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Certainly, Walton believes greatly in the potential of genomics to change medicine at its core, but the obstacles preceding that shift are numerous and substantial, he argued.
In a speech at the Precision Medicine Summit in Boston, Nephi Walton, a Genetics Fellow at Washington University School of Medicine, threw some cooling perspective on genomics’ well-deserved hype. Certainly, Walton believes greatly in the potential of genomics to change medicine at its core, but the obstacles preceding that shift are numerous and substantial, he argued.
Walton mentioned that the notion of genetic medicine as a potentially preventative tool has been around since the 1940’s, though science didn’t even have a correct count of human chromosomes for another decade after that. “We were doing genetics before we even knew about genes, essentially,” he said.
Now, our understanding explodes by the day, with about 3 billion known base pairs in the human genome. Walton points out that BRCA2, the much-researched variant often linked to breast cancer, actually comprises 83,736 base pairs, or “83,000 ways to screw that gene up,” in his words. “We’re all mutants.”
The sheer volume and newness of genetic information presents countless problems, from his perspective. There are now in excess of 6,000 known genetic diseases, and not every geneticist has memorized them all, obviously: that seems impossible. That number grows daily, as science finds new connections at a rate of more than one per day.
“The system is completely overloaded,” Walton says, and that’s before the “tsunami” of new scenarios created by healthy patients coming into the system looking for signs in the consumer genomic tests they have purchased. “We don’t even have the bandwidth for the unhealthy ones,” he says. Many labs have a backup of 7 months to 1 year, incapable of delivering quick information for patients who have already exhausted the potential explanations from traditional specialists.
Walton also described a dearth of access to essential data, as genomic tests take many steps to interpret, and must be passed between multiple entities for analysis. “The vast majority of physicians are not prepared to understand, deliver, or manage genetic test results,” he said. “The things I see are a little bit scary…even neurologists, who I feel like have the best handle on genetic testing, even they do things that show they just don’t understand genetics. We need to educate physicians better and it’s got to start early on.” He believes genetics training should take place in medical school from year 1.
In addition to that, novelty creates a vacuum of framework. Medicine, according to Walton, has not yet established tangible guidelines for the use of a patient’s genomic information, and this has two huge implications. For one, there is no established standard for reimbursement, which stands in the way of value-based care efforts. As an example, he pointed to the prevalence of MRI testing, oft-used in hospitals, as compared to WES and WGS mapping. The MRI is more expensive at a base level, but is often covered by insurance; the genomic tests are less expensive to run but unlikely to be covered. Those unpaid-for genomic tests, however, can have significantly higher diagnostic yield.
The other danger of novelty is liability, particularly given that as much as science knows of genomics now, understanding is young. There remains great uncertainty about the exact implications of most variations: he pointed to a significant amount of discordance in variant classification of BRCA1 and 2 across different laboratories, 22% of which might affect medical management. BRCA1 and 2 are among the most studied in the human genome, “and we’re screwing those up,” he said.
This, Walton said, is dangerous: it results in drastic decisions based on science still not fully understood. With that may come legal ramifications. On the other hand, the absence of set standards may also shield from litigation, if there remains no protocol to violate.
CRISPR editing, additionally, is not as sharp as it could be. “We’re messing up a lot of mice,” Walton cracked.
Still, his outlook on the power of genomics in personalized medicine is by no means dour: if anything, he thinks the potential may even be underestimated. “In summary,” though, “we have a lot of work to do…we must embrace the genomic revolution that is taking place and find ways to enable it, rather than resist the inevitable.”