Capital shuns risk . \u00a0\u2014\u2014\u00a0The essence of science is exploration of the unknown.<\/p>\n
Science and Capitalism is not exactly a match made in heaven. \u00a0Government 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. \u00a0This has translated into a disastrous attitude of risk aversion. \u00a0A \u201chard-headed\u201d business model prevails at the funding agencies, and they are now funding only those projects that they deem \u201cmost likely to succeed.\u201d<\/em><\/p>\n 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.<\/em><\/p>\n A high failure rate is inseparable from good science. \u00a0But NSF prefers to fund low-risk work, which is really\u00a0engineering. \u00a0<\/em><\/p>\n \u2014\u2014\u2014\u2014<\/p>\n One irony is that capitalism is pretty good at allocating funds for engineering. \u00a0Once the science is well developed, the marketplace isn\u2019t a bad model for deciding where to invest engineering resources. \u00a0We probably don\u2019t need NSF to fund the \u201cD\u201d half of \u201cR&D\u201d. \u00a0But the reason that we need NSF (and NIH and NIA) as public funding institutions is that the rewards of science are difficult to predict. \u00a0I venture to propose Mitteldorf\u2019s Law of Experimentation:<\/p>\n The more unpredictable the result, the more important the experiment. <\/i><\/b><\/p>\n <\/p>\n Perverse Incentives and the Law of Unintended Consequences<\/b><\/p>\n Government funding pays a minor portion of each contract for salaries, equipment, and operating expenses. \u00a0The major portion is called \u201coverhead\u201d, and it goes back to the university (or other institution, some of them for-profit) that houses the research. \u00a0The proportion allocated to overhead \u201cranges from 20% to 85% at universities, and has an even wider spread at hospitals and non-profit research institutes.\u201d [from a 2014 article in Nature<\/a>; also,\u00a0background and recent news here<\/a>]<\/p>\n At a prominent\u00a0midwestern 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. \u00a0For 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.<\/p>\n There were cranes and bulldozers and signs of new construction everywhere. \u00a0It looks like healthy expansion in the health sciences. \u00a0But the reality beneath the surface is that the existing buildings were less than 70% occupied. \u00a0Why was the university building more space when they couldn\u2019t fill the space they had? \u00a0Because the \u201coverhead multiplier\u201d is negotiated with NIH for the university as a whole, and has enormous consequences, dwarfing the cost of any one building. \u00a0This university had an overhead rate of 53% and the new construction was part of a push to justify raising it to 54%. \u00a0If they succeed, the University will be a little richer, and each of their research scientists will be a little poorer.<\/p>\n <\/p>\n Pharmaceutical Companies are the Worst Case<\/b><\/p>\n 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. \u00a0So 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\u2014how will we know? \u00a0This represents a huge distortion of spending priorities, a sacrifice of health to profit.<\/p>\n There is a well-documented tendency<\/a> of pharmaceutical companies to research small tweaks to their competitors\u2019 successful drugs, rather than strike out in new areas with new ideas. \u00a0The 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. \u00a0And even if the new drug is not even marginally better, frequently the company finds a way<\/a>…<\/p>\n The system that we have provides that pharmaceutical companies are responsible for testing their patented products for safety and efficacy. \u00a0This is an invitation to corruption. \u00a0In 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. \u00a0It is too much to ask scientists to be objective under these conditions. \u00a0How 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\u2019s funding depends on a favorable result. \u00a0Does anyone believe that scientific data reported under such circumstances can be reliable? \u00a0Among the horror stories of fraud and suppressed data in the pharmaceutical industry, antidepressants top the list because criteria are subjective and markets are huge. \u00a0In addition to antidepressants, many of the drugs on this list<\/a> are psychiatric drugs that have been promoted \u201coff-label\u201d for depression because this expands their potential market.<\/p>\n Pain medications are sold in a shadow street market<\/a>. \u00a0Arthritis drugs have been promoted despite the dangers they pose for cardiovascular damage<\/a>.<\/p>\n Abuse of antibiotics and the unfolding global crisis of antibiotic-resistant bacteria<\/a> is too big a topic even to summarize.<\/p>\n The right way to fund pharmaceutical research is through university grants to target high-priority specific diseases, including aging. \u00a0All 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.<\/p>\n <\/p>\n Positive directions<\/b><\/p>\n The best prospects for future scientific breakthroughs lie in the direction of things that we already \u00a0know but don\u2019t understand–things that don\u2019t make sense<\/a>. \u00a0Most 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. \u00a0I 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.<\/p>\n Within the field of aging research, readers of these pages already know that my dark horse favorites are telomerase<\/a>, decoding the language of\u00a0epigenetic programming<\/a>, identifying the relevant blood factors from parabiosis experiments<\/a>, and replication of promising Russian experiments with epithalon<\/a> and other short peptides.\u00a0 Here are a few topics that have piqued my interest from further afield in biology.<\/p>\n <\/p>\n I could go further\u2026<\/b><\/p>\n I could say that \u201cprofessional scientist\u201d is already a oxymoron. \u00a0Scientists work best when they are driven by curiosity and a passion to find out, when they are doing what they love. \u00a0How can that be consistent with centralized decision-making and bureaucratic control of research priorities? \u00a0If we pay a scientist to do science, we should not make the payment contingent on studying anything in particular.<\/p>\n No one in a government bureaucracy has the wisdom to predict next year\u2019s breakthroughs, or to single out the scientists most likely to achieve them.<\/p>\n Since 1996, I have pursued the science of aging without funding or support or a university appointment. \u00a0(Every year or two, I ask a colleague to arrange for an unpaid \u201ccourtesy appointment\u201d so that I can have a university affiliation behind my name when I submit papers for peer review.) \u00a0Some of my closest friends are at universities, with large research staffs and successful careers. \u00a0I envy their daily contact with colleagues, access to seminars, and (aboe all) the opportunity to mentor and supervise the next generation of researchers. \u00a0They tell me I am lucky to avoid grantwriting, faculty meetings and academic politics. \u00a0Most of my academic friends and colleagues have paid for their success with their health in one way or another. \u00a0I am privileged to manage my time so as to make self-care a priority–nutrition, exercise, meditation, and sleep.<\/p>\n 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. \u00a0By the time a proposal was written, we had worked out the science in sufficient detail that we knew the results. \u00a0If the proposal was funded, we would use the proceeds to support us while we worked on next year\u2019s proposal.<\/p>\n We may be\u00a0outraged at 70% overhead rates for administration, and think of this as \u201cslush money\u201d that is ripe for abuse. \u00a0I agree that bureaucrats receive too big a share of the pie, and scientists too little.\u00a0\u00a0But 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.<\/p>\n 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. \u00a0He was doing it with soft funding for a follow-on to previously successful research. \u00a0He had prudently kept the funders in the dark about this specific project. \u00a0There\u2019s plenty of time to tell them about it if we succeed.<\/p>\n","protected":false},"excerpt":{"rendered":"\n