What will having your genome sequenced reveal about you? Long life? Luck? Impending doom? I think that many of us are under the impression that personal genome sequencing is now both accessible to the average Joe (kinda sorta true) and provides accurate predictions to effectively guide treatment for most patients (ummm…errr….).
My hesitation in responding to the second claim isn’t to say that believing in the promise of personal genomics is anything other than an eminently reasonable position. Think back to the year 2000 when Craig Venter of Celera Genomics (a commercial company) and Francis Collins of the NIH (government funded) effort sat down over a choreographed beer and pizza summit to work out their differences and jointly announce the completion of the human genome sequence. The year 2000 seemed to be as good a year as any to make the announcement, even though there were still several years of postdoctoral blood to burn to get past (a very blurry) finish line.
During this time, the popular press was eagerly imprinting grand visions upon the public’s collective mind. There are many quotes, but perhaps the narrative is captured best by Bill Clinton’s announcement:
It will revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases. In coming years, doctors increasingly will be able to cure diseases like Alzheimer’s, Parkinson’s, diabetes and cancer by attacking their genetic roots. Just to offer one example, patients with some forms of leukemia and breast cancer already are being treated in clinical trials with sophisticated new drugs that precisely target the faulty genes and cancer cells, with little or no risk to healthy cells. In fact, it is now conceivable that our children’s children will know the term cancer only as a constellation of stars.
I have no doubt there were labcoats backstage who were shuddering while Bill Clinton was uttering those words. Talk to anyone honest in the disease business and they will tell you that Clinton’s quote comes across as, in polite terms, optimistic. Government representatives responsible for spending decisions and communicating to the public seem to have a habit of upselling the whole “end of cancer” thing.
Questioning the value of the knowing one’s genome sequence may seem silly to some, after all more information can’t do us any harm, can it? Information on its own certainly doesn’t do any harm, but acting on information in face of risks and uncertainties can certainly do more harm than good. Consider recent calls to reduce mammogram screenings, pelvic exams and colonoscopies in certain populations.
Now we need to be clear here, a small set of diseases do seem to be related to single mutations; these include cystic fibrosis, Huntington’s and sickle cell anemia. While we don’t need genome sequencing to diagnose these conditions (they were genetically characterized long before the human genome sequence was complete), understanding the underlying biology of these diseases is clearly worthwhile. The problem with many other diseases is that we are having a hard time finding useful treatments, and the “one gene one disease” narrative doesn’t seem to apply to a lot of things (especially cancer). Even the idea that we have only one genome is being looked at critically these days.
So is human genome sequencing useful? There are a lot of “rah-rah” articles that have a sort of apologist tone (things are “finally” changing!), but lets be a little more critical and split the question up into a few smaller ones.
Is human genome sequencing useful for biological research?
Yes, with complete certainty. The fact that we can almost effortlessly look up a gene sequence in a given organism and run all sorts of interesting comparisons has enabled a cornucopia of wonderful (biological, computer and statistical) science that has fundamentally expanded our understanding of what life is. It is important to remember though, great science alone is not sufficient for finding cures to diseases.
Has the human genome sequence led to the cure of any diseases?
This is a little difficult to answer. Yes, knowing the gene sequence of proteins involved in disease pathways has been utilized to deliver effective treatments to the market (but I am almost sure that every drug target gene sequence was found before the human genome project). Using gene sequences of individual patients is a different story.
Does personal genome sequencing offer any benefit to patients in terms of predicting or treating disease?
Not for healthy people, since the tradeoff between the clinical benefits and risks of sequencing don’t make sense in terms of current practice. The article in the previous link does go on to demonstrate effective applications of clinical sequencing for appropriate patients and suggests a very careful approach including pre-sequencing counseling so that patients can be braced for trying to understand any test results they could receive (perhaps something like this comic could be a part of a standard kit). Perhaps the most common instance of clinical sequencing today is the partial sequencing of tumor samples for some cancers to identify subtypes susceptible to particular treatments.
Will personal genome sequencing ever be useful to patients?
No one knows yet. I don’t think it would surprise anyone if partial sequencing did play a significant role for the treatment of some diseases, but you have to remember how difficult a time we have when it comes to discovering cures for diseases. No one really knows how to do it; there are some of us who think an army of monkeys might be just as good at it as a building full of people with chemistry degrees.
You can find a whole host of criticism of genome sequencing and Genome Wide Association Studies (GWASs, the studies you usually read about in the popular press with headlines like “Scientists Find Genetic Clues Related To X”). Even prominent bioinformatics scientists like Lior Pachter who work in the field suggest that careful regulation of companies like 23andMe is probably a good idea (23andMe has been having a bit of trouble with the FDA recently).
Genome sequencing cheerleaders like Eric Lander have remained staunch in supporting the imminent value of personalized gene sequencing. I think few people would have a problem with the cheerleading if only proponents would care enough to provide the public that funds them with a little more respect and realism about what we think sequencing can and will be able to do. But, then again, measured words aren’t really a good way to go about getting government funding.