In 2023, it will be forty years since Barbara McClintock (1902-1992) became the first and only woman to win the Nobel Prize in Medicine alone for her discovery of “jumping genes”, a scientific milestone that revealed that human genomes they are not static, but can self-modify and reorganize.
Looking at an ear of corn most of us would not imagine that it could contain the secrets of life. Barbara McClintock dedicated her life to the study of maize and with her investigative passion she discovered the possibility of changes in the human genome. Her discovery of what would come to be called “jumping genes” revealed that a genome is not static, but can change and rearrange itself.
This idea laid the foundation for current genetics, including the possibilities of genome editing with CRISPR techniques.
A solid and tenacious research career
McClintock was born in Connecticut in 1902 to a conservative family that expected her to devote her life to being a wife and mother. It couldn’t be because young Barbara had a passion for research. At Cornell University, she earned a BS and a Ph.D. in botany before beginning research on corn in graduate school.
There, at just 28 years old, he described for the first time the crossing over that occurs between homologous chromosomes during meiosis. In 1934, after the rise of Nazism ended a Guggenheim fellowship with which he was doing research in Germany, he returned to Cornell.
At that time, the conservative New York university did not hire female professors, so in 1936 he had to settle for a position at the much more modest university in Missouri. But the most decisive change in her career occurred in 1941, when she joined the prestigious Cold Spring Harbor Laboratory on Long Island, New York, where she would continue for the rest of her life.
The discovery of transposons
At Cold Spring Harbor, McClintock focused on investigating how the different colors of corn kernels could be transmitted, linking that inheritance to changes in chromosomes. So far nothing new: it was a typical case of Mendelian inheritance. What truly constituted a milestone in genetic research was demonstrating that changes in the position of a genetic element on a chromosome could cause nearby genes to be turned on or off.
By studying the maize genome in depth, that is, by observing the thousands of “letters” that make up its DNA, McClintock saw for the first time that there were series of genetic sequences that could, without knowing how, change position.
In a famous paper, published in 1950, he called them “controller elements” because by varying their position in the genome they could in some unknown way “turn on” or “turn off” the expression of other genes in maize.
These “jumping” genes were later called transposons.
PNAS
McClintock’s finding was not only revolutionary: it was also theoretically highly complex. The “jumping genes” changed to a large extent the conceptual paradigm that was held on genetics at that time. Although the idea of segments of DNA that can change position was widely accepted by geneticists in the 1950s, its broader applications were not recognized until the 1970s, when molecular biologists began to note the widespread presence of transposons. in viruses, bacteria and in the human genome.
Transposons and human health
When the nucleotide sequence of the 3 billion base pairs that make up the human genome was obtained at the beginning of this century, it was confirmed that more than 60% is made up of transposons or sequences related to them, such as certain viruses.
Transposons invaded the genome of our ancestors throughout evolution. Because they mostly inserted into non-functional genomic regions, they spread through genomes even though they did not carry useful molecular functions for cells or organisms.
Thus, despite not being functional, they did not cause negative effects and accumulated as “genomic parasites”.
Currently, the transposons in our genome are fixed in their innocuous positions and have generally lost the ability to transpose. However, exceptionally some can be moved again when the early reproductive or embryonic cells are formed, integrating into the interior of some genes, altering their expression and being able to cause some diseases such as certain cases of hemophilia or leukemia, colon or breast cancer and certain neurological degenerative disorders caused by their integration into key genes of adult somatic cells.
On the shoulders of giants
Science advances to steps, not leaps. Despite the effort to build an epic in which ideas are like lightning that suddenly illuminates the darkness of ignorance, reality does not work that way. A good hypothesis or a great discovery are not sparks that suddenly ignite a bonfire. They are, with absolute certainty, an ember detached from a bonfire that others had already fed.
Ramón y Cajal won the 1906 Nobel Prize in Medicine using a simple monocular microscope. The equipment used by McClintock in his early days at Cornell was also very elementary: a monocular microscope made in 1927 that is preserved in the National Museum of American History.
Although much more understated and simple than many of today’s models, the rack and pinion adjustment system and glass stage are still familiar to modern scientists. When one contemplates that microscope, one realizes that any scientific discovery is more than a simple “eureka!”: it is the accumulation of years of hard work and multidisciplinary collaboration.
Bernardo de Chartres said that “we are like dwarfs on the shoulders of giants. We can see more, and further than them, not because of any physical distinction of ours, but because we walk lifted up by their great height. The phrase was taken up by Luis Vives and reached the scientists of the 17th century who, like Isaac Newton, had no qualms about recognizing that his achievements stood above the work of his predecessors.
In 1902, Sutton and Boveri’s chromosome theory stated that the alleles that Mendel had postulated in 1865 as regulators of heredity were located on the chromosomes. One hundred years later, the Human Genome Project was successfully completed. A century of progress made possible by giants like Barbara McClintock, on whose shoulders hundreds of geneticists have ridden.