Science Funding

The British agricultural and industrial revolutions took place in the 18th and 19th centuries in the complete absence of the government funding of science. It simply wasn’t government policy. The British government only started to fund science because of [World War I​]. The funding has increased heavily ever since, and there has been absolutely no improvement in our underlying rate of economic growth.

But the really fascinating example is the States, because it’s so stunningly abrupt. Until 1940 it was American government policy not to fund science. Then, bang, the American government goes from funding something like $20 million of basic science to $3,000 million, over the space of 10 or 15 years. I mean, it’s an unbelievable increase, which continues all the way to the present day. And underlying rates of economic growth in the States simply do not change. So these two historical bits of evidence are very, very powerful…

It’s a myth that science is a public good. Science is constructed in “invisible colleges”–small groups of people who understand each individual discipline. So the number of people who can really understand the scientific papers is few. To become a member of this club, you have to pay a very high entrance fee. [The late] Ed Mansfield, an economist at the University of Pennsylvania, showed empirically that the average cost to one company of copying the science of another company is 70 percent. But it’s worse than that because you’ve also got to pay for the costs of information. The company has got to have enough scientists out there to read the papers, to read the patents, to go to the conferences, so that you actually know what people are discovering, so you know how to copy it. Add that to the 70 percent, and add the premium you pay in the scientist’s salary for all the training he’s gone into, and the costs of copying and the costs of doing things originally come out exactly equal. That’s in Mansfield, and others have shown this as well.

The Economics of Science: Interview with Terence Kealey, JR Minkel, March 3, 2003, http://www.scientificamerican.com/article.cfm?id=the-economics-of-science&print=true.

http://vimeo.com/12598733

http://www.youtube.com/watch?v=C_PVI6V6o-4

The big myth about scientific research is that government must fund it. The argument is that private companies will not fund science, especially pure science, for fear that their competitors will “capture” the fruits of that investment. Yet, in practice, companies fund pure science very generously, and government funding displaces private research money.

Without government funding of science, the United States overtook Britain around 1890 as the richest country in the world.

War changed everything. The National Academy of Sciences was created in 1863, at the height of the Civil War, to help build ironclads to beat the South. The Office of Scientific Research and Development, which ultimately spawned the National Science Foundation and the National Institutes of Health, was created in 1941.

Then the USSR launched Sputnik, the first artificial satellite, in 1957. The Soviets were going to destroy us from space! So in 1958 the National Aeronautics and Space Administration was created, and the U.S. Congress passed the National Defense Education Act to pour money into higher education and science. Yet, remarkably, U.S. economic growth was unaffected. The U.S. per capita gross domestic product has grown at around 2 percent a year since 1820, and the government largesse of the last 50 years has not altered that.

Further, government funding of university science is largely unproductive. When Edwin Mansfield surveyed 76 major American technology firms, he found that only around 3 percent of sales could not have been achieved “without substantial delay, in the absence of recent academic research.” Thus some 97 percent of commercially useful industrial technological development is, in practice, generated by in-house R&D. Academic science is of relatively small economic importance, and by funding it in public universities, governments are largely subsidizing predatory foreign companies.

End Government Science Funding, Terence Kealey, April 11, 1997, http://www.cato.org/pub_display.php?pub_id=6168.

 

Peer Review

Over the past 12 years, anesthesiologist Scott Reuben​ revolutionized the way physicians provide pain relief to patients undergoing orthopedic surgery for everything from torn ligaments to worn-out hips. Now, the profession is in shambles after an investigation revealed that at least 21 of Reuben’s papers were pure fiction, and that the pain drugs he touted in them may have slowed postoperative healing.

Paul White, another editor at the journal, estimates that Reuben’s studies led to the sale of billions of dollars worth of the potentially dangerous drugs known as COX2 inhibitors, Pfizer’s Celebrex (celecoxib) and Merck’s Vioxx (rofecoxib), for applications whose therapeutic benefits are now in question. Reuben was a member of Pfizer’s speaker’s bureau and received five independent research grants from the company.

A 2007 editorial in Anesthesia & Analgesia stated that Reuben had been at the “forefront of redesigning pain management protocols” through his “carefully planned” and “meticulously documented” studies… In 2004, Vioxx and Bextra were pulled from the market because of their link to an increased risk of heart attacks and strokes, leaving Pfizer’s Celebrex as the only COX2 inhibitor available. Celebrex sales plunged 40 percent after a study that same year suggesting that it, too, posed a heart attack risk. Despite this, Reuben continued to present “findings” in research funded by Pfizer that trumpeted Celebrex’s alleged benefits and downplayed its potential negative side effects.

The question is: Why did it take 12 years before a “routine audit” revealed Reuben’s widespread data fabrication? “Baystate publishes about 200 [studies] every year, and of those [articles], the audit rate might only be 5 percent.”

A Medical Madoff: Anesthesiologist Faked Data in 21 Studies, Brendan Borrell, March 10, 2009, http://www.scientificamerican.com/article.cfm?id=a-medical-madoff-anesthestesiologist-faked-data&print=true.

How can two (reasonably) well-regarded organisations peer review the same work — Ewen and Pusztai’s research on the effects of feeding genetically modified potatoes to rats — and yet come to such radically opposite conclusions about its validity, as did the Royal Society and The Lancet? All six Royal Society reviewers pronounced the research “flawed”, while five out of six of The Lancet’s reviewers judged that Ewen and Pusztai’s work should be published. Peer review as a reliable technique for assessing the validity of scientific data is surely discredited.

The mistake, of course, is to have thought that peer review was any more than a crude means of discovering the acceptability — not the validity — of a new finding. Editors and scientists alike insist on the pivotal importance of peer review. We portray peer review to the public as a quasi-sacred process that helps to make science our most objective truth teller. But we know that the system of peer review is biased, unjust, unaccountable, incomplete, easily fixed, often insulting, usually ignorant, occasionally foolish, and frequently wrong. A recent editorial in Nature was right to conclude that an over-reliance on peer-reviewed publication “has disadvantages that should be countered by adequate provision of time and resources for independent assessment…”

Genetically modified food: consternation, confusion, and crack-up, Richard Horton, Editor, The Lancet, The Medical Journal of Australia, 2000, http://www.mja.com.au/public/issues/172_04_210200/horton/horton.html.

One suspects that peer review is a bit like democracy – a bad system but the best one possible. It seems to be one that takes different forms in different (scientific) cultures and can be tweaked to improve its operation. Let us hope that future research will discover and disseminate the best ways to fine-tune the system within the constraints of each type of journal.

Quality and value: How can we research peer review?, Joan E. Sieber, Nature, 2006, http://www.nature.com/nature/peerreview/debate/nature05006.html.

Why Most Published Research Findings Are False

 

Nine Hearts

Yes, flies have hearts, in fact they have nine. In some way they are similar to your own heart for their purpose – a muscular pump that moves blood around the body, but in most ways the circulatory system of this insect is a little bizarre.

The principal heart is a muscular tube running down the middle of the fly under the skin. It is closed behind and extends forward through the breast to open behind the head. It has six slits in the abdominal portion, and beats at about 370 times per minute. The blood simply percolates back through the body until it reaches the belly to enter the slits again after several minutes. The blood of the fly carries no oxygen, as red blood cells do in your blood. Flies get their oxygen through a system of tubes connected directly to the atmosphere through 22 small holes along the sides of the fly’s body. When you play hard, your heart must pump faster to supply more oxygen to your muscles, but the heart of a fly does not because oxygen flows directly through the other set of tubes.

While the principal heart helps move blood forward, most movement of blood in insects occurs by simply sloshing around in the open system, and sometimes the principal heart beats backwards, moving blood from the front to the back.

Ignore the Awkward: How the Cholesterol Myths are Kept Alive, Uffe Ravnskov PhD, 2010, http://www.amazon.com/Ignore-Awkward-Cholesterol-Myths-Alive/dp/1453759409.

 

Recent Clinical Trails on Diets

In this study, premenopausal overweight and obese women assigned to follow the Atkins diet, which had the lowest carbohydrate intake, lost more weight and experienced more favorable overall metabolic effects at 12 months than women assigned to follow the Zone, Ornish, or LEARN diets. While questions remain about the long-term effects and mechanisms, a low-carbohydrate, high-protein, high-fat diet may be considered a feasible alternative recommendation for weight loss.

Comparison of the Atkins, Zone, Ornish and LEARN Diets for Change in Weight and Related Risk Factors Among Overweight Premenopausal Women,
Christopher D. Gardner, PhD et al, The Journal of the American Medical Association (JAMA), 2007, http://www.ncbi.nlm.nih.gov/pubmed/17341711?dopt=Abstract&otool=stanford.

http://www.youtube.com/watch?v=eREuZEdMAVo

 

Carbohydrate Withdrawal

When you replace the carbohydrates you eat with fat, you’re creating a radical shift in the fuel that your cells will burn for energy. They go from running primarily on carbohydrates (glucose) to running on fat– both your body fat and the fat in your diet.

As mentioned in passing earlier, insulin signals our kidneys to reabsorb sodium, which in turn causes water retention and raises blood pressure. When insulin levels drop, as they do when we restrict carbohydrates, our kidneys will excrete the sodium they’ve been retaining and with it water. For most people this is beneficial, and it’s the reason why blood pressure comes down with carbohydrate restriction. For some individuals, though, the body will perceive the water loss as something to be prevented. It does so through a web of compensatory responses that can lead to water retention and what are called electrolyte imbalances (the kidneys excrete potassium to save sodium), and the results are [the potential side effects of weakness, fatigue, nausea, dehydration, diarrhea, constipation and dizziness when standing up quickly]. The reaction can be countered by adding sodium back into the diet: taking a gram or two of sodium a day (a half to one teaspoon of salt) or drinking a couple of cups of chicken or beef broth daily.

If you happen to be diabetic or hypertensive, then a doctor’s guidance is critical. Since restricting carbohydrates will lower both blood sugar and blood pressure, if you’re already taking drugs to do the same, the combination can be dangerous. Abnormally low blood sugar (known as hypoglycemia) can cause seizures, unconsciousness, and even death. Abnormally low blood pressure (hypotension) can induce dizziness, fainting, and seizures.

The potential side effects of carbohydrate withdrawal confuse the short-term effects with the long-term benefits of overcoming that withdrawal. The more technical term for carbohydrate withdrawal is keto-adaptation, because the body is adapting to the state of ketosis that results from eating fewer carbohydrates. These symptoms have nothing to do with the high fat content of the diet. Rather, they appear to be a consequence of either eating too much protein and too little fat, of attempting strenuous exercise without taking the time to adapt to the diet, or, in most cases, of the body’s failure to compensate fully for the restriction of carbohydrates and the dramatic lowering of insulin levels that ensue… It’s like telling smokers who are trying to quit that their withdrawal symptoms are caused by a ‘need for cigarettes’ and then suggesting they go back to smoking to solve the problem.

Why We Get Fat, Gary Taubes, 2010, http://www.amazon.com/Why-We-Get-Fat-About/dp/0307272702.

 

Lipophilia, Insulin, Progressive Lipodystrophy

The reason for this book is straightforward: despite the depth and certainty of our faith that saturated fat is the nutritional bane of our lives and that obesity is caused by overeating and sedentary behavior, there has always been copious evidence to suggest that those assumptions are incorrect, and that evidence is continuing to mount… Moreover, it’s also quite possible that the low-fat, high-carbohydrate diets we’ve been told to eat for the past thirty years are not only making us heavier but contributing to other chronic diseases as well.

Heart-disease death rates have indeed dropped… but there is little evidence that the incidence of heart disease has declined, as would be expected if eating less fat made a difference… The New England Journal of Medicine in 1998… suggested that the death rates are declining largely because doctors and emergency-medical-service personnel are treating the disease more successfully…

The Minnesota Coronary Survey was, by far, the largest diet-heart trial carried out in the United States… the results of the study went unpublished for sixteen years, by which time the controversy had been publicly settled. The principal investigator on the trial was Ivan Frantz, Jr… Frantz retired in 1988 and published the results a year later… Half of the patients were served a typical American diet, and half a cholesterol-lowering diet… it was low in saturated fat and dietary cholesterol and high in polyunsaturated fat… Men on the diet had a slightly lower rate of heart attacks, but the women had more. Overall, the cholesterol-lowering diet was associated with an increased rate of heart disease… When I asked Frantz in late 2003 why the study went unpublished for sixteen years, he said, “We were just disappointed in the way it came out.”

Good Calories, Bad Calories, Gary Taubes, 2007, http://www.amazon.com/Good-Calories-Bad-Challenging-Conventional/dp/1400040787.

Productivity in Heart Attack Treatments, Economic Research, Federal Reserve Bank of San Francisco, July 5, 2002, http://www.u.arizona.edu/~gowrisan/pdf_papers/heartattacktreatments.pdf.

Hospitalization Rates for Heart Failure, Ages 45–64 and 65 and Older, U.S., 1971–2005

Age-Adjusted Prevalence of Cardiovascular Disease Risk Factors in Adults, U.S., 1961–2004

Deaths From Cardiovascular Diseases, U.S., 1900–2005

Deaths Attributed to Heart Failure,* U.S., 1970–2004

NHLBI Factbook, National Heart Lung and Blood Institute, Fiscal Year 2007, http://www.nhlbi.nih.gov/about/factbook-07/chapter4.htm.

Globally, there are more than 1 billion overweight adults, at least 300 million of them obese.

Obesity and Overweight, World Health Organization, 2003, http://www.who.int/hpr/NPH/docs/gs_obesity.pdf.

Obesity, Type 2 Diabetes, and Fructose, Department of Biology, Indiana University, 2010, http://www.indiana.edu/~oso/Fructose/Fructose.html.

 

Feminism and Libertarianism

Libertarian temptations to the contrary notwithstanding, it makes no sense to regard the state as the root of all social evil, for there is at least one social evil that cannot be blamed on the state — and that is the state itself. If no social evil can arise or be sustained except by the state, how does the state arise, and how is it sustained? As libertarians from La Boétie to Rothbard have rightly insisted, since rulers are generally outnumbered by those they rule, the state itself cannot survive except through popular acceptance which the state lacks the power to compel; hence state power is always part of an interlocking system of mutually reinforcing social practices and structures, not all of which are violations of the nonaggression axiom. There is nothing un-libertarian, then, in recognizing the existence of economic and/or cultural forms of oppression which, while they may draw sustenance from the state (and vice versa), are not reducible to state power. One can see statism and patriarchy as mutually reinforcing systems (thus ruling out both the option of fighting statism while leaving patriarchy intact, and the option of fighting patriarchy by means of statism) without being thereby committed to seeing either as a mere epiphenomenon of the other (thus ruling out the option of fighting patriarchy solely indirectly by fighting statism)…

The relationship between libertarianism and feminism has not always been so chilly… For Dunoyer, primitive patriarchy constituted a system in which a parasitic governmental élite, the men, made their living primarily by taxing, regulating, and conscripting a productive and industrious laboring class, the women. Herbert Spencer concurred:

The slave-class in a primitive society consists of the women; and the earliest division of labour is that which arises between them and their masters. For a long time no other division of labour exists.

Moreover, Spencer saw an intimate connection between the rise of patriarchy and the rise of militarism… Accordingly, Spencer likewise saw the replacement of militarized hierarchical societies by more market-oriented societies based on commerce and mutual exchange as closely allied with the decline of patriarchy in favor of increasing sexual equality; changing power relations within the family and changing power relations within the broader society stood in relations of interdependence.

To the same extent that the triumph of might over right is seen in a nation’s political institutions, it is seen in its domestic ones. Despotism in the state is necessarily associated with despotism in the family.

[I]n as far as our laws and customs violate the rights of humanity by giving the richer classes power over the poorer, in so far do they similarly violate those rights by giving the stronger sex power over the weaker… To the same extent that the old leaven of tyranny shows itself in the transactions of the senate, it will creep out in the doings of the household. If injustice sways men’s public acts, it will inevitably sway their private ones also. The mere fact, therefore, that oppression marks the relationships of out-door life, is ample proof that it exists in the relationships of the fireside.

Spencer, for his part, did not confine attention to those forms of patriarchal oppression that were literally violent or coercive in the sense of violating libertarian rights; he denounced not only the legal provision that “a husband may justly take possession of his wife’s earnings against her will” or the “statute, which permits a man to beat his wife in moderation and to imprison her in any room in his house,” but the entire system of economic and cultural expectations and institutions within which violent forms of oppression were embedded. He complained, for example, of a variety of factors—more often cultural than legal—that systematically stunted women’s education and intellectual development, including such facts as that women “are not admissible to the academies and universities in which men get their training,” that “the kind of life they have to look forward to, does not present so great a range of ambitions,” that “they are rarely exposed to that most powerful of all stimuli — necessity,” that “the education custom dictates for them is one that leaves uncultivated many of the higher faculties,” and that “the prejudice against blue-stockings, hitherto so prevalent amongst men, has greatly tended to deter women from the pursuit of literary honours.” In the same way he protested against the obstacles to women’s physical health and well-being deriving from patriarchal norms of feminine attractiveness and propriety that promoted in the training of girls “a certain delicacy, a strength not competent to more than a mile or two’s walk, an appetite fastidious and easily satisfied, joined with that timidity which commonly accompanies feebleness.”

The 19th-century libertarians’ attitude toward (what was called) the “woman question” has much in common with their attitude toward the (analogously labeled) “labor question.” 19th-century libertarians generally saw the existing capitalist order as a denial, rather than as an expression, of the free market. For most of these thinkers, “capitalism” meant, not economic laissez-faire (which as libertarians they favored), but rather government intervention in the marketplace on behalf of capitalists at the expense of laborers and consumers, and they condemned it accordingly as the chief prop of plutocratic class oppression. But rather than simply calling for an end to pro-business legislation, they also favored private cooperative action by workers to improve their bargaining power vis-à-vis employers or indeed to transcend the wage system altogether; hence their support for the labor movement, workers’ cooperatives, and the like. Similarly, while calling for an end to legislation that discriminated against women, 19th-century libertarians like Spencer did not confine themselves to that task, but also, as we’ve seen, addressed the economic and cultural barriers to gender equality, “private” barriers which they saw as operating in coordination with the governmental barriers…

As historians of second-wave feminism such as Susan Brownmiller have shown, many of radical feminism’s most striking achievements were brought about through efforts that were both clearly political in nature but also independent of State political processes—such as consciousness-raising groups, “ogle-ins” and WITCH “hexes” against street harassment and sexist businesses, and the creation of autonomous women-run institutions such as cooperative day-care centers, women’s health collectives, and the first battered women’s shelters and rape crisis centers.

The 19th-century libertarians would thus not have been surprised to learn that, in our day, anti-pornography law written with feminist intentions has been applied by male police and male judges to censor feminist publications, or that sex discrimination law has, in the hands of male legislators and judges, been used to reverse 19th century feminist gains in custody and divorce law. Hand the he-ist state a club, and you can be sure the club will be used in a he-ist manner.

Since the 19th century, libertarianism and feminism have largely parted ways — perhaps, in part, because libertarians allowed the advance of state socialism in the early 20th century to drive them into an alliance with conservatives, an alliance from which libertarians could not hope to emerge unmarked. (Few libertarians today even remember that their 19th-century predecessors often called their position “voluntary socialism” — “socialism” to contrast it, not with the free market, but with actually existing capitalism, and “voluntary” to contrast it both with state socialism and with anti-market versions of anarchist socialism.)

Since this parting of ways, feminists have developed increasingly sophisticated analyses and demystifications of patriarchy, but their understanding of statism has grown correspondingly blurred; libertarians have developed increasingly sophisticated analyses and demystifications of statism, but their understanding of patriarchy has grown correspondingly blurred. A 19th-century libertarian feminist, if resurrected today, might thus have much to learn from today’s libertarians about how statism works, and from today’s feminists about how patriarchy works; but she or he would doubtless also see present-day feminists as, all too often, extraordinarily insensitive to the pervasive and inherently destructive effects of state hegemony per se, and present-day libertarians as, all too often, extraordinarily insensitive to the pervasive and inherently destructive effects of male hegemony per se. A contemporary marriage, or remarriage, of feminism with libertarianism thus seems a consummation devoutly to be wished — but not if it is now to be a patriarchal marriage, one in which the feminism is subordinated to or absorbed into or muffled by the libertarianism, a marriage in which one party retains, while the other renounces, its radical edge. Our concern about the nature of libertarian feminism in its contemporary form is precisely that it tends to represent this sort of unequal union.

Why not follow the 19th-century libertarians, who neither denied the existence and importance of private discrimination, nor assimilated it to legal compulsion? There is nothing inconsistent or un-libertarian in holding that women’s choices under patriarchal social structures can be sufficiently “voluntary,” in the libertarian sense, to be entitled to immunity from coercive legislative interference, while at the same time being sufficiently “involuntary,” in a broader sense, to be recognized as morally problematic and as a legitimate target of social activism.

Libertarianism and feminism are, then, two traditions—and, at their best, two radical traditions—with much in common, and much to offer one another. We applaud the efforts of those who have sought to bring them back together; but too often, in our judgment, such efforts have proceeded on the assumption that the libertarian tradition has everything to teach the feminist tradition and nothing to learn from it. Feminists have no reason to embrace a union on such unequal terms. Happily, they need not. If libertarian feminists have resisted some of the central insights of the feminist tradition, it is in large part because they have feared that acknowledging those insights would mean abandoning some of the central insights of the libertarian tradition. But what the example of the 19th century libertarian feminists should show us—and should help to illuminate (to both libertarians and feminists) in the history of Second Wave feminism—is that the libertarian critique of state power and the feminist critique of patriarchy are complementary, not contradictory. The desire to bring together libertarianism and feminism need not, and should not, involve calling on either movement to surrender its identity for the sake of decorum. This marriage can be saved: as it should be, a marriage of self-confident, strong-willed, compassionate equals.

Libertarian Feminism: Can This Marriage Be Saved?, Roderick Long and Charles Johnson, May 1st, 2005, http://charleswjohnson.name/essays/libertarian-feminism/.

The things the men’s movement has wanted are things worth having. Intimacy is worth having. Tenderness is worth having. Cooperation is worth having. A real emotional life is worth having. But you can’t have them in a world with rape. Ending homophobia is worth doing. But you can’t do it in a world with rape. Rape stands in the way of each and every one of those things you say you want. And by rape you know what I mean. A judge does not have to walk into this room and say that according to statute such and such these are the elements of proof. We’re talking about any kind of coerced sex, including sex coerced by poverty.

I Want a Twenty-Four-Hour Truce, During Which There Is No Rape, Andrea Dworkin, 1983, http://www.nostatusquo.com/ACLU/dworkin/WarZoneChaptIIIE.html.

 

Saturated Fat, Cholesterol, and Heart Disease

http://www.youtube.com/watch?v=exi7O1li_wA&list=PLFA5DF26671114F37

In 2001, rumors were circulating in Greek hospitals that surgery residents, eager to rack up scalpel time, were falsely diagnosing hapless Albanian immigrants with appendicitis. At the University of Ioannina medical school’s teaching hospital, a newly minted doctor named Athina Tatsioni… eventually produced a formal study showing that, for whatever reason, the appendices removed from patients with Albanian names in six Greek hospitals were more than three times as likely to be perfectly healthy as those removed from patients with Greek names…

[John Ioannidis] first stumbled on the sorts of problems plaguing the field, he explains, as a young physician-researcher in the early 1990s at Harvard. At the time, he was interested in diagnosing rare diseases, for which a lack of case data can leave doctors with little to go on other than intuition and rules of thumb. But he noticed that doctors seemed to proceed in much the same manner even when it came to cancer, heart disease, and other common ailments. Where were the hard data that would back up their treatment decisions? There was plenty of published research, but much of it was remarkably unscientific, based largely on observations of a small number of cases. A new “evidence-based medicine” movement was just starting to gather force, and Ioannidis decided to throw himself into it, working first with prominent researchers at Tufts University and then taking positions at Johns Hopkins University and the National Institutes of Health. He was unusually well armed: he had been a math prodigy of near-celebrity status in high school in Greece, and had followed his parents, who were both physician-researchers, into medicine. Now he’d have a chance to combine math and medicine by applying rigorous statistical analysis to what seemed a surprisingly sloppy field. “I assumed that everything we physicians did was basically right, but now I was going to help verify it,” he says. “All we’d have to do was systematically review the evidence, trust what it told us, and then everything would be perfect.”

It didn’t turn out that way. In poring over medical journals, he was struck by how many findings of all types were refuted by later findings. Of course, medical-science “never minds” are hardly secret. And they sometimes make headlines, as when in recent years large studies or growing consensuses of researchers concluded that mammograms, colonoscopies, and PSA tests are far less useful cancer-detection tools than we had been told; or when widely prescribed antidepressants such as Prozac, Zoloft, and Paxil were revealed to be no more effective than a placebo for most cases of depression; or when we learned that staying out of the sun entirely can actually increase cancer risks; or when we were told that the advice to drink lots of water during intense exercise was potentially fatal; or when, last April, we were informed that taking fish oil, exercising, and doing puzzles doesn’t really help fend off Alzheimer’s disease, as long claimed. Peer-reviewed studies have come to opposite conclusions on whether using cell phones can cause brain cancer, whether sleeping more than eight hours a night is healthful or dangerous, whether taking aspirin every day is more likely to save your life or cut it short, and whether routine angioplasty works better than pills to unclog heart arteries.

But beyond the headlines, Ioannidis was shocked at the range and reach of the reversals he was seeing in everyday medical research. “Randomized controlled trials,” which compare how one group responds to a treatment against how an identical group fares without the treatment, had long been considered nearly unshakable evidence, but they, too, ended up being wrong some of the time. “I realized even our gold-standard research had a lot of problems,” he says. Baffled, he started looking for the specific ways in which studies were going wrong. And before long he discovered that the range of errors being committed was astonishing: from what questions researchers posed, to how they set up the studies, to which patients they recruited for the studies, to which measurements they took, to how they analyzed the data, to how they presented their results, to how particular studies came to be published in medical journals.

This array suggested a bigger, underlying dysfunction, and Ioannidis thought he knew what it was. “The studies were biased,” he says. “Sometimes they were overtly biased. Sometimes it was difficult to see the bias, but it was there.” Researchers headed into their studies wanting certain results—and, lo and behold, they were getting them. We think of the scientific process as being objective, rigorous, and even ruthless in separating out what is true from what we merely wish to be true, but in fact it’s easy to manipulate results, even unintentionally or unconsciously. “At every step in the process, there is room to distort results, a way to make a stronger claim or to select what is going to be concluded,” says Ioannidis. “There is an intellectual conflict of interest that pressures researchers to find whatever it is that is most likely to get them funded.” …

In 2005, he… laid out a detailed mathematical proof that, assuming modest levels of researcher bias, typically imperfect research techniques, and the well-known tendency to focus on exciting rather than highly plausible theories, researchers will come up with wrong findings most of the time. Simply put, if you’re attracted to ideas that have a good chance of being wrong, and if you’re motivated to prove them right, and if you have a little wiggle room in how you assemble the evidence, you’ll probably succeed in proving wrong theories right. His model predicted, in different fields of medical research, rates of wrongness roughly corresponding to the observed rates at which findings were later convincingly refuted: 80 percent of non-randomized studies (by far the most common type) turn out to be wrong, as do 25 percent of supposedly gold-standard randomized trials, and as much as 10 percent of the platinum-standard large randomized trials…

Sure, a lot of dubious research makes it into journals, but we researchers and physicians know to ignore it and focus on the good stuff, so what’s the big deal? The other paper headed off that claim. He zoomed in on 49 of the most highly regarded research findings in medicine over the previous 13 years, as judged by the science community’s two standard measures: the papers had appeared in the journals most widely cited in research articles, and the 49 articles themselves were the most widely cited articles in these journals. These were articles that helped lead to the widespread popularity of treatments such as the use of hormone-replacement therapy for menopausal women, vitamin E to reduce the risk of heart disease, coronary stents to ward off heart attacks, and daily low-dose aspirin to control blood pressure and prevent heart attacks and strokes. Ioannidis was putting his contentions to the test not against run-of-the-mill research, or even merely well-accepted research, but against the absolute tip of the research pyramid. Of the 49 articles, 45 claimed to have uncovered effective interventions. Thirty-four of these claims had been retested, and 14 of these, or 41 percent, had been convincingly shown to be wrong or significantly exaggerated. If between a third and a half of the most acclaimed research in medicine was proving untrustworthy, the scope and impact of the problem were undeniable. That article was published in the Journal of the American Medical Association…

Studies have gone back and forth on the cancer-preventing powers of vitamins A, D, and E; on the heart-health benefits of eating fat and carbs; and even on the question of whether being overweight is more likely to extend or shorten your life. How should we choose among these dueling, high-profile nutritional findings? Ioannidis suggests a simple approach: ignore them all…

“If we don’t tell the public about these problems, then we’re no better than nonscientists who falsely claim they can heal,” he says. “If the drugs don’t work and we’re not sure how to treat something, why should we claim differently? Some fear that there may be less funding because we stop claiming we can prove we have miraculous treatments. But if we can’t really provide those miracles, how long will we be able to fool the public anyway? The scientific enterprise is probably the most fantastic achievement in human history, but that doesn’t mean we have a right to overstate what we’re accomplishing.”

We could solve much of the wrongness problem, Ioannidis says, if the world simply stopped expecting scientists to be right. That’s because being wrong in science is fine, and even necessary—as long as scientists recognize that they blew it, report their mistake openly instead of disguising it as a success, and then move on to the next thing, until they come up with the very occasional genuine breakthrough. But as long as careers remain contingent on producing a stream of research that’s dressed up to seem more right than it is, scientists will keep delivering exactly that.

“Science is a noble endeavor, but it’s also a low-yield endeavor,” he says. “I’m not sure that more than a very small percentage of medical research is ever likely to lead to major improvements in clinical outcomes and quality of life. We should be very comfortable with that fact.”

Lies, Damned Lies, and Medical Science, The Atlantic, November 2010, http://www.theatlantic.com/magazine/print/2010/11/lies-damned-lies-and-medical-science/8269/.

Chronic diseases are much more difficult to deal with than acute diseases. It is more difficult to establish causal relations unambiguously; it is more time consuming and expensive to prove efficacy of treatment…

Even though many of the early clinical trials yielded positive results, those results were unconvincing. The numbers were small and the design was in many cases flawed… The data from the early clinical trials of diet and drug treatment of hypercholesterolemia were suggestive but, admittedly, not conclusive. However, those data, considered in the context of the extensive epidemiologic and experimental evidence, strongly suggested that hypercholesterolemia was indeed causative and that intervention would have a beneficial effect. That turned out to be the case. We can anticipate that this kind of issue will recur. While it may seem “antiscientific,” it may be not only justifiable but necessary to consider all relevant lines of evidence in reaching a judgment. That judgment will take into account not only the strength of the evidence for a causative relation, but also the kind of intervention, its risks, and its potential benefits. Like most medical decisions, it will have to be made using common sense as well as statistical analyses.

The cholesterol controversy is over. Why did it take so long?, Daniel Steinberg, MD, PhD, Circulation, 1989, http://circ.ahajournals.org/content/80/4/1070.full.pdf.

 

Epidemiology

By the mid-1990s, the American Heart Association, the American College of Physicians and the American College of Obstetricians and Gynecologists had all concluded that the beneficial effects of [hormone-replacement therapy] (H.R.T.) were sufficiently well established that it could be recommended to older women as a means of warding off heart disease and osteoporosis. By 2001, 15 million women were filling H.R.T. prescriptions annually; perhaps 5 million were older women, taking the drug solely with the expectation that it would allow them to lead a longer and healthier life. A year later, the tide would turn. In the summer of 2002, estrogen therapy was exposed as a hazard to health rather than a benefit, and its story became what Jerry Avorn, a Harvard epidemiologist, has called the “estrogen debacle” and a “case study waiting to be written” on the elusive search for truth in medicine…

In the case of H.R.T., as with most issues of diet, lifestyle and disease, the hypotheses begin their transformation into public-health recommendations only after they’ve received the requisite support from a field of research known as epidemiology. This science evolved over the last 250 years to make sense of epidemics — hence the name — and infectious diseases. Since the 1950s, it has been used to identify, or at least to try to identify, the causes of the common chronic diseases that befall us, particularly heart disease and cancer. In the process, the perception of what epidemiologic research can legitimately accomplish — by the public, the press and perhaps by many epidemiologists themselves — may have run far ahead of the reality. The case of hormone-replacement therapy for post-menopausal women is just one of the cautionary tales in the annals of epidemiology. It’s a particularly glaring example of the difficulties of trying to establish reliable knowledge in any scientific field with research tools that themselves may be unreliable… the question of how many women may have died prematurely or suffered strokes or breast cancer because they were taking a pill that their physicians had prescribed to protect them against heart disease lingers unanswered. A reasonable estimate would be tens of thousands… between 2002 and 2004, breast cancer incidence in the United States dropped by 12 percent, an effect that may have been caused by the coincident decline in the use of H.R.T. (And it may not have been. The coincident reduction in breast cancer incidence and H.R.T. use is only an association.)…

At the center of the H.R.T. story is the science of epidemiology itself and, in particular, a kind of study known as a prospective or cohort study, of which the Nurses’ Health Study is among the most renowned. In these studies, the investigators monitor disease rates and lifestyle factors (diet, physical activity, prescription drug use, exposure to pollutants, etc.) in or between large populations (the 122,000 nurses of the Nurses’ study, for example). They then try to infer conclusions — i.e., hypotheses — about what caused the disease variations observed. Because these studies can generate an enormous number of speculations about the causes or prevention of chronic diseases, they provide the fodder for much of the health news that appears in the media — from the potential benefits of fish oil, fruits and vegetables to the supposed dangers of sedentary lives, trans fats and electromagnetic fields. Because these studies often provide the only available evidence outside the laboratory on critical issues of our well-being, they have come to play a significant role in generating public-health recommendations as well.

The dangerous game being played here, as David Sackett, a retired Oxford University epidemiologist, has observed, is in the presumption of preventive medicine. The goal of the endeavor is to tell those of us who are otherwise in fine health how to remain healthy longer. But this advice comes with the expectation that any prescription given — whether diet or drug or a change in lifestyle — will indeed prevent disease rather than be the agent of our disability or untimely death. With that presumption, how unambiguous does the evidence have to be before any advice is offered?

The catch with observational studies like the Nurses’ Health Study, no matter how well designed and how many tens of thousands of subjects they might include, is that they have a fundamental limitation. They can distinguish associations between two events — that women who take H.R.T. have less heart disease, for instance, than women who don’t. But they cannot inherently determine causation — the conclusion that one event causes the other; that H.R.T. protects against heart disease. As a result, observational studies can only provide what researchers call hypothesis-generating evidence — what a defense attorney would call circumstantial evidence.

Testing these hypotheses in any definitive way requires a randomized-controlled trial — an experiment, not an observational study — and these clinical trials typically provide the flop to the flip-flop rhythm of medical wisdom. Until August 1998, the faith that H.R.T. prevented heart disease was based primarily on observational evidence, from the Nurses’ Health Study most prominently. Since then, the conventional wisdom has been based on clinical trials — first HERS, which tested H.R.T. against a placebo in 2,700 women with heart disease, and then the Women’s Health Initiative, which tested the therapy against a placebo in 16,500 healthy women. When the Women’s Health Initiative concluded in 2002 that H.R.T. caused far more harm than good, the lesson to be learned, wrote Sackett in The Canadian Medical Association Journal, was about the “disastrous inadequacy of lesser evidence” for shaping medical and public-health policy. The contentious wisdom circa mid-2007 — that estrogen benefits women who begin taking it around the time of menopause but not women who begin substantially later — is an attempt to reconcile the discordance between the observational studies and the experimental ones. And it may be right. It may not. The only way to tell for sure would be to do yet another randomized trial, one that now focused exclusively on women given H.R.T. when they begin their menopause…

These studies have also been invaluable for identifying predictors of disease — risk factors — and this information can then guide physicians in weighing the risks and benefits of putting a particular patient on a particular drug. The studies have repeatedly confirmed that high blood pressure is associated with an increased risk of heart disease and that obesity is associated with an increased risk of most of our common chronic diseases, but they have not told us what it is that raises blood pressure or causes obesity. Indeed, if you ask the more skeptical epidemiologists in the field what diet and lifestyle factors have been convincingly established as causes of common chronic diseases based on observational studies without clinical trials, you’ll get a very short list: smoking as a cause of lung cancer and cardiovascular disease, sun exposure for skin cancer, sexual activity to spread the papilloma virus that causes cervical cancer and perhaps alcohol for a few different cancers as well.

Richard Peto, professor of medical statistics and epidemiology at Oxford University, phrases the nature of the conflict this way: “Epidemiology is so beautiful and provides such an important perspective on human life and death, but an incredible amount of rubbish is published,” by which he means the results of observational studies that appear daily in the news media and often become the basis of public-health recommendations about what we should or should not do to promote our continued good health…

While the tools of epidemiology — comparisons of populations with and without a disease — have proved effective over the centuries in establishing that a disease like cholera is caused by contaminated water, as the British physician John Snow demonstrated in the 1850s, it’s a much more complicated endeavor when those same tools are employed to elucidate the more subtle causes of chronic disease.

And even the success stories taught in epidemiology classes to demonstrate the historical richness and potential of the field — that pellagra, a disease that can lead to dementia and death, is caused by a nutrient-deficient diet, for instance, as Joseph Goldberger demonstrated in the 1910s — are only known to be successes because the initial hypotheses were subjected to rigorous tests and happened to survive them. Goldberger tested the competing hypothesis, which posited that the disease was caused by an infectious agent, by holding what he called “filth parties,” injecting himself and seven volunteers, his wife among them, with the blood of pellagra victims. They remained healthy, thus doing a compelling, if somewhat revolting, job of refuting the alternative hypothesis…

All of this suggests that the best advice is to keep in mind the law of unintended consequences. The reason clinicians test drugs with randomized trials is to establish whether the hoped-for benefits are real and, if so, whether there are unforeseen side effects that may outweigh the benefits. If the implication of an epidemiologist’s study is that some drug or diet will bring us improved prosperity and health, then wonder about the unforeseen consequences. In these cases, it’s never a bad idea to remain skeptical until somebody spends the time and the money to do a randomized trial and, contrary to much of the history of the endeavor to date, fails to refute it.

Do We Really Know What Makes Us Healthy?, Gary Taubes, The New York Times Magazine, September 16, 2007, http://gemini.econ.umd.edu/jrust/econ623/files/econ623/16epidemiology-t.html.

 

The Rational Optimist


I have presented the case for sunny optimism. I have argued that now that the world is networked, and ideas are having sex with each other more promiscuously than ever, the pace of innovation will redouble and economic evolution will raise the living standards of the twenty-first century to unimagined heights, helping even the poorest people of the world to afford to meet their desires as well as their needs. I have argued that although such optimism is distinctly unfashionable, history suggests it is actually a more realistic attitude than apocalyptic pessimism. ‘It is the long ascent of the past that gives the lie to our despair,’ said H.G. Wells.

These are great sins against conventional wisdom. Worse, they may even leave the impression of callous indifference to the fact that a billion people have not enough to eat, that a billion lack access to clean water, that a billion are illiterate. The opposite is true… It is precisely this ‘evitable’ misery that is the reason for pressing on urgently with economic progress, innovation and change, the only known way of bringing the benefits of a rising living standard to many more people. It is precisely because there is so much poverty, hunger and illness that the world must be very careful not to get in the way of the things that have bettered so many lives already — the tools of trade, technology and trust, of specialisation and exchange. It is precisely because there is still so much further to go that those who offer counsels of despair or calls to slow down in the face of looming environmental disaster may be not only factually but morally wrong…

Take the twelfth century as an example of how close the world once came to turning its back on the catallaxy. In one fifty-year period, between 1100 and 1150, three great nations shut down innovation, enterprise and freedom all at once. In Baghdad, the religious teacher Al-Ghazali almost single-handedly destroyed the tradition of rational enquiry in the Arab world and led a return to mysticism intolerant of new thinking. In Peking, Su-Sung’s astronomical clock, the ‘cosmic engine’, probably the most sophisticated mechanical device ever built to that date, was destroyed by a politician suspicious of novelty and reason, setting the tone for the retreat to autarky and tradition that would be China’s fate for centuries to come. In Paris, St. Bernard of Clairvaux persecuted the scholar Peter Abelard, criticised the rational renaissance centred on the University of Paris and supported the disastrous fanaticism of the second crusade. Fortunately, the flames of free thought and reason and catallaxy were kept burning — in Italy and North Africa, especially…

The wrong kind of chiefs, priests and thieves could yet snuff out future prosperity on Earth. Already lords don boiler suits to destroy genetically modified crops, presidents scheme to prevent stem-cell research, prime ministers trample on habeas corpus using the excuse of terrorism, metastasising bureaucrats interfere with innovation on behalf of reactionary pressure groups, superstitious creationists stop the teaching of good science, air-headed celebrities rail against free trade, mullahs inveigh against the empowerment of women, earnest princes lament the loss of old ways and pious bishops regret the coarsening effects of commerce. So far they are all sufficiently localised in their effects to achieve no more than limited pauses… but could one of them go global?

I doubt it. It will be hard to snuff out the flame of innovation, because it is such an evolutionary, bottom-up phenomenon in such a networked world… So long as human exchange and specialisation are allowed to thrive somewhere, then culture evolves whether leaders help it or hinder it, and the result is that prosperity spreads, technology progresses, poverty declines, disease retreats, fecundity falls, happiness increases, violence atrophies, freedom grows, knowledge flourishes, the environment improves and wilderness expands. Said Lord Macaulay, “We see in almost every part of the annals of mankind how the industry of individuals, struggling up against wars, taxes, famines, conflagrations, mischievous prohibitions, and more mischievous protections, creates faster than governments can squander, and repairs whatever invaders can destroy.”

Human nature will not change. The same old dramas of aggression and addiction, of infatuation and indoctrination, of charm and harm, will play out, but in an ever more prosperous world… So the human race will continue to expand and enrich its culture, despite setbacks and despite individual people having much the same evolved, unchanging nature. The twenty-first century will be a magnificent time to be alive.

Dare to be an optimist.

The Rational Optimist, Matt Ridley, 2010, Pages 180-184, http://www.amazon.com/Rational-Optimist-How-Prosperity-Evolves/dp/006145205X.