Barbara McClintock
Lived 1902 – 1992.
Barbara McClintock made a number of groundbreaking discoveries in genetics. She demonstrated the phenomenon of chromosomal crossover, which increases genetic variation in species. She also discovered transposition – genes moving about within chromosomes – often described as jumping genes, and showed that genes are responsible for switching the physical traits of an organism on or off.
Beginnings
Barbara McClintock was born on June 16, 1902 in Hartford, Connecticut, USA. She was christened Eleanor McClintock, but her parents soon started calling her Barbara: they considered this name a perfect match for her forthright, no-nonsense character; they had come to believe that Eleanor was too feminine and gentle a name for their daughter.
Her father, Thomas Henry McClintock, was a family doctor whose parents had come to America from Britain. Her mother, Sara Handy, came from an upper-class Boston family; she was a housewife, poet and artist. Barbara was the third of the couple’s four children.
From the start, Barbara and her mother got on rather badly. Between the ages of three and five, to help reduce the stress on her mother, Barbara spent most of her time living with her aunt and uncle in Massachusetts.
Barbara returned to her parents in Hartford to begin school. In 1908 the whole family moved to Brooklyn, New York.
In contrast to her shaky relationship with her mother, Barbara always got on very well with her father. Both parents did everything they could to allow Barbara to grow into the person she wanted to be, even allowing her to skip school if she wished to do something else. From an early age, being the person she wanted to be meant being alone. Barbara preferred her own company to anyone else’s.
At Brooklyn’s Erasmus Hall High School her teachers could see that Barbara was exceptionally clever, and perhaps destined for life as a college professor. Her mother was very uncomfortable about this, believing that female college professors were bizarre creatures. Afraid that it would turn Barbara into an oddball nobody would ever want to marry, she refused to allow her daughter to go to college.
Starting College
Eventually, in September 1919, Barbara’s father overcame her mother’s objections and, aged 17, Barbara rushed off to enroll at Cornell University in Ithaca, New York. Leaving home was a liberating experience for Barbara. She grew happier, more relaxed, and enjoyed her time as an undergraduate. Her intense desire to be alone also faded: she socialized with other students, joined a jazz band, and was elected president of the women’s freshman class.
Dr. McClintock
Barbara McClintock took her first genetics course in 1921. Her ability in this field soon caught the attention of her teacher, Claude Hutchison, who recommended that she should jump straight on to the graduate-level course the following year. She was delighted to do this, all the time growing ever more fascinated by the genetics of plants. After receiving a B.S. in agriculture in 1923, she decided to pursue her fascination at graduate school.
Barbara McClintock and her father in about 1923, the year she got her B.S. degree. Image courtesy of BMC Collection Photographs, Cold Spring Harbor Laboratory.
1925 McClintock was awarded an M.S. in botany and in 1927 a Ph.D. in botany, both earned at Cornell.
Her M.S. and Ph.D. degrees involved investigations of plant genetics. This would be the focus of her research for more or less the rest of her life.
After she completed her Ph.D., Cornell appointed McClintock to the role of instructor in the Botany Department.
Cytogenetics
McClintock worked in plant cytogenetics, meaning she used microscopes to investigate plant genetics at the cellular level – particularly studying chromosomes, the chunks of genetic code sitting inside cells. Cytogenetics had begun to reveal more of the secrets of life than traditional style genetics could.
Traditional style genetics involved breeding successive generations of an organism and observing differences visible to the naked eye. Gregor Mendel’s work on heredity exemplified the older style of genetics studies.
Cytogeneticists did everything a traditional geneticist would do, plus they also correlated their observations with changes taking place within cells.
Barbara McClintock’s Contributions to Science
Chromosomal Crossover
In addition to her own individual research work and her teaching load, McClintock began guiding Harriet B. Creighton, a graduate student. In 1931 the pair published a major discovery.
McClintock and Creighton had been researching the behavior of chromosomes
Cells carry their genetic code in structures called chromosomes, which contain DNA. (The role of DNA in chromosomes was unknown when McClintock & Creighton were doing their chromosomal crossover work.)
McClintock had developed improved staining techniques, which allowed her to see chromosomes under the microscope better than anyone else had before.
Using these staining techniques McClintock and Creighton proved the existence of chromosomal crossover.
Chromosomal crossover happens when the cells that take part in sexual reproduction are being made in a process called meiosis. In animals these are the egg and sperm cells.
Like many of the other cells in our bodies, sex cells contain chromosomes.
BUT… egg and sperm cells are different from normal cells because they only contain half the normal number of chromosomes. In the case of a human, a normal cell contains 46 chromosomes, while sex cells contain 23.
When egg and sperm cells merge during reproduction, they each provide 23 chromosomes to produce a new cell with 46 chromosomes. This new cell will grow into a new person. Half of its chromosomes come from mom and half from dad.
What McClintock & Creighton discovered is that when sex cells are being manufactured, nature can shuffle the genetic pack of cards to produce chromosome variations before sexual reproduction has happened.
Imagine a cell in dad’s body. This is a special cell that is going to produce sperm cells. This cell contains 46 chromosomes, 23 of which dad inherited from his dad (paternal chromosomes) and 23 from his mom (maternal chromosomes). Each paternal chromosome in the cell is paired with a maternal chromosome to form 23 chromosome pairs.
A chromosome contains a strand of DNA. This is one of the 23 chromosomes dad inherited from his dad.
Each paternal chromosome is paired with a maternal chromosome.
Each of the 23 chromosomes dad inherited from his dad is paired with one he inherited from his mom, making 23 pairs of chromosomes in a typical cell.
To make new cells, every chromosome makes a copy of itself so now there are two identical packages of DNA attached in a single chromosome, as shown.
This paternal chromosome now consists of two identical strands of genetic material linked together making an X shape.
This paternal chromosome continues to be paired off with its maternal partner as shown below.
McClintock & Creighton showed that these chromosomes line up and then crossover as shown below:
The chromosomes swap sections of genetic material (we now know that these are sections of DNA) to produce new chromosomes. In the image below you can see that the new chromosomes now have different genetic coding from the originals.
So genetic variations are being introduced even before the sperm cell meets an egg cell.
The two chromosomes shown above split in half to produce the genetic material for four sperm cells. Each of the four sperm cells will be genetically different.
Each human sperm cell contains 23 different chromosomes ready to pair with 23 chromosomes in an egg cell to make a genetically unique new living being.
Chromosomal crossover had been proposed as a theory 20 years earlier by Thomas Morgan to account for the way offspring inherit genes from their parents. McClintock & Creighton showed that the theory was correct. They did this by showing how the changes they saw in chromosomes during the production of maize sex cells exactly matched the changes in traits observed in maize plants grown from the fertilized seeds.
X-rays, Breaking, Fusion & Bridging, and the Centromere
In 1936, at the age of 34, McClintock became an assistant professor at the University of Missouri, where she worked until 1941.
A few years earlier, in the summers of 1931 and 1932, McClintock had visited Missouri and learned how to use X-rays to cause mutations in cells.
When she returned in 1936, she began using X-rays again. She discovered that large-scale mutations can arise from breaking, fusion and bridging of chromosomes. This BFB cycle, discovered by McClintock, leads to chromosomal instability, which means daughter cells have a different number of chromosomes from the cell that produced them. Although she discovered the phenomenon in the late 1930s, this is still an active research field today. Chromosomal instability is common in cancers.
In 1938 McClintock analyzed the cell genetics of the chromosome’s centromere, for the first time describing how it functions.
The centromere (the dull yellow circle in the image) links two identical strands of genetic material in the chromosome.
Her time at the University of Missouri was relatively unhappy. Although she could be rather abrasive and intimidating herself, at Missouri she came up against the even more abrasive and intimidating Mary Guthrie, another assistant professor, who also worked in cytology. McClintock and Guthrie got on exceptionally badly, making McClintock’s life miserable all too frequently. She also (incorrectly) saw no prospects of ever getting a secure, tenured position at Missouri. She decided it was time to move on.
The Final Professional Move
In early 1941, aged 38, McClintock became a visiting professor at Columbia University in New York.
In 1942 she accepted a temporary genetics position at the Cold Spring Harbor Laboratory on Long Island. Within a year she had been offered and accepted a permanent faculty position. She was very pleased with her new role. She no longer had teaching duties, and she had freedom to do whatever research she liked. She would work at Cold Spring Harbor for the rest of her career.
In 1944 she became the third woman ever to be elected to America’s National Academy of Sciences.
Mobile Genetic Elements & the Nobel Prize
Jumping Genes
Beginning in 1944 McClintock studied the relationship between color patterns on corn plants and the look of their chromosomes.
One of the colors she was most interested in was purple. She wanted to understand the genetic reasons for purple-spotted corn.
The corn plants from one generation to the next were self-pollinated. Comparing offspring with parent chromosomes, she found it looked like the offspring chromosomes were reorganized versions of parent chromosomes. Parts of the chromosomes looked like they had been snipped out and shifted to entirely new locations.
She had discovered parts of the chromosome – she called them Dissociators (Ds) and Activators (Ac) – which could cause insertions, deletions, and relocations of genes in the chromosome.
The theory of the time said genes were in fixed positions on the chromosome: McClintock’s work showed this was wrong.
The Dissociator could break the chromosome and alter the behavior of genes around it, but only in the presence of the Activator. The purple color could be switched on or off by the Dissociator. In other words, physical traits were being controlled by Dissociators and Activators.
In 1948 she discovered that Dissociators and Activators could transpose – in other words, jump to different places on the chromosome. They are often, therefore, called transposable elements.
Mobile/Controlling Elements
McClintock produced a theory that the Dissociators (Ds) and Activators (Ac) were in fact gene controllers – she called them controlling elements. They controlled the genes on a chromosome – they could inhibit or modify their behavior. This explained why an individual living thing, such as a person, can produce all sorts of different cells even though every cell has the same genetic code. The gene controllers make the difference by giving specific instructions in specific circumstances.
In McClintock’s view, genes could no longer be thought of as unchangeable instructions handed from parents to offspring. They could react to specific circumstances in the environment. Mobile genes could jump around within chromosomes and switch physical traits on or off.
She studied this phenomenon until 1950 before she began publishing her work.
In a scientific world that believed genes were very stable and could only change a little at a time, her findings were so radical that she was worried about how people would react to them.
You can see why I have not dared publish an account of this story. There is so much that is completely new and the implications are so suggestive of an altered concept of gene mutation that I have not wanted to make any statements until the evidence was conclusive enough to make me confident of the validity of the concepts… The size of the job ahead is staggering to contemplate, however.”
Her Machines Came From Too Far Away
McClintock presented her work in 1951 to an audience of key players from America’s universities at Cold Spring Harbor’s annual summer symposium. She focused on her theory of controlling elements as gene regulators. She was dismayed by the reaction. Other scientists could not follow her line of thought.
Although she had won plenty of recognition for her previous work, McClintock regarded her work on mobile genetic elements as her most important work by far, yet nobody seemed to be taking any notice of it. Feeling ignored, she became depressed. She stopped publishing her work in this field.
McClintock’s dismay has close parallels with Richard Feynman’s dismay three years earlier when he presented his revolutionary ideas in quantum field theory at the Pocono Conference in 1948. In the end, after getting nowhere with his presentation to America’s best physicists, he realized: “I had too much stuff. My machines came from too far away.”
In Feynman’s case, a young mathematical physicist by the name of Freeman Dyson came to his rescue. He translated Feynman’s work into terms other physicists could understand. Unfortunately, in cytogenetics, there was no Freeman Dyson to act as Barbara McClintock’s white knight.
Slowly Moving Forward
In 1960 Francois Jacob and Jacques Monod started to publish their work describing genetic regulation in bacteria. Realizing the similarities between their work and hers, McClintock responded in 1961 with a paper: Some Parallels Between Gene Control Systems in Maize and in Bacteria.
Slowly, her theory of transposable elements and gene control began to gain credibility.
At the beginning of the 1970s molecular biologists discovered transposition taking place in bacteria and viruses. They began to see that transposition was important in immunology and cancer. Scientists also saw the potential importance of transposition in manipulating genes to function in the way scientists wanted them to – genetic engineering.
Today we know that 50 percent of the human genome is made up of transposable elements!
Major Official Recognition
In May 1971 McClintock received the National Medal of Science from President Richard Nixon. A large number of other awards and honorary degrees followed, culminating in the 1983 Nobel Prize in Physiology or Medicine “for her discovery of mobile genetic elements.”
She was, by this time, 81 years old.
Some Personal Details and the End
Although she abandoned her life as a loner when she started college, McClintock never made close friends. She regarded herself as a free spirit; coming too close to anyone might have robbed her of some of that precious freedom. She enjoyed her privacy. She did not marry and had no children.
Barbara McClintock died aged 90 of natural causes in Huntington, New York, on September 2, 1992. She died peacefully. Her mind remained clear and intellectually vigorous to the end. She was buried in the Huntington Rural Cemetery.
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