Abundance

Katalin Karikó, a Hungarian-born scientist, came to the University of Pennsylvania to work and study mRNA. Though not as commonly studied as DNA, mRNA presented the opportunity to turn human cells into factories to produce many kinds of crucial proteins. Despite these biological possibilities, Karikó’s frequent applications for government-funded grants were rejected throughout the entirety of her career. By the late 1990s, Karikó’s science career and the study of mRNA both seemed stuck.

In 2020, the novel coronavirus pandemic hit the world. Globally, countries scrambled to make policies to contain the contagion, keep people safe, and prevent the spread of infection. Scientists began researching masking procedures and the efficacy of masking in preventing contagion spread. Though masking could potentially reduce the risk of infection, a medicine that could create collective immunity became increasingly necessary. Before 2020, no vaccine had gone from the lab to the public in less than three years. The COVID vaccine did it in 10 months. The US issued an emergency authorization for two COVID therapies based on mRNA technology, from Pfizer and Moderna. The vaccines were immediately effective at reducing mortality in adults in every country. The pandemic presented a new challenge for the US to “invent” instead of “build” itself out.

The Politics of Invention

Invention is the basis of human progress, and invention makes modern liberal politics possible, as the products and services liberals seek to make universal rely on recent developments in technology. With these technological developments, it can be tempting to shift the focus from further invention to the fair distribution of this technology, but Klein and Thompson assert that a failure to keep inventing robs future generations of further progress, as the world is still filled with problems that cannot be solved without further invention.

Government plays a role in invention, as it subsidizes innovation, like in 2010 when the government gave money to Tesla to continue developing electric vehicles. Though Tesla CEO Elon Musk now decries the very subsidies he’s received as a popular voice in the American right, which condemns the use of government subsidies, the money Musk and Tesla received helped develop the electric Model S. The state does more than regulate technology; it is a key actor in its creation. Federal spending is so integral to innovation that government-funded research and development have been responsible for 25% of productivity growth in the US since the end of World War II. The COVID pandemic again proved the necessity of the government’s role in innovation with the development of mRNA vaccines, but it would have been impossible without Karikó and the luck of a well-placed Xerox machine.

A Shot to Save the World

In the fall of 1997, after Karikó’s demotion at Penn, she went to Xerox copies of several academic articles. The machine was in another building, and she talked to immunologist Drew Weissman while waiting to use the machine. Karikó told Weissman about her interest in utilizing mRNA as a medical therapy, and Weissman, who was working on an elusive HIV vaccine, was interested. They began working together, and despite limited grants and funding from the government, they made a breakthrough in the early 2000s by creating an mRNA therapy that could enter the cell without sending the immune system into a frenzy. When they submitted their findings to publications, they failed to find traction, and Karikó left academia.

Despite the scientific field ignoring it, the private sector took an interest in mRNA research. In the US, a brash group of postdoctoral researchers, professors, and venture capitalists founded Moderna, while German scientists founded BioNTech to research mRNA therapies for cancer. In 2013, BioNTech made Karikó a vice president. Both Moderna and BioNTech researched for years without releasing a product, thanks to capital from investors and philanthropic groups.

However, COVID offered an opportunity for the application of mRNA therapies. Once Chinese scientists released the genetic sequence of the virus in January 2020, Moderna’s mRNA vaccine recipe was finalized within 48 hours. By December 2020, the vaccine was finalized and approved, the fastest vaccine approval in history. In 2023, Karikó and Weissman won the Nobel Prize in Physiology or Medicine, finally receiving recognition for their work. Karikó is not the only scientist to encounter frequent funding rejection from the government. American science is becoming biased against scientists who want to take bold risks. Like the housing and clean energy sectors, science rewards those who know how to work the system rather than those with the best ideas, something that Klein and Thompson call “the Karikó problem” (141).

The Karikó Problem and the Great Science Slowdown

The business of academia in America has never been bigger, and the search for knowledge has never been easier. Collaboration is easier across long distances, and technology is more readily available than ever. Despite an exciting new landscape for innovation and invention, some fields are slowing down. In 2020, economists found that from medicine to agriculture, basic science is becoming less productive.

Klein and Thompson question the puzzle of this slowdown, wondering why “more scientists, more money, more years of education, more knowledge, more technology, and more papers” often equate with “slower progress” (143). In 2008, economist Benjamin Jones proposed a theory to explain this with two observations: no one is born an expert, and total expertise in subjects grows over time while the mysteries of the natural world are unraveled. As expertise is built, it’s like plucking fruit from a tree: the low-hanging fruit goes first. As research continues, it is harder to build expertise, like it is harder to pick fruit higher in the tree. Jones calls this “the burden of knowledge” (143), which Klein and Thompson state is both plausible and obvious. An example is Gregor Mendel’s study of genetics in pea plants, which yielded discoveries about genetic inheritance. As the field of genetics grew over time, the discoveries became more complex and difficult. The unsolved problems in science are more difficult than the solved ones.

A solution to this problem would be to devote more resources to research and development. However, the funding for scientific research has declined, and recruiting intelligent scientists from other countries has become more difficult as immigration legislation becomes more restrictive. The H1-B visa is a particular problem. This visa began in 1990 and capped the number of visas for highly skilled workers at 65,000. It was raised to 85,000 in the early 2000s, but the number has not increased since. Many promising foreign students must leave after completing their studies, taking their knowledge and skills elsewhere. If Karikó had entered the US later, she would not have been able to stay under the H1-B system, and her mRNA research may have been lost. Klein and Thompson encourage doubling the number of H1-B visas available and increasing wages to transform the system.

Money alone cannot solve the Karikó problem, which Klein and Thompson define clearly: “American science funding has become biased against young scientists and risky ideas” (147). American science is becoming older, as scientists receiving government grants are older than ever before. Publishers also prefer papers that do not contribute to new knowledge and overlook papers with new ideas. Scientists are all looking at the same trees, following the low-hanging fruit analogy. The idea that the NIH is biased against risky or novel research is deeply embedded in the scientific community, but the NIH has been central to many crucial scientific breakthroughs, even risky ones like developing HIV blood tests or the Human Genome Project. To understand how the NIH went from risk-taking to risk-averse, Klein and Thompson seek to understand the history of the NIH itself.

The Growth of the American Innovation System

During the 20th century, science and invention were the jobs of individual entrepreneurs. By the start of World War II, America was technologically unequipped to take on the Axis powers. President Franklin D. Roosevelt approved the creation of the Office of Scientific Research and Development (OSRD), which Klein and Thompson describe as “a multibillion-dollar hydra of wartime science and technology operations that supported the work of thousands of scientists and engineers” (150). The Manhattan Project was funded by OSRD, as was radar, malaria treatments, and an early version of the influenza vaccine. After the war, as OSRD wound down, the medical research was transferred to the NIH. Though NIH had a measly beginning, soon medical schools and students overwhelmed the NIH with proposals. The NIH soon became irreplaceable to the American healthcare system, and its budget increased accordingly.

One complaint is that the NIH evolved with too many rules that limit efficiency. Scientists and others worried that the politicians’ involvement in the NIH would create more bureaucratic hoops to jump through, which was the case in the 60s and 70s. Today, scientists spend up to 40% of their time filling out research grants or administrative documents, and funding agencies can take up to seven months to review applications. Another complaint of the NIH system is that the onerous grant application process prioritizes status-seeking over actual science. Finally, the NIH plays it too safe, as illustrated by its failures to fund Karikó’s mRNA research. It relies on an archaic peer-review system in which highly novel proposals consistently fail. Novelty and risk are important, as many scientific breakthroughs are surprises, like the discovery of GLP-1, the substance commonly known as Ozempic that treats diabetes and other conditions, which was found in the salivary venom of the Gila monster lizard. Some novel ideas are happy accidents, and some need careful work to develop and grow.

The NIH has tried to earmark funds and create grant programs for newer, riskier ideas and younger scientists, and while these programs have had some success, the NIH funding going to scientists under the age of 35 continues to decline. To find a new approach to fund breakthrough science, people should look outside the NIH for how to accelerate invention.

The Idea Factories

In 1957, the Soviet launch of Sputnik ignited the space race. In 1958, the United States Department of Defense established the Defense Advanced Research Projects Agency (DARPA) to produce new technology, and GPS, the internet, personal computers, and self-driving cars trace their roots to DARPA. DARPA even invested $25 million in Moderna years before COVID. With a smaller budget than NIH, DARPA punches above its weight, as it has project managers who don’t face peer review and can take scientific risks. Project managers also bring together collaborators from different fields and firms to accomplish goals, like the invention of the first internet, called ARPANET.

DARPA works because it empowers its project managers to pursue their radical ideas. Bell Labs, the research arm of AT&T and Western Electric, also had numerous scientific breakthroughs surrounding solar cells. AT&T had a state-sanctioned monopoly, so it could heavily invest in Bell Labs’s innovative and ambitious projects without concern about short-term profits. Institutions shape the way people think, and new institutions can make new kinds of thinking possible. American innovation relies on agencies and habits from the 19th and 20th centuries; the world has changed, and risk-taking science is more important than ever.

Experimenting With Experiments

Today’s politics is vacant in the context of the question of accelerating scientific research and invention. Neither liberals nor conservatives have a clear politics of invention, nor do they prioritize public policy in the sciences. To fix this, Klein and Thompson suggest the study of “metascience,” or a scientific study of science itself. Klein and Thompson suggest running experiments on the NIH to eliminate aspects of the application process and then studying the results of these experiments. Tinkering with the basic funding models of science and making steps toward a novel approach to science and invention could help create groundbreaking scientific achievements, but this system requires a better science of science.