Roundworms Facilitate Grasp Of Genetic Coding

May 8, 2018 at 5:36 p.m.
By Max [email protected]
A number of simple organisms are used as models for biological research, but perhaps the most unusual and likely the most important is the roundworm, Caenorhabditis elegans. 

Model organisms — including fruit flies, mice and zebrafish — are the bedrock on which the tower of basic biology is built and used extensively in genetic research. Such research helps to develop a complete understanding of the genetic control of development and behavior. 

Dr. Sydney Brenner was one of the first scientists to use the roundworm in his research in biology and neurology. It subsequently became the true life's work for Dr. John Sulston. The organism is a small (about 1 mm in length), nonparasitic, free-living, transparent worm (nematode) found in the soil. It feeds on bacteria, and can be easily housed and cultivated in large numbers (10,000 worms per petri dish) in the laboratory. The worm grows from fertilized egg to adulthood in a mere three days, and has a life span around two to three weeks under suitable living conditions.

Because the worm is transparent, it can be observed easily. C. elegans is multicellular and develops from a fertilized egg to an adult just as a human being does. According to Natalie Angier in her book “The Beauty and the Beasty,” "C. elegans is a proxy for the rest of us, a specimen that can be manipulated, irradiated, assortatively mated, plucked apart, scrambled up, over-easied, put back together, sacrificed, and finally understood in a way that a human being could never be." 

Sulston was renowned for his work ethic and happiest working in the laboratory and while there developed a number of freezing, drying and handling techniques. His findings on genetics, together with Brenner and H. Robert Horvitz, won each of them the Nobel Prize for physiology in 2002 and helped prepare the scientific world for the project of mapping the human genome. Sulston described their work modestly, as the ability to read the language of evolution. 
To fully understand the significance, it is necessary to know more about the makeup of the human genome, which makes up a complete set of human genes, and comes packaged in 23 separate pairs of chromosomes. Of these, 22 pairs are numbered in approximate order of size, from the largest (number 1), to the smallest (number 22), while the remaining pair consists of sex chromosomes: two large X chromosomes in women, one X and one small Y in men. One set of the genome comes from the mother and one from the father. Each set includes the same 30,000 to 80,000 genes on the same 23 chromosomes. (The chromosomes are located in the nucleus of each of the 100 trillion cells found in the human body. Inside the nucleus are two complete sets of the human genome, except in egg cells and sperm cells, which have one copy each, and red blood cells which have none.)

The research performed by Sulston, Brenner and Horvitz was monumental and instrumental in discovering the genetic coding needed to make a human being. Surely this may be the most celebrated scientific triumph of the 20th century, offering treatments for a whole host of neurological and other diseases. One example is human leukemia, where large numbers of immature white blood cells, which normally die before entering the blood stream, are found in the patient's circulation. The study of programmed cell death in C. elegans helps to understand why the same process does not occur in human patients.

Sulston was the workhorse of the group, driven and known for his tenacity, for years he sat in a darkened room peering through a microscope in the Medical Research Council's Laboratory of Molecular Biology up to 12 hours per day watching cells dividing, first in the worm larva and then in its embryo, day after day, until he had the entire lineage from one to all of the 959 cells that made up the organism. Of these, 302 are nerve cells, and Sulston was able to determine the complete wiring diagram, and know what every neuron looks like, how it branches and how the connections are made with other nerve cells. Some of the cells mysteriously died within 30 minutes, paving the way for the surviving cells to fulfill their function.

This work has been shared via the internet and with other researchers from around the world. The collaboration has provided a wealth of information and the means to understand the massive cell degeneration found in Alzheimer's, Parkinson's and other diseases of aging. 

Max Sherman is a medical writer and pharmacist retired from the medical device industry. He has taught college courses on regulatory and compliance issues at Ivy Tech, Grace College and Butler University. Sherman has an unquenchable thirst for knowledge on all levels. Eclectic Science, the title of his column, will touch on famed doctors and scientists, human senses, aging, various diseases, and little-known facts about many species, including their contributions to scientific research. He can be reached by email at [email protected]. 
 

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A number of simple organisms are used as models for biological research, but perhaps the most unusual and likely the most important is the roundworm, Caenorhabditis elegans. 

Model organisms — including fruit flies, mice and zebrafish — are the bedrock on which the tower of basic biology is built and used extensively in genetic research. Such research helps to develop a complete understanding of the genetic control of development and behavior. 

Dr. Sydney Brenner was one of the first scientists to use the roundworm in his research in biology and neurology. It subsequently became the true life's work for Dr. John Sulston. The organism is a small (about 1 mm in length), nonparasitic, free-living, transparent worm (nematode) found in the soil. It feeds on bacteria, and can be easily housed and cultivated in large numbers (10,000 worms per petri dish) in the laboratory. The worm grows from fertilized egg to adulthood in a mere three days, and has a life span around two to three weeks under suitable living conditions.

Because the worm is transparent, it can be observed easily. C. elegans is multicellular and develops from a fertilized egg to an adult just as a human being does. According to Natalie Angier in her book “The Beauty and the Beasty,” "C. elegans is a proxy for the rest of us, a specimen that can be manipulated, irradiated, assortatively mated, plucked apart, scrambled up, over-easied, put back together, sacrificed, and finally understood in a way that a human being could never be." 

Sulston was renowned for his work ethic and happiest working in the laboratory and while there developed a number of freezing, drying and handling techniques. His findings on genetics, together with Brenner and H. Robert Horvitz, won each of them the Nobel Prize for physiology in 2002 and helped prepare the scientific world for the project of mapping the human genome. Sulston described their work modestly, as the ability to read the language of evolution. 
To fully understand the significance, it is necessary to know more about the makeup of the human genome, which makes up a complete set of human genes, and comes packaged in 23 separate pairs of chromosomes. Of these, 22 pairs are numbered in approximate order of size, from the largest (number 1), to the smallest (number 22), while the remaining pair consists of sex chromosomes: two large X chromosomes in women, one X and one small Y in men. One set of the genome comes from the mother and one from the father. Each set includes the same 30,000 to 80,000 genes on the same 23 chromosomes. (The chromosomes are located in the nucleus of each of the 100 trillion cells found in the human body. Inside the nucleus are two complete sets of the human genome, except in egg cells and sperm cells, which have one copy each, and red blood cells which have none.)

The research performed by Sulston, Brenner and Horvitz was monumental and instrumental in discovering the genetic coding needed to make a human being. Surely this may be the most celebrated scientific triumph of the 20th century, offering treatments for a whole host of neurological and other diseases. One example is human leukemia, where large numbers of immature white blood cells, which normally die before entering the blood stream, are found in the patient's circulation. The study of programmed cell death in C. elegans helps to understand why the same process does not occur in human patients.

Sulston was the workhorse of the group, driven and known for his tenacity, for years he sat in a darkened room peering through a microscope in the Medical Research Council's Laboratory of Molecular Biology up to 12 hours per day watching cells dividing, first in the worm larva and then in its embryo, day after day, until he had the entire lineage from one to all of the 959 cells that made up the organism. Of these, 302 are nerve cells, and Sulston was able to determine the complete wiring diagram, and know what every neuron looks like, how it branches and how the connections are made with other nerve cells. Some of the cells mysteriously died within 30 minutes, paving the way for the surviving cells to fulfill their function.

This work has been shared via the internet and with other researchers from around the world. The collaboration has provided a wealth of information and the means to understand the massive cell degeneration found in Alzheimer's, Parkinson's and other diseases of aging. 

Max Sherman is a medical writer and pharmacist retired from the medical device industry. He has taught college courses on regulatory and compliance issues at Ivy Tech, Grace College and Butler University. Sherman has an unquenchable thirst for knowledge on all levels. Eclectic Science, the title of his column, will touch on famed doctors and scientists, human senses, aging, various diseases, and little-known facts about many species, including their contributions to scientific research. He can be reached by email at [email protected]. 
 
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