South African Microbiologist Sydney Brenner began his 2002 Nobel Prize lecture for the discovery he made with two other colleges concerning genetic regulation of organ development and programmed cell death (apoptosis) with the use of the then newly discovered microorganism known as Caenorhabditis elegan.
“The winner of the Nobel prize this year is Caenorhabditis elegans,” Brenner said. “It deserves all the honor but, of course, it will not be able to share the monetary award.”
Years of groundbreaking scientific research would stem from this moment, leading to two more Nobel prizes to C. elegans’ name.
The first of which came in 2006 for the discovery of RNA interference and gene splicing of double-stranded RNA known as RNAi, a method that can be used in cancer treatments by silencing oncogenes — a mutated gene that is cancer-causing.
The third and last prize came in 2008 for the discovery of green fluorescent protein tagging using C. elegans, a versatile bioluminescent that has the ability to light up specific genes and cells.
According to the Harvard School of Public Health, C. elegans is a non-parasitic nematode worm typically found in rotting soil or vegetation. Today, they have become a staple in hundreds of biology labs around the world for their reliability, efficiency and their biological composition.
According to WormAtlas, a typical C. elegans is between 1-1.5 millimeters long, making it easy to farm large batches in a small petri dish.
They have four major stages of development once they have fully hatched into larvae — which can take a total of 13.3 hours — known as the L1, L2, L3 and L4 stages.
The L1 stage begins with gonad, neuron and coelomocyte development. L2 and L3 are the continuations of neuronal and reproductive development. The final stage, L4, is where they reach full sexual maturity 72 hours post-hatch, after which they have a life cycle of about two weeks.
In addition, C. elegans are hermaphrodites, meaning they possess both male and female reproductive organs. With the ability to self fertilize, they are able to lay up to four-10 eggs every hour, according to WormAtlas.
All that is required to maintain C. elegans is E. coli cultures for substance, a Nematode Growth Medium to maintain constant moisture and a consistent temperature of 20C, according to WormBook. Any temperature above or below that and a low food source will force them to enter an alternative L3 embryonic stage called a Dauer.
A Daurer, according to WormAtlas, is “developmentally-arrested” — they do not eat or produce any waste, but maintain the ability to move, similar to hibernation. Daurers are in no way immobile. They can be seen moving and interacting with the environment around them. Even with no food and a less-than-ideal habitat, they live almost four to eight times longer than the typical two week lifespan of a C. elegan.
C. elegans is the first animal to have its entire genome mapped out. Every single neuron has been identified and named. Because of this, the process of cellular decision is understood at every step of the animal’s life span. However, how the cells interact with each other and the different cellular pathways between neurons for the stage of a Daurer to occur is still not completely understood, leaving more to the unknown.
The biological composition of C. elegans has been one of the most useful features to scientists from the mid-’90s to now. A C. elegans only has 1000 cells in their body, 959 of them being somatic cells, and they are all transparent. This, coupled with green fluorescent protein tagging, allows scientists to monitor specific cell function, the exact location of genes and witness protein synthesis in real-time as the tagging makes the proteins glow bright green under a microscope. About 38% of the genes in C. elegans have human ortholog, giving us a complementary approach of how to solve a range of human diseases.
Margaret Nelson, professor of biology and biochemistry, commented on the usefulness of C. elegans as a model organism.
“C. elegans is fairly cheap, easy to grow and has a fairly short lifespan,” Nelson said. “It’s clear so you can see what’s going on, and you can do a lot of genetic manipulation. This was important because in the time of Sydney Brenner’s work, this was simply too hard and or too expensive using other organisms.”
Nelson explained that she uses C. elegans both in the classroom and further commented on their implementation for today’s research.
“In my introductory biology setting and junior seminar I talk about work done on C. elegans studying signal transduction pathways, a kind of intercellular relay race,” Nelson said. “In the worm, it’s important for certain cells to take on a particular role. It may not seem too important to humans, but this has allowed scientists to construct some pathways and understand signaling which has a correlation to cancer.”
This usefulness and versatility led Bradley Hersh, associate professor of biology and biochemistry, to choose C. elegans to study apoptosis and specific cell death for his doctorate thesis at Michigan Institute of Technology,
“When I was in graduate school, I was most interested in the genetics of development of how an organism goes from one cell to a lot of cells,” Hersh said. “At MIT, there were lots of labs that were studying that in flies, worms, mice and frogs… but C. elegans seemed like a simple yet elegant system in which I could do that work.”
The tools created alongside C. elegan, like green fluorescent protein, are still being used all over the country to see the actual biological function happening in real-time.
“With C. elegans it’s really quite cool because they are transparent,” Hersh said. “You basically can shine an ultraviolet light through them and see glowing green neurons running from one end of the body to the next. It’s really quite beautiful work.”
“C. elegans show us that we can learn about the human body by studying simple things,” Hersh said.
Today C. elegans are being used in neurobiology to try to understand the neurodegenerative disorders known as Alzheimer’s disease — the sixth leading cause of death and number one cause of dementia in the U.S for the elderly, according to the CDC. Scientists do this by tagging neurons with the aforementioned GFP tagging and watching them die, they can then see what genes cause this process to happen.