The worm that helped explain the development of the human body

Have you heard of the Caenorhabditis elegans? He is an exceptional being, a celebrity in laboratories, who was indispensable to many discoveries and contributed to the success of six Nobel Prize winners.

Its name is a mixture of Greek words (mud, which means “new” or “recent”, and rhabditis, something like “stick”) and in Latin (elegans, which means elegant). But, for short, it’s called C. elegans.

In its natural environment, this tiny worm lives in the space between the earth’s grains, and it was in the Algerian soil that French zoologist Émile Maupas found it—he was the first to isolate, describe and select it as his own. reference species in 1900.

Several scientists followed in his footsteps, particularly French biologist Victor Nigon and American biologist Ellsworth Dougherty.

But it was thanks to South African biologist Sydney Brenner’s search for a new animal model that could help him explore the mysteries of human development and behavior that the worm became famous in 1963.

“We needed an organism with which we could properly study genetics,” Brenner said at the time.

“Since you had to see where one cell ended and the other began, it had to be with the electron microscope, so I needed a small organism that would fit in the window of these microscopes. Finally, I decided on these little nematode worms, C. Elegans, and I started working with them.”

“Sydney Brenner is a god in the worm community for choosing this model organism,” says Gordon Lithgow, vice president of the Buck Institute for Research on Aging in the United States.

“What he really did was make a very wise decision that allows him to study really complex biology in a simple system. And that was the real genius. translated for humans and the understanding of diseases.”

Appearances can’t be deceiving

In fact, the appearance of the C. elegans is one of your many attractions to become a model.

“The big advantage is that it’s transparent. You can see it through your skin!” exclaims Lithgow.

“You can actually see cells and biological processes going on just by looking through a microscope.”

“Plus, it’s small. It’s less than a millimeter in size, so you can grow hundreds of thousands of these worms in the lab, and that’s very important if you’re looking for a rare gene or something like that.”

“Sydney Brenner’s genius was to realize that although we have hundreds of billions of cells in our brain, the worm only has 302 neurons, and you can look at them through its transparent skin and study them.”

Why is it so ideal?

– Don’t give it to the nematoide C. elegans it’s much simpler than humans — it doesn’t have, for example, bones, heart, or circulatory system — but it shares many genes and molecular pathways with us;

– In addition, many of the molecular signals that control its development are also found in more complex organisms, such as humans;

– Many of the genes in the genome of the C. elegans they have functional equivalents in humans, making them an extremely useful model for exploring human diseases;

– Ways to C. elegans in which specific genes are altered can be produced very easily to study the function of genes closely;

– These mutations provide models for many human diseases, including neurological disorders, congenital heart disease and kidney disease;

– Can be used to test thousands of potential drugs for major diseases.

“The worm is spectacular as a model organism for a number of reasons,” says the BBC Bob Waterston, professor of Genome Sciences at the University of Washington in the United States.

“It has less than 1,000 cells in adulthood and we know what all these cells are and what they do. It’s small, so you can get a lot of them, and that’s important for genetics, because it allows us to observe many rare events. It’s hard to do the genetics of a rhinoceros, as Sydney used to say!” adds Waterson, who joined Sydney Brenner’s Cambridge, UK, laboratory in the early 1980s and is best known for his work on the Human Genome Project.

But in preparation for this gigantic task, he was part of the small team that mapped the genome of the C. elegans, the first animal to have its genome fully sequenced.

Unfounded doubts

“At the time, there was a lot of skepticism,” he recalls.

“First, they wondered if it was worth sequencing an entire genome, or if they should do something cheaper…or not do anything at all, just study individual genes.”

“The second problem was that nobody knew how to do it. What we did was really an experiment to see if the technologies of the time could be adapted, refined enough to sequence a genome the size of C. elegans. If we could do this with something the size of an average human chromosome, it would probably be possible to extend it to the entire human genome.”

This, as we now know, turned out to be possible.

And despite initial doubts about whether the mission was worth it or not, having the complete map of the worm’s genome turned out to be more useful than anyone expected, as Gordon Lithgow says.

“It turns out that the worm and humans are very similar in their basic biology.”

“When the genome of the C. elegans was sequenced, we found that something like 2/3 of the genes involved in human disease were in the worm. This meant that it was possible to study this biology which is vitally important for human diseases in this little creature.”

More life

In 1988, scientists working with mutant worms in the United States by chance discovered a mutation in a single gene that increased the life of the worm. C. elegans by up to 65%.

Five years later, the worm made headlines when they found another single-gene mutation that could extend its life up to tenfold. Furthermore, the worms remained healthy until the end.

“In a way, it changed the way people think about aging,” says Lithgow.

“We thought the shelf life was like a fixed amount, but what the worm showed us was that the shelf life is plastic, that it could actually be altered ten times as big… It’s amazing!”

“It turns out that at the molecular level, at the cellular level, the processes that drive the 20-day shelf life of the C. elegans are very similar to the processes we believe drive aging in humans. And most importantly, it’s not just about getting older; it is about the diseases of aging”, emphasizes the specialist.

“We believe that the mechanisms we are studying in the worm are the drivers, even the causes, of diseases like Alzheimer’s, cancer, osteoporosis, osteoarthritis, Parkinson’s, etc.”

“So: the worm changed the way people thought about aging and life expectancy. And then, because of the connection to disease, the worm changed the way we think about chronic human disease.”

nature’s gift

No one was more surprised than Sydney Brenner to see how much was being revealed by studying the C. elegans.

“It was very surprising, because at the time it was a completely new field, and I think it took off; now it’s a whole industry,” he declared at the time.

Several Nobel prizes have come from the study of the worm, including the one Brenner received.

“The title of my talk is ‘Nature’s Gift to Science’ (…), and it will be about how biological diversity can be —and has been— used to advance scientific research. Nobel Prize winner this year is the Caenorhabditis elegans and I think he deserves most of the honor, although of course he won’t share the cash reward! (Laughter),” Brenner said in his Nobel lecture in 2002.

This little “gift from nature to science” proved invaluable… and what won Sydney Brenner and two colleagues the Nobel Prize was the discovery of the cell suicide program.

Cell suicide is the process that sculpts our bodies in the womb, removing the web of skin between our fingers and toes, emptying the tubes, shaping our organs and building our brains.

“In the worm, cells divide and produce more cells,” explains Bob Waterston.

“But sometimes you don’t need one of the daughter cells that are manufactured. And, surprisingly, biology has basically invented a system for cell suicide. The cell is programmed to decide that it’s not needed and activates this program that it Woods.”

“This has turned out to be very important in all of biology. In cancer, it’s incredibly important: if you don’t have proper control of cell death, if you don’t have this suicide program activated, it can lead to certain types of cancer.”

from earth to heaven

And it doesn’t stop there: the little worm has been used to test the limits of biology in more extreme environments.

“C. elegans has been in space,” says Lithgow enthusiastically.

“It was part of one of the biological experiments initially carried out on a space shuttle. And more: it was possibly the first terrestrial organism to reproduce in space. They are hermaphrodites, so they self-fertilize, and these worms sent into space were able to reproduce, the which was very exciting. “

But they were also part of a tragedy.

In 2003, to the horror of those who controlled the mission and the millions who turned on their televisions to watch the space shuttle return, Columbia disintegrated upon entering Earth’s atmosphere.

“Sometime after the disaster, the worms were recovered from the container in which the experiment was being carried out and were alive!”

“It’s amazing that they were there, they went through it and came back to Earth,” says Lithgow.

“O C. elegans made one contribution after another to our knowledge,” says Waterston.

And everything seems to indicate that it will continue to contribute.

Today, they are also used to test all kinds of drugs, including those that scientists hope will slow and improve aging processes.