Where are the heroes of pharma research?

Since accepting my new position with Keck Graduate Institute and switching my industry orientation from ICT to the life sciences, I’ve been struck by the difference in how the two sectors are treated in popular culture — particularly drug discovery, whether “big pharma” or the scrappy biotech startups.

One metric is news articles. When I pick up my copy of Business Week every Friday morning, there will be three or four articles about the major computing, communications or other electronics companies, but many weeks nothing about pharma, big or small. Reading the Wall Street Journal or the New York Times (back before they started charging) suggests a similar pattern.

It’s even more pronounced with books. The weekend brought news of the death of Tom West, a longtime engineering manager for Data General. Most people have forgotten his name, but every computer engineer of my generation read about his success creating the Eclipse minicomputer in The Soul of a New Machine — the book that both created Tracey Kidder’s reputation and also the first to apply “new journalism” to study a complex engineering design problem.

I own at least three bookshelves of memoirs and histories about PC, software, Internet and other ICT companies. (I say at least three because some are in boxes and some are mixed in with other books). These books were written in the past 30 years — since the IPOs of Apple and Microsoft made these firms a household name — and include at least 10 Apple books and 5 each on IBM and HP. (Some of these books are on companies that were never consumer brands, including DEC is Dead, Long Live DEC about the once-great Digital Equipment Corp.)

However, when I went to find similar books about drug discovery companies in the San José public library, almost nothing was to be found. In fact, the only book held by more than one branch was Poison Pills: The Untold Story of the Vioxx Drug Scandal, which as the title suggests is a one-sided “exposé” about Merck & Vioxx.

Along the same lines, watching CNN in an airport waiting lounge — the only time I ever watch CNN — today I saw a similar breathless exposé about allegedly FDA lax approval processes. In this case, the guests were a couple of geriatric contributing editors of Vanity Fair, who wrote an article (“Deadly Medicine”) about Avandia, arguing that prescription drug deaths mean that the FDA standards are too lax.

From the TV interview was no evidence that either man knew anything about small molecule drug discovery, PPAR ligands, risk assessment or the steps necessary to gain a Ph.D. in any of the life sciences. In contrast, before my friend Randy Stross wrote Planet Google, he’d lived in Silicon Valley for decades and written six other books, including a biography of Steve Jobs.

One would reasonably assume this sort of media coverage impacts legislative and judicial decision, class-action lawsuits and even the career intentions of high school and college students. The folks that create privacy-invading breakthroughs like Google and Facebook are lionized while people who try to save lives are (often) demonized.

One notable exception was the 2010 movie “Extraordinary Measures,” based on the memoir of serial entrepreneur John Crowley about his efforts to find a cure for Pompe disease. As one promo put it:

An uplifting, inspirational drama, chronicles John Crowley, the man, who defied conventional wisdom and great odds, and risked his family's future to pursue a cure for his children's life-threatening disease.

Of course, any success of the movie is due more to Brendan Fraser in the lead role with two cute ailing kids, and of course Harrison Ford playing a cross between Harrison Ford and Scottie (“I’m givin’ it all aye got, captain!”).

So are the companies that produce therapeutics and diagnostics as evil as one would think watching CNN or browsing books in the personal health section of Barnes & Noble? If not, what can be done about it?

Lost in translation

Any big pharma CEO or shareholder would love to see a stronger link from basic research to the bottom line. But it’s not something that can be achieved via administrative fiat.

Writing at the WSJ Health Blog, Shirley Wang reports

When former NIH head Elias Zerhouni ran the $30 billion federal research institute, he pushed for so-called translational research in which findings from basic lab research would be used to develop medicines and other applications that would help patients directly.

Now the head of R&D at French drug maker Sanofi, Zerhouni says that such “bench to bedside” research is more difficult than he thought.

When Dr. Zerhouni tried to make Sanofi more like a nimble small biotech, he found it didn’t work because (as the WSJ put it) “small biotechs are no more successful than large drug makers at coming up with new drugs.”

Blogger Derek Lowe remarks that Zerhouni “was, in all likelihood, living in sort of a bubble at NIH.” And, Lowe suggests, knowledge of how to fix this is more likely to be found in an industry veteran than a government refugee.

On the one hand, Lowe notes that current NIH head Francis Collins wants to create a new NIH translational research institute. On the other hand, Wang cites its earlier posting, in which the ex-head of Merck said NIH is not well suited for translational research and instead should stick to basic science.

BTW, Lowe and Wang don’t seem to understand “open innovation” is or why Zerhouni is recommending it.

Defining open innovation is much easier than fixing the difficulties of pharma commercialization. A definition can easily be found with Google and there now are a large body of research, an online community and blog on the topic.

Spending on millions on lottery tickets

The recent difficulties of big pharma creating new blockbuster drugs are well known in the industry. Every time they bring a compound to trials, they’re placing a multimillion dollar bet that it will both be effective and also will make it through (increasingly difficult) FDA approvals.

However, these same sort of gambles also apply far upstream, when a new molecule, new technique or even basic science is being pursued by university scientists.

In his blog (In the Pipeline), Derek Lowe today highlights an example of this from the 1980s — one that brought a Nobel Prize in physiology.

He quotes from the new book Adapt by Tim Harford, as summarized in a recent Slate article.

In 1980, Mario Capecchi applied for a grant from the U.S. National Institutes of Health. . .Capecchi described three separate projects. Two of them were solid stuff with a clear track record and a step-by-step account of the project deliverables. Success was almost assured.

The third project was wildly speculative. Capecchi was trying to show that it was possible to make a specific, targeted change to a gene in a mouse's DNA. It is hard to overstate how ambitious this was, especially back in 1980. . .The NIH decided that Capecchi's plans sounded like science fiction. They downgraded his application and strongly advised him to drop the speculative third project. However, they did agree to fund his application on the basis of the other two solid, results-oriented projects. . .

What did Capecchi do? He took the NIH's money, and, ignoring their admonitions, he poured almost all of it into his risky gene-targeting project. It was, he recalls, a big gamble. If he hadn't been able to show strong enough initial results in the three-to-five-year time scale demanded by the NIH, they would have cut off his funding. Without their seal of approval, he might have found it hard to get funding from elsewhere. His career would have been severely set back, his research assistants looking for other work. His laboratory might not have survived.

The problem is, he did exactly what NIH didn’t want him to do, and its process was designed to screen out. Again quoting Harford:

The NIH's expert-led, results-based, rational evaluation of projects is a sensible way to produce a steady stream of high-quality, can't-go-wrong scientific research. But it is exactly the wrong way to fund lottery-ticket projects that offer a small probability of a revolutionary breakthrough. It is a funding system designed to avoid risks—one that puts more emphasis on forestalling failure than achieving success.

Both Lowe and Harford praise the Howard Hughes Medical Institute — in other words a foundation that can take big risks with its own money.

Once upon a time, big rich R&D intensive companies existed to take these sort of risks. In one 20 year period, AT&T invented the mobile phone, the transistor, error correction codes, solar cells, transatlantic telephone cables, the laser and the communications satellite. While the reconstituted AT&T is now a duopoly, the old Bell Labs is long gone.

A long time ago, big pharma made the great breakthroughs. More recently, they let university professors create biotech startups and then bought them. But now such startups look like a bad bet for VCs, and a new financing model is badly needed.

We don’t know who will fund the next round of great breakthroughs. By their nature, we don’t know what they are or where they will come from. Perhaps if we’re lucky, the new tools for computational biology and chemistry will reduce the time and costs of making such discoveries — reducing the amount of money that scientists have to beg for and improve the odds of getting it.