Monday, October 07, 2024

Nobel

Nobel Prize in Physiology or Medicine Honors Ambros and Ruvkun for MicroRNA Discovery - The New York Times

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Discovery in Tiny Worm Leads to Nobel Prize in Physiology or Medicine for 2 Scientists

The prize was awarded to Victor Ambros and Gary Ruvkun for their discovery of microRNA, which helps determine how cells develop and function.

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Two Americans Are Awarded the Nobel Prize for Medicine

Victor Ambros and Gary Ruvkun were awarded the Nobel Prize in Physiology or Medicine for their discovery of microRNA, which plays a role in organism development and gene regulation.

“The Nobel Assembly at Karolinska Institutet has today decided to award the 2024 Nobel Prize in Physiology or Medicine jointly to Victor Ambros and Gary Ruvkun for the discovery of microRNA and its role in post-transcriptional gene regulation.” “Oh, I was astonished and surprised. Delighted. Everything you might expect. Honestly, it was this was not something that I expected.” “There are a lot of awards, but the Nobel is in its own class in terms of how much attention it gets. So, I don’t know, I’ve probably gotten 10 different awards over the last 20 years. There’s never been a press conference like this or TV cameras or, you know, nothing like this. So it’s a completely different world.”

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Victor Ambros and Gary Ruvkun were awarded the Nobel Prize in Physiology or Medicine for their discovery of microRNA, which plays a role in organism development and gene regulation.CreditCredit...Jonathan Nackstrand/Agence France-Presse — Getty Images

Victor Ambros and Gary Ruvkun were awarded the Nobel Prize in Physiology or Medicine on Monday for the discovery of microRNA, a tiny class of RNA molecules that play a crucial role in determining how organisms mature and function — and how they sometimes malfunction.

Working with curious, millimeter-size roundworms of the species Caenorhabditis elegans, the two laureates’ discovery revealed a new principle of gene regulation that is crucial for the development and health of multicellular organisms, including humans, Nobel Prize officials said.

Dr. Ambros is a professor of natural science at the University of Massachusetts Chan Medical School in Worcester, Mass., and Dr. Ruvkun is a professor of genetics at Harvard Medical School and a researcher at Massachusetts General Hospital.

Gene regulation determines differences between types of cells, and if it goes off track it can lead to diseases such as cancer, diabetes or autoimmunity, the Nobel committee said. Researchers now know that the human genome provides instructions for over 1,000 forms of microRNA.

“That opened up a whole new understanding of how diseases happen, which means that we have new possibilities for reversing them,” said Jon Lorsch, director of the National Institute of General Medical Sciences and an institute director at the National Institutes of Health.

Treatments based on microRNA are in clinical trials for heart disease, cancer and neurodegenerative disease.

Other scientists saw another message in the Nobel committee’s selection.

Geraldine Seydoux, a biologist who wrote about the history of the microRNA discovery, said the field had been especially excited for this prize, because it was awarded to two scientists who worked together to understand a problem, despite their appointments at separate universities, which might have ordinarily bred competition.

“It is a Nobel that celebrates curiosity-driven science,” she said, “and also the friendship and collaboration between these two scientists who were just eager to figure out a puzzle.”

The RNA molecule, or ribonucleic acid, is often explained to high school biology students as carrying instructions from DNA to cells, enabling the creation of proteins.

Dr. Ambros and Dr. Ruvkun’s findings suggested that this process, so fundamental that it is often referred to as the “central dogma of molecular biology,” might be more complex.

But the two Nobel laureates didn’t set out to alter the basic understanding of human genetics.

Scientists often study the roundworm C. elegans in basic research because it has less than 100 cells, each of which you can watch develop through the worm’s transparent body. Dr. Ambros and Dr. Ruvkun were trying to understand why, at the genetic level, some roundworms developed a specific developmental mutation — a somewhat niche subject that seemed distant from human health at the time.

Dr. Lorsch, who was a graduate student working one floor above Dr. Ruvkun’s lab, saw the discovery unfold in real time.

Dr. Ruvkun walked upstairs to Dr. Lorsch’s lab, as he often did to bounce ideas off graduate students, and held up a picture of the novel molecule, microRNA, attached to a larger strand of RNA.

“What do you think’s going on here?” he asked.

ImageA microscope image with several tiny roundworms in the frame.
Scientists often study the roundworm C. elegans in basic research because it has less than 100 cells, each of which you can watch develop through the worm’s transparent body.Credit...ABS Natural History/Shutterstock

The graduate students, who Dr. Lorsch said were usually “of zero help to him,” shrugged their shoulders, and Dr. Ruvkun went back downstairs with his finding.

Dr. Ruvkun, at Massachusetts General Hospital, and Dr. Ambros, then at Harvard, had been postdoctoral fellows at the same time at Massachusetts Institute of Technology. As they studied C. elegans, they at first felt a smidgen of friendly competition as they each started their own labs in the Boston area, Dr. Ambros said.

“I better see if I can see everything that Gary might see so I don’t look stupid,” he often thought.

Researchers, he said, often have an instinct to hold their findings close to their chest — the field has a “publish or perish” culture that incentivizes scientists to submit their discoveries in academic journals first.

But he said the moment that he and Dr. Ruvkun discovered their research had collided, the competition faded.

He remembered the phone call when they realized that the microRNA discovered in Dr. Ambrose’s lab attached onto the larger RNA that Dr. Ruvkun’s lab worked on, as if they were two perfect puzzle pieces coming together.

“Do you see it?” he remembered shouting into the landline. “Do you see it?”

As its name suggests, microRNA is much shorter than its RNA counterpart. While typical RNA might have hundreds or thousands of basic building blocks, microRNA might have only dozens.

What the two Nobel laureates eventually showed was that microRNA act as “controllers” of the process that produces proteins, telling the larger RNA when to slow down or stop.

This is important because too much or too little of a given protein can result in diseases like cancer or osteoporosis. Mutations in the genes that have instructions for microRNA have been linked to congenital hearing loss, and eye and skeletal disorders, Nobel Prize officials said.

The discovery was originally described in 1993 in two separate papers published in the journal Cell. The first author on Dr. Ambros’s paper was Rosalind Lee, his wife, who celebrated the Nobel committee’s call with him Monday morning.

But the papers at first were met with “almost deafening silence,” the Nobel committee wrote, because many scientists believed this process to be unique to roundworms, and not relevant to humans or other more complicated animals.

The duo didn’t realize how influential their discovery would be until years later, when Dr. Ruvkun found evidence that the same gene responsible for microRNA in his worms was present in the human genome.

He called scientists from around the world and begged them to ship RNA samples from clams, earthworms, zebrafish, whatever he could get his hands on.

One after another, his lab tested the mailed samples and found microRNA genes, an indication to him that this genetic regulation process appeared across the animal kingdom.

When Dr. Ambros read Dr. Ruvkun’s paper in Nature, he came to a similar conclusion:

“That was the moment when I realized this is something way bigger than I ever expected,” he said.

As they worked together, the two were “always on the phone with each other,” Dr. Ruvkun said, comparing research and marveling at their results, even late at night while Dr. Ambros tended to a newborn.

Dr. Ambros said he hoped that their award also highlights the importance of public funding of research. Throughout their careers, the two researchers received more than $62 million from the National Institutes of Health, according to an agency spokeswoman.

“It supported me all my career,” he said. “Taxpayers of the United States should feel proud.”

Luisa Cochella, a microRNA researcher and a proud “worm person” at Johns Hopkins University, said this discovery underscored the importance of doing basic research on simpler, maybe less glamorous, animals, even if there are no obvious applications to human biology.

“When you are really trying to deeply understand how something works, you get these unexpected findings,” she said.

Katalin Karikó and Drew Weissman recognized work that led to the development of potent Covid vaccines that were administered to billions around the world.

The prize for physiology or medicine is the first of six Nobel Prizes that will be awarded this year. Each award recognizes groundbreaking contributions by an individual or organization in a specific field.

  • The Nobel Prize in Physics will be awarded on Tuesday by the Royal Swedish Academy of Sciences in Stockholm. Last year, Pierre Agostini, Ferenc Krausz and Anne L’Huillier shared the prize for work that let scientists capture the motions of subatomic particles moving at impossible speeds.

  • The Nobel Prize in Chemistry will be awarded on Wednesday by the Royal Swedish Academy of Sciences in Stockholm. Last year, the prize went to Moungi G. Bawendi, Louis E. Brus and Alexei I. Ekimov for discovering and developing quantum dots that are expected to lead to advances in electronics, solar cells and encrypted quantum information.

  • The Nobel Prize in Literature will be awarded on Thursday by the Swedish Academy in Stockholm. Last year, Jon Fosse of Norway was honored for plays and prose that gave “voice to the unsayable.”

  • The Nobel Peace Prize will be awarded on Friday by the Norwegian Nobel Institute in Oslo. Last year, Narges Mohammadi, an activist in Iran, was recognized “for her fight against the oppression of women in Iran and her fight to promote human rights and freedom for all.” Ms. Mohammadi is serving a 10-year sentence in an Iranian prison where her attorneys have raised concerns about her well-being.

  • Next week, the Nobel Memorial Prize in Economic Sciences will be awarded on Monday by the Royal Swedish Academy of Sciences in Stockholm. Last year, Claudia Goldin was awarded for her research uncovering the reasons for gender gaps in labor force participation and earnings.

All of the prize announcements are streamed live by the Nobel Prize organization.

Teddy Rosenbluth is a health reporter and a member of the 2024-25 Times Fellowship class, a program for journalists early in their careers. More about Teddy Rosenbluth

Derrick Bryson Taylor covers breaking and trending news and is based in London. More about Derrick Bryson Taylor

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