BARBARA McCLINTOCK (1902-1992)
Pioneer of Micro-Cellular Directed Genetics
King-Thom Chung, Department of Biology, The University of Memphis
Barbara McClintock never worked directly with bacteria or viruses, but she was a great microbiologist. Her pioneering directly affected the genetics of the microbial world. When we use the word "microbiologist," we customarily think of virologists or bacteriologists. But we need to remember that many helminths (and we think of them as the "parasites" even though bacteria and viruses are also parasites!) are microscopic. Considering life cycles, starting with the egg and sperm, all "life" is microscopic at some stage. All living things are at any one time, divided into the microscopic or the macroscopic. The microscopic, the world of invisible, is as vast and surprising as the macroscopic universe, with its enormous solar systems and spiral nebulae. Barbara McClintock was a true pioneer of the microscopic world.
Barbara McClintock worked with cellular and sub-cellular life and its denouement in the adult plant. She was able to view chromosomes and even their components and determine their effect upon the adult corn plant, which allowed her to visualize genes before the name "gene" was known. McClintock published her work thirty years before it was generally acknowledged and accepted. Today biologists can learn from her life the need for courage and the ability to "go at it alone" when necessary.
McClintock was born on June 16, 1902 in Hartford, Connecticut. She was the youngest of the three sisters. She grew up first in rural Massachusetts and later in Brooklyn, NY. She was active in sports, but also enjoyed just "thinking" and especially a wide range of subjects reading. After graduating from high school in 1918, McClintock enrolled in Cornell University as a Botany major, a field in which she remained for her entire life. While in college McClintock was president of her freshman class and very socially active, playing the banjo in the school band. She earned her BS degree in 1923 and immediately began graduate work. One of her first advances was in identifying individual maize (corn) chromosomes under microscope. In 1925 she completed the MA degree and started work on her PH.D., which she completed in the field of plant genetics in 1927. In addition she also received an honorary Doctor of Science degree from Rochester University.
The new Dr. McClintock took a position as an instructor in botany at Cornell, whre she stayed until 1931. She also served brief periods at the Western College for Women, Smith College, and Williams College. During all of her years as a teacher of botany, McClintock also did research on the genetics of the maize plant. One important paper published in 1931 was on the exchange of genetic information in meiosis, a form of cell division; this paper was in the Proceedings of The National Academy of Science. She also received a National Research Council Fellowship for further work on maize. In this year she also was appointed a research fellow at the California Institute of Technology. In 1933 she received a Guggenheim Fellowship and did research in Germany. Her work on maize continued.
In 1936 she was appointed Assistant Professor of Botany at the University of Missouri where she taught and did her research until in 1941. The following year she accepted a research position at the Carnegie Institute's Department of Genetics at Cold Spring Harbor, Long Island, New York. While here, she made her home in Cold Spring Harbor. She continued her research at the Institute until her death on September 2, 1992.
The life of Barbara McClintock is one that every science student and teacher needs to study! In the time in which she did her work, science was largely a male institution. Her pioneering was done over a 30 year period when geneticists did not understand the work she was doing and institutions were not prepared to accept it. As stated before, she was also a women working in a predominantly male field. In addition to these big obstacles, she was an intensely individualistic person. She did not need the approval of others, but enjoyed her own observations and her own private experiences. To some extent she was like Gregor Mendel, the monk who worked with peas to initiate the science of genetics. His work was done in the garden of a monastery in Brunn, Moravia, part of Austrian empire. Monks were not supposed to be learning or teaching biology and science itself was considered an enemy of the church. Mendel selected such contrasting characters in his peas as tall/short, wrinkled/smooth, and green/yellow. He planted the peas, pollinated accurately and kept track of the percentage of the plants; he continued this work for 8 years. From his work he deduced that hereditary characteristics were controlled by factors. These factors were in pairs, one from each parent. The factor pairs separated during the formation of the sex cells, with the egg receiving one factor and the sperm the opposite but related factors, such as tall/short. He found that in crossing the plants, one factor may prevent the expression of the other; one factor was dominant and the other recessive. Like McClintock later, his results were not recognized. Although he published his results and the journals were widely received, science was not yet ready for his findings.
The great emphasis in science at the time was on spontaneous generation; the scientific world was shocked by Pasteur's refutation of this idea; in addition Pasteur startled the scientific world with his demonstration of microbial disease and the saving of animals and humans from death by such diseases. Mendel, living in the same general period, was not able to show his factors under a microscope, but instead, had to offer mathematical proof. Pasteur was recognized as a devout man as well as a scientist; Mendel as a monk was not regarded as a scientist, but as a peripheral person and somewhat of an "enemy" to the church. Mendel's work, like McClintock's , was rediscovered many years later at the turn of the century. Among the discoveries of science which helped in the rediscovery of Mendal ( and also McClintock) was that of nuclear material which took stain more deeply; it was called chromatin. The chromatin went through a cycle; at cell division chromatin threads split lengthwise, then consolidated and shortened to become definite bodies called chromosomes. Barbara McClintock became an expert in the study of these chromosomes under the microscope. Her history was very much like Mendal's, whom she updated and whose work she modernized. Barbara McClintock was recognized as a brilliant scientist and an impeccable worker, but she was also considered acerbic, with a sharp tongue, too specialized in her interest in corn and a bit eccentric. But one is quick to raise the question: are not these typical of many professors? The answer is yes--but at that time, only male professors! Such characteristics were considered a detriment in a woman! Cornell University did not grant a full professorship to a woman until 1947--and that was in home economics! Barbara grew her own corn, and with minimal support through fellowship with the National Research Council and later, the Carnegie Institution. In the 1940s she carried out experiments which ultimately led to the 1983 Nobel Prize. Both careful observation of the macroscopic plants and the chromosomes under the microscopic were required, plus some unusual sharp insight regarding unusual happenings. The kernels of some plants showed a purple color and others were colorless. But some kernels which should have been colorless were purple in color! She was astute enough not to bypass the unusual. After many trials she noticed a regularity to the pattern. This was the basis for her discovery of transposition, for which she received the Nobel Prize. She discovered not only the major genes (she called them "controlling elements" as this was long before the name "gene" was given) but also other factors which caused the genes to be expressed or not expressed. These factors were on the 10 chromosomes of the corn plant, which she studied extensively as a true "microbiologist," and microscopist.
She discovered also that the chromosomes can cross over during the formation of sex cells, sperm and ova. The cross-over point were called chiasmata; these resulted in an actual exchange of genetic material between chromsomes.
There are "band-wagons" in science, but Barbara was not one to get on them! Barbara McClintock stuck with her corn plants for the study of genetics. Corn takes a year to grow. The mice reveal genetic characteristics in months; fruit-flies respond in weeks; bacteria reveal them in days and viruses may do so in hours! Most geneticists therefore used the more rapidly growing species for their genetic experiments. Nevertheless, chromatin and genes are characteristic of all living matter and the findings of Barbara on corn were applicable to microbes. The findings of Watson, Crick and Wilkins regarding DNA and RNA applied to all genetics; but we will find there are differences, also. The organisms microbiologists worked with, largely bacteria and viruses, seldom had chromosomes (some microscopic parasites, as well as blue-green bacteria do have chromosomes); genetic material was found throughout the organism and genes were formed at reproduction. All living things were first divided into 2 "kingdoms"--plant and animal. Then the "kingdoms" became the "karyote" and "non-karyote" kingdoms, since this seemed to be a more general division. Microscopic organisms, mostly, were placed in the non-karyote kingdom--living forms without nuclei. Nucleated organisms were placed in the "karyote" kingdom. Recently, a third kingdom has been proposed: the "archeobacteria". These bacteria are often found around ocean vents and live on the sulphurous fumes which come from the interplay of the magma of the earth and the ocean. Giardia lamblia, a parasite, is related to these, and by some biologists is considered a "missing link." One of the characteristics of the archeobacteria is a double nucleus with two sets of chromsomes which remain through life [ this name for the third kingdom will probably be changed, since more than bacteria are found in it ].
The scientific world was highly excited about the work of Watson and Crick, unlike the response to Barbara McClintock. They published their findings in Nature (1953) and became instant heroes. One reason was the clarity of the model which they developed. This was the basic model of DNA with the double helix and the repeating subunits, the nucleotide with phosphate, sugar and hydrogen bonds. Ten years later they shared with Maurice Wilkins (who had done photographic analyses of DNA) the Nobel Prize in Medicine and Physiology. Barbara McClintock's work helped form the "central dogma" of DNA, but she remained outside the core group during the development of the concepts. The central dogma was far more rigid than the concepts fostered by McClintock and her "jumping genes", which moved about and affected other genes. She also called attention to the differences between the smaller and larger organisms in regard to genetics. Jacques Monod, 1965 winner of the Nobel Prize in Physiology and Medicine once said: "What is true for E. coli (an intestinal bacterium) is true for the elephant." There are elements of truth to this, but McClintock pointed out that in the larger animals the cells were more complex and in the embryonic stage actually directed the development of an entire large organism, which might become an elephants, a whale or a gigantic redwood tree. The cell, she said, had to make "wise decision" in these cases. Bacteria and viruses had genes and DNA, but were not destined to become enormous multi-celled beings, whose development was guided by the original embryonic cells. These were exceedingly formidable concepts, well ahead of their time. Monod's concepts were a hold-over from the non-living world of physics, but McClintock knew better! An organism consisting of cells in corn stalk tassels and kernels which is starting a corn plant has a great many more decisions to make than a single-celled Escherichia coli bacterium! The largest chromosome of a Drosophila fruit-fly is nineteen times the size of E. coli and the human genome is a thousand times its size. McClintock stated that molecular biologists had no "feel" for what these biological cells did. This was heresy when molecular geneticists with a physics background were at the top of the scientific world.
It is well for the new microbiologist and scientist--and his professor--to see that the advances in sciences often come not from the "central dogma", but from the peripheral areas, of which Barbara McClintock was an ideal example. Since 1945 on, she showed that genes were not immutable and that they moved--opposite to many ideas in classical Mendelian genetics, which she, herself, had helped modernize. New discoveries often refute the "central dogma", as the examples of Columbus and Galileo reveal. Even when her work was available, Jacques Monof and Francois Jacob, two French geneticists who corroborated her work, failed to read and cite her findings, because there was no settled terminology and they may have been difficult to find. A scientist therefore needs to search diligently and be aware that terms a little different from his may be in use.
One scientist has stated that after 60 years of work, geneticists are back to the original questions: "How does the egg from the organism?" Many scientists are uncomfortable with Barbara McClintock's answer. Intuition! Speaking of chromosomes and genes, she said that the more she worked with them, the bigger and bigger they got. Finally, as she looked through her microscope as all microbiologists must, she began to "feel" that she was there with the genes! She said, "you forget yourself--it surprised me that I actually felt that---these were my friends. As I looked at the genes they became part of me.--The main thing about it is that you forget yourself."
As you try to find the field in science which most appeals to you, can you apply Barbara McClintock's way?