Though the medical benefits of genome science have been marginal thus far, the government’s multi-billion-dollar investment could pay off with the right policy adjustments.
By Michael White
A printed copy of the Human Genome. (Photo: johnjobby/Flickr)
On days when the research isn’t going so well, my colleagues in the biomedical sciences will sometimes quip that, if we really wanted to make a difference in people’s health, we’d leave the lab and go work on an anti-smoking campaign. Rather than the product of high-tech lab work or complex scientific ideas, the biggest life-saving advances in medicine are often fairly simple things that broadly affect public health: access to clean water, hand washing before surgery, vaccination, or simple antibiotics like penicillin. High-tech treatments like cancer immunotherapy may grab headlines, but some of the biggest weapons against cancer are low-tech — by one estimate, nearly half of all cancers could be prevented by getting people to quit smoking, to lose weight, and to be more physically active.
Over the long run, what comes out of the lab certainly does improve medical care in profound ways, but the path from lab to clinic is usually indirect. The rare exceptions, like vaccines, have a dramatic effect because they become part of broad public-health efforts that affect the routine medical care of hundreds of millions, or even billions of people. Few high-tech drugs or technologies thus have the same kind of immediate impact as, say, a nationwide anti-smoking campaign.
However, the federal government has made a multi-billion-dollar bet that one high-tech, scientifically complex effort will have an enormous impact on public health — the Human Genome Project and its successors. Since 1988, the government has invested billions of dollars in genomics research, hoping for a giant payoff that will benefit everyone’s health. As President Bill Clinton said back in 2000, upon completion of the first phase of the Human Genome Project: “Genome science will have a real impact on all our lives.” Clinton predicted that the benefits of genomics could be so large that possibly “our children’s children will know the term cancer only as a constellation of stars.”
That was more than 16 years ago, and the federal government has recently upped the ante with the Obama administration’s new Precision Medicine Initiative. So is there evidence that this bet on genomics will pay off?
In terms of science and technology, it already has. But when it comes to broadly helping people lead healthier lives, the impact has been marginal. An analysis of your DNA is not yet a routine part of your medical care, and few diseases have been newly cured with therapies derived from genomics. A decade out from the Human Genome Project, the director of the National Institutes of Health, Francis Collins, admitted that, while genomics has been great for science, “the consequences for clinical medicine, however, have thus far been modest.” The Massachusetts Institute of Technology’s Eric Lander, one of the Human Genome Project leaders, recently argued that we should temper our expectations and practice a “realistic optimism.” Citing recent genomics research on schizophrenia, Lander noted that “the insights are still fragmentary, and therapies based on them will probably take decades.”
High-tech treatments like cancer immunotherapy may grab headlines, but some of the biggest weapons against cancer are low-tech.
This may seem like a cop-out: We made a bet on a project that was supposed to radically transform medicine, but now we’re told that genomics is going to be a lot like ordinary science — slow and indirect, with medical benefits gradually emerging from new insights into the basic workings of biology.
But genomics is not supposed to be just ordinary science; it is also expected to broadly improve public health. For this to happen, genome science needs to achieve two goals. First, the technology for comprehensive genetic testing has to be so cheap that it becomes a routine part of everyone’s medical care. And second, such routine genetic testing needs to deliver actionable results that lead to better health.
Genomics has almost delivered on the technology goal already. Key parts of a patient’s DNA can now be sequenced for less than $1,000, a big drop from the several-hundred-million-dollar figure it cost to finish the first human genome. That puts routine genetic analysis within a range where insurers could find it cost-effective to cover it for everyone — if resulting analyses produce real medical benefits.
How likely is it that routine genetic tests will be beneficial? Based on evidence from two recent studies, very likely. The New York biotechnology company Regeneron partnered with Geisinger Health System, a large Pennsylvania medical provider, on a genetic analysis for more than 50,000 patient volunteers as part of their routine health care. The Regeneron and Geisinger researchers then examined those patients’ medical records, to look for opportunities where the genetic analysis could make a difference.
In one study, Regeneron and Geisinger researchers identified patients with genetic mutations that increase the risk of heart disease, the leading cause of death in the United States. They found that people with mutations causing “familial hypercholesterolemia,” a condition characterized by high levels of “bad” LDL cholesterol and a high risk for heart disease, were often not properly diagnosed, and were under-treated with cholesterol-lowering drugs. By adding routine genetic information as part of a medical evaluation, almost everyone who should be diagnosed with the disease would be, leading to treatments that reduce the risk of a heart attack. Given the rates of this disease, genetic testing could benefit more than one million people with mutations for familial hypercholesterolemia.
In a companion study, the Regeneron and Geisinger researchers looked for “medically actionable” mutations among their patients, meaning mutations that carry a risk for disease that, with existing knowledge, can be treated or prevented. They found that 3.5 percent of the more than 50,000 patients had such mutations. If this result holds for the entire U.S. population, that means more than 10 million people would likely benefit from a routine genetic analysis as part of their health care. And that’s an underestimate of the ultimate potential of genomics, since the actionable mutations used in this study were conservative, covering only 76 out of more than 20,000 genes. As the science progresses, the catalog of actionable mutations will grow, and more people will benefit.
Our bet on genomics is expensive, but, compared to the potential benefits, the government was right to make it. If the promising results of these two studies hold, genomics could improve the health of millions of people relatively soon. That means the major roadblocks to reaping the benefits of genomics won’t be science, but policy. Doctors and health-care systems will need to learn how to bring routine genetic tests into their care, and insurers will need to be willing to pay for them. Most importantly, to realize broad public benefits from genomics, routine genetic testing will have to be available to all, rather than just a wealthy sliver of patients. If we get the policy right, genomics will be a smart bet for everyone.