Blue sky research pays big dividends – eventually
Research finds many critical medicines began with basic discoveries. Paul Biegler reports.
The tussle between basic scientific research, curiosity-driven with only serendipitous practical outcomes, and the applied variety, targeted from the outset at solving real world problems for the public good, can seem at times like a feud worthy of the Montagues and Capulets.
The bookie’s nod, however, would appear to be with applied research.
According to the United Nations Educational, Scientific and Cultural Organisation (UNESCO) basic science gets only 22% of the research spend of countries in the Organisation for Economic Co-operation and Development (OECD).
But a new study published in the journal Science Translational Medicine strikes a hefty blow for basic, at least when it comes to drug discovery in medicine.
A team led by stem cell biologist Mark Fishman, from Harvard University in the US, assembled medical experts to engage in a “wisdom of crowds” exercise known, somewhat mystically, as the Delphi method, after the ancient Greek oracle.
Unlike its namesake, however, the modern method uses rounds of learned discussion and feedback to reach an evidence-based consensus. The task in this case was to name the 28 “most transformative” medicines approved by the US Food and Drug Administration (FDA) between 1985 and 2009.
It’s an impressive list.
There are the blood pressure agents known as angiotensin-converting enzyme (ACE) inhibitors, the leukaemia drug imatinib, cholesterol-lowering statins, the AIDS lifesaver zidovudine and a drug used to deliver (mostly) hangover-free anaesthetics – propofol.
Armed with this compendium of top shelf drugs the authors went on a sleuthing mission through history to answer two questions.
“For each medicine, we asked whether it began with a basic discovery, meaning an observation about biology or pathophysiology of disease,” they write.
“We also queried whether it was apparent at the time that this discovery held the promise of a new therapeutic and, if not, how long it took for this to be appreciated.”
The results will boost morale for practitioners of basic science research across Australia, the vast bulk of which happens, according to the National Commission of Audit, in universities and publicly-funded agencies such as the CSIRO.
About 80% of the drugs could be traced back to basic discoveries, with an average time to FDA approval of 31 years. The timeline was shorter for newer medicines, at 26 years.
For example, the introduction of the first ACE inhibitor, Captopril, in 1977, a drug some will remember for the annoying cough it brought on, would have been impossible without the 1956 revelation of the actions of the molecules involved. That, in turn, hinged on the 1939 discovery of angiotensin and, going back further to 1898, the enzyme renin that produces it.
Commenting on the study, chief medical advisor of the Australian Heart Foundation, Garry Jennings, says “[M]any in basic research feel under threat at present because of the shift by many funding agencies towards translational research.
“However translational research has to start somewhere and as [these authors] show ... it generally starts with fundamental blue sky research.”
And it seems the odds could be shortening on fundamental science. According to UNESCO, China, dissatisfied with its return on R&D, is ramping up basic research funding. The authors think that’s on the money, at least in the world of pharma.
It would be prudent, they conclude, to “boost support for basic scientific discovery, knowing that this is the best route to the generation of powerful new medicines.”