Last month, Obama revealed the details of his administration’s Precision Medicine Initiative, “a bold new research effort to revolutionize how we improve health and treat disease.” In his speech, the President described it as an effort to support “one of the greatest opportunities for new medical breakthroughs that we have ever seen,” by figuring out how to deliver “the right treatments, at the right time, every time to the right person.” Medicine’s next revolution just needs a good, well-funded push to become reality.
But precision medicine isn’t going to be a revolution—it will be a slow, medical evolution.
The war on cancer has turned out to be a drawn-out guerrilla war, made up of many small victories rather than one grand one.
The rhetoric surrounding precision medicine sounds a lot like the rhetoric that was used to promote another medical revolution that never happened: the War on Cancer. President Nixon launched a major, well-funded initiative to fight cancer in 1971. “I hope that in the years ahead,” Nixon said when he signed the National Cancer Act, “that we may look back on this day and this action as being the most significant action taken during this administration.” As it turned out, the Nixon administration would be best remembered for other actions. And more than 40 years later, the question I get asked most frequently as a biomedical scientist is: “Why haven’t we cured cancer?”
The answers are complicated, but perhaps the simplest one is that it was misguided to think we were going to cure cancer in a single, dramatic medical revolution. Instead, what we’ve seen over the past 40 years is a gradual but steady evolution in our ability to detect, treat, and prevent cancer, an evolution that is still ongoing. Without question, you are much better off with a diagnosis of cancer today than you would have been in 1971. But cancer is still a leading cause of death in the United States, second only to heart disease.
Why wasn’t there a dramatic medical revolution that produced a cure for cancer? Because cancer is not one disease; it’s many diseases, each with different causes and requiring different treatments. We knew that in 1971, but we didn’t appreciate just how many different kinds of cancer there are. Even cancers of the same tissue or organ will differ greatly in their molecular details and have different responses to treatments. The war on cancer has turned out to be a drawn-out guerrilla war, made up of many small victories rather than one grand one.
For the same reasons, precision medicine, based largely on genetic testing, won’t be a revolution. People have known for centuries that individuals inherit different risks for disease, but it has been hard to put that awareness to practical use. Writing in the late 16th century, Montaigne remarked that he alone, of all his brothers and sisters, inherited a predisposition to the debilitating gallstones that afflicted his father. The disease only developed later in life, after decades of vigorous health,D prompting Montaigne to ask, “where could his propensity to this malady lie lurking all that while?”
By the middle of the 20th century, geneticists came up with a general answer: The propensity to disease lurks in our DNA. But being more specific than that was, in most cases, an enormous challenge. To track down a gene that was linked to a disease easily took teams of researchers more than a decade, as in the case of the famous breast cancer-linked genes BRCA1 and BRCA2. A big part of the problem was technology: Cutting-edge methods used for working out the chemical text of DNA were still extremely slow, preventing scientists from applying the genetics knowledge we already had. The science had run ahead of the technology.
But now it’s the other way around. Technological breakthroughs have opened the floodgates, and researchers can generate terabytes of genetic data—more than we can make sense of. The National Institutes of Health has a telling infographic for the new Precision Medicine Initiative: The only reasons it provides as explanation for the new pursuit are the new technological resources we have, and not any new, revolutionary scientific concepts.
We shouldn’t underestimate these new technologies: They have made it possible to push hard at the frontiers of our knowledge of genetics and disease. But turning this into medical progress will be difficult, because the genetic underpinnings of disease, and not just cancer, are extremely complex.
Back in 2002, we could still hope that things wouldn’t be quite so hard. Jonathan Pritchard, a leading geneticist at the University of Chicago, wrote that, “At the present time, little is known about the determinants of complex diseases”—that is, diseases that, unlike Huntington’s or Cystic Fibrosis, aren’t caused by damage to just a single gene. Unfortunately, that includes most common diseases: diabetes, heart disease, and, in most cases, cancer. Pritchard explained that working out the genetic underpinnings of these complex but common diseases could turn out to be relatively simple, or dishearteningly complex.
In the simple case, which is known as the “common disease, common variant” hypothesis, the same small set of DNA mutations turn up over and over in studies of a particular disease. Someone’s actual risk for a disease would depend on what combination of mutations they carry, plus environmental influences. The mutations themselves would be easy to track down, and you could then start to build an informative genetic risk profile.
In the more complex case, there are many genetic paths to the same disease, and each person’s path is paved with different mutations. Finding these mutations is much more of a challenge, because you need studies with large numbers of subjects to get the necessary statistical power. The reality has turned out to lie, messily, somewhere in between. As a consequence, genetic tests currently don’t predict risks for common but complex diseases very well. And prediction is only the start. We still need to find drugs and health interventions to go with the genetic predictions of disease risk. There is a long, difficult road ahead.
Obama’s Precision Medicine Initiative is still a good thing, because it includes funds for putting a regulatory and ethical infrastructure in place as the medical practice develops. But scientists and politicians have to be careful when they sell precision medicine to the public. Just how much the public’s trust in science is damaged by hype is unclear, but any biomedical scientist will tell you that people remember when the health benefits of big scientific initiatives, from the War on Cancer to the Human Genome Project, are oversold. Medicine, with few exceptions, grows by evolution, not revolution.
