an individual to pass more of their genes to the next generation. It is scientific common sense that a genetic abnormality, such as PLK4, should have disappeared generations ago if it made women less fertile.  Yet the Stanford scientists provide evidence that this mutation has become more common with the passage of time.  So, what could possibly explain such a counterintuitive finding?

To answer that question we need to look for a moment at the evolution of human sexual behavior. Our closest primate relatives, chimpanzees, are highly promiscuous.  Males defend a territory, but they do nothing to nurture the children. I've been lucky enough to watch the wild chimpanzees studied by Jane Goodall, and I have observed firsthand what hard work it is bringing up a baby chimp without anyone else to help. A newborn human baby is even more difficult to keep alive than a newborn chimpanzee, unless the mother has some direct assistance from a male partner.

Like nearly all female mammals, chimpanzees advertise the time of ovulation – in their case with a massive swelling of the external genitals. We are an unusual species in that neither the woman nor the man knows when ovulation occurs.  This leaves men with two options. Like a male chimpanzee, a man can have a one night stand and then abandon the child.  Or he can have frequent sex with the same woman, fall in love, remain close to her and help nurture his child, which in turn will then be much more likely to survive. Human beings can perhaps be best described as a promiscuous species struggling to be monogamous.

To return to PLK4. Women with this mutation will lose embryos more frequently than other women, but in a strange way having more spontaneous abortions may be beneficial. On average, a woman with PLK4 will have to have sex for a longer interval than other woman before she eventually gets pregnant and has a normal baby. The honeymoon is more protracted. From a biological perspective, a few wasted embryos are small price to pay for the possibility of a stronger emotional bond between the parents.

A number of state legislatures, such as North Dakota, have tabled laws defining a fertilized eggs as a "person," deserving the same legal rights as a  new born child. In my own research, focused on the first 10 days of embryonic development following fertilization, I saw how common embryonic abnormalities are.

It seems to me to be profoundly misleading to frame embryos as "persons," and nonsensical to perceive abnormal embryos as ‘persons’ whose loss we might grieve over. An early embryo is not a ‘person’ – it is not baby without a diaper seen through the wrong end of a telescope. It is part of a remarkable, profoundly different error-filled world of awesome complexity and incredible potential that we are only just beginning to fully understand.

One in three American women will have an induced abortion. As a physician I have performed abortions and I have seen safe and unsafe abortions all over the globe. In my experience, most women seeking abortion do so because they know they cannot give the child, if born, the love and care that they know every child deserves.

When I first read McCoy’s paper it seemed to me quirky that one reason spontaneous abortions are so common in human development may be because they give potential parents longer to fall deeply and genuinely in love. Now, like so much in human reproduction, I think it is rather wonderful that a mutation that makes spontaneous abortions more common could also be a fountain of parental love. It also makes attempts to define fertilized eggs as ‘persons’ even more shallow, obtuse, and potentially extremely harmful.

[i]  McCoy et al., Science 348 (6231): 235-238. DOI: 10.1126/science.aaa3337

Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryo.