Genomics, Google, and Medical Ethics

The topic for the next meeting of the Harvard Pilgrim Health Care (a not for profit health insurer in Massachusetts, New Hampshire and Maine) Ethics Advisory Group, which I chair, is "Anticipating the Ethical Challenge of Genomic Medicine." I've been reading and thinking about what genomic medicine will mean for health plans for the past few weeks.

Yesterday, Sergey Brin, co-founder of Google, wrote in his blog about finding that he has a genetic mutation that increases the likelihood that he will develop Parkinson's Disease. I've quoted his wonderfully lucid posting below (in italics), followed by observations about some of the ethics and policy implications of his comments:

"For more than 20 years, my mother has worked with computers at NASA. So, when she developed a pain in her hands the diagnosis seemed easy -- Repetitive Stress Injury. Except that it wasn't so easy. As her mysterious symptoms progressed it varied -- RSI, fibromyalgia (unexplained pain), Lyme Disease, and so forth. It was only after visits to many specialists over a number of years that the diagnosis settled -- Parkinson's Disease. Since there is no clear test for Parkinson's -- it is defined by its symptoms -- we only grew certain as those symptoms developed and as her medications began to alleviate them."

What Mr. Brin's mother experienced is common in medicine - significant symptoms with no clear cause. As often happens, she saw many specialists and many different diagnoses were made. Happily, it does not appear that she went through a period of being "blamed" for her symptoms, as by "imagining" them or being "too sensitive to normal pain."

My mother had always been haunted by Parkinson's because her aunt had suffered from it. I had often reasoned with her that since Parkinson's is not hereditary (there is not a strong correlation of Parkinson's incidence among close relatives), she had little to fear.

Many people, perhaps most of us, are "haunted" by images of our future derived from experiences in our families. Mr. Brin's responses to his mother were based on the best information available at the time. But as emerges below, new facts emerged.

"In 2004, my wife, Anne, introduced me to her future cofounders in 23andMe as they were studying the genetics of Parkinson's Disease. As with my mother's fear, I was skeptical about the study. I reasoned that if there was much to be learned about Parkinson's in the genome, there would have to be a high percentage of inherited cases. In fact, I appeared to be right in that this particular study did not bear immediate fruit."

23andMe is a harbinger of the future - one of the new "personal genetics" enterprises that will provide genomic analysis directly to individuals who submit biological samples, typically saliva (23andMe sends a "spit kit"). How these services will be used and how individuals will react to and use the results are questions we won't know about until more experience accumulates.

"Nonetheless, there are some cases of familial Parkinson's but they are quite rare. Over the past few years researchers have been honing in on the genes that are responsible for those cases. One gene that stands out in those studies is LRRK2. There is one particular mutation of the LRRK2 gene -- known as G2019S -- that, while rare even among people with the disease, accounts, in some ethnic groups, for a substantial proportion of familial Parkinson's.

As a customer of 23andMe, I have always been excited about the product. I have found what pieces of DNA I share with various relatives. I checked whether other Brins were related. I explored my various gene journals -- learning, for instance, that I have one copy of the fast twitch muscle fiber. I also looked over the health related entries and found that my genetic risk for most diseases is modestly lower than average but for a few diseases it is modestly higher.

Because there are only a small number of genes which are known to have a very substantial effect on health (e.g. 10 times the average risk), I felt the possibility of discovering something very important to my health was just a hypothetical exercise. So, when my wife asked me to look up G2019S in my raw data (23andMe scientists had had the forethought to include it on their chip), I viewed it mostly as entertainment.

But, of course, I learned something very important to me -- I carry the G2019S mutation and when my mother checked her account, she saw she carries it too.

The exact implications of this are not entirely clear. Early studies tend to have small samples with various selection biases. Nonetheless it is clear that I have a markedly higher chance of developing Parkinson's in my lifetime than the average person. In fact, it is somewhere between 20% to 80% depending on the study and how you measure."

As a customer of 23andMe, Mr. Brin, not surprisingly, is stunningly well informed and logical in his thinking. If all users of the new, entrepreneurial genomic services were as sophisticated as Mr. Brin, concerns like those expressed in a January New England Journal of Medicine article - "Letting the Genome Out of the Bottle - Will We Get Our Wish?" would vanish.

"This leaves me in a rather unique position. I know early in my life something I am substantially predisposed to. I now have the opportunity to adjust my life to reduce those odds (e.g. there is evidence that exercise may be protective against Parkinson's). I also have the opportunity to perform and support research into this disease long before it may affect me. And, regardless of my own health it can help my family members as well as others.

I feel fortunate to be in this position. Until the fountain of youth is discovered, all of us will have some conditions in our old age only we don't know what they will be. I have a better guess than almost anyone else for what ills may be mine -- and I have decades to prepare for it."

Mr. Brin is an ideal user of genomic services. He interprets the findings as well as could be hoped for. He has deep intellectual curiosity. He responded to the bad news about the G2019S mutation in a profoundly constructive manner: (1) He considers what he can do to reduce the risk; (2) His wealth allows him to support research, which might benefit him directly, but will also contribute to the public good; (3) He puts the news into perspective - there is no fountain of youth and we will all encounter significant health problems in our lives; and, (4) He shows emotional resilience, and uses the news as an opportunity to "prepare" rather than despair.

There are, however, less happy scenarios that can be imagined. Here are two. (1) From my experience as a psychiatrist it is not hard to picture someone less resilient than Mr. Brin, perhaps subject to depression, who would take this kind of news as a death sentence, and perhaps even become suicidal. (2) In light of how costly health insurance is, it is not hard to picture people testing their genomic pattern with the idea of going without insurance in the absence of major risks and becoming heavily insured if the predicted risks are great. For individuals this is rational behavior, but in the fragmented U.S. health system this information asymmetry could ultimately undermine the insurance process. (Interestingly, the increasing availability of genomic information might give a push to the single payer option. Only if everyone is in the system is there is no advantage to using genomic information to game it!)