When Scott Johnson was diagnosed with multiple sclerosis as a college senior in 1976, his doctors told him it would be decades before scientists found a cure. Still, Johnson remained optimistic. Sooner or later, he figured, the pharmaceutical industry would concoct some drug that would stop his body from attacking the protective sheath of fat and protein that surrounded his nerve cells -- an essential substance called myelin. Determined not to let his MS hold him back, Johnson eventually plunged into the startup world with a string of small companies that did everything from scrubbing dirty air to distributing indie films.
But as the years went by and no miracle drug materialized, Johnson found it harder to ignore the limitations MS imposed. He started limping when he walked, and his right arm hung uselessly by his side. And the more he learned about how Big Pharma went about creating and vetting new drugs, the more frustrated he became. "Pharma has doubled research funding in real terms," he says, "but the number of new drugs is flat or declining." Ever the problem solver, Johnson thought, What if I could do better?
As he began to research the roadblocks to drug development, he zeroed in on the negative impact of an academic culture that encourages scientists to keep their most promising discoveries hidden until they can be published in scientific journals. The process helps stars with prolific publication records get tenure, but it also causes years-long delays before scientists can build upon one another's work. So in 2002, Johnson set up a new kind of not-for-profit, the Myelin Repair Foundation. Just as he would in launching a startup company, he began to assemble a crack team of the best experts in a chosen field -- in this case, four myelin-repair experts from Northwestern, Case Western Reserve, Stanford, and the University of Chicago. He lured them with the promise that MRF would foot the bill for their research and give them a cut of the profits if their discoveries ever became drugs for the 2.5 million MS sufferers. All four agreed to exchange data as soon as they gather them. "Our idea was, let's get the best and the brightest and create this protective environment where all ideas can be shared," Johnson says. "You've got this huge brain trust you can use."
The next step was to find a way to bridge the ever-widening gulf between academia and industry. Even exciting MS discoveries in university labs rarely lead to new drugs -- partly because Big Pharma doesn't scour the academic landscape for leads, partly because many scientists seem to have no idea how to make drug companies take notice of their research. "Academics expect that if they make a brilliant discovery, it will become a drug," Johnson says, "but they just don't know what's required by industry."
To remedy this cultural disconnect, he recruited about half a dozen seasoned veterans from the pharmaceutical industry, including Jay Tung, a former senior director at Elan Pharmaceuticals, and Tassie Collins, a former scientific director at Amgen, both of whom have years of experience selecting promising drug candidates in industry settings. Just as analysts comb the market for breakout stocks, Tung, Collins, and an advisory board of other ex-Big Pharma execs scan the MRF teams' work to determine which experimental approaches have the best potential to evolve into future MS drugs. Then they work closely with the researchers to make sure they keep the pharmaceutical industry's requirements front and center as they perform their studies. "You're injecting this compound into mice," Collins told Jason Dugas, part of brain-trust member Ben Barres's research team at Stanford, during a recent lunch meeting. "But when you try to get something into Phase I [clinical trials], it almost always goes through rats."
After Collins, Tung, and their colleagues pinpoint a potentially significant discovery -- as when Barres and Dugas found proteins that encourage the differentiation of certain key types of myelin-producing cells in the brain, for instance -- it needs what's called "target validation" before it can attract serious interest from the pharmaceutical industry. That means the initial experiments need to be replicated to demonstrate that a particular experimental therapy slows down the disease process in multiple animal models. This kind of repetitive work hardly appeals to the academics in the brain trust, so MRF outsources it to contract research organizations (CROs). That leaves the principal investigators free to concentrate on their primary objective of finding new drug targets like genes or proteins -- and cements their loyalty to the foundation. At lunch at Stanford, Dugas gushed about telling a colleague that the team could delegate some data-analysis grunt work to a CRO. "I mentioned that we might be able to automate this," Dugas recalls telling Collins, "and, oh my gosh, she was so happy."
|Scott Johnson's Myelin Repair Foundation takes an entrepreneurial approach to drug development.|
|Investment in core research at Stanford, Case Western Reserve, Northwestern, and the University of Chicago:
|Payments to contractors to validate research:
|Partnerships being discussed with pharmaceutical and biotech companies:
|Genes or proteins that could be MS drug targets discovered by MRF scientists:
|First clinical trial: expected in 2014|
The tangible results of MRF's unorthodox approach to drug discovery speak for themselves. In the eight years since its founding, MRF has devised 18 patentable inventions (including a method that figures out which compounds cause nerve cells to lose their myelin), uncovered 150 new possible myelin-repair drug targets, and placed upward of 80 articles in scientific journals. Earlier this year, an MRF scientist, Brian Popko of the University of Chicago, isolated a gene mutation in mice that causes an MS -- like condition, a discovery that made waves in the media. "MRF has allowed me to collaborate with a superb group of scientists," Barres says. "It's made it possible for me to do much more work on myelin repair than I otherwise could have done." And MRF is on pace to have at least one clinical trial in place by 2014, just 12 years after its launch; for-profit biotech startups often take much longer.
"MRF is truly working to break down barriers around drug discovery," says Anne Quinn Young, vice president of communications for the not-for-profit Multiple Myeloma Research Foundation. She credits its focus on collaboration at every stage of the development process. "A cure is not going to come from a single target, a single lab, a single researcher. It's only going to come from bringing researchers together to share their data in real time and bringing industry into the fold."
Of course, when it comes to the drug-development process, streamlining is a relative term. It will be five years or more after the first clinical trial before MRF manages to get any therapies on the market. But the important thing, in Johnson's view, isn't how many years it takes, or whether the drugs come soon enough to help him. It's whether MRF's approach becomes a blueprint that changes the way drug discovery is done everywhere. "It's almost embarrassing when people say this is revolutionary," Johnson says. "If you do things in a commonsense startup way, you can have a big impact."