Meet Barbara McClintock, who used corn to decipher 'jumping genes'
Through meticulous crossbreeding, she showed that DNA is far more complicated than scientists originally thought
I love corn. My favorite way to have it is cooked over a grill until charred, and then lathered with cilantro mashed up in Mexican sour cream, feta cheese, chilli, lime, and lots of garlic. Yummy. I really do love corn, but not as much as one woman: Barbara McClintock. For nearly 70 years, she could not get enough of the stuff and, in 1983, her fixation won her a Nobel Prize. By meticulously crossbreeding corn, McClintock showed that DNA is far more complicated than scientists originally thought. DNA, the blueprint of life, is about two meters long when unfurled and packaged into tightly coiled, thread-like structures called chromosomes, of which we have 23 pairs. You may have been told that our genes are instructions stored on DNA in our chromosomes like information stored on magnetic tape in the 1980s. Read out those instructions and voilà! You can build an organism. However, in the 1930s and 40s, McClintock's work showed that some genes did not exist in fixed position on chromosomes, but could actually jump around from one part of the chromosome to another. These “jumping genes” are now called transposable elements. She also found that the genome is not just a passive database of information but a sensitive and dynamic system, containing a whole host of elements that interact with their environment and each other. Her ideas were completely radical at the time and met with “puzzlement, and even hostility” as she described it. It took everyone else over 20 years to catch up. Early education and research McClintock was born in 1902 in Hartford, CT. Her father was a homeopathic doctor whose parents emigrated to America from Britain, and her mother was a housewife, poet, and artist from an upper-middle-class Bostonian family. Growing up, McClintock, one of four children, liked being alone, often reading by herself in an empty room for hours. Her comfort with solitude was also true in adulthood, where she became a pioneer in corn cytogenetics, the combination of classic genetic techniques and microscopic examination of corn chromosomes. Her love affair with genetics started in 1921, when she took a genetics course as an undergraduate at Cornell's University of Agriculture led by plant breeder and geneticist C.B. Hutchison. Hutchison was impressed by McClintock and invited her to participate in the graduate genetics program. That was it. In 1923 she received her bachelors, in 1925 her masters, and in 1927 a PhD - a feat quite commendable for a 24-year-old woman at the time. After earning her PhD at Cornell, McClintock stayed on as an instructor and assembled a close-knit group of plant breeders and cytologists in the Department of Plant Breeding there, including two fellow graduate students, Marcus Rhoades and George W. Beadle (who went on to also win a Nobel Prize) and the department head Rollins A. Emerson. "We were considered very arrogant," she said. "We were ahead of all these other people, and they couldn't understand what we were doing. But we knew, and we were really a very united, integrated group." Back in the 1930s, the tools that we now have available to simply read a genetic code and link it to a particular trait did not exist; the fact that genes were encoded in DNA had not even been discovered yet. To understand the mechanisms of inheritance in plants, Barbara McClintock had to rely on cross-breeding corn and developing hybrids. Her research focused on finding a way to visualize corn chromosomes and characterize their shape in the resulting hybrids, igniting the field of corn cytogenetics at Cornell. In 1932, McClintock moved to the University of Missouri to work with geneticist Lewis Stadler, who taught her how to use X-rays to introduce mutations into chromosomes. She turned out to be very gifted at doing so. Nobel-caliber research In 1941, McClintock took up a research position at Cold Spring Harbor on Long Island and later became a permanent faculty member there, becoming known for her tenacity. My favorite story about McClintock is the one about her telling off a group of students – including a young James Watson, one of the scientists who would go on to discover the double helix structure of DNA – for wayward balls landing in her crop during their baseball games. Watson described McClintock as “like your mother” - and not in the good way. Little did he know that her research on corn genetics would go on to challenge the simplified version of DNA his work would later support. McClintock remained at Cold Spring Harbor for the rest of her career. She spent much of her time there studying the relationship between color patterns on corn plants and the look of their chromosomes under a microscope. Drawing upon what she had learnt in Missouri, she used X-rays to destroy sections of chromosomes in order to work out where genes were, what they did and how they mutated, linking changes in genes on the chromosomes to changes in traits on the plant. However, there were two genetic elements that McClintock could not locate on the chromosome and concluded that this was because they were not fixed to one particular position – they appeared to be jumping around the chromosomes and explained why some corn had a mosaic pigmentation pattern rather than being one solid color. This phenomenon had been described before – they were called ‘transposable elements’ – but McClintock had a new theory about them: she thought that they were responsible for controlling and regulating how the genes that they found themselves next to were expressed, and that this was a deliberate feature of how the genome worked not just in corn but in other organisms like humans. McClintock was not completely right. Firstly, jumping genes – transposons – do exist in abundance; today we know that they make up 50 percent of the human genome. Secondly, though there are controlling elements in the genome that are responsible for switching genes ‘on’ and ‘off’ like molecular switches, they're not transposons. These elements, which regulate the expression of different genes and traits at different stages of development and allow different cell types with the same genome to have different patterns of gene expression, actually sit next to the genes they control and stay put. Still, she had stumbled upon an important fundamental idea about genetics. But when she presented what she believed to be the most important findings of her career at Cold Springs Harbor annual symposium in 1951, her work was not well received; her peers could not follow her theories, which they considered to be preposterous. Disheartened, she decided not to bother publishing her work again after that. But she did not stop working on corn genetics – “When you know that you are right, you know that sooner or later it will come out in the wash,” she said. In the 1960s and 70s, independent groups of scientists began to describe genetic regulation and the phenomenon of transposition in bacteria. In 1960, Francois Jacob and Jacques Monod described genetic regulation in bacteria. (Not missing a beat, McClintock responded in 1961 with a paper: "Some Parallels Between Gene Control Systems in Maize and in Bacteria".) McClintock’s earlier work started to gain credibility and finally, in 1984, at the age of 82, she got the recognition she deserved and was awarded the Nobel Prize in Physiology or Medicine for "The discovery of mobile genetic elements." Apparently, McClintock had no telephone at the time and happened to hear the news on the radio. Gender Discrimination? McClintock’s profound discovery was dismissed by her male colleagues for years. In the book A Feeling for the Organism: The Life and Work of Barbara McClintock, Evelyn Fox Keller paints this as gender discrimination, putting her late recognition down to the fact that she was a woman. This a story we hear a lot. Watson and Crick vs Rosalind Franklin and the Nobel Prize in Physiology in Medicine, Hewish and Ryle vs Jocelyn Bell Burnell and the Nobel Prize in Physics. However, this may not have been the case for McClintock. As research for his book The Tangled Field: Barbara McClintock’s Search for the Patterns of Genetic Control, historian of biology Nathanial Comfort spent many hours looking through McClintock’s correspondences, research notes, and interviews and argues that this notion of gender discrimination is not consistent with the facts. She was enormously well respected in her time by both her male and female colleagues. Describing this story of gender discrimination as mythology, arising only when she gained popularity in the run up to her Nobel Prize in the 70s and 80s and began to give more interviews, he explained in an interview on the BBC in April 2018 that her late recognition really was down to the fact that movable elements were reinvented in the 1960s when they were discovered in bacteria and given a different context. Barbara McClintock died in 1992, eight years after her Nobel Prize. Whatever the reason for her late recognition, she didn’t seem to mind – saying to People magazine 1983, “It might seem unfair to reward a person for having so much pleasure over the years.”