The Billion-Dollar Heartbreak

Fellow blogger, current colleague and friend Keith and I spent an enjoyable evening two days ago at an event which I wouldn’t have anticipated if you had asked me about it before: a sort of fund-raiser/pitch for a movie based on Barry Werth’s book about the creation of Vertex Pharmaceuticals, “The Billion-Dollar Molecule”.

I have to confess being blown away by the book when I first read it in graduate school. The breathless descriptions of the science and the scientists, the glitter of structure based drug design and and the sheer effort of drug discovery really left an impression of me. After working in the reality of drug discovery for a decade or so, I perhaps don’t feel as breathless as I did the first time around. Yes, drug design is exciting, but no, most of the work that we do in the field is far more mundane and boring than what appears in the book (and this is true for the rest of science). And the science of drug design is also far more sobering and limited than what it seemed in the 80s. Nonetheless, if there was a short list of books on biopharmaceutical research that would seem likely to transition to the silver screen, Werth’s volume would probably be on top of that list for me because of its sheer novelistic qualities.

The event itself featured a panel of three scientists and one lawyer who were present at the creation and subsequent developments at Vertex in the late 80s and early 90s: Manuel Navia, Mark Murcko, Roger Tung and Ken Boger would all be familiar to anyone who has read the book. The event was fittingly organized in the old Vertex building near 3^rd street in Cambridge, and not surprisingly it drew a lot of Vertex old timers which inadvertently turned it into a Vertex reunion. An ancillary side session featured a silent auction for photographs taken by Nobel Laureate (and Keith’s graduate school co-advisor) Wally Gilbert who was also there.

Much of the discussion really focused on the scientists’ views of what they thought should really come across from the movie, and I largely agreed with their suggestions. The overwhelming consensus was that the movie needs to communicate the sheer and appalling rate of failure – probably unprecedented relative to any other industry – that we in pharma and biotech have to deal with. 99% of everything that we do, right from the most basic research to the most applied clinical work, simply fails. Almost all of us go through our entire careers without contributing to the discovery of a single important drug. And it all fails because of one overriding factor which I and others have discussed before – our ignorance of basic biology and human disease. It seems that this is probably the preponderant feature of drug discovery that simply fails to make its way across to the public: almost every argument that the public makes against drugs, from their high cost to their side effects, boils down to the simple fact that we simply don’t know how to do it any better. I agree with the participants that if there’s one message that really needs to shine forth from any movie about drug discovery it needs to be this one about attrition, failure and ignorance. Not exactly an uplifting message, but essential for an accurate perception of drug research.

One of the panelists also raised the very relevant issue of how to accurately strike a balance between the sheer tedium of everyday research and the occasional breakthroughs that permeate the entire practice of science. If there’s one flaw in “The Billion Dollar Molecule” it’s that it seems to downplay the former aspect and really emphasize the latter. Yes, drug discovery is a high stakes enterprise and yes, the scientists who do drug discovery can have titanic-sized egos and can have their emotions running high and wild and yes, the science of drug design can sometimes seem as exciting as the ‘science’ in ‘Avatar’, but for every one of these facts the opposite is also true: drug discovery scientists are normal people with a spouse and kids and a mortgage, and 90% of the science of drug discovery is like 90% of science in general – incremental, unflashy and mundane; less Holmesian detective work and more 9 AM-5 PM office job. What the book did was compress all of this into a heady, heroic 350-page narrative, and one wonders if the movie should try to do the same. Another way to tackle the issue might be to make a documentary that’s more realistic, although admittedly it would then be harder to get Kevin Spacey to play Josh Boger (one of the more fanciful suggestions bandied about).

Curiously, the entire project that the book hinges on - the quest to find a breakthrough immunosuppressant - actually failed because they were looking at the wrong target (the curse of biological ignorance struck again), so communicating the reality of the fantastic failures that emerge from a fantastic effort should come naturally to the narrative in the movie. It's a testament to the vision and resilience of the company's BOD and management that they successfully pivoted away from this major failure. It also seems that the movie should heavily capitalize on the sequel to “The Billion-Dollar Molecule” (“The Antidote”): while that’s far less sensational, it deals with the two breakthrough projects at Vertex (hepatitis C and cystic fibrosis) that actually succeeded in a very big way.

Notwithstanding the challenges, I have to say I am game for any cinematic, literary or other endeavor that makes the science, art and business of drug discovery more comprehensible to the layman. There are few activities both more profoundly misunderstood and more fundamentally important to human society than the creation of new entities that save or improve the lives of millions, and any project whose express goal is to make the general public appreciate this reality – even at the expense of some glamorization – would be one I fully support. Good luck to the film-makers!