November 30, 2012 | The Skeptical Outsider Guest Commentary | You know scientists are getting desperate when National Cancer Institute (NCI) researchers publicly boast that their approach is not limited to the realm of rational behavior. Heck, as long as funding is infinite, why not keep going back to re-drill the same dry holes hoping dumb luck will produce a gusher?
I did a double-take when I read a series of news articles describing an ongoing study in which 100 existing cancer drugs were tested in pairs to see if their abysmal effectiveness could be improved via combination therapy. Experimenters at NCI’s Division of Cancer Treatment and Diagnosis ran 300,000 experiments to test 5,000 possible drug combinations against a panel of 60 cancer cell lines looking for an improvement in kill rates. The idea is to identify a few combinations that might be worthy of progressing into clinical trials.
If this isn’t a sign of intellectual exhaustion, I don’t know what is.
So-called rational approaches to combination therapy, in which pairs of chemotherapy agents are used to block redundant metabolic pathways, at least pass the logic sniff test. Perhaps improved outcomes can be found by simultaneously shutting down known parallel pathways that enable runaway cell growth. But for a disease characterized by the rapid proliferation of cells that survive chemotherapy—due largely to the resiliency from natural selection observed long ago by Darwin—dosing patients with two poisons at the same time, rather than sequentially with a first and then a second line treatment, is looking for a triumph of hope over reason.
This study basically admits that we’re so helpless to rationally impact our fate that we think we’ll get better results fighting cancer by randomly guessing a few thousand test points for a few years, defying evolution’s ability to do the same with billions of points over millennia.
There’s got to be a better way.
Interestingly enough, one of the rationales for this blunderbuss approach is that because all the agents have already been approved by the U.S. Food and Drug Administration (FDA) for individual use, using them in pairs would offer a quicker and cheaper path to the clinic. Isn’t this like looking for your car keys under the lamppost because the light is better even though you lost them around the corner?
And if by some miracle, it can be shown that a random combination of poisons allow patients to die in 12 months instead of 10, would this be considered a victory? Does anyone really believe we are going to cure cancer by extending survival one month at a time by slowly optimizing existing approaches that don’t really work?
What will it take to shake the medical/government establishment into diversifying its funding strategy beyond the same exhausted approaches? Imagine if some portion of the billions Uncle Sam spends on the War on Cancer were reserved for truly novel approaches, much like a pension fund places a portion of its portfolio not in publicly traded stocks and bonds from mature Fortune 500 companies, but in alternative investments comprised of a diverse selection of high risk/high reward schemes. Sure, alternative investments include unproven businesses into which no prudent investor would sink more than a fraction of his assets, due to their high failure rate. On the other hand, that’s where Apple, Cisco, Google, and Facebook came from.
Technically this is supposed to exist within the National Institutes of Health via something called an R21 Exploratory grant. In practice R21 grants are only slightly less conservative than standard grants thanks to peer review by entrenched Principal Investigators, who ensure that R21s go to their buddies first. In addition, the “pay it forward” strategy used in many labs chases these grants using work that is already done. Those results then get published while the money is used to fund their next idea. While this does encourage a bit of uncontrolled innovation, it clearly favors established players, putting up enormous barriers for new entrants.
Imagine if the peer review process that keeps the money flowing to the same Principal Investigators year after year were cleaved in two. Most of the money would go to a smaller number of first-rate scientists pursuing business as usual, while second- and third-rate scientists who clutter the literature with me-too studies and irreproducible results are cut off. This would free up funding for out-of-the-box innovators operating outside the entrenched scientific establishment. Imagine if the reviewers for those out-of-the-box grants were chosen not from the same tired old cast of characters—who have done so little with so much—but from technology-based industries with a track record of success when it comes to innovation?
Does that sound crazy? Crazier than spending 40 years and hundreds of billions on a War on Cancer that has yet to deliver a cure? What are we waiting for, the day when cancer replaces heart disease as the number one killer in America? If so, it won’t be long.
Remember when the telecommunications industry was a controlled monopoly served by history’s most storied R&D center, Bell Laboratories? Long held up as the model for innovation, lauded for its invention of the transistor, Bell Labs had become an ossified bureaucracy by the late 1970s. Aside from the replacement of rotary dials with touch-tone keypads, can you recall any significant differences in making a phone call between 1960 and 1980? Now, do you remember the unprecedented explosion in innovation that took place after the Bell System was broken up and a tsunami of upstart innovators completely transformed the global telecommunications business?
If something like this doesn’t happen in cancer research, we may soon be reading about experiments in which all possible combinations of three existing cancer drugs are tried looking for that magic bullet—then four, then five, and so on. Like the razor blade arms race, no matter how many blades you have, you’re still shaving the same face.
The Skeptical Outsider is a contributed column by Bill Frezza. Frezza is a fellow at the Competitive Enterprise Institute and a Boston-based venture capitalist. He can be reached at firstname.lastname@example.org. If you would like to have his columns delivered to you by email, click here or follow him on Twitter @BillFrezza. The views in this column are those of the author and do not necessarily reflect the opinion of Bio-IT World.