Andy Grove: Where are the Cures?!

If you envy the lab rats with paralyzing spinal-cord injuries that have walked again, the legions of lab mice whose tumors have melted away thanks to experimental drugs, and the mice whose rodent version of Alzheimer’s has been cured—while human Alzheimer’s, paralysis and many cancers remain incurable and sometimes untreatable—join the club. For at least four years even biomedical scientists have been saying what many used to dismiss as the whining of no-nothing laymen who failed to grasp the value of basic biomedical research. Namely, “patients have been too patient with basic research,” as immunologist Ralph Steinman of Rockefeller University put it in 2003.

He meant that the basic discoveries that fill medical journals, reflecting research that has been generously supported by U.S. taxpayers (the National Institutes of Health received just over $28 billion in each of the last three years), do not result in enough new treatments soon enough. After all, there is no cure for Parkinson’s disease, for many cancers, for multiple sclerosis, for cystic fibrosis—or even for baldness, for pete’s sake. That failure threatens to shred the implicit understanding that taxpayers spend billions of dollars on cellular and molecular biology—from the genetics of slime molds to the neurology of the giant squid—for one reason and one reason only: because some of the resulting basic knowledge will lead to medical treatments for human diseases.

Now some big guns are taking aim at what more and more critics see as a broken system. This afternoon Andy Grove, co-founder of computer-chip giant Intel and its former CEO and chairman, is unleashing a no-holds-barred critique of the nation’s biomedical establishment for falling woefully short in its search for disease treatments. Speaking at the annual meeting of the Society for Neuroscience, he issues a wake-up call that should be heeded by every congressman who votes for multi-billion-dollar NIH budgets, by every CEO of a big pharma company who hasn’t had an important new compound approved in ages, by every dean of a biomedical center who bases tenure and promotion and hiring decisions on a scientist’s number of published papers with no regard to whether the research is leading to something that can alleviate the suffering of humankind.

Just to elaborate on that last point. The culture of academic biology is part of the problem. There is little prestige in “translational research,” in which basic discoveries are turned into medical treatments. Look at the very name: who gets more prestige, the author writing a great novel in her native tongue or the translator who produced a version for other audiences? So it is in biology. The basic discoveries bring the glory. Translating them is—and I exaggerate only slightly—considered the work of drones. Also, it’s easier to get an NIH grant for a simple animal experiment that is likely to yield clean results, rather than a human one that’s probably going to be ambiguous because humans—who are genetically diverse—are more complicated than fruit flies.

As Rockefeller’s Steinman told me when I first asked him about his “patients have been too patient” declaration, “Most of our best people work in lab animals, not people. But this has not resulted in cures, or even significantly helped most patients.”

Drug companies are also in Andy Grove’s crosshairs. Drawing a comparison to the semiconductor industry he knows so well, and to high-tech in general, he argues that pharma could learn something from how tech industries learn from their successes and failures. As an example of the latter, Grove notes that when Intel started new production lines, invariably a large fraction of the chips it made were faulty. Rather than throwing them out, he said, engineers scrutinized the manufacturing process to determine the cause of the failure.

Drug companies, in contrast, tend to abandon compounds that fail in clinical trials. As a result, they lose potentially valuable information on, say, whether the drug works in certain patients (those with particular genetic variations, for instance). Those rare successes, which Grove calls "golden nuggets," are washed out by the averaging of results across the whole patient population.

To take just one sorry example of the slow pace of drug discovery, in the 1960s the mainstay of treatment for Parkinson’s disease, from which Grove suffers, was L-dopa. In the 2000s the mainstay of treatment for Parkinson’s disease is . . . L-dopa. Need we contrast to the gains that the computer industry has made in 45 years?

It will be interesting to see whether a shot across biomedicine’s bow by someone of Andy Grove’s stature will give the system the shaking up it needs.