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Nobel Prize in medicine goes to two American biologists for work on the discovery of microRNA

By Christian Edwards and Katie Hunt, CNN

(CNN) — The 2024 Nobel Prize in physiology or medicine has been awarded to US scientists Victor Ambros and Gary Ruvkun for their work on the discovery of microRNA, a molecule that governs how cells in the body function.

Their research revealed how genes, which contain the instruction manual for life, give rise to different types of cells within the human body, a process known as gene regulation.

The Nobel Prize committee announced the prestigious honor, seen as the pinnacle of scientific achievement, in Sweden on Monday. It praised the “groundbreaking discovery,” which the committee said “revealed an entirely new dimension to gene regulation.”

The discovery of gene regulation by microRNA – a family of molecules that helps cells control the sort of proteins they make that has been at work for hundreds of millions of years – was the result of decades of work by Ambros, a professor of natural science at the University of Massachusetts Medical School, and Ruvkun, a professor of genetics at Harvard Medical School.

“Their discovery… is of fundamental importance to understand how cells work, and thus how organisms develop,” said Love Dalén, a professor of evolutionary genomics at Stockholm University. “This finding was groundbreaking, and has affected more or less all fields of biology and medicine,” he told CNN via email.

How cells do different things

“The information stored within our chromosomes can be likened to an instruction manual for all cells in our body. Every cell contains the same chromosomes, so every cell contains exactly the same set of genes and exactly the same set of instructions,” the committee said in a statement, detailing the duo’s work.

And yet, different cell types – such as muscle and nerve cells – have different characteristics. The two biologists have spent their careers investigating how these differences arise.

“The answer lies in gene regulation, which allows each cell to select only the relevant instructions. This ensures that only the correct set of genes is active in each cell type,” the committee said.

Gene regulation by microRNA has aided the evolution of increasingly complex organisms. If gene regulation goes awry, it can lead to cancer and other conditions found in humans and other animals, like hearing loss and skeletal disorders.

“MicroRNAs are very much implicated in cancer. There is ongoing research to make treatments or utilize micro RNAs – mimic microRNA or block microRNA – to treat cancer. There’s some technical hurdles in that so there’s not been any drugs yet,” said Thomas Perlmann, secretary-general of the Nobel Assembly.

“We’re awarding this because of its fundamental importance for the basic understanding of physiology. We know historically that these big discoveries, they translate into clinical improvements but it takes time,” he told CNN.

From ‘oddity’ to fundamental discovery

In their early work, the pair studied the genetic make-up of a tiny 1 millimeter-long roundworm, C. elegans. Despite its small size, this worm possesses many specialized cell types, such as nerve and muscle cells, that are also found in larger, more complex animals, making it a useful model for investigating how tissues develop and mature in multicellular organisms.

“The first micro RNA was discovered by Victor Ambros in 1993 but it was thought to be an oddity, peculiar to a small worm, C. elegans, for more than seven years,” said Olle Kämpe, a professor in endocrinology at the Karolinksa Institutet and vice chair of the Nobel medicine committee.

That 1993 discovery was met by “deafening silence” and initially thought irrelevant to humans, the committee said, until Ruvkun published his discovery of another microRNA, which is now known to be present throughout the animal kingdom.

“Then the field exploded,” said Kämpe. “Now, more than tens of thousands of microRNAs have been identified in different organisms.”

Nobel recognition for Ambros and Ruvkun has been anticipated by many for years, said David Pendlebury, head of research analysis at Clarivate’s Institute for Scientific Information.

“They (microRNAs) offer potential diagnostic and therapeutic opportunities in treating cancer and other diseases. Clinical trials are underway to utilize microRNA profiling for patient prognosis and clinical response,” Pendlebury told CNN.

Janosch Heller, an assistant professor in biomedical sciences at Dublin City University, said that the work “opened our eyes to the wonderful machinery that is tightly controlling what is happening in our cells.”

The discovery of microRNA also helps explain why many organisms have a similar number of genes despite displaying varying levels of complexity, said Joshua Rosenthal, a senior scientist at the Marine Biological Laboratory, part of the University of Chicago.

“Over the past two decades we’ve sequenced the entire genomes of an incredibly wide variety of organisms. One surprising result is that the number of genes required to encode a tiny nematode worm, a fish and a human being is about the same. If that’s the case, then how is complexity generated?” he told CNN.

“The answer appears to be in the sophisticated ways that the information within these genes, like a light, can be turned on, off and dimmed. We now know that microRNAs, once discarded by scientists as a contaminant getting in the way of studying ‘more important’ RNAs, are key components for regulating genes in virtually every cell in every tissue in every plant and animal,” Rosenthal added.

Last year, the prize was awarded to Katalin Karikó and Drew Weissman for their work on MRNA vaccines, a crucial tool in curtailing the spread of Covid-19.

The prize carries a cash award of 11 million Swedish kronor ($1 million).

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