Baltimore Sun Sunday

The best science is often accidental

- By Arturo Casadevall and Ferric C. Fang

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, openended 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 cellphone, 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.

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