What Andy Grove still gets wrong about the life sciences — and how he could help fix them

(UPDATED: See below.)

Like DNA co-discoverer James Watson, whose career ended last month after he linked genetic intelligence differences to race, former Intel chairman Andrew Grove seems to be falling into the trap of assuming that expertise in one field automatically translates into wisdom in others. In this Newsweek interview and in a recent speech to the Society of Neuroscience, for instance, Grove has launched a new jeremiad against the pharma/biotech industry and the life sciences in general, essentially blaming them for failing to produce medical cures as quickly as Moore’s law doubles the number of semiconductors on a microprocessor chip.

This isn’t the first time Grove has ventured into these waters. Back in May, I took issue with his misguided prescription for U.S. healthcare, which struck me as so much tinkering around the edges of a deeply broken system. If anything, his thinking has gone downhill since then, since his critique of the drug-discovery process is so uninformed as to be embarrassing. Even when Grove makes valid points, such as addressing the careerist attitude of many academic scientists and the paucity of “translational” research designed to move basic-science discoveries into commercial development, he tends to settle for cheap shots instead of grappling with the fundamental problems in medical discovery and development of new therapies.

For starters, Grove seems to think that the historically breathtaking advances in semiconductor technology were mainly the result of a corporate emphasis on “time to market, or time to money” — in other words, a fervent desire to get product out to customers — and the tinkerer’s mentality of engineers who saw failure as an opportunity. For instance:

Why is the speed of progress so different in semiconductor research and drug development?
The fundamental tenet that drives us all in the semiconductor industry is a deeply felt conviction that what matters is time to market, or time to money. But you never hear an executive from a pharmaceutical company say, “Before the end of the year I’m going to have xyz drug,” the way Steve Jobs said the iPhone would be out on schedule. The heart of every high-tech executive has been, get the product into customers’ hands and ramp up production. That drive is just not present in pharma; the drive to get sufficient understanding and go for it is missing.

How do the two industries deal with failure?
When I started Intel we couldn’t make a device twice in a row in the same way. I earned my reputation by being part of a team that figured out why a thing was not reproducible, what you need to do to make results come out the same way twice in a row. The attitude [in high-tech] is, something went wrong for a reason, let’s find the gold nugget. In 1970, Dov Frohman [at Intel] was investigating insulator leakage, and it led him to invent a brand-new device that is now a fundamental building block of cellphones, cameras, MP3 players and computers. But in pharma, if a clinical trial doesn’t work–which means the average of all the patient responses is not better than the average of a placebo treatment–they just throw [the drug] away, when in fact the averages may hide stuff that did work, and something that made patients different [such as genetics]. I’ve never heard anyone talk about the opportunity costs of a good drug being thrown away. But a good drug wrongfully convicted means the loss of benefits goes on forever.

Is Grove really under the impression that pharma and biotech executives spend their days sitting around twiddling their thumbs and inventing new roadblocks to toss in the path of life-saving therapies? Or that drug companies aren’t eager to take apart clinical-trial results in order to salvage some shred of success from failure?

The fact, of course, is that chip development and drug development are so different that you have to take great care with direct comparisons lest your argument collapse in a ludicrous mess, and there’s no evidence that Grove has taken that sort of care here. Semiconductors are based on well-understood principles of solid-state and quantum physics a century or more old, whereas our fundamental knowledge of human biology is still in its infancy, notwithstanding the advances of the past several decades. Engineers know more about how even the most complex Intel CPU works than anyone does about how biochemical signals direct the activity of individual cells — much less tissues, organs, or, God forbid, networks as complex as the immune or central nervous systems.

Chips can be improved by tinkering, whereas the same is rarely true of a drug, since even minor changes can cause toxic side effects. (A commenter at Derek Lowe’s blog In the Pipeline likens drug discovery to writing software for a buggy operating system — only you can’t test your code on the OS until the very end, and can never, ever let it crash.) It’s often even difficult to know whether a given drug works — thus the need for expensive and lengthy clinical trials — whereas semiconductors are fairly straightforward to test.

Finally, the consequences for screwing up a semiconductor design are fairly trivial compared to those for producing a drug that ends up actually killing people. Intel, for instance, spent as much as $2 billion to develop a new microprocessor called Itanium that flopped in the marketplace, a struggle I wrote about for the WSJ (to read it, though, you have to see the version ZDnet reprinted here). Contrast that to Merck’s experience with Vioxx, a now-withdrawn painkiller linked to heart attacks, and tell me again that all the drug industry really needs is more gumption about getting products to market quickly.

(Lowe, a medicinal chemist, has also dissected Grove’s attack on the drug industry at length, so check out his post — not to mention a very interesting discussion in comments — if you’d like to know more.)

Grove may have more of a point when he critiques the herd mentality of academic scientists, although the U.S. has always been much better about giving its scientific mavericks room to explore crazy ideas that have other countries. But he misses a much bigger — and more constructive — opportunity to really address the problem when he overlooks the real Achilles’ heel of the life sciences, which is the still-considerable gap between basic research and commercial development.

Such translational research, in fact, is an area where someone of Grove’s stature, accomplishment and wealth might reasonably make a difference. At the risk of oversimplifying what can be a vastly complex issue, many promising academic findings — say, the discovery of a protein that could be useful in the early detection of cancer — end up sitting on the shelf. That’s not because they’re worthless — it’s just that the work necessary to prove the clinical usefulness of an initial finding often falls through the cracks. Academics tend to view such “validation” studies as unsexy, tedious drudgery, while pharmas and biotechs are generally loathe to put up the big bucks such studies require without a greater assurance they’ll end up with a potential product at the end.

The last few years have seen a few public and private efforts spring up in an attempt to bridge this translational gap, although they’re still woefully insufficient given the scale of the challenge. Part of the problem, of course, is that translational research is a pretty abstract notion, one that lots of people find tough to get too worked up about. In fact, it’s too bad that a fabulously wealthy former corporate titan with a particular interest in speeding the pace of medical discovery hasn’t chosen to embrace the issue in order to help make it a national priority. Maybe someone should ask Andy Grove — he might be able to suggest a name or two.

UPDATE: Expanded by several paragraphs to lay out the critique of Grove’s argument in greater detail.