What Do Vitamins and Fish Oil Tell Us about Drug Research?
Thursday, August 6, 2009
There is a second world of drug research, a world in which patents do not exist and for-profit research is permanently moribund. Its history should stop ‘reformers’ in their tracks.
Every so often, the debate over healthcare reform dwells on the pharmaceutical industry, particularly prices, costs, the benefits of expensive drugs, and sometimes, the benefits of the tens of billions of dollars spent annually on research and development in this most research-intensive of all industries. When talk turns to price controls or importing drugs at low prices dictated by foreign governments, it is usually met with arguments about the dangers of suppressing for-profit R&D. Then come the counterarguments to the effect that for-profit R&D is really not very productive, and we should avoid excessive hand-wringing about R&D incentives in a post-reform healthcare system.
These debates usually take for granted that no one can really know what life would be like without the pharmaceutical industry R&D enterprise. But in fact, we know quite a bit. That is because there is a second world of drug research, a world in which patents do not exist and for-profit research is necessarily moribund.
These thoughts were triggered when the Washington Post ran an excellent story on August 3 about vitamin D deficiencies among American youth, especially blacks and Mexican-Americans. The Wall Street Journal health blog is also very useful, with links to the Post article, academic journal articles, and more. Based on two new articles in the journal Pediatrics, plus interviews with the authors and other experts, the Post article featured some useful graphs and several quotes to the effect that there are good reasons to be alarmed at dangerously low average levels of vitamin D. Prominent among those dangers are higher rates of heart disease and diabetes. Oddly, the article did not mention cancer despite a considerable body of evidence that vitamin D can prevent cancer (see Jane Brody’s story in the New York Times on February 19, 2008). This adds up to quite a tally of potential uses compared to a few decades ago when the entire list consisted of nothing but rickets, a bone disease caused by vitamin D deficiency.
Just about everyone in the scientific community knows why research is moving so slowly on such important topics. There is no intellectual property.
The real news is that so many serious conditions are now thought to be influenced by vitamin D and that there are so many ways that health might be improved by boosting vitamin D intake. For most people, that means taking a supplement in addition to eating fortified foods such as milk and, of course, getting sunlight without using too much sunscreen. The scientific literature has seen a small barrage of research in the past few years on vitamin D, most of it based on laboratory exercises or epidemiological studies that track diet, health, and other factors through time. The result is a treasure trove of enticing results which, if they pan out, would open the door to immense improvements in human health simply through increasing vitamin D intake.
Also arriving this week was the August 4 daily update from theheart.org, which described an article about fish oil in the Journal of the American College of Cardiology. The most important components of fish oil are omega-3 fatty acids. Again, a series of studies (mainly via laboratory or epidemiological research but in this case, supplemented by a few small clinical trials) has provided immensely interesting results. Essentially, it looks like fish oil in diets can dramatically reduce the incidence of coronary heart disease and therefore of heart attacks and even death. If these results pan out, then, again, science would open the door to immense improvements in human health through relatively simple changes in diet or dietary supplements (fish oil pills are on the market).
There are only two problems. First, we do not know for sure that either vitamin D or fish oil do what we hope they do. Enticing epidemiological and laboratory results often fail to pan out. That has happened to vitamin E, for example, in prevention trials for heart attacks. So the vitamin D and fish oil stories appropriately included quotes from doubters (just as qualified as the scientists who did the studies) who argued quite reasonably that epidemiological and laboratory research, even small clinical trials, simply cannot tell us whether dietary changes really can prevent cancer, heart disease, and so forth. Indeed, the frustration in the public health community on such matters is almost palpable.
Proving that the odds of a certain kind of birth defect could be dramatically reduced by folic acid also took decades. Does anyone think this kind of research would have taken so long if a drug company had owned the patent to folic acid?
The second problem is that it will be quite a while before we know what most want to know about vitamin D and fish oil. Research is proceeding very slowly on the most important front, the mounting of large-scale human trials necessary to provide definitive tests of the most essential hypotheses. These trials cost hundreds of millions of dollars to run, possibly even a few billion when one takes account of the difficulty of devising exactly the right kind of trials.
Just about everyone in the scientific community knows why research is moving so slowly on such important topics. There is no “intellectual property,” i.e., no one owns patents on substances like fish oil and vitamin D, which were discovered and isolated decades or more ago. But that should be no problem if government steps in to fill the gap. After all, the main reason to fund the National Institutes of Health is to make up for the research deficits that arise from lack of private incentives to devise and explore important scientific hypotheses whose resolution would benefit public health. We tend to hear about the virtues of the NIH enterprise whenever Congress gets ready to do something that might undermine drug R&D incentives. Sure, private incentives are useful, as the story goes, but they are not essential. That is because we have NIH, run by smart scientists under the stewardship of a watchful Congress eager to push money at the solution of whatever would provide the biggest payoff for the health of voters. The implication is that private, for-profit research, despite its occasional triumphs, is not so very necessary after all.
The list of hugely important but unexploited research opportunities for the public sector is depressingly long.
But this public R&D option does not really hold up to even casual scrutiny. Vitamin D and fish oil are just two parts of a longstanding history that happened to pop up in the news this week. The list of hugely important but unexploited research opportunities for the public sector is depressingly long. Antibiotics are an example. Because even the most powerful drugs are beginning to encounter drug-resistant bacteria, medical literature is full of pleas for powerful new types of antibiotics. But that same literature makes clear that when a new antibiotic is approved, doctors will use it as little as possible in order to delay the development of yet more drug-resistant bacteria. That eats up patent life, greatly undermining private research incentives. Tuberculosis is another example. It has been decades since a new TB drug has been approved, despite thousands of deaths annually in poor nations where, tragically, there is scant payoff for new drug development. The creation of a malaria vaccine has also been glacially slow for essentially the same reason: a dearth of intellectual property and therefore of private R&D incentives. It took decades to demonstrate the ability of simple aspirin to prevent heart attacks—eventually saving millions of lives, although even more millions died in the meantime—even though many cardiologists had for years been taking their daily aspirin because scientific reasoning and a narrow research base suggested that this old drug would in fact prevent heart attacks. Proving that the odds of a certain kind of birth defect could be dramatically reduced by folic acid also took decades. Does anyone think this kind of research would have taken so long if a drug company had owned the patents to aspirin and folic acid? (The Bayer patent on aspirin died early in the 20th century.) In the meantime, the solution to one of the great riddles in all of cardiology apparently waits for the discovery of patentable drugs that safely increase HDL (the so-called “good” cholesterol, in contrast to LDL or “bad” cholesterol). One patented HDL-booster, torcetrapib from Pfizer, has failed, at a cost of more than a billion dollars to that firm. A substance that works could bring untold benefits to mankind, because the connections between heart disease seem even stronger for HDL than for LDL. Another example of unexploited research awaiting an intellectual-property foundation: ways to exploit what appears to be an extraordinary ability for ethanol (that is, alcohol that most of us drink) to prevent coronary heart disease.
The practical lesson in this brief excursion into scientific history is simple. Before we cripple for-profit pharmaceutical research—by implementing, say, an ill-conceived form of healthcare reform that severely limits the profits from new drug development—we need to make sure we have a good drug development substitute in place. And one thing we know from experience is that no such substitute now exists.
John E. Calfee is a resident scholar at the American Enterprise Institute.
FURTHER READING: Calfee recently wrote “Tough Challenges at the FDA,” on how Obama’s Food and Drug Administration commissioner should avoid actions that make the drug development process more costly and inefficient, and “A Troubling Supreme Judgment” on the Supreme Court’s decision in Wyeth v. Levine. He also wrote “A Public Health Disaster in the Making” on how Congress is poised to pass one of the worst public health laws ever conceived.
Image by Darren Wamboldt/Bergman Group.