Barbara McClintock: biography and contributions of this American scientist

Although in the 1930s it was already suspected that chromosomes harbored genes, the pieces of genetic material that encode who we are, this was not empirically proven. Many had tried, but no one had found visual proof of the chromosome-gene relationship.

But Barbara McClintock arrived, who with her corn plants grown by herself, would be able to prove it, despite many seeing her as a mere botanist with the air of a geneticist.

The figure of this researcher is that of a person who, due to how advanced she was at her time, was misunderstood. Next we will discover what her story was through a biography of Barbara McClintock, in which we will see why it has been so important for the history of genetics.

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Short Biography of Barbara McClintock

Barbara McClintock was an American scientist specializing in cytogenetics who was awarded the Nobel Prize in Medicine or Physiology in 1983, being the seventh woman to receive such recognition.

Her work accurately answered the most interesting question of the 1930s: in what structure of the cell are genes found? McClintock's research, together with her doctoral student Harriet Creighton, served to empirically demonstrate that genes were located on chromosomes. Her work with corn plants provided for the first time a visual connection between certain inherited traits and their basis on chromosomes.

Her research also found that genes don't always occupy the same place on the chromosome. McClintock discovered gene shuffling, something that clashed with her time idea that genetic material was static. It was, therefore, a much more complex and flexible element than was assumed in her time, a dynamic structure capable of reorganizing itself.

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Childhood and adolescence

Barbara McClintock was born in Hartford, Connecticut (United States) on June 16, 1902. She was initially registered as Eleanor, but she changed the registration at four months to the name by which she was known, Barbara. She was the third child of the marriage of physician Thomas Henry McClintock and Sara Handy McClintock. She showed greater closeness to her father than to her mother and, in her adulthood, she emphasized that they had both been very supportive, although her relationships with her mother had been rather cold.

From a young age McClintock showed great independence, something that she herself would describe as a great ability to be alone. From the time she was three and until she started school, McClintock lived with her uncles in the neighborhood. from Brooklyn, New York, to help her family financially while her father established a consulting room.

She finished her secondary education at Erasmus Hall High School in Brooklyn. Since she was young, she showed an interest in science, so she decided to continue her studies at Cornell University. Her mother was opposed to it, not wanting her daughters to receive higher education, believing that it impaired their chances of marrying. Added to this, the family was going through certain financial problems that prevented it from paying for her children's university studies.

Fortunately, Barbara McClintock was able to attend Cornell School of Agriculture without paying tuition, and upon completion of her secondary education, she was able to combine her work in an employment office with self-taught training derived from going to the library public. Finally and thanks to the intervention of her father, she began to attend Cornell in 1919 where her success would not be only academic but also social, being she elected president of a student association in her first course.

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Training and Research at Cornell

McClintock began studying at the Cornell School of Agriculture in 1919, where he would study botany and obtain his Bachelor of Science (BSc) degree in 1923. His interest in genetics was awakened in 1921, while he was attending the first course in this subject, led by the plant breeder and geneticist C. B. Hutchison. Because of McClintock's great interest, Hutchinson invited her to participate in a graduate genetics course in 1922. This would mark a before and after in McClintock's career, focusing his vital efforts on delving into genetics.

Both while studying the degree and already working as a botany professor, McClintock dedicated himself to what was then a novel field of maize cytogenetics. Her research group consisted of plant breeders and cytologists, including Charles R. Burnham, Marcus Rhoades, George Wells Beadle, and Harriet Creighton.

The main goal of McClintock's work at the time was to develop techniques to visualize and characterize corn chromosomes. She created a technique based on carmine staining to be able to see these chromosomes through light microscopy, showing for the first time the shape of the ten chromosomes in corn. By studying the morphology of these chromosomes, she was able to relate characters that are inherited together with chromosome segments and confirm that chromosomes were the home of genes.

In 1930, Barbara McClintock she was the first person to describe the crossovers that occur between homologous chromosomes during meiosis. Together with her doctoral thesis student, Harriet Creighton, in 1931 she demonstrated that there is a relationship between this meiotic chromosome crossover and the recombination of heritable traits. McClintock and Creighton found that chromosome recombination and the resulting phenotype resulted in the inheritance of a new trait.

During the summers of 1931 and 1932 she worked in Missouri with the prestigious geneticist Lewis Stadler., who showed him the use of X-rays as an element capable of inducing mutations. Using mutagenized maize lines, McClintock identified ring chromosomes, that is, circular DNA structures generated by fusing the ends of a single irradiated chromosome. During this period she also demonstrated the existence of the nucleolar organizer in a region of maize chromosome 6, which has been shown to be essential for nucleolus assembly.

Barbara McClintock was awarded a Guggenheim Foundation scholarship that paid for her six months of apprenticeship in Germany during 1933 and 1934. Her initial plan was to work with geneticist Curt Stern, a researcher who demonstrated interbreeding in Drosophila (flies) for weeks. after she and Creighton did the same with corn, but she just so happened that Stern immigrated to America right there moment. For this reason, the laboratory that ultimately accepted McClintock was Richard B. Goldschmidt.

Due to the political tension in Germany at the time, in which she saw how the Nazi rise was imminent, McClintock returned to Cornellher, where she would remain until 1936. That year she obtained the position of assistant professor in the Department of Botany at the University of Missouri-Columbia.

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Experiences in Missouri

While at the University of Missouri, McClintock continued the line of X-ray mutagenesis. She observed that chromosomes break and fuse under these conditions, but so do endosperm cells spontaneously. She found out how the ends of the broken chromatids were joined after DNA replication in the phase of mitosis.

Specifically, it was at anaphase that the broken chromosomes formed a chromatid bridge, which disappeared when the chromatids moved towards the cell poles. These ruptures disappeared, forming unions during the interphase of the next mitosis, repeating the cycle and causing massive mutations, which led to the appearance of endosperm variegated.

This cycle of chromosome breaking, merging and bridging was considered a crucial discovery at the time.. First, because she showed that chromosome binding was not a random process, and second, because she identified a mechanism for the production of large-scale mutations. In fact, this finding is so important that it is still used today, especially in the study of cancer research.

Although her research was producing very green shoots in Missouri, McClintock was not at all satisfied with her position. She felt excluded from faculty meetings and was not notified of vacancies at other institutions. Although she initially had a lot of support from her classmates, the academic competitiveness and the fact that she was an independent and lonely woman she caused her to become alienated in her investigations every time plus.

An unpleasant anecdote that would show how little valued she was by some of her classmates is that In 1936, an engagement announcement for a woman with the same name and surname as hers appeared in the newspapers. Mistaking this woman for her, her department head threatened to fire her if he married her. By then McClintock was already vice president of the Genetics Society of America.

McClintock had lost confidence in her coordinator Stadler and in the administration of the University of Missouri. Therefore, when in 1941 she received an invitation from the director of the Department of Genetics at the Cold Spring Harbor Laboratory to spend the summer there, she accepted it immediately. She did it as a way of looking for a job somewhere other than Missouri, trying her luck.

She, too, around this time she would accept the visiting professor position at Columbia University, where her colleague Marcus Rhoades was a professor. He offered to share her line of investigation with Long Island's Cold Spring Harbor. In December 1941 she was offered a research position at the Cold Spring Harbor Laboratory, belonging to the Department of Genetics of the Carnegie Institution of Washington. I would end up accepting it.

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Investigations at Cold Spring Harbor

After a year working part-time at Cold Spring Harbor, Barbara McClintock accepted a full-time investigator position at Cold Spring Harbor. There she would continue her work on the break-merge-bridge cycle, being an extraordinarily productive period in scientific publications.

Because of these prolific investigations, McClintock she was recognized in 1944 as an academic at the United States National Academy of Sciences, being the third woman to be elected. A year later she was named president of the Genetics Society of America, an honor that had never been bestowed on a woman.

On the recommendation of geneticist George Beadle, in 1944 she did a cytogenetic analysis on the Neurospora crassa fungus. Beadle had demonstrated a gene-enzyme relationship by working with this fungus for the first time. McClintock determined the karyotype of the fungus as well as its life cycle and, since then, N. crassa is used as a model organism in genetic studies.

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Discovery of gene regulation

McClintock she dedicated the summer of 1944 to finding out the biological mechanism behind the genetic mosaic phenomenon, a genetic condition that caused the seeds of the same ear of corn to have different colors. She found two places on the chromosomes (locus) that she named "Dissociator" (Ds) and "Activator" (Ac). Ds was related to chromosome breakage, in addition to affecting the activity of nearby genes when Ac was present. In 1948 she discovered that both loci were transposable elements that could change their place on the chromosome.

McClintock studied the effects of the transposition of Ac and Ds she analyzing the patterns of coloration in the maize kernels throughout generations of crosses. Her observations led him to conclude that Ac controlled the transposition of Ds on chromosome 9, and that its transposition was the cause of the breakdown of the chromosome.

When Ds moves, the gene that determines the color of aleurone (corn seed) is expressed, since the repressive effect of Ds is lost and, consequently, the appearance of color occurs. This transposition is random, which means that it will not affect all cells, which explains why mosaic occurs in fruitlessness. McClintock also determined that the transposition of Ds is determined by the number of copies of Ac.

During the decade of the 50 ' he developed a hypothesis that explained how transposable elements regulate the action of genes, inhibiting or modulating them. She defined Ds and Ac as control units or regulatory elements, to clearly separate them from genes. With this he hypothesized that gene regulation can explain how multicellular organisms can diversify the characteristics of each cell, despite the fact that their genome is identical. This idea completely changed the concept of the genome, which until then was interpreted as a mere set of static instructions.

McClintock's work on gene regulation and control elements was so complex and novel that the rest of the scientific community was somewhat suspicious of his discoveries. In fact, she herself described that response as a mixture of bewilderment and hostility. Despite this, she McClintock went ahead and continued with her line of investigation.

She later identified a new regulatory element called "Supressor-mutator" (Spm) that, although it was similar to Ac and Ds, carried out more complex functions. However, given the reactions of the scientific community at that time and McClintock's perception that she was drifting away from mainstream science, she made him stop publishing his results of it.

Recognitions and last years

In 1967 McClintock retired from her position at the Carnegie Institution.her, being her named distinguished member of the same. This distinction allowed her to continue working as an emeritus scientist at Cold Spring Harbor Laboratory with her fellow graduate students. In fact, she remained affiliated with the laboratory until the day of her death.

In 1973 she confessed the reason why she decided not to continue publishing her findings on regulatory elements, despite continuing to investigate on her own. She commented that because of her experience in labs, it is very difficult to make someone else aware of her unspoken assumptions. She considered that, due to the fixed ideas of many scientists, some advances cannot be shared at a certain moment, since criticism will be assured. You must wait for a conceptual change to occur and communicate them at the right time.

Her experience strengthened her views in this regard, it took decades for her findings to be taken into account. Barbara McClintock's work was only fully appreciated when, in the 1960s, geneticists François Jacob and Jacques Monod reached similar conclusions with their respective studies, presented in a 1961 work entitled “Genetic regulatory mechanisms in the synthesis of proteins”. proteins ”). McClintock read the work and compared her findings with those raised by the French.

Fortunately, McClintock was finally widely recognized for her work. Her discovery of her transposition was valued when this same process was described by other authors in bacteria and yeasts in the 1960s and 1970s. In the 70's, Ac and Ds were cloned, showing that they were class II transposons.

Ac is a complete transposon, encoding in its sequence a functional transposase, which allows the movement of the element through the genome. Instead, Ds encodes a non-functional, mutated version of the transposase and requires the presence of Ac in order to jump into the genome, something that fits McClintock's functional description. Later studies showed that these sequences do not move if they are not stressed, such as break by irradiation or others, for this reason its activation could provide an evolutionary source of variability.

McClintock she understood the role of these agents as evolutionary agents before even other scientists suspected it. In fact, today the Ac / Ds system is used as a mutagenesis tool in plants, to characterize genes of unknown function and in species other than those of corn.

Thanks to the fact that the truth of her findings and the value of her work, applicable beyond the field of botany, were finally recognized, Barbara McClintock received the Nobel Prize in Physiology in 1983, being the seventh woman to obtain it and, unlike other occasions, to receive it only one person. Normally, the Nobel Prize in Science is won by research teams, but since McClintock had to be self-employed for most of her life, the credit went to her alone.

Barbara McClintock died of natural causes on September 2, 1992 at Huntington Hospital, near the Cold Spring Harbor Laboratory where she lived so many moments. She was ninety years old, and she passed away without leaving children or ever having married?