Monday, June 29, 2009

Henry VIII (Marin IJ)

Dr. Dustin Ballard: Genetic testing - crystal ball for parents?

Dr. Dustin Ballard

Henry VIII, the 16th-century British monarch, was plagued for years by a vexing reproductive problem. By the time he was on his third wife (out of six) and numerous conceived pregnancies, Henry had yet to father a living male heir. In 1536, not long before arranging the beheading of Queen Ann Boleyn, the dismayed Henry is said to have exclaimed, "I see God will not give me male children." Back in his day, this type of misfortune was blamed on God or, as in Henry's case, the wives. Henry (who is thought to have been clinically depressed and/or paranoid schizophrenic,) certainly didn't seem to blame himself. Several hundred years later, however, there is now evidence that perhaps Henry's problem was caused by his own DNA; it seems that some men are genetically predisposed toward fathering girls.

Last year, a Newcastle University study found evidence of just this type of link. A team led by Corry Gellatly examined nearly a 1,000 family trees dating back to 1600 - tracing the lineage of brothers and sisters. They found that men inherit a tendency to father girls or boys from their parents. Thus, a man with four sisters is more likely to father girls of his own than a man with two brothers (Henry VIII had two brothers and three sisters).

This would seem to explain the well-documented phenomenon of increased rates of male births in war-torn countries; men with multiple sons are more likely to have a son (or sons) survive and these sons have a genetic tendency to conceive

more male children. Based on Gellatly's work, it is likely that a yet undiscovered gene controls the composition of a man's sperm - in some cases directing greater production of X sperm (daughter sperm) than Y sperm (son sperm) and in some cases directing an even or Y-dominant distribution.

Now that we have evolutionary evidence, I imagine it won't be long before geneticists locate this specific "gender gene." And once they do, an inquisitive fella with a few greenbacks to burn will be able to discover his own gender gene via "direct to consumer" genetic testing. Perhaps you've heard of these Web-based companies such as 23andMe and Navigenics that allow you (for $1,000 and up) to "search and explore your genome;" providing a breakdown of nearly 100 genetic tendencies, ranging from the likelihood of developing diabetes or breast cancer to the risk of sticky earwax.

This technology has seemingly blossomed overnight. In the not too distant past, it took 13 years and $3 billion to sequence the entire human genome and now Knome Technologies ("Know Thyself") will sequence yours in a few months for the tidy price of $350,000. But, as with any explosion in medical technology, there are some valid concerns. First, some worry if there are enough protections in place to keep employers and health plans from discriminating on the basis of genetic information (a federal nondiscrimination law was passed last year, but it is too early to say how effective it will be). Second, as addressed in a recent editorial in the New England Journal of Medicine, many gene-disease risk associations are rather weak and likely to be revised with further study. Thus, personal genetic-testing in its current form is much like the nutritional supplement industry: ripe with hype and subject to manipulation. Consider, which advertises, based on immunity-related genetic compatibility evidence, the ability to genetically match couples and fill the world with better sex, more orgasms and healthier children.

Many medical providers wonder whether it is wise to obtain and interpret genetic information without a physician's involvement and counsel. And to what degree do we really want to genetically "know ourselves"? If we are talking about a screenable and treatable disease, such as breast cancer, it makes sense to look for genes (such as BRCA 1&2) that significantly increase risk. But too much risk-awareness about less clear-cut associations could lead to paranoia. Predisposition to earwax? Not sure I need to know about that.

As for the gender of one's unborn children, this can be one of life's great surprises. Some people choose to learn early on in a pregnancy, and others wait until the delivery room. No matter which, it is impossible to predict, before you experience the moment, what it feels like to hear the words "It's a boy" or "It's a girl." It would be a shame if genetic knowledge led someone to decide not to have children, based on whether they thought they were likely to have girls or boys. It is worth remembering that some of life's great accomplishments can stem from circumstances clouded by ambivalence.

Consider Henry VIII; his eventual male heir Edward VI, died a sickly lad of 15 while his daughter Elizabeth ruled the kingdom during a period of 45 years of enlightenment. If Henry had known the type of queen Elizabeth would become, he might not have blamed God, but instead thanked his DNA.

Dr. Dustin W. Ballard is an emergency physician at Kaiser Permanente San Rafael and the author of "The Bullet's Yaw: Reflections on Violence, Healing and an Unforgettable Stranger." His Medically Clear column will return July 6.