We've all heard this paradoxical claim: If we want tangible, scientific solutions to society's urgent problems, then we need to invest in basic, curiosity-driven research that’s not motivated by its potential for practical applications. As Vannevar Bush, director of the United States government's chief science agency during World War II famously put it: "Basic research is scientific capital." By investing in basic research— research that is "performed without thought of practical ends"—we create "the fund from which the practical applications of knowledge must be drawn."
It's easy to pay lip service to this idea, but harder to put it into practice, especially when we have to choose how to spend a limited budget. Basic research can seem terribly inefficient. Its practical results are hard to predict, and they often have little to do with the original research goals. Vannevar Bush argued that the best way to support basic research is to give federal funding to academic scientists, who are not under pressure to produce immediately practical results and are “free to pursue the truth wherever it may lead." But this approach is often hard for many to accept because scientists sometimes undertake what seem like wasteful projects with no practical benefits. This leads to accusations that scientists are making poor decisions—in a recent op-ed written with Senator Rand Paul (R-Kentucky), Congressman Lamar Smith (R-Texas), chair of the House Science Committee, complained that, "The academic community forgets that federal science funding should be in the national interest."
Jennifer Doudna, a scientist at University of California-Berkeley who co-led one of the research teams that turned CRISPR/Cas9 into a useful tool, recently said that “this is probably the most obscure thing I ever worked on.”
Smith has been making this complaint for several years now, and he is determined to make science more efficient by re-shaping both peer review and the funding priorities of the National Science Foundation. From his perch as chair of the House Science Committee, he has attacked what he sees as wasteful spending on unimportant research, including a study of the impact of climate change on ocean chemistry and a project focused on tackling an important problem in mathematics. Last year he introduced a bill that would require the NSF to explicitly certify that all grants it funded were in the national interest. And this year, Smith is proposing to sharply limit the amount of money the NSF spends on certain research areas, particularly the geosciences—which include climate change research—and the social sciences. The NSF has resisted Smith's efforts to control the funding priorities for federally sponsored science, and the wider scientific community has roundly criticized him. But Smith has vowed that "our efforts will continue until NSF agrees to only award grants that are in the national interest."
Ironically, this contentious dispute over funding priorities is happening at the same time as the spectacular development of the revolutionary DNA editing technology known as CRISPR/Cas9, a game-changing biotechnology with origins that lie in an obscure line of research that would have been hard to certify as clearly in our national interest. Less than three short years after its introduction, CRISPR/Cas9 technology is a must-have tool in biomedical research that allows researchers to carry out genetic experiments that were previously impossible. And according to a recent review, it’s being actively developed by more than a dozen companies for applications in agriculture, health, and other biological research, with some expecting a market size of more than $40 billion.
The story behind CRISPR/Cas9 is a clear example of just how difficult it is to know which basic research will lead to important practical applications. The discovery of CRISPR began in the late 1980s and early '90s, when scientists first observed strange, repeating patterns in the DNA of certain species of bacteria. These mysterious patterns, which were named "clustered regularly interspaced short palindromic repeats," or CRISPRs, had no clear biological function. But their widespread presence among different species of bacteria made them scientifically interesting, and so a few teams of biologists decided to look at them more closely.
A few years later, the function of CRISPRs, along with a set of CRISPR-associated or "Cas" enzymes became clear: They were the components of a remarkably simple and elegant immune system that bacteria use to defend themselves against infections by viruses. The mysterious CRISPR repeats are, roughly speaking, the bacterial version of antibodies, which target invading viruses for destruction. This discovery was made partly through basic, curiosity-driven research, and partly by research with a more practical purpose—though one very different from what CRISPR/Cas9 is primarily used for today. The key discovery came during a 2007 study conducted by scientists at the food company Danisco, which was looking for ways to protect its yogurt-making bacterial cultures from viral infections.
Apart from the scientists at Danisco, the basic researchers who studied CRISPR were mainly pursuing an interesting scientific question without regard to its practical value. Jennifer Doudna, a scientist at the University of California-Berkeley who co-led one of the research teams that turned CRISPR/Cas9 into a useful tool, recently said that “this is probably the most obscure thing I ever worked on.” But as they worked out the molecular details of the CRISPR system, its potential as a powerful DNA editing tool became clear, and the researchers made the crucial leap from basic science to biotechnology breakthrough. In a 2012 study, Doudna and her team created a modified CRISPR system that could be directed to make highly targeted DNA edits in a way that was much easier and more reliable than older DNA editing technologies. The ability to accurately edit DNA is critical not only for basic research, where scientists must manipulate genes to study them, but also for gene therapy and genetic engineering in agriculture. The programmable CRISPR/Cas9 system make this process remarkably easy, by giving biologists what is essentially a reliable way to accurately place the cursor in the DNA text.
Nobody could have predicted that studying mysterious repeating DNA patterns in bacteria would lead to a major new biotechnology. But at this point in history, we shouldn't be surprised: Fundamental research, driven by the desire to understand how nature works, has scored huge practical payoffs, over and over again. Other success stories aren't hard to find. Last year, the National Academy of Sciences issued a report arguing that "truly transformative scientific discoveries often depend on research in a variety of fields," and listing dozens examples of how basic research had led to technologies that now play central roles in our society and our economy. More recently, a group of faculty members at MIT detailed more than a dozen recent cases of basic research leading to scientific solutions to important societal problems. They warned that "basic research is often misunderstood, because it often seems to have no immediate payoff." Yet by failing to properly invest in this research, we are creating "a growing U.S. innovation deficit."
The seemingly wasteful nature of basic research can be maddening, especially to someone like Smith, whose job is to ensure that federal dollars are spent appropriately. But the track record of basic research is clear: Letting scientists, rather than politicians, define important scientific questions is definitely in our national interest.
Inside the Lab explores the promise and hype of genetics research and advancements in medicine.