This year’s Nobel Prize in medicine celebrates another big step toward understanding a mystery in biology.

How do cells carrying the full suite of genetic instructions manage to differentiate into many hundreds of very different appearing and functioning cells such as those that line the gut to the many types of brain cells that differ in size, shape and connections?

Yet, that is precisely what young cells do beginning with the fertilized egg, part of which develops into the placenta and the other part of which develops into the body — step by step, developing into cells that take on different jobs and appearances. 

The answer is that while the same genomes are capable of directing cells down different developmental paths such as, say, Purkinje cells in the cerebellum, they must also be capable of turning off (silencing) whole suites of genes related to the many other cells in the genome’s repertoire, while retaining generic properties common to other nerve cells and general functions such as energy production, which are common to all cells in the body. 

That may have been the working hypothesis, but how did scientists prove it?

The answer was often to turn to simple biological systems, banking on the now well-established proposition that the kingdom of all life, while varying wildly in how its members look and behave, goes about its business by sharing many proven genetic solutions to life’s diverse challenges across the broad spectrum of evolution’s lifeforms — past and present.

This approach of studying simple organisms to understand better more complex ones has paid off handsomely.

For example, to sort out the biophysical basis of the transmission of nerve impulses in nerve fibres, Alan Hodgkin and Andrew Huxley chose the giant squid axon because it was sturdy and much easier to insert electrodes within the giant nerve fibres than would be the case with smaller diameter mammalian nerve fibres.

The tack paid off handsomely and led to a Nobel Prize in 1963.

Or what about turning to aplasia, whose nervous system is relatively simple, to solve the physical and chemical basis of memory, as Eric Kandel did?

His efforts laid the groundwork for our current understanding of the molecular basis memory for which he was awarded a Nobel Prize in 2000. 

More to the point of this year’s Nobel Prize in medicine, if we want to understand how cells go about developing and specializing, why not choose Caenorhabditis Elegans (C. elegans for short) a tiny, one-millimetre worm with precisely 302 nerve cells and 959 somatic cells in one version and the same number of nerve cells, but 1,031 somatic cells in the other version, as well as a variable number of germ cells in each version, each cell countable and visible through the transparent worm?

Elegans was just the right mix of simplicity and complexity to solve big questions whose answers were generalizable to far more complex lifeforms like you and me. 

Sidney Brenner chose C. elegans as his tool for understanding some of the most mysterious and puzzling questions in biology and in so doing together with worthy colleagues, he became one of the most outstanding biologists of the 20th century and chose other promising cell biologists to join the growing team.

Their collective studies led to eight Nobel laureates beginning in 2002 and most recently this year’s 2024 laureates in medicine or physiology, Victor Ambros and Gary Ruvkun, all for work inspired by Brenner.

Brenner and his colleagues Robert Horvitz and John Sulston won their Nobel Prize in 2002 for their studies of programmed cell death and the genetics of organ development.

In the case of programmed cell death, some cells play interim roles in development — products of less differentiated cells but not yet fully specialized and destined to serve for a time and then die.

Other cells are casualties of competition to make the best connections with other cells in which process the best survive and the losers disappear without a trace. 

This year’s laureates discovered small snippets of RNA, which they called microRNAs that silenced genes, not by silencing genes directly, but by blocking the messenger RNA (mRNA) the genes created.

It was elegant collaborative work by Ambros and Ruvkun, but when they published their findings they were greeted by silence.

No one was interested, that is until thousands of other microRNAs were discovered in a wide spectrum of species, and it became clear that microRNAs played a large role in evolution. 

It’s not the end of the story of the biology of differentiation — that exquisitely choreographed sequence of events between the first cell and the complete organism, but it was a big step forward by Ambros and Ruvkun. 

Sidney Brenner was the key to the many pivotal discoveries made using C. elegans for good reasons. Brenner was a prodigy who showed his talents early.

He was brilliant, imaginative, focused, determined and had a winning way with people. He led by example with hard work and integrity and a knack for bringing out the best in others. He also possessed a wonderful sense of humour.

Brenner inspired people — they wanted to work with him and hence the Worm Society, which continues to this day to meet and trade stories, many about Brenner and share their studies with those in the C. elegans club.

Brenner’s leadership skills were very similar to another great chemist, Carolyn Bertozzi who won her Nobel Prize in 2022.

In the sciences where teamwork often makes the difference between success and failure, Brenner and Bertozzi stand out as does Madame Marie Curie, who possessed many of the same qualities and managed to win two Nobel Prizes, one in physics and the other in chemistry in the early 20th century.   

Dr. William Brown is a professor of neurology at McMaster University and co-founder of the InfoHealth series at the Niagara-on-the-Lake Public Library.