More important, the drama over vaccines has masked a bigger and untold story, which is the vast promise of mRNA technology. Messenger RNA has shown enormous potential for medical applications beyond Covid to other infectious diseases, as well as vaccines and treatments for conditions from cancer to multiple sclerosis. Its development is a tale of scientific perseverance and serendipity that deserves more attention, with a prominent role by an American immigrant from communist Hungary.
The Omicron variant is an example of mRNA’s promise and adaptability. Omicron has some 30 mutations on its spike protein that could make it harder for vaccine-induced antibodies to recognize and neutralize the virus. But mRNA vaccines can be reformulated for the new variant.
BioNTech and Pfizer say they could begin shipping vaccines that target Omicron within 100 days if protection from their existing vaccines declines substantially against the new variant. Moderna has already started testing booster shots designed to anticipate mutations. It also says it would rapidly advance an Omicron-specific booster shot, which could be available early next year.
That quick pivot would be impossible with conventional vaccine technologies, which usually take between six and 36 months just to manufacture and deliver. It can take many more years to design vaccines. With mRNA, vaccine makers only need about six weeks to adapt a shot and then take it from the lab to production.
from degradation and facilitate its entry into cells. Once the mRNA is injected into the muscle, human cells become vaccine mini-factories that churn out pseudovirus particles, which in turn prompt the immune system to produce antibodies that respond when confronted with the real thing. The vaccines also induce T cells, which provide a backup defense to antibodies. If a virus mutates, scientists can easily swap new genetic code into the mRNA.
The Moderna and Pfizer/BioNTech Covid vaccines are the first commercially approved mRNA products, but they were made possible by decades of experimentation, innovation and determination. Geneticists established the existence of mRNA in the early 1960s. RNA regulates how genes are expressed and is a single-stranded molecule similar to the double-helix DNA. Messenger RNA carries the instructions from DNA to the protein-making machinery in cells, known as ribosomes.
That’s where Katalin Kariko comes in. The 66-year-old Hungarian-born biochemist, now a scientist at BioNTech, first began working with RNA as a graduate student in the late 1970s at the University of Szeged. Researchers were interested in manipulating what is known as small RNA to generate antiviral effects. In 1985 the biological center where she was a researcher ran out of funding, and her postdoctoral position was terminated.
She applied for three research positions in Europe but wasn’t eligible for funding. Then she landed a postdoctoral position at Temple University. She and her husband sold their car for £900 (about $1,200), sewed the notes into their 2-year-old daughter’s teddy bear—Hungary didn’t allow citizens to take cash out of the country—and moved to Philadelphia.
Years later the University of Pennsylvania hired her as an adjunct professor. At the time, she envisioned using mRNA to create therapeutic proteins that could substitute for medications. But because she failed to obtain grants, she was passed up for promotions. Government, nonprofit institutions and investors were skeptical about mRNA since the genetic material was considered fragile and produced too little protein to be effective. “For two years every month I submitted for a grant and got none,” Ms. Kariko says in an interview. Research on mRNA “was a backwater.”
Relying on senior faculty to support her research, she was determined to show that mRNA could be used for medical treatments. For a time she collaborated with a cardiologist on designing mRNA coded for proteins that could prevent blood clots after heart-bypass surgery. Later she worked with a neurologist to design mRNA that would instruct cells to create an enzyme that produces nitric oxide, which could dilate the brain’s blood vessels to relieve a hemorrhage.
One day she bumped into the immunologist Drew Weissman at a copy machine. “He was interested in doing a vaccine, and he says he was working with Anthony Fauci. I didn’t know who Fauci was. He was not in the television at the time,” she says. “Drew said he wanted to make a vaccine that can be therapeutic and prophylactic.”
She performed many experiments in animals and on cells cultured in Petri dishes. Yet when Dr. Weissmann tested her synthetic mRNA, it triggered an inflammatory response from human immune cells.
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