Capital shuns risk . —— The essence of science is exploration of the unknown.
Science and Capitalism is not exactly a match made in heaven. Government and foundation funding has always been behind the curve of innovation, but the recent contraction in US science funding has engendered an unprecedented intensity of competition. This has translated into a disastrous attitude of risk aversion. A “hard-headed” business model prevails at the funding agencies, and they are now funding only those projects that they deem “most likely to succeed.”
The difference between science and engineering is that scientific research starts without understanding and tries out various hypotheses until one seems to work; while an engineer works with a paradigm that she knows to be reliable enough to be a basis for results of her innovations in advance.
A high failure rate is inseparable from good science. But NSF prefers to fund low-risk work, which is really engineering.
One irony is that capitalism is pretty good at allocating funds for engineering. Once the science is well developed, the marketplace isn’t a bad model for deciding where to invest engineering resources. We probably don’t need NSF to fund the “D” half of “R&D”. But the reason that we need NSF (and NIH and NIA) as public funding institutions is that the rewards of science are difficult to predict. I venture to propose Mitteldorf’s Law of Experimentation:
The more unpredictable the result, the more important the experiment.
Perverse Incentives and the Law of Unintended Consequences
Government funding pays a minor portion of each contract for salaries, equipment, and operating expenses. The major portion is called “overhead”, and it goes back to the university (or other institution, some of them for-profit) that houses the research. The proportion allocated to overhead “ranges from 20% to 85% at universities, and has an even wider spread at hospitals and non-profit research institutes.” [from a 2014 article in Nature; also, background and recent news here]
At a prominent midwestern medical school where I was visiting last week, my host had just received word of renewed funding for his research, breathed a sigh of relief. For the first time in many months, he was able to put grant-writing in the background and devote his attention to the substance of his research.
There were cranes and bulldozers and signs of new construction everywhere. It looks like healthy expansion in the health sciences. But the reality beneath the surface is that the existing buildings were less than 70% occupied. Why was the university building more space when they couldn’t fill the space they had? Because the “overhead multiplier” is negotiated with NIH for the university as a whole, and has enormous consequences, dwarfing the cost of any one building. This university had an overhead rate of 53% and the new construction was part of a push to justify raising it to 54%. If they succeed, the University will be a little richer, and each of their research scientists will be a little poorer.
Pharmaceutical Companies are the Worst Case
Private companies are motivated to research the drugs that can be sold most profitably, not the ones that can provide the most good to the public at the least cost. So there are orphaned drugs and there are untested nutraceuticals that are unpatentable and therefore unprofitable, but may be safer and more effective than the patented drugs—how will we know? This represents a huge distortion of spending priorities, a sacrifice of health to profit.
There is a well-documented tendency of pharmaceutical companies to research small tweaks to their competitors’ successful drugs, rather than strike out in new areas with new ideas. The former has a lower risk, and if the program is successful, the company can take over an entire profitable market from a competitor, with a drug that is only marginally better. And even if the new drug is not even marginally better, frequently the company finds a way…
The system that we have provides that pharmaceutical companies are responsible for testing their patented products for safety and efficacy. This is an invitation to corruption. In Phase III trials, a company has already invested so much in their product that if the trial results are negative then the company is on the hook for hundreds of millions of dollars. It is too much to ask scientists to be objective under these conditions. How can they make unbiased judgments about the message of their data, let alone design experiments and tests and criteria, when their funding and their boss’s funding depends on a favorable result. Does anyone believe that scientific data reported under such circumstances can be reliable? Among the horror stories of fraud and suppressed data in the pharmaceutical industry, antidepressants top the list because criteria are subjective and markets are huge. In addition to antidepressants, many of the drugs on this list are psychiatric drugs that have been promoted “off-label” for depression because this expands their potential market.
Pain medications are sold in a shadow street market. Arthritis drugs have been promoted despite the dangers they pose for cardiovascular damage.
Abuse of antibiotics and the unfolding global crisis of antibiotic-resistant bacteria is too big a topic even to summarize.
The right way to fund pharmaceutical research is through university grants to target high-priority specific diseases, including aging. All patents accruing from this work should be placed in the public domain, and pharmaceutical companies can compete at what they do best, which is devising inexpensive ways to manufacture and distribute known chemicals.
The best prospects for future scientific breakthroughs lie in the direction of things that we already know but don’t understand–things that don’t make sense. Most of these will turn out to be mistakes in experimental technique or interpretation; but there are some that have such broad corroboration from diverse laboratories that this is unlikely. I have a personal passion for collecting stories of scientific results that defy theory, and a portion of my research and reading time is always devoted to looking for neglected or fringe science that just might lead someplace new and interesting.
Within the field of aging research, readers of these pages already know that my dark horse favorites are telomerase, decoding the language of epigenetic programming, identifying the relevant blood factors from parabiosis experiments, and replication of promising Russian experiments with epithalon and other short peptides. Here are a few topics that have piqued my interest from further afield in biology.
- Cell phones and cancer. I don’t know whether the risk from RF radiation is small or large, but I do know that it ought to be zero from everything we know about biology and physics. Interactions between RF radiation and biological systems took the entire scientific community by surprise, and whatever the mechanism turns out to be, it is likely to open doors into new fields of research.
- Animal navigation. From salmon to monarchs, from whales to homing pigeons, the means by which animals know where they are and where they want to be are just beginning to be elucidated. Some are amazingly reliable. Surprising uses of quantum physics by plants and animals have already been a fruit of this research.
- Perhaps related is (presumed) epigenetic inheritance of acquired cognitive information. Knowledge (as far as we know) is coded in synapses in the brain. How can it be transmitted in DNA? The case of monarch butterflies “remembering” the tree 2000 miles away where their great great great great grandmother overwintered is a well-known example. Less known is this article on metamorphosis and learning from PLoS One.
- Anomalous cures. For every “incurable” disease, there is some small percentage of people who manage to cure themselves. These cases are ignored by most medical scientists because they don’t fit the model of statistical evidence and “one disease ⇒ one cure” that predominates in the community. But perhaps we can learn some basic biology from studying them.
- Lamarckian inheritance. Darwin believed that the individual traits of your offspring depend on your activities as well as your genes. “Use and disuse” was his term. But for 100 years since August Weismann, bedrock evolutionary science tells us that the genes you inherit are the genes you pass on, with only purely random mutations. In recent decades, there are exceptions to this law. One is epigenetic inheritance, through which your life experience can affect your children and grandchildren and perhaps great grandchildren through their inherited gene expression. The other is what James Shapiro calls natural genetic engineering. He has documented the ability of bacteria to alter their genes in response to stress, and in a way that responds explicitly to the kind of stress that is experienced. Is anyone looking to see if higher organisms can do this, too?
I could go further…
I could say that “professional scientist” is already a oxymoron. Scientists work best when they are driven by curiosity and a passion to find out, when they are doing what they love. How can that be consistent with centralized decision-making and bureaucratic control of research priorities? If we pay a scientist to do science, we should not make the payment contingent on studying anything in particular.
No one in a government bureaucracy has the wisdom to predict next year’s breakthroughs, or to single out the scientists most likely to achieve them.
Since 1996, I have pursued the science of aging without funding or support or a university appointment. (Every year or two, I ask a colleague to arrange for an unpaid “courtesy appointment” so that I can have a university affiliation behind my name when I submit papers for peer review.) Some of my closest friends are at universities, with large research staffs and successful careers. I envy their daily contact with colleagues, access to seminars, and (aboe all) the opportunity to mentor and supervise the next generation of researchers. They tell me I am lucky to avoid grantwriting, faculty meetings and academic politics. Most of my academic friends and colleagues have paid for their success with their health in one way or another. I am privileged to manage my time so as to make self-care a priority–nutrition, exercise, meditation, and sleep.
In the late 1970s, when I was a low-level researcher at a government contract research house on Route 128, we always worked one year ahead of our funding. By the time a proposal was written, we had worked out the science in sufficient detail that we knew the results. If the proposal was funded, we would use the proceeds to support us while we worked on next year’s proposal.
We may be outraged at 70% overhead rates for administration, and think of this as “slush money” that is ripe for abuse. I agree that bureaucrats receive too big a share of the pie, and scientists too little. But there is some portion of the overhead money that finds its way back through departments to the researchers themselves, and offers them some slack between contracts, their only real freedom to think and to innovate.
I asked my collaborator at Prominent Midwestern U whether he had funding for the exploratory, groundbreaking work on population dynamics that he was doing with me, but I already knew the answer. He was doing it with soft funding for a follow-on to previously successful research. He had prudently kept the funders in the dark about this specific project. There’s plenty of time to tell them about it if we succeed.