Will Gathering Vast Troves of Information Really Lead To Better Health?

Dec 28, 2017
Originally published on December 28, 2017 8:25 pm

The Mayo Clinic is building its future around high-tech approaches to research known as "precision medicine." This involves gathering huge amounts of information from genetic tests, medical records and other data sources to ferret out unexpected ideas to advance health. But one longtime scientist at the Mayo Clinic isn't playing along.

Dr. Michael Joyner is a skeptical voice in a sea of eager advocates. Joyner's lab studies exercise. It is, fittingly enough, in a hospital building founded in the 1880s. While Mayo has built all sorts of new labs at its sprawling campus in Rochester, Minn., Joyner can conduct his work without glitzy DNA sequencers and other high-tech tools of precision medicine.

And it's not simply that he's an old-school devotee. He believes that the solution to our most pressing health problems lies in thinking about whole human beings, not breaking everything down to DNA sequences.

"The enthusiasm for this [precision medicine] is occurring in a country where life expectancy is actually falling," he says as he walks through the old linoleum-tiled halls of St. Mary's hospital.

That fact alone leads Joyner to ask whether the money being poured into high-tech medical research is really solving the nation's stark health problems, like obesity, heart disease, high blood pressure, diabetes, Alzheimer's disease and cancer.

Joyner says there are certainly appropriate places to use this technology, and he doesn't dispute the individual stories of success his colleagues tout. But he believes the best way to address the health concerns facing the nation is by studying — and treating — whole people, not by breaking the problems down to billions of genetic bits and pieces.

He practices what he preaches in both his personal life — his thorough exercise routine includes commuting by bicycle — and his physiology lab.

On the day I visited at the end of August, volunteer Greg Ruegsegger was outfitted with monitors, a catheter threaded into a vein and a mask to capture his breath. He would exercise to the point of exhaustion while scientists studied him. This is far more informative than any genetic test, Joyner says.

"People have looked at 3,000 elite endurance athletes — these are people who compete in the Tour de France and win Olympic medals in cross-country skiing and distance running — and [scientists] have been unable to find any genetic marker for superior performance."

And when it comes to the health of ordinary people, Joyner talks about real-world studies, which show that walking or biking to work has four- or fivefold more influence on a person's body mass index than that person's genetic profile.

Joyner is focused on how the body's systems work together during exercise, but the same interconnectedness applies to many diseases. That's why cancer drugs that target one biological pathway generally don't last long. Tumor cells simply find workarounds, exploiting the redundancies deeply embedded in biology. And that's why Joyner has so little faith in science that keeps trying to focus down on smaller and smaller details.

"One of the things we have to ask ourselves when we get these big initiatives is, 'What's the definition of success?' " he says.

Scientific discoveries alone don't do it for him. Doctors need to build effective treatments — and patients need to follow along. This is the promise of precision medicine in the long run, but Joyner has published articles (like this one) skeptical of the drive to collect vast piles of information, hoping to make sense of it later.

"Is this just going to be a biological Tower of Babel," he asks, or will this information also lead to discoveries that translate beyond the laboratory and actually change public health for the better?

He doesn't doubt that DNA sequencing and other tools of precision medicine are useful in specific instances, such as for diagnosing rare diseases. There are a few uses in cancer treatment, but so far there has been just one randomized study of patients assigned to treatments based on their tumor's DNA profile, and it showed no advantage over traditional medical judgment.

This isn't a popular point of view elsewhere at the Mayo Clinic, which is sinking hundreds of millions of dollars a year into precision medicine. The shiny new labs across campus seem a world apart from Joyner's physiology lab.

After my conversation with Joyner, Mayo public affairs officers eagerly led me to a series of scientists there who disagree with him. One stop was at the Medical Genome Facility.

This room is chock-full of machines that cost many hundreds of thousands of dollars apiece. They can analyze DNA from a person, a tumor or even a single human cell. They can read out an entire genome, or just a subset, which is called the exome.

"I really do believe that understanding our genome is fundamental," says Julie Cunningham, one of the facility's three co-directors. Like other scientists at Mayo, she has had swaths of her own exome sequenced.

"I learned that by and large I'm really lucky, but I learned that I have two [genetic] variants that affect how I respond to particular drugs that are out there." She had actually known that before for one of those drugs, "but now I know exactly why I have it and it's potentially serious. That has to be good. There's nothing wrong with that."

Bad drug reactions are a serious medical problem, so in principle, a genome profile should help reduce that risk. The reality, though, is that the vast majority of genomic tests for drug sensitivity give ambiguous answers.

One of the most carefully studied examples involves the blood thinner warfarin. Four separate studies show that people who got genomic testing for this susceptibility did no betteror only marginally better — than patients whose dosages were determined by traditional strategies.

This lack of strong data is a problem for many areas of precision medicine.

"Although we think conceptually this is going to be of high value, and it will ultimately improve health care with better quality and lower cost, we have to prove that," says Keith Stewart, a hematologist who directs Mayo's Center for Individualized Medicine. "If it doesn't all pan out the way we expect that's OK. But I think there will be plenty of unexpected areas that we haven't conceptualized yet, so I think it's a very worthwhile investment on the taxpayers' point of view."

Whether precision medicine is going to be a boom or a bust, "right now it's just speculation on both sides," he says.

"It is somewhat inevitable that every person in this country will have their genome sequenced." he adds.

Gianrico Farrugia, a gastroenterologist who is chief executive officer of the Mayo Clinic in Florida, agrees.

"What we're beginning to see is that technology is invading and replacing traditional testing," says Farrugia. For example, it is already used to determine treatments for lung cancer and diagnose rare diseases.

And, in any event, he says medicine is already moving aggressively into this new territory and there's no going back. "That's not only wrong," he says, "it's impossible."

With the momentum now built up behind this enterprise, precision medicine will be judged like much of modern medicine: in hindsight, after it becomes entrenched in clinical practice.

You can contact Richard Harris via email.

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ROBERT SIEGEL, HOST:

The Mayo Clinic prides itself in working at the cutting edge of medicine. And these days, that means an approach called precision medicine. It's an effort to integrate genetic scans and personal information to better understand disease. It has its skeptics, and one of them is a medical researcher at the Clinic's campus in Rochester, Minn. NPR's Richard Harris went there to explore both sides of the debate.

RICHARD HARRIS, BYLINE: Good morning - Richard Harris.

MICHAEL JOYNER: Yeah. Nice to meet you. How's everything going?

HARRIS: Nice to meet you - great, thanks. How are you?

JOYNER: Perfect.

HARRIS: Michael Joyner has rolled up on his bike to meet me as he heads to work. He practices what he preaches, which is that exercise and diet matter much more to your health than whatever's written in your genes.

JOYNER: My lab is over at St. Mary's Hospital, which was founded in the 1880s.

HARRIS: We approach the beautiful, old building. Though many of the Mayo Clinic's research labs have moved on to much more modern, fancier facilities, it still suits Dr. Joyner and his colleagues. He's been at the Mayo Clinic more than 30 years, and he finds himself increasingly out of step with the devotion to high-tech and high-price strategies like DNA analysis that have increasingly swallowed up the research dollars and captured the intellects at Mayo.

JOYNER: The enthusiasm for this is occurring in a country where life expectancy's actually falling.

HARRIS: That fact alone leads Joyner to ask whether the billions being poured into high-tech medical research are really solving the nation's stark health problems like obesity, heart disease, high blood pressure, diabetes, Alzheimer's, cancer. Joyner says for sure there are appropriate places to use this technology and individual stories of success, like diagnosing rare diseases. But he believes the way forward in medicine is by studying whole people and focusing less on their genes.

JOYNER: So here we go.

HARRIS: We head into his group's lab where volunteer Greg Ruegsegger is outfitted with monitors, a catheter threaded into a vein and a mask to capture his breath. Scientist Steven Chase outlines the experiment, which will involve a ride on a stationary bike to the point of exhaustion.

STEVEN CHASE: So yeah, we'll have you breath on the mask for about 10 minutes, get you on the bike, do those pulmonary function tests and then move into the max test.

GREG RUEGSEGGER: The fun part.

CHASE: Yeah, the really fun part (laughter) - any questions?

RUEGSEGGER: No, we're good to go.

HARRIS: Joyner studies human performance and says studying people as whole systems yields far more insight than sequencing their genomes.

JOYNER: People have looked at 3,000 elite endurance athletes. These are people that compete in the Tour de France, win Olympic medals in cross-country skiing and distance running. And they've been unable to find any genetic signals associated with the superior performance in these people.

HARRIS: And when it comes to the health of ordinary people, Joyner talks about real-world studies which show that walking or biking to work has a much bigger influence on your weight than the gene variants that are the focus of precision medicine studies.

CHASE: Going to start that metronome again. Sync your breathing with it.

(SOUNDBITE OF METRONOME TONE)

CHASE: Out and in...

HARRIS: As we've been talking, Ruegsegger has gotten on the stationary bicycle and has gradually been pushing the limits of his endurance.

CHASE: Go ahead and start taking those big, fast breaths. Try and move as much air as you can. There you go - a little bit bigger breaths, if you can, a little bit deeper.

HARRIS: Joyner monitors Ruegsegger's vital signs and blood gases as the exercise gets more intense. And in a few minutes, the test approaches its climax.

UNIDENTIFIED MAN: Get up this hill. Come on, Greg.

CHASE: Keep it going. Keep it going.

UNIDENTIFIED WOMAN: Greg, you got it.

CHASE: There you go. Good job.

UNIDENTIFIED MAN: (Inaudible). Push to the end, man. Come on.

CHASE: You got this. Keep it turning.

UNIDENTIFIED MAN: Come on. Push. Push.

CHASE: Push it one more time - one more time. Recover.

(CROSSTALK)

CHASE: Great work.

JOYNER: So now we'll get some recovery. He'll rest for about 45 minutes, and then we'll do the hypoxia trial.

HARRIS: Joyner is focused on how the body's systems work together during exercise. The same interconnectedness applies to many diseases. That's why cancer drugs that target one pathway generally don't last long. Tumor cells simply find other pathways in the network to exploit. And that's why Joyner has so little faith in science that keeps trying to focus down on smaller and smaller details.

JOYNER: One of the things I think we have to ask ourselves when you get these big initiatives is, what's the definition of success?

HARRIS: In his mind, this flood of information doesn't matter unless doctors can use it to create effective and affordable treatments, treatments that patients will actually follow. This is the promise of precision medicine in the long run, but Joyner sees little evidence of success to date, particularly in the drive to collect vast piles of information, hoping to make sense of it later.

JOYNER: And the question is, is this just going to be kind of a biological Tower of Babel, or will we be able to actually sort meaningful information out of this?

HARRIS: Now, his views aren't popular elsewhere at the Mayo Clinic, which is sinking hundreds of millions of dollars into precision medicine, like in the shiny new labs across campus. They seem a world apart from Joyner's lab in the old hospital.

JULIE CUNNINGHAM: And so this is our new space that's been remodeled. And so we've got plenty of room for everything to happen.

HARRIS: Julie Cunningham is 1 of 3 co-directors of Mayo's Medical Genome Facility which the clinic's public affairs officers are eager to show me. This room is chock full of machines that cost many hundreds of thousands of dollars apiece. They can analyze DNA from blood, a tumor or even a single human cell. They can read out an entire genome or just a subset, which is called an exome. Yes, this costs real money, Cunningham says.

CUNNINGHAM: But I do believe that understanding our genome is fundamental. I mean, I've had my exome sequenced.

HARRIS: What did you learn?

CUNNINGHAM: I learned that by and large, I'm really very lucky (laughter). But I do have two variants, actually, that affect my ability to respond to particular drugs that are out there.

HARRIS: Drugs you've ever taken or...

CUNNINGHAM: Oh, yes. In fact, I know I have a sensitivity to one, and I've known it for a long time. But now I know exactly why I have it. And it's potentially serious. And that has to be good. There's nothing wrong with that.

HARRIS: But it's not clear how valuable that is, either. Though DNA tests can help doctors avoid a few potentially dangerous reactions during cancer chemotherapy, the DNA tests do little or nothing to improve outcomes in other instances, such as among patients getting the blood thinner warfarin. Keith Stewart, a physician who heads the Mayo's Center for Individualized Medicine, says these are early days for precision medicine. Give it time.

KEITH STEWART: Although we think conceptually this is going to be of high value and it will ultimately improve health care with better quality and lower cost, we have to prove that. If it doesn't all pan out the way we expect, that's OK. But I think there will be plenty of unexpected areas where it's beneficial that we haven't even conceptually realized yet.

HARRIS: And in the meantime, medical practice is forging ahead.

GIANRICO FARRUGIA: What we're beginning to see is that technologies is invading and replacing traditional testing.

HARRIS: Dr. Gianrico Farrugia, a vice president of the Mayo Clinic, says there's no turning back now.

FARRUGIA: That's not only wrong. It's impossible.

HARRIS: And with the momentum now built up behind this enterprise, precision medicine will be judged like much of modern medicine - in hindsight after it becomes entrenched in clinical practice. Richard Harris, NPR News.

(SOUNDBITE OF HOT CHIP SONG, "THE WARNING") Transcript provided by NPR, Copyright NPR.