Lately it seems like we're wired to want information. In the health sphere, we just can't get enough. At the national level, the HITECH act would save our system, or at least give it some needed blood. Evidence-based medicine is all there is: data or die. At the personal level, knowing, or at least gauging all those glucose peaks and pressure dips might just make us feel better. Or maybe all these gadgets just make us feel like we're in control of our bodies and health, even when we're not.
Don't get me wrong, I'm a facts-lover myself. When I practiced medicine, I couldn't learn enough about the molecular details of my patients' cases. In my own health situations, I'm on top of it, believe me. I read the fine print, and I read most everything. At home I'm a blogger and technophile - not bad for a woman who's a half-century old and commands several chronic illnesses.
So I hope you'll believe my enthusiasm in this new information age. And as for health care and medicine, you couldn't find a greater advocate for patients' rights. Your chart is yours to know and have, at least by sharing. Your results are yours to keep and to know. Health decisions are yours to make, if you choose.
With that as background, I'm puzzled by some recent developments on the personal health information front. My question has to do with our personal genomes and why some people are so charmed by the idea of knowing their DNA sequences. My sense, as a physician and scientist, is that most of the personal genetics data that would be sold, or bought, is nearly useless to most individuals who are not ill.
On its homepage, 23andMe would have the consumer "choose the DNA test that's right for you." You can take charge with a health package that lists at $429, fill in your family tree for $399 or "have it all" for a carefully-priced $499. Pathway Genomics offers package deals -- for "pre-pregnancy planning," drug response disposition and more. While I support the public's having the right to this kind of information, and the freedom to purchase genetic about oneself, it seems that much of what these companies and similar ventures would sell us, is not worth the cost of knowing.
Let's break down the kinds of genetic information you might buy on the Internet personal genomics marketplace:
Tests for mutations that are known to cause disease:
These assays test for specific, known variants in the genetic code -- usually SNPs, or single nucleotide polymorphisms -- that cause disease. Some well-understood examples of these sorts of mutations include the single base pair changes that lead to cystic fibrosis, sickle cell anemia or other, rarer hereditary diseases like familial dysautonomia or acid maltase disease (a.k.a. Glycogen storage disease type II or Pompe disease, as was featured in recent Harrison Ford flick Extraordinary Measures). With few exceptions, if there's no family history for any of these ailments, and a person is clinically well, I don't see the reason to run a check on one's carrier state for all of these conditions.
Some special cases, I admit, might include tests for the actionable genetic variants that dispose a person to hemochromatosis, a condition characterized by iron overload in organs including the liver and endocrine glands -- and which is included in most of the commercial panels; or to blood clots, which are not usually included in direct-to-consumer kits. As to whether it's worth screening for these at the population level, I'm not certain. For purposes of this discussion, what I'd suggest is that the price of screening for a short list of conditions for which proactive behavior matters is reasonable. But an undirected sort of fishing expedition for any and all known disease-linked mutations in each seems pointless, besides costly.
Tests for genetic alterations that may be associated with some inherited conditions:
These evaluations fall into the fuzzy area of hard data (many sequences -- GATTACA ... some 3 billion base pairs in each of us, times two for each genetic strand's pair) with relatively little, if anything at all, in the way of clear clinical connections. Since completion of the HapMap project in 2005, researchers and entrepreneurs can tell, quickly and inexpensively, if you or your neighbor has any of hundreds of known SNPs that tend to occur more or less frequently among people who have some common diseases, like Type II diabetes, hypertension or schizophrenia.
But these linkages are weak; most people who have these sorts of disorders, syndromes perhaps, don't have known genetic variants. In this week's issue of The New England Journal of Medicine, the authors of an excellent and (notably!) open-access primer on genomics state: "most SNPs associated with common diseases explain a small proportion of the observed contribution of heredity to the risk of disease -- in many cases less than five to 10 percent -- substantially limiting the use of these markers to predict risk." They go on to explain that there are no evidence-based guidelines for the use of this sort of information in clinical risk assessment.
This may change in the future, as technology and organized research on the real relationships of particular diseases to specific DNA findings progress. But for the time being, I'm not convinced there's value in knowing you have, say, a four-fold greater than average risk of developing heart disease, or even a seven-times higher than usual risk for depression according to the latest studies, when, in fact, most people with these conditions lack the particular genetic variants tested.
Assays for gene variants that affect drug metabolism:
In these tests, advertised as drug response profiles, the companies check for some DNA segments that encode enzymes involved in metabolizing some drugs like tamoxifen, methotrexate, Plavix (clopidogrel), coumadin and others. As a physician, and as a patient who's been on several of these meds, I see the potential value of knowing, before you take something that's got side effect, if you need a special dose or way of monitoring.
But let's say you're a man or don't otherwise need to take tamoxifen; it's hard to understand why testing for this is useful. The same goes for each of these meds. Unless the DNA assays becomes so inexpensive that it's cheaper to test for all of these, at once and for all, than to test for individual drug responsiveness, I support that these be measured only for a reason, i.e. when people plan or need to take these drugs.
Whole Genome Sequencing:
In 2003, it cost around $500,000 and several months of a research team's efforts to fully sequence an individual human's genome. Now, the price is estimated to run around $50,000, enough to keep most of the non-movie stars among us from considering this option. But it's expected the price will come down to the range of $1000, soon. Surely, more people -- perhaps some friends and neighbors -- will splurge for this modern window into our nature as individuals.
Really I'm not sure what would be the point, but I can't say I object if people choose to spend their money on this sort of extreme recreational genomics. What an educated consumer might want to know in advance, as is indicated in this week's review, is that even with equipment and tools that provide results that are 99.9999 percent accurate, if you sequence 6 billion base pairs in a person you'll wind up with some 6,000 errors (not mutations, just errors in the report). Even if you're not a worrier and you're armed with information, it seems to me like sorting through those thousands of false positives would be a big headache, at the very least.
Heredity Profiling:
These sorts of evaluations are not marketed as "medical" and instead, are geared for the person who wants to understand his or her ancestry.
Genetic Testing in Cancer:
Oncologists have, for years, routinely tested their patients' tumor specimens for mutations that help define the tumor type and, sometimes, its potential responsiveness to specific treatments. This is a huge and valuable topic -- but is relevant only to people who have cancers. The kinds of DNA changes in tumors, somatic mutations, aren't the same sort of genetic variants that doctors or personal genomics companies look for in the person's whole, inherited genome. It's a different story.
Putting it together, with the recent news:
This month, the FDA stepped in on Pathway Genomics' plan to mass-market DNA spit kits in Walgreens pharmacies. In the same week, Congress got involved; the House Committee on Energy and Commerce sent letters to the CEOs of Pathway, Navigenics and 23andMe asking for more information on how these companies go about their businesses.
A key question, now, is whether these sorts of tests - that check our genetic sequences for disease-associated variants - must be run through a doctor or other health care provider's offices. A concern is that ordinary people "can't handle" this sort of information without a doctor or geneticist's guidance. I don't see it that way; I agree with the position that people have the right to access their medical details as they deem fit. My issue, rather, is in the value, or absence of value, of running so many tests in people who are not sick.