Genome advances move to mainstream, says Collins

Scientists have had results of the Human Genome Project for 5 years. The project leader shares what happens next

With the signing of the Genetic Information Nondiscrimination Act alive in his memory, Dr. Francis Collins, former director of the National Human Genome Research Institute, talked about his vision of personalized medicine before an overflow crowd of about 500 people at the University of Florida Health Science Center.

His message? Save “Rhonda.”

“Can you tell I’ve been to a Beach Boys concert?” said Collins, who was a featured guest in October at Florida Genetics 2008, the annual symposium of the UF Genetics Institute.

Francis Collins was the guest speaker at the UF Genetics Institute's annual symposium in October. Photo by Sarah Kiewel

Francis Collins was the guest speaker at the UF Genetics Institute’s annual symposium in October. Photo by Sarah Kiewel

In his example, Collins weaves a story that begins in 2018 when Rhonda, at age 21, has her genome sequenced and learns that she potentially has cardiac problems. Working with enlightened care-givers and insurance providers, she embarks upon a designer program of prevention based on diet, exercise and medication – not a generic, one-size-fits-all approach.

As the story unfolds, at 75 Rhonda’s “smart shirt” alerts doctors that she is having a heart attack. Health-care workers quickly intervene. She lives into the 22nd century.

Then Collins told the same story without the happy ending, and it was replete with missed opportunities, uninformed decisions and provider problems. An overweight, hypertensive and uninsured Rhonda dies at 50.

“We can’t be complacent here people,” he said. “The whole story can be summed up in two words: Save Rhonda. Because Rhonda is you and me, and our families and friends, and our children and grandchildren. And today we have a chance to transform medicine into a much more effective way of treatment.”

In his tragic tale, fear that Rhonda’s genomic data would be used to deny her health insurance derailed any chance of enlightened treatment.

But in the positive scenario, Collins referenced the signing of the Genetic Information Nondiscrimination Act, which Collins witnessed at the Oval Office in May.

“All of this great science is only going to be beneficial if we pay attention to the policy aspects. One of the things people have most been concerned about is genetic discrimination,” Collins said. “The nondiscrimination act means that genetic information of a predictive sort cannot be used against you in health insurance or the workplace. That should be of great reassurance to people who are ready to take advantage of this information today.”

Collins said bioscience companies are already offering limited individual genetic profiles. Understanding the information, or using it to guide a treatment, is much further away -but individual genomic data is available, today.

In his tale with the happy ending, Rhonda’s genome was sequenced for $500, a figure scientists are approaching. Collins believes within five years personal genetic maps may cost as little as $1,000.

That’s fantastic progress considering it took Collins and a network of scientists about $300 million and 13 years to map the approximately 20,000-25,000 genes that make up human DNA. The landmark project was completed ahead of schedule and under budget in April 2003, according to UF Genetics Institute Director Kenneth Berns.

“If the primary health-care providers of the future are doing what they should do, they will know what your genome profile is, the diseases you’re subject to getting, and the drugs that will be good for you,” Berns said. “That’s all going to be an offshoot of the Human Genome Project.”

The effort “poetically” finished on the 50th anniversary to the month of James Watson and Francis Crick’s publication of the double helix structure of DNA, Collins noted.

With that, he made his way through a David Letterman-style Top 10 list of scientific advancements since the human genome was sequenced.

In one regard, scientists can largely circumvent the 1990’s approach of investing time and money in the pursuit of suspect disease genes, only to discover they had reached a dead end.

“The candidate gene approach helped in some instances because people were fortunate enough to pick the right genes, but clearly this was not going to do in the long run because of its similarity to the guy who loses his keys coming out of the bar at night and searches for them in the one place he can see, under the lamppost,” Collins said. “That was all we could really do because in the past we couldn’t be comprehensive, we didn’t have the technology. Now we have it. The HAPMAP project made a major contribution by both building a catalog of human variation and explaining how variation is organized in neighborhoods, so if you know the boundaries of those neighborhoods, you don’t have to check all 10 million variants in the genome, you can check maybe half a million and infer the rest.

“This was still unthinkable until technology came roaring along to drop the cost of a genotype,” Collins said. “That made it possible to take something like sampling the whole genome for one disease that would cost millions of dollars in 2002 and now bring it down to something you can do for less than a million. Lot of groups got on board with this because it is the equivalent of lighting up the whole street, making every gene a candidate, and not having to go by a hunch.”

Collins mentioned advances in comparative genomics, which allows scientists to look at evolution’s lab notebook and determine which parts of the genome have been conserved and must therefore be functionally relevant in mice, chimps, dogs, sea urchins, bees, people and other organisms.

He also talked about how recognition of the countless microbes within and without the human body is presenting a whole new view of biology.

“You might not want to think about the fact that there are more cells in you or on you that are microbial than your own cells, but that is the case,” Collins said. “Initially we are trying to define the normal microbiome. What happens after you take a week of antibiotics to your gastro-intestinal and skin microbiomes? How long does it take to come back and get to where it was? Do identical twins have the same microbiome? We don’t know that stuff. But we are getting little glimpses of it. Then we can really ask the question, what about disease? There is already an implication that maybe obesity is related to the microbiome of the individual. Clearly Crohn’s disease is looking more and more like an interaction between the host’s genetics and the microbiome. If we understood that we might be in a better place.”

Collins emphasized the idea that broad advances in genomics research are coming so quickly that it’s difficult to keep up, even at major biomedical research institutions, such as UF.

“As you’re thinking about your own research or clinical practice,” Collins said, “I think it behooves you to imagine that we are on an exponential curve of knowledge gathering and that things that you might approach a certain way today, next year, you will do in a different way because you have a better opportunity.”