Get yer genome sequenced for better health! Meet Dr. Reality
Here (“Human genetics: Genomes on prescription,” NatureNews, 5 October 2011), we read “The first clinical uses of whole-genome sequencing show just how challenging it can be”:
As prices fall further, some say that prescribing a genome sequence or analysis will become akin to requesting a magnetic resonance imaging (MRI) scan. “It’s just like any other test in medicine. There’s nothing remotely special about it,” says David Bick, a clinical geneticist at the Medical College of Wisconsin in Milwaukee. But, he adds, “people will cry and scream and yell about that statement”. That’s true: unlike the results of most medical tests, a genome sequence provides a vast amount of difficult-to-interpret data, not all of which will be necessary for diagnosing or treating the patient’s condition and which could provide unwanted clues to future health risks. The few success stories published so far also suggest that wringing information from the human genome and counselling patients and their families adequately may be too big a burden for medical systems that are already stretched to their limits. “You can’t immediately jump from those few profound but limited stories and think that you can reduce this to practice for clinical care,” says Eric Green, director of the National Human Genome Research Institute (NHGRI) in Bethesda, Maryland. Still, from the pioneering cases, much can be learned.
Clinical geneticists often talk about tackling Mendelian disorders: diseases thought to involve a single gene and that roughly obey the rules of inheritance drawn up by Gregor Mendel in the nineteenth century. These conditions may account for as many as 20% of paediatric hospitalizations worldwide and a large share of health-care costs. Yet their genetic basis is often unknown. The compendium of such conditions, called Online Mendelian Inheritance in Man (OMIM), currently contains just under 7,000 disorders, about half of which have been assigned a molecular cause. This autumn, Green says, the NHGRI will announce the winners of its Mendelian Disorders Genome Centers grants, which will fund sequencing centres looking for causes of the rest.
A promising approach, but here’s a hitch:
Still, many researchers worry that it will be difficult to make clinical use of most genomes. At the Undiagnosed Diseases Program, the misses have certainly outnumbered the hits so far. “I think we’ve learned a lot about how hard evaluating an exome is,” says Thomas Markello, from the medical-genetics branch of the NHGRI. “I’m most concerned that people don’t recognize that what’s been published to date are the success stories.”
Ah, the “Reader’s Digest” syndrome. The one who makes it gets written up for the checkout counter, the hundred who don’t, get written up in online obits that only a few loved ones read.
It’s the same as with the cancer doc’s comments the other day about how we are approaching a wall with strategies that depend on finding suitable binding sites on harmful proteins. Many of the worst offenders don’t haves such binding sites. And with genome mapping, the real world of exomes may be difficult to evaluate. Besides which, as PayPal’s Peter Thiel points out, pharmaceutical research currently crests on funding provided by patents, so a shutdown can come when a push for new strategies is required.
One might add that pharmaceutical firms face another hitch: Sick elderly people fund much medical care: And we’re not talking only about life support, here; consider people who could live another ten reasonably tolerable years with help. Progressively smaller generations coming up to old age will surely not be as rich a source of research funds.
Or, as that sitcom lead likes to say, “Reality is inherently messy,” which is why real progress is usually slow and halting.