Virus World

Katalin Karikó and Drew Weissman laid the groundwork for immunizations that were rolled out during the pandemic at record-breaking speed. This year’s Nobel Prize in Physiology or Medicine has been awarded to biochemist Katalin Karikó and immunologist Drew Weissman for discoveries that enabled the development of mRNA vaccines against COVID-19. The vaccines have been administered more than 13 billion times, saved millions of lives and prevented millions of cases of severe COVID-19, said the Nobel committee. Karikó, who is at Szeged University in Hungary, and Weissman, at the University of Pennsylvania in Philadelphia (UPenn), paved the way for the vaccines’ development by finding a way to deliver genetic material called messenger RNA into cells without triggering an unwanted immune response. They will each receive an equal share of the prize, which totals 11 million Swedish krona (US$1 million). Karikó is the 13th female scientist to win a Nobel Prize in medicine or physiology. She was born in Hungary, and moved to the United States in the 1980s. “Hopefully, this prize will inspire women and immigrants and all of the young ones to persevere and be resilient. That’s what I hope,” she tells Nature.

A new chapter

The COVID-19 vaccines developed by Moderna and the Pfizer–BioNTech collaboration deliver mRNA that instructs cells to create copies of a protein that is found on SARS-CoV-2 virus particles, called the spike protein. This stimulates the body to make antibodies that target the protein, as well as triggering other immune responses. For decades, mRNA vaccines were considered unfeasible because the injection of mRNA into the body triggered an immune reaction that immediately broke down the mRNA. In the mid-2000s, working at UPenn, Karikó and Weissman demonstrated that swapping one type of molecule in mRNA, called uridine, with a similar one called pseudouridine bypasses the cells’ innate immune defences1. “I’m delighted to see them recognized,” says Robin Shattock, a vaccine scientist at Imperial College London, who has worked on mRNA vaccines. “Their contribution was really fundamental in the success of the COVID-19 vaccines, and I think will underlie RNA technology for some time to come.” “They demonstrated that changing the type of the RNA nucleotides within the vaccine altered the way in which cells see it,” said John Tregoning, a vaccine immunologist at Imperial College London, in a press statement for the UK Science Media Centre. “This increased the amount of vaccine protein made following the injection of the RNA, effectively increasing the efficiency of the vaccination: more response for less RNA.” “This discovery has opened a new chapter for medicine,” said Nobel committee member Qiang Pan Hammarström, an immunologist at the Karolinska Institute in Stockholm, at a press conference after the prize announcement. “Investment in long-term basic research is very important.”

doi: https://doi.org/10.1038/d41586-023-03046-x

Harvey Alter, Michael Houghton and Charles Rice share the award for research on a virus that causes hundreds of thousands of deaths a year. A trio of scientists who identified and characterized the virus responsible for many cases of hepatitis and liver disease — hepatitis C — are the recipients of the 2020 Nobel Prize in Physiology or Medicine. The winners are Harvey Alter at the US National Institutes of Health in Bethesda, Maryland; Michael Houghton, now at the University of Alberta in Canada; and Charles Rice, now at Rockefeller University in New York City. Their work on the hepatitis C virus paved the way for effective treatments against the infection that are now available. The World Health Organization (WHO) estimates that 71 million people worldwide are chronically infected with hepatitis C, which causes nearly 400,000 deaths per year, mostly from cirrhosis and liver cancer. The prize is well deserved, says Ellie Barnes, who studies liver medicine and immunology at the University of Oxford, UK. “It stands out as an emblem of great science,” she says. “We’ve got to a point where we can cure most people who are infected.” The prizewinners will share an award of 10 million kronor (US$1.1 million).

Blood-borne pathogen

In the 1970s, Alter studied the transmission of hepatitis, or liver inflammation, as a result of blood transfusions. Earlier work had identified hepatitis A and B viruses, but Alter showed that a third, blood-borne viral pathogen could transmit the disease to chimpanzees. Houghton, then working at Chiron Corporation in Emeryville, California, and his colleagues identified the virus on the basis of genetic material from infected chimpanzees, showing that it was a new kind of RNA virus that belonged to the Flavivirus family. They named it hepatitis C virus. 

A team led by Rice, then based at Washington University in St. Louis, Missouri, used genetic-engineering techniques to characterize a portion of the hepatitis C genome responsible for viral replication, demonstrating its role in causing liver disease. Some researchers had considered virologist Ralf Bartenschlager at the University of Heidelberg a candidate for a Nobel prize for hepatitis C, for his research into ways to propagate the pathogen in the laboratory. But Bartenschlagerhe says that the Nobel committee made a reasonable choice. “It’s a really difficult decision,” he says. “I think the way they have approached it is fairly well understandable.” In the past, Houghton has been vocal critic of scientific prizes that limit the number of recipients; the maximum number of awardees for a single Nobel prize is three. In 2013, he declined a prestigious Canada Gairdner Award — which came with a $100,000 prize — because the award did not recognize his collaborators Qui-Lim Choo and George Kuo at Chiron. “He always wants to see his discovery as a team approach,” says Thomas Baumert, a virologist and hepatologist at the University of Strasbourg in France.

Vaccine difficulties

The result of research by the prizewinners and others has led to significant improvements in hepatitis testing and treatment. In the past decade, harsh and poorly effective treatments for the infection have been replaced by drugs that directly block the virus. These medicines have the potential to cure the vast majority of hepatitis C infections, but their high cost has limited access in many low- and middle-income countries. Treatment requires following a drug regimen for 8–12 weeks, says Barnes. “Many of the people living with hepatitis C remain in vulnerable settings or are i.v. drug users, where it’s actually quite hard to get the drugs to the people affected.”  Bartenschlager says that he hopes that the Nobel will bring attention to the “silent epidemic” of hepatitis C around the world. The WHO has set a goal of eradicating the hepatitis C virus by 2030, which Barnes says could be achievable. But to do so, she adds, might require a vaccine.

Emmanuelle Charpentier and Jennifer A. Doudna developed the Crispr tool, which can change the DNA of animals, plants and microorganisms with high precision.  The Nobel Prize in Chemistry was jointly awarded on Wednesday to Emmanuelle Charpentier and Jennifer A. Doudna for their 2012 work on Crispr-Cas9, a method to edit DNA. The announcement marks the first time the award has gone to two women. “This year’s prize is about rewriting the code of life,” Goran K. Hansson, the secretary-general of the Royal Swedish Academy of Sciences, said as he announced the names of the laureates. Dr. Charpentier and Dr. Doudna, only the sixth and seventh women in history to win a chemistry prize, did much of the pioneering work to turn molecules made by microbes into a tool for customizing genes — whether in microbes, plants, animals or even humans.“I’m over the moon, I’m in shock,” Dr. Doudna, a professor at the University of California, Berkeley, said at a news conference on Wednesday. It has been only eight years since Dr. Doudna and Dr. Charpentier — now the director of the Max Planck Unit for the Science of Pathogens in Berlin — co-authored their first paper demonstrating the power of Crispr-Cas9. Since then, the technology has exploded. Doctors are testing it as a cure for genetic disorders such as sickle cell disease and hereditary blindness. Plant scientists are using it to create new crops. Some researchers are even trying to use Crispr to bring species back from extinction.