A research paper published earlier this year in the World Journal of Clinical Oncology sheds some light on the phenomenon. Using a 1999 study and three later-published books, a team of New Zealand researchers earlier this year found that 5.8% of all drugs on the market at publication—84 of 1,437 drugs—resulted from serendipity. Of that 84, indications for 53 were discovered in a clinical setting while indications for the other 31 were discovered in the laboratory.
However, when the researchers expanded their definition to include additional drugs derived from the 84 (147 derivatives from the clinically discovered drugs, and 116 from the lab-discovered drugs) they concluded that 347 drugs had been aided during their discovery by a serendipitous event—nearly one-quarter (24.1%) of all drugs on the market.
Categories of drugs seeing the most frequent instances of serendipitous development include central nervous system, accounting for 22 of the 84 serendipitous drugs (26.2%); cardiovascular (15 or 17.9%); and anticancer (13 or 15.5%). CNS drugs also had the highest percentage in clinical settings (17 of the 53 clinically discovered drugs, 32.1%): “This reflects the difficulty in developing drugs that need to pass the blood-brain barrier, and the dearth of biochemical assays modeling the diseases of the mind and pain,” the researchers reported.
“This serves to highlight the unpredictability in drug research and the necessity to allow for and encourage freedom in research directions and promote the intellectual freedom of the scientists involved,” University of Auckland researchers Emily Hargrave-Thomas, Bo Yu, and Jóhannes Reynisson concluded.
[The full study, “Serendipity in Anticancer Drug Discovery,” can be read here]
The New Zealand researchers should be credited with attempting to quantify serendipity’s influence in drug discovery, and mostly succeeding. An anecdotal 2006 study published in Dialogues in Clinical Neuroscience by Thomas A. Ban, M.D., of Vanderbilt University noted a serendipitous drug omitted by the New Zealand study, the schizophrenia drug chlorpromazine.
A 2009 essay by Sean B. Seymore, assistant professor of law at Washington & Lee University School of Law, observed a structural bias against accidental discoveries by the recently superseded U.S. patent law, since it required two separate acts—initial discovery, then reduction to practice—before inventors could pursue patent applications for inventions.
Since then the Leahy-Smith America Invents Act (AIA), enacted last year, changed the awarding of patents from “first to invent” to “first inventor to file.” That key AIA provision, set to take effect March 16, 2013, removes the incentive for rivals to claim their inventions were conceived before the filing date. However, the new law allows first filers to reduce their inventions to practice after filing, requiring money and staff more typical of corporate giants than startups or the proverbial solo inventor in the garage.
That aside, the chief obstacle to serendipity has less to do with patent law or intellectual freedom than with containing expenses. The cost of drug development can be anywhere from $1 billion (Tufts Center for the Study of Drug Development) to between $4 billion and $11 billion (InnoThink Center for Research In Biomedical Innovation), with both think tanks agreeing that it takes more than a decade to develop most new drugs. Biopharma giants have responded mostly by scrambling in recent years to cut R&D expenses through partnerships with smaller biotechs and university research labs.
Biopharmas simply can’t wait as long as they used to for the lightning of chance or serendipity to strike in a bottle. That helps explain brisk interest in a recently launched federal agency-industry pilot program aimed at finding new therapeutic uses for shelved proprietary drug candidates.