By DEREK LOWE, PHD

I wrote here the other day about the NIH’s new translational medicine plans. The New York Times article that brought this to wide attention didn’t go over well with director Francis Collins, who ended up trying to disabuse people of the idea that the NIH was going to set up its own drug company.

But there’s been an overwhelming negative response from the academic research community, largely driven (it seems) by worries about funding. Given the state of the budget, flat funding would be seen as a victory by NIH, so this isn’t the best environment to be talking about putting together a great new institute. The money for it will, after all, have to come out of someone else’s pile. Collins spends most of that statement linked above denying this, but it’s hard to see how there won’t be problems.

I think, though, that there’s an even more fundamental problem here. In the latest BioCentury, there’s an interesting sidelight on all this:

In comments submitted to NIH, Joseph Zaia, associate director of the Center for Biomedical Mass Spectrometry at the Boston University School of Medicine, argued against setting timetables for research results. “I do not believe that running medical science on a short sighted business time schedule will produce more cures faster. It will, however, deplete NIH resources very rapidly and possibly tear down an infrastructure of knowledge that took decades to create.” Zaia complained that the NCATS “process seems to be driven by the FasterCures movement sponsored by Michael Milken,” which he said has “been masterful in manipulating the political system for their purposes, and forcing NIH into this reorganization.”

FasterCures’ Margaret Anderson, executive director of the non-profit group that advocates for accelerating medical innovation, submitted a letter strongly endorsing NCATS, which she said “will provide a significant stimulus to moving ideas out of the lab and into the clinic.”

And that’s the problem. Over the last few years, an idea has taken hold that there are all kinds of great ideas for all kinds of diseases that no one is doing anything with. Now, I’m not going to claim that everyone is trying every single thing that could possibly be tried, but I really don’t see how there’s this treasure chest of great discoveries that aren’t being followed up on. Drug companies of all sizes are always watching for such opportunities – I’ve been a part of many such efforts to jump on these as they show up.

My guess is that many of these advocates have a different definition of what a “great discovery” is than I do. There are all kinds of things that come out in the literature, often with breathless press releases from the university PR office, that make it sound like the latest JBC paper has the cure for cancer in it. But the huge majority of these things don’t pan out, generally because they’re just part of a much, much larger (and more complicated) story. And that’s why things tend to fail on the way to (and through) the clinic.

Am I exaggerating? Well, many advocates in this area have taken to using the phrase “valley of death” to describe the gap between basic research and success in the clinic. Here’s Amy Rick of the Parkinson’s Action Network:

Rick said patient groups are concerned that the valley of
death is growing, and they want government to help bridge it. The prospect that there are “good discoveries that are basically collecting dust” is “terrifying to patients,” she said. “What we are finding from a patient perspective is that discoveries that are being made in very exciting basic research are not being acted upon,” Rick told BioCentury This Week. “They are not moving through the pipeline. So the patient community is pushing very hard — if private money isn’t filling that space, the government should be moving some of its funding into that space.”

I have a great deal of sympathy for the patient population – they’re our customers in this business, after all, and any one of us could join their ranks at any time. (Drug company researchers come down with all the maladies that everyone else does). But the patient population is not the group of people discovering and developing drugs. What looks like agonizingly slow progress from outside is often just the best that can be done. It can be hard to imagine how crazy, complex, and frustrating medical research can be unless you’ve tried doing it. Nothing else quite compares.

I worry that some of these people have an unrealistic view of how things work (or should work). This all reminds me of Andrew Grove, ex-Intel, and his complaints that the drug research business wasn’t moving as fast as the semiconductor industry. It sure isn’t. That’s because it’s a lot harder.

The Biocentury article is right in line with my thinking here:

FASEB’s Talman argues that patient groups and the public are overly optimistic about the breakthroughs that could be made by shifting resources to translational science. He believes basic scientists are partly to blame because “there is too much of a tendency for basic or clinical scientists to sell our work.” In the process, he said, “we can come across as saying that the newest discovery can lead to a cure.” Senior NIH officials have contributed to the belief that cures are around the corner by dangling the prospect of quick payoffs in front of congressional appropriators. For example, in 1999, Gerald Fischbach, then director of the National Institute of Neurological Diseases and Stroke, told a Senate committee that with sufficient funding it was reasonable to expect a cure for Parkinson’s disease within five years. The NINDS budget has increased from $902 million in FY99 to $1.6 billion in FY10, but PD hasn’t been cured.

Starting in 2004, National Cancer Institute Director Andrew von Eschenbach claimed in numerous public speeches that it would be possible to “end suffering and death from cancer by 2015,” a claim that current NCI Director Harold Varmus has repudiated.

When he led the human genome sequencing effort, NIH Director Collins himself made comments that the press, public and politicians interpreted as promising that it would directly and quickly lead to new medicines for common diseases.

“There is a real danger of over-promising,” Keith Yamamoto, executive vice dean of the University of California San Francisco School of Medicine, told BioCentury. “Scientists too often take an intellectual short cut. They think they will not be able to explain the nuances of why basic discovery takes so long, so they just say if you give me the money we are about to cure the disease.”

He added: “That’s thin ice — it is our responsibility to explain why things are as difficult as they are.”

It sure is. I know that patients and the general public get tired of hearing about how it’s hard, how discoveries take time, all that sort of thing, while the diseases just keep marching on and on. But it’s all true. I honestly don’t think that most people realize, despite that huge amounts of knowledge we’ve managed to accumulate, just how little we know about what we’re doing.

Derek Lowe, PhD, received his doctorate in organic chemistry from Duke University and pursued post-doctorate research in Germany on a Humboldt Fellowship. He’s worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer’s, diabetes, osteoporosis and other diseases. He comments about drug discovery and the pharma industry at In the Pipeline.