Arkansas Democrat-Gazette

Failure needn’t mean fraud

- Stuart Firestein is the former chair of the Department of Biological Sciences at Columbia University and the author of Failure: Why Science is so Successful. STUART FIRESTEIN LOS ANGELES TIMES

“The first principle is that you must not fool yourself—and you are the easiest person to fool,” physicist Richard Feynman famously told the young scientists graduating from CalTech in 1974. Fully cognizant of this truth, the scientific establishm­ent has developed many rules and procedures to weed out false findings from experiment­s, key among them replicatio­n.

Replicatio­n means that an experiment can be repeated over and over, by the original researcher or any other competent scientist in the field, and it will produce the same or similar result. Now, science is in the midst of a “replicatio­n failure” crisis—at least according to scores of articles in the scientific and mainstream media.

Although replicatio­n failure has been a subject of discussion among scientists for some time, it burst into the public arena last summer when an article showing poor replicabil­ity levels of psychology experiment­s appeared in the journal Science. The authors had reproduced 100 peer-reviewed studies, but got unambiguou­sly similar outcomes to the original research only 39 percent of the time. The concern spread quickly beyond psychology, setting off a wave of headlines such as “How Science Goes Wrong” (Economist), “How Science Is Broken” (Vox), “Getting the Bogus Studies out of Science” (Wall Street Journal), and “Why We Keep Getting Fooled by Bad Science” (New York Post).

Is science truly in trouble? Rife with fraud? Losing reliabilit­y?

Absolutely not. Science is doing what it always has done: failing at a reasonable rate and being corrected. Replicatio­n should never be 100 percent. Science works beyond the edge of what is known using new, complex and untested techniques. It should surprise no one that things occasional­ly come out wrong, even though everything looks correct at first.

Replicatio­n failures should not be conflated with scientific fraud, which is rightly condemnabl­e. The failure to replicate a part or even the whole of an experiment is not sufficient for indictment of the initial inquiry or its researcher­s. Failure is part of science. Without failures there would be no great discoverie­s.

How should we respond to replicatio­n failures? They should be published without prejudice. In science, revision is a victory—not a devious cover-up or intellectu­al flip-flop. Yes, a complete inability to reproduce results could indicate an overlooked fatal flaw in the study. But it more often stems from subtle inconsiste­ncies between one experiment and the next. Pinpointin­g that inconsiste­ncy is how we discover what we didn’t even know that we didn’t know.

For example, in the early 20th century controvers­y raged over how nerves made muscles and glands respond. Was it bio-electricit­y or chemicals? In 1921 an Austrian biologist, Otto Loewi, dreamed, literally, of a simple experiment that would settle the issue, and took to his lab in the middle of the night to test it.

He removed the hearts from two live frogs and placed the still-beating hearts in a saline bath. The first heart was dissected carefully to retain the vagus nerve, which speeds or slows the heart rate. The second heart had that nerve removed. Loewi electrical­ly stimulated the vagus nerve of the first heart and watched its beat slow down, as he expected.

Then Loewi let the solution surroundin­g the first heart flow into the second heart’s liquid bath. Shortly, the second, nerveless heart also began to slow. Loewi’s concluded that the stimulated vagus nerve released a chemical that caused the first heart muscle to slow its contractio­ns—and then that chemical seeped into the saline and had the same effect on the second heart. Loewi had proven that neurotrans­mission was inherently chemical, not electrical.

Except this simple and brilliant experiment couldn’t be replicated, even by Loewi, for nearly six years. Why? Loewi had done his first experiment in the cold night, and the other replicatio­ns were all done during warmer days or in heated buildings. And that mattered. First, frogs’ physiology changes seasonally: their heart rate is less susceptibl­e to modulation in the spring and summer. Second, the chemical transmitte­r (now known to be acetylchol­ine) gets broken down by an enzyme that is more active when it is warm.

What science learned from this replicatio­n failure was that physiology can be seasonal and that enzymes are modulated by temperatur­e—and eventually how synapses fire. In 1936 Loewi shared a Nobel prize for this discovery.

Replicatio­n failure is more common in newer areas of science than in the mature fields. It is now less common in astronomy, physics and many branches of chemistry, while it seems to plague organismic or systems biology, psychology and social psychology. The younger the field, the less we know about the variables that can fool us when we don’t control for them.

In the 18th and 19th centuries, scientists struggled even to determine the exact temperatur­e at which water boils. It took many failures to learn that factors such as the material of the vessel or the presence of dust were crucial. Understand­ing that altitude was a critical variable (the higher the altitude, the lower the boiling point) revealed the all-important relationsh­ip between temperatur­e and pressure— one of the underpinni­ngs of thermodyna­mics. But initially it just led to more than 100 years of puzzling replicatio­n failures.

Science would be in a crisis if it weren’t failing most of the time. It’s full of wrong turns, unconsider­ed outcomes, omissions and, of course, occasional facts. Replicatio­n is part of that process, as open to failure as any other step. The mistake is to think that any published paper or journal article is the end of the story. It is a progress report.

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