The best science is often accidental

Thirty years ago a group of Japanese scientists published a DNA sequence that they didn't understand. The DNA came from a common bacterium called E. coli and contained a set of repeating sequences separated by spacer regions. As similar sequences were subsequently recognized in other bacteria, they became known as “clustered regularly interspaced short palindromic repeats,” or CRISPR for short. Eventually it was realized that CRISPR sequences are part of a bacterial immune system that protects bacterial cells from viruses. In just the past five years, other scientists have discovered that the same system can be used to edit DNA, and the CRISPR revolution is now finding widespread applications in medicine and agriculture.

The Japanese scientists who discovered the CRISPR system never dreamed that their work could eventually lead to new treatments for cancer or the creation of improved crops. They simply stumbled upon something curious and told the rest of the scientific community about it. The realization that the work could be useful came much later.

This sequence of events has played out time and again throughout scientific history. In “Science the Endless Frontier,” the blueprint for the creation of the U.S. research enterprise following World War II, Vannevar Bush wrote that “basic science is performed without thought of practical ends … yet the further progress of industrial development would eventually stagnate if basic scientific research were long neglected.”

Sadly, these lessons seem to have been forgotten. Today when scientists apply for federal grants, they must justify their proposed work on the basis of its "significance" and practical usefulness to society. In recent weeks Congress announced that research should be done “in the national interest,” implying some similar utilitarian purpose. Requiring scientists to explain the significance of their work before receiving research funding may seem perfectly reasonable, given the expectation that society should receive some future benefit from taxpayer-supported research. However, this may paradoxically reduce the return on investment by discouraging scientists from the kind of curiosity-driven, open-ended research that often precedes true breakthroughs.

The most transformative discoveries are often unanticipated. Take for example Einstein’s theory of general relativity which redefined our view of the universe and reality a century ago. That theory posits that time flows differently in high and low gravity. Is this relevant for everyday life? Yes, if you use a cell phone, given that global positioning satellites require a gravitational adjustment for their clocks to synchronize with those on Earth. When Oswald Avery and his team at Rockefeller University discovered that DNA was responsible for heredity, they were merely trying to understand why bacterial colonies on agar plates had different appearances. They could scarcely have imagined that recombinant insulin, DNA evidence used in court cases, and the 23andMe biotechnology company, among countless other products of the molecular genetic revolution, would result from their research.

Requiring researchers to justify their work on a utilitarian basis can dumb down science by channeling scientists into less adventurous research avenues. As Vannevar Bush recognized in 1945, discoveries “have often come from remote and unexpected sources, and it is certain that this will be true in the future.” Allowing scientists to follow their unbridled curiosity about how nature works is the best way to encourage new discoveries.

Whenever we are tempted to target research dollars to practical ends, it is worth recalling that antibiotics were accidentally discovered on moldy plates, that many genes associated with cancer were first discovered in viruses, that insulin was discovered by following a trail of ants to the urine of diabetic dogs, and that Viagra was developed after patients receiving a drug for heart disease reported some unusual side effects. Revolutionary discoveries occur when scientists follow their curiosity and not when they pursue a prescribed research program. The assessment of whether science is significant and in the national interest can only be made long after the research is completed and certainly not before.

Modern society has reaped great benefits from scientific discovery. Like all humans, scientists respond to incentives and disincentives. History has taught us that curiosity is the most effective incentive for transformational research. Politicians should abandon the misguided attempt to justify individual basic research projects on the basis of anticipated benefits and focus instead on fostering a rigorous and inventive research enterprise that continues to pay society big dividends.

Dr. Arturo Casadevall (acasade1@jhu.edu) is professor and chair of the department of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health; his editorial opinion is made in a personal capacity and is independent of his affiliation with Johns Hopkins. Dr. Ferric C. Fang (fcfang@uw.edu) is a professor of laboratory medicine, microbiology, medicine and pathobiology at the University of Washington School of Medicine.

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