THIS LESSON IS ABOUT A TINY WOMAN WITH A BIG MIND WHO JUMPED WITH SOME GENES AND HELPED CREATE MODERN GENETICS
It is 1921 and Barbara McClintock has enrolled in the only course in genetics open to undergraduate students at Cornell University. Her timing is propitious. Some biologists who consider themselves forward looking are now paying serious attention to Gregor Mendel’s 19th century experiments. Mendel was fascinated by statistics as well as biology, so he grew peas and kept track of thousands of them. A paper he wrote about what he learned has led, in the 20th century, to the idea of the gene. Now scientists are trying to locate Mendel’s units of inheritance on chromosomes, and are calling these units 'genes.' But no one actually knows exactly what a gene is.
Physics is the attention-grabbing science of the day, with Albert Einstein's star power adding luster to the field. By contrast, life science is a toddler finding its balance. And it has problems: Darwin’s theory of evolution (change over time), which is being taken seriously, depends on a source of natural changes. Darwin write about “survival of the fittest,” which means that the fittest forms of life usually survive and breed. So, over time, life’s direction has been toward more sophistication and more success in dealing with life problems. But there needs to be choice to find a fittest. No one is sure where choice comes from.
Complicating things: some of Darwin’s Cambridge friends have given evolutionary biology an unnecessary anti-religious taint that will keep more than a few from delving into this vital science.
Besides all that, the life science world is in flux. For those at biology’s center, this is a pioneering era. Feisty Barbara McClintock, just under 5’2”, will stand tall among them.
Cornell’s department of plant breeding is one of the best in the country and McClintock soon realizes that in genetics she has found her future. But do genes really exist? If so, what are they made of? How do they replicate? Just what is the link between chromosomes and genes (if there is one)? These are some of the questions McClintock and her colleagues would like to answer.
After getting her Ph.D., McClintock stays at Cornell
to do research on Indian corn (maize). Fruit flies are buzzing in some labs, but maize is still a favorite for most researchers. Maize has appeal: every ear of corn holds several hundred kernels and each one of them represents an independent fertilization. The downside: you usually get only one corn crop a year.
By the 1930s, biologists are separating themselves into species: some are Drosophiliacs (focused on flies); some are Maiziacs (the corn groupies); some are falling for bacteria and viruses. McClintock is hooked on Indian corn and will stick with it. One of her professors, Rollins Emerson, has made Cornell a center of maize research.
McClintock dazzles her peers with her skill at seeing what others seem to miss. While still a graduate student, she identifies each of the ten maize chromosomes. She has amazing visual, as well as intellectual, gifts. Her training is in cytogenetics—which is cellular genetics focused on chromosomes. Her concentration is on breeding; she knows the look and properties (the phenotype) of each of the ten corn chromosomes.
Sometimes maize cobs appear with kernels of mixed colors: on one cob there may be red, purple, yellow, or brown kernels, in an array of patterns. This melange is fascinating to artists, but puzzling to scientists. As for farmers, they are unhappy when patches of unpredictable color turn up on healthy corncobs. No one knows why those rogue kernels appear.
McClintock is intrigued. Why, in the middle of a bright yellow cob, should some kernels be brown? They are not rotten, just brown in color. Her mentor, Rollins Emerson, finds that the colors on Indian corn come from a specific allele soon labeled P. An allele is a single form of a gene. Some genes have many alleles. Some function well, some don’t. Different alleles of P create different colors. Keep in mind; any given plant or animal has only two alleles of a specific gene. Those alleles occupy the same place on a chromosome.
This is not easy. A corncob with stripes has active alleles of P in all its kernel cells. Trying to figure this out is like tackling a very tough crossword puzzle; Barbara McClintock loves puzzles.
She develops a variety of corn with waxy purple cobs; then she finds that the ninth chromosome in that corn is extra-long and has, on one of its ends, an unusual bump. Working with her best student, Harriet Creighton, McClintock breeds waxy purples with yellow corn and, much like Mendel, tracks the next generations. Some offspring are both waxy and purple, some have neither trait, some inherit one trait. Checking cell nuclei, this scientist, who knows every bump and characteristic of each maize chromosome, becomes aware that some bumps and some long tips exchange places with others. They move. Why? How?
McClintock watches and soon can pinpoint genes as they move on a chromosome and even as they move between chromosomes. She finds that when gene position shifts, mutations (changes) appear.
Using the best microscopes of the day, with skills that are remarkable, she sees something hard to believe: genes jump about and change locations.
McClintock watches it happen. Then she discovers that genes act differently when they are in different locations on a chromosome. Which means that when genes move, change happens. This is a huge insight. It confirms that genes determine traits. It helps explain biological diversity
Thomas Hunt Morgan, who is a big Columbia University guru, has described genes as fixed; when he visits Cornell he changes his mind on that. He urges McClintock to publish her results, which she does. Her paper, published in 1931, is now seen as one of the greats in modern biology; it brings her fame in the field, but no job offers. Cornell is not giving tenured faculty positions to women. Nor are most other universities.
McClintock is a woman out of sync with her time. Her mother didn’t want her to go to college; it didn’t seem a feminine thing to do. Only after she convinced her father could she head off to Cornell.
Again, and again, because of her gender, she is denied jobs, opportunities, and recognition. Mostly she relies on fellowships in order to keep doing research.
In 1933 a Guggenheim fellowship takes her to Germany. Later she will write, "I couldn't have picked a worse time. . . There were almost no students from other countries. The political situation and its devastating results were too prominent."
Adolf Hitler and the Nazis are grabbing power; Jewish scientists are losing their jobs (later they will lose their lives). Richard Goldschmidt, a zoologist who is head of the Kaiser Wilhelm Institute and a Jew, has been safe because of his renown, but soon that isn’t enough.
McClintock meets Goldschmidt in Berlin in 1933 and they connect. “We immediately became intimate friends because he had nobody to turn to but me,” McClintock reminisced later. “We stayed that way until he died. We understood one another, we liked one another.”
Goldschmidt coins the biological term, “hopeful monster,” after seeing for himself what X-rays can do to fruit flies. A Hopeful Monster is the scientific term for an organism that appears unexpectedly bearing evolutionary changes that can be inherited.
But mainstream science is still timid about genes, and, because of Nazism, a horrendous conflict is brewing in the political world. So Goldschmidt’s findings are mostly ignored, but not by McClintock.
The European trip has exposed her to ideas unknown or marginalized in America. She will think differently than most of her colleagues, who believe that change happens one gene at a time. McClintock’s work shows that with hopeful monsters several genes can change in unison.
Peering through a magnifying microscope, McClintock sees broken chromosomes and discovers that the tattered ends of those chromosomes often fuse with other broken ends; sometimes they form a ring. Unbroken chromosomes don’t fuse. Much later, telomeres, which are the unbroken ends of chromosomes will get public attention.
Geneticists will learn that it is the products of genes–proteins and enzymes–not the genes themselves, that determine cell behavior; those proteins and enzymes are builders of life.
But exactly what are genes? What is their chemistry? How are they constructed? How do they replicate? What is their purpose? No one knows.
In 1936, the Russian/American geneticist Theodoxius Dobzansky publishes a game-changing book: Genetics and the Origin of Species. It says mutations provide genetic variation, suddenly Darwin’s theory makes sense.]
Meanwhile, after a stint as a college professor in Missouri, teaching classes as well as doing research, Barbara McClintock is told there are no senior jobs at that university for women and that she can expect to be fired. She leaves Missouri without a job prospect. Then she learns of a lab at Cold Spring Harbor on New York’s Long Island where scientists (including women) can experiment. There she can grow maize and do research. It will be the right place for her talents.
Cold Spring Harbor is a kind of rural seaside camp for biologists set in an old whaling village and initially called the Bilab (pronounced bye lab). It was founded in 1890, after waterside biology labs got established at Naples, Italy (1872) and at Woods Hole, Massachusetts (1888).
In 1902, business tycoon Andrew Carnegie donated $10 million in U.S. Steel Corporation bonds to set up the Carnegie Institution of Washington. That organization built the Station for Experimental Evolution on Long Island, right next to the Bilab; eventually they merge. When McClintock arrives in 1941, Cold Spring Harbor has become a summer retreat for a parade of biologists and a year-round home for a few who are free of classroom duties and can follow their research wherever it leads.
Which is exactly what McClintock does. Biology has big questions that need answering and she is eager to try. If a group of cells (like the cells in a body) all carry the same DNA why don’t they all turn out alike? In other words: why are your skin cells different from your liver cells since their DNA is identical?
McClintock churns out research papers. Studying corn ears with patchwork colors, McClintock discovers a relationship between the movement of chromosomes and the corn cob patches. Going further (it is now 1944) she finds that parts of the chromosome, what she calls “genetic elements,” can do more than move within a chromosome, they can move between chromosomes.
She is right. They will be known as “jumping genes” or “transposons” and the jumping process known as transposition.
Those mobile genes, when transposed, impact their neighboring genes: Sometimes they leave them inactive. Sometimes they create significant mutations.
It becomes clear to McClintock that genes turn on and off as needed. They also cut, copy, paste and edit their DNA (much as a newspaper editor does with a story). This is not random mutation. It is targeted editing.
By 1950, she has nailed that procedure and explains it in a letter to a colleague.
The next summer, at the annual symposium held at Cold Spring Harbor, McClintock describes her work. She has found and tracked genetic insertions, deletions, and crossovers. She has learned that jumping genes can determine characteristics like color on maize cobs and that transposons can exchange information.
This is a huge insight, but she doesn’t explain her accomplishments well and no one at the 1951 symposium seems to understand what she has achieved. Many young biologists think both maize and Drosophila research are old-fashioned. They have moved on to bacteria, viruses, and a scruffy little plant Arabidopsis thaliana with only 5 chromosomes and a life cycle of 6 weeks. (In the 21st century it will become the first plant to have its genome sequenced.)
Hardly anyone pays attention to McClintock’s findings and she goes into what might be called a big pout; mostly, she stops publishing and waits for the scientific world to catch up.
Some twenty years later it does. In the 1970s, “transposable elements,” or “transposons” (one kind of jumping gene), get discovered in bacteria and McClintock’s years of research finally get attention. In 1983 she receives a Nobel Prize for her discovery of “mobile genetic elements,” which are those transposons. In her acceptance speech, Barbara McClintock makes this amazing statement:
“The conclusion seems inescapable that cells are able to sense the presence in their nuclei of ruptured ends of chromosomes, and then to activate a mechanism that will bring together and then unite these ends, one with another. . . The ability of a cell to sense these broken ends, to direct them toward each other, and then to unite them so that the union of the two DNA strands is correctly oriented, is a particularly revealing example of the sensitivity of cells to all that is going on within them. They make wise decisions and act upon them.”
Here’s what the Nobel committee says, “The initial discovery of mobile genetic elements by Barbara McClintock is of great medical and biological significance. It has also resulted in new perspectives on how genes are formed and how they change during evolution.”
This is a Story With a Lot of Big Words: Some are from the World of Science. Some just seemed like good words to use. It would be a good idea to look them up, define them, and make them your own by using them in a sentence or story of your own. Here they are some from science: mutation, genetics, radiation, chromosomes, fertilization. And some others: propitious, taint, flux, rogue, ruptured, marginalized, maize, symposium…If you want to go farther: draw pictures of these words so their meaning is clear. Or sing about them.
Box: Why did the science world take so long to deal with McClintock’s breakthroughs? Maybe because at mid-century, despite years of experimentation, hardly anything is known about genes themselves. And maybe the thoughtless bias against women scientists had something to do with it.