The big headline from the OVP Tech Summit last week came when UW computer science professor Ed Lazowska called on everyone to quit being so smug, and get serious about turning Seattle into a major league innovation cluster. But later that day, I was lucky to be the only journalist in the room, along with a couple dozen VCs and entrepreneurs, for a fascinating 90-minute conversation on how biology is going digital and what it means for society. Two world-class biologists, Leroy Hood and Irv Weissman, weighed in on the profound questions this technology raises for science, medicine, politics, and, yes, religion.
OVP managing director Carl Weissman, son of the above-mentioned Stanford University stem cell researcher, got the ball rolling. He asked about when full human genomes will be sequenced for as little as $1,000, and for the participants to comment on the implications. Hood, a pioneer in the field of high-speed gene sequencing, said he sees the $1,000 genome coming within five years—and that it could cause a lot of trouble if not handled correctly.
If the goal is to gain a far deeper understanding of what causes diseases, and what makes us human, then simply having cheap genome sequencing doesn’t necessarily mean scientists will get the answers they need, the researchers said. There’s a risk that people could put too much weight on the idea that genes determine who we are, rather than serve as one important piece of the puzzle in combination with environmental factors, Hood said. Scientists will face a huge challenge of trying to integrate genetic data with information on a person’s surrounding environment, to understand how it all adds up to the person’s current condition, or phenotype, he said.
It sounded like a replay of the old debate about nature versus nurture, which most scientists acknowledge is really all about a complex interplay of the two factors.
“One danger is in if we don’t integrate the two data sets,” Hood said. “The genome is one big piece of data, but there are other big pieces. Integrating them all is essential.” He added that this is a staggeringly complicated notion, because genome sequencing, with 3 billion DNA data points on every human, already creates a limited amount of valuable data amid a sea of noise.
“How do you do experiments that put together genotype and environment to equal phenotype?” Hood asked rhetorically. Funding agencies like the National Institutes of Health aren’t really set up to tackle the kind of experiments to answer these kind of questions, because they embrace what Hood calls “small science”-the sort of incremental advances, building on the work of peers, that tends to get published in top journals. The pharmaceutical industry won’t do it either, “because they invest in things that run a year or two out at most,” Hood said.
Still, with technology marching forward and making the $1,000 genome a possibility, Carl Weissman wanted to know what sort of experiments this will enable in the lab and how it will change scientists’ jobs.
The $1,000 genome will probably lead to a bigger opportunity to do experiments on the genetic profiles of people with common neurodegenerative diseases linked to multiple genes being out of whack instead of just one, Irv Weissman said. Stem cells grown in a lab dish with all sorts of diverse genotypes, he argued, will give biologists a new window into these multi-factorial diseases that have stumped scientists for decades (he didn’t name names, but it made me think of Alzheimer’s and Parkinson’s.)
“This will help us begin to understand correlations between genes gone wrong, and the cells that sustain motor neurons for life,” Irv Weissman said. “We can fix one gene at a time, and see if it fixes the problem.” Eventually, this will become so compelling that Big Pharma companies will get interested, the elder Weissman said.
Will scientists run into barriers with getting the general public to participate on a broad enough scale to learn anything valuable from the genome? To make this practical on a society-wide basis, it will have to come from pinpricks of blood, and scientists will have to extract all kinds of data from these tiny pinpricks, Hood said. That includes genetic makeup, how genes are turned on or off, how they are transcribed into RNA, and the resulting proteins. It’s a “trivial procedure” for people to get a pinprick, and scientists must better explain the benefits of it to get people to accept it, he said.
But who will create valuable, tangible products off this, Carl Weissman asked? Do consumer genetics companies like 23andMe, Navigenics and deCODEme have anything valuable to offer in the short-term? A couple people in the room argued about whether they even want to know the information about themselves, but I’m not sure this was the place to get a finger on the pulse of consumer sentiment.
“You can really find out a lot about where you came from” with the tests from these companies, Hood offered, although the ability to spot genetic warning signs that might modify a person’s behavior is pretty limited, he said.
“If you take 100 people, you’d be lucky if you found one who could change their lifestyle and improve their health” by taking the tests, Hood said. Then again, Hood said a friend of his who took one of these tests discovered he had a rare genetic abnormality that creates Vitamin D deficiency, and was able to take aggressive supplements that can ward off early osteoporosis. Yet, he added, “that’s really rare.” He said that he knew another person who had his genotype tested, as well as his wife’s and children’s, just to see what the children inherited from each parent. That could be the real business opportunity for some of the consumer genetics companies, he said. “These are largely vanity companies,” Hood said.
So who’s poised among Corporate America to take advantage of this shift toward greater knowledge of individual genomes? It’s unlikely Big Pharma will be first to pounce, Hood said. It’s more likely that major consumer brands, like Coca-Cola, Pepsi, and Procter & Gamble will find ways to capitalize on this first, because they are investing heavily in wellness, he said.
The real opportunity for the pharmaceutical industry to seize is using genomic data to once and for all bring down the skyrocketing cost of drug development, and the abysmal one-in-10 success rate for drugs that enter clinical trials. Yet Hood says the pharmaceutical business still hasn’t really embraced the opportunity to develop niche drugs, with better success rates, through genomics.
Even so, he predicted the cost of drug development will come down dramatically from an estimated $1 billion per drug, once drug companies can accurately stratify who’s likely to benefit from an experimental drug, and who won’t, Hood said. The FDA will quickly approve a drug with a 95 percent chance of really helping a small pool of patients, rather than a mass-marketed cancer drug with a much lower probability of helping people, Hood said.
What will it take to ignite the drug-development revolution? Hood was asked. “Spectacular successes” would be one way, Hood said. Until then, the barriers to adoption remain high.
One of those big barriers will be educating an entire generation of physicians to think about personalized genetics, and wellness, rather than reactively treating illness, Hood said. He didn’t sound optimistic about this. “In essence, many physicians do not like to learn new things,” he said. Younger physicians who get trained “after the revolution has come” will offer a greater opportunity to usher in personalized medicine, he said.
Then there’s another big question of the politics. Irv Weissman stepped into that arena by pointing out—to a roomful of capitalists—that the masses will not submit to wide scale, deeply penetrating genetic screening unless a policy is put in place that says insurers can’t drop their health insurance if the test discovers something bad. “Until the U.S. gets universal health care, this will be held back dramatically,” he said.
Hood didn’t seem to want to go that far. He pointed out the U.S. now has the Genetic Information Non-Discrimination Act on the books, which took 10 years to get through Congress. “It’s not perfect, but it’s a big first step,” Hood said.
Carl Weissman, who didn’t appear to share his dad’s view on universal health care, then started probing with further questions. Who will pay for the $1,000 genome screens? Who will own the data? What parts will be revealed? Will babies get genomes screened at birth, or earlier? What happens when genomic data reveals far greater detail into worrisome health conditions in a developing fetus?
Nobody stepped straight into all of those questions. They will inevitably fire up religious and cultural debates about abortion and stem cells. But the data that will raise these questions is definitely coming, whether we’re ready or not, the scientists said.
“I think it will be a fundamental part of your medical record, I suspect it will be required,” Hood said, because genomic data will be valuable in promoting wellness. He noted that privacy and security of this data is “an enormously big challenge” and that he’s working on it now with computer security experts at the University of Luxembourg, as part of the ISB’s partnership with the small European country.
Big policy decisions over the next year, like whether the U.S. goes toward universal access to healthcare, will probably be the big landscape-altering theme up for discussion at next year’s OVP Tech Summit, Carl Weissman surmised.
But before wrapping up, Perry Fell, the chairman of Seattle-based Nanostring Technologies, wondered if universal health care access will provide “a floor that people can not fall below.” He also wondered out loud whether it will still allow room for a profit motive to drive innovation in healthcare.
Nobody really had the answer to that one, but Hood gave it a shot.
“There are lots of big problems in the world now,” Hood said, citing healthcare, energy, nutrition, and food. To start thinking about solving them, he said, “We really have to think about how we fund discovery that’s never going to be done by industry. Most funding is based on a history of small science. The problems that we are talking about can’t be touched by this.”
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