Not So Fast With the Genome

Posted on March 6, 2019

As the Human Genome Project neared completion in 2003, Dr. Francis Collins ’77 (MD) wrote an article for the World Economic Forum under the headline, “Genomics: The Coming Revolution in Medicine.”

“The world’s leading scientists are laying the foundation for a genomics revolution that will change the face of medicine in the 21st century,” wrote Collins, then the head of the U.S. National Genome Research Institute and now director of the National Institutes of Health. “Obtaining the sequence of the human genome is not an end in itself, merely the end of the beginning — and the start of the next exciting chapter in genomics and genetics.”

Drafting that next chapter — translating bold promises into the messy reality of real-world medicine — has been the life’s work of Dr. James Evans. A renowned cancer researcher and editor-in-chief of the journal Genetics in Medicine, he’s helped make UNC a powerhouse in genomic research by keeping a healthy skepticism toward Collins’ promised revolution.

“It’s a long, hard slog from taking technology breakthroughs to actually benefiting patients,” Evans said. “I think UNC has a great reputation for the practical and realistic application of genetic science to patient care. That’s the niche we’ve tried to fill.”

Evans retired at the end of the fall semester, having helped propel the University’s genetics department to among the top five in the country, as measured by federal research funding. “We’ve recruited really good people, and we’ve multiplied our impact through grants,” Evans said. “It’s nice to be able to leave on that footing.”

A focus on practical applications is the throughline in Evans’ work. He’s naturally suspicious of the hype that surrounds genetic medicine, the bold promises of pathbreaking treatment that always seems to be just around the corner. Too many researchers, he thinks, are imagining a splashy TED talk instead of focusing on the slow, frustrating work of proving the real-world benefits of genomics.

“Both scientists and journalists can be shortsighted. They want the easy answer, the exciting breakthrough. ‘This is going to lead to great stuff, and we’re going to change the world with it!’ So we set expectations too high.”

Those expectations can breed disappointment. A scientific community that is continually promising breakthroughs can undermine the patience of the policymakers and the public, patience sorely needed to maintain support for basic science.

“We cannot predict where the great therapeutic advances will emerge from, so we need to encourage and fund and allow people to do curiosity-driven research. What my career has taught me is that technology and basic science understanding will be increasing rapidly … if we live in a society that values it.”

The history of medicine, he pointed out, is filled with extraordinary advances that grew from the laboratory equivalent of messing around — people tinkering with new technologies just for the sake of tinkering, not toward any specific outcome.

“The whole edifice of genetics is based on this research done by a monk in the Czech Republic working on wrinkled peas and smooth peas,” Evans said, referring to the friar Gregor Mendel and his methodical study of inherited traits in plants. That long-term scientific project was only possible because Mendel’s monastic life left him with the time and freedom to experiment without economic pressures. “We need to keep funding undirected research.”

That means not only patience but also a strong dose of humility about medical progress. Evans is thrilled with the advances he’s seen over his career, and he thinks the next generation of researchers will make even more progress thanks to the acceleration of gene-mapping techniques. But he’s a deep believer in incremental progress, not overnight transformation.

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“What my career has taught me is that technology and basic science understanding will be increasing rapidly … if we live in a society that values it.”

–Dr. James Evans

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In 2017, Evans drew national attention for exactly the kind of instant, painless cure he tends to downplay. A woman named Elizabeth Davis was referred to UNC’s neurology department after more than 30 years of struggling with debilitating pain and weakness in her joints. She was unable to walk without crutches, and doctors had failed for decades to come up with a definitive diagnosis. “I was always in pain,” Davis told UNC’s Endeavors magazine. “Some weeks were really, really bad — to the point where I couldn’t even move.”

Evans and his team analyzed Davis’ genome — and immediately found a mutation that led to a clear diagnosis and an easy treatment. Within months, and with nothing more than a common pill to treat muscle rigidity, Davis was walking.

“This is the kind of thing you live for as a researcher,” Evans said. “It’s also very rare that we’re able to cure someone like that.”

The story was shared all over the world — Evans joked that earning a mention in Cosmopolitan was the first time he truly impressed his children. But to Evans, Davis is the exception that proves the rule. A patient who can miraculously walk again because of a genetically guided treatment is newsworthy because she’s unusual.

“The human body is extraordinarily complicated, and there are all sorts of unintended consequences. When we do X, we affect X, Y and Z.” Years of careful experimentation — the tried-and-true scientific method — is the only way to separate helpful interventions from harmful ones.

Evans has been singing this gospel to policymakers for years, serving as an adviser to the U.S. secretary of health and human services and testifying before Congress about genetics and privacy. Some of his best-known work is in training judges, who often are asked to weigh complex scientific evidence without any formal background. Former N.C. Supreme Court Justice Robert Orr ’68 (’75 JD) approached UNC’s medical school years ago and set up a series of workshops to help judges navigate scientific evidence. Evans was happy to get involved.

“It’s been one of the most satisfying parts of my career,” he said. “The judiciary ends up de facto setting policy in this country. Judges don’t want to sort out policy, but they do. And since so much of our society now hinges on science and technology, clear-headed analysis of evidence has never been more important.”

Judicial education is one of the few places Evans plans to remain professionally engaged in retirement. Otherwise, he’s looking for a clean break from academics and medicine.

The unconstrained life is likely to include a lot more reading — Evans made four book recommendations in the course of an hourlong interview, while insisting he doesn’t get enough time to read — along with more travel. The wall of his office is filled with postcards from all over the world, from the Oregon coast to Bratislava, and he’d like to expand the collection.

“If my work has taught me anything, it’s that life is fragile and unpredictable,” he said. “I want to live my life consciously and self-directedly in a way I really haven’t been able to.”

No revolutionary changes. Just incremental improvement, earned through patience and focus.

— Eric Johnson ’08

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