The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race

Growing up lanky and blonde in Hilo, Hawaii, Doudna often felt like “a freak.” Isaacson notes that feelings of alienation are common in other creative people he has chronicled, including Leonardo Da Vinci and Steve Jobs. However, though Doudna sometimes felt like an outsider, she had a relatively happy childhood. One of three sisters, Doudna was championed by her mother Dorothy, who was a community college teacher, and her father Martin, a professor of English literature at the University of Hawaii. In Hilo, Doudna learned how to deal with bullies and developed an avid sense of curiosity about nature. Lush and rich in diverse flora, Hawaii was paradise for someone like Doudna, who was interested in how nature worked. Family friend and biology professor Don Hemmes further fanned this interest by taking Doudna on excursions to study fungi and seashells. Martin, a voracious reader himself, often brought books for Doudna to read and expand her interests. One such book made an incalculable impact on 12-year-old Doudna: The Double Helix by James Watson, which chronicles how he and Francis Crick discovered the structure of human DNA in 1953. The book featured Rosalind Franklin, an unsung hero of the discovery, and awoke Doudna to the fact that women could be major scientists. It also led her to realize that biological phenomena govern every wonder of nature.

Though Watson and Crick revealed the structure of DNA in 1953, the path to the discovery dates back to the 1850s, when British naturalist Charles Darwin published The Origin of the Species, and Czech monk Gregor Mendel bred peas in the garden of his abbey. On an exploratory mission to the Galapagos Islands, Darwin collected the carcasses of what he thought were different species of birds, from blackbirds to finches. Back in England, Darwin was surprised to learn that the beaks of all the carcasses were from different sorts of finches. Darwin realized that all the finches had a common ancestor. Like farmers bred better-performing batches of cows and horses, nature too produced a few mutations in every generation of finches, leading to variations. Over time, the mutations more adept at survival became the dominant new species, in a process called natural selection. Darwin’s work was inspired by that of Thomas Malthus, an English economist who had hypothesized that a rise in human population would lead to food scarcity, ultimately causing weaker sections to perish.

Darwin believed evolution always occurred in the context of a competition for resources. Though Darwin’s theory was paradigm-bending, he searched for the mechanism that enabled heredity, or the passing of traits from one generation to another. He abandoned his initial speculation that male and female traits “mixed” in an embryo, since this would mean a dilution of traits over generations. In another corner of Europe, Mendel was observing the mechanism of heredity in action.

Mendel, a mathematician, scientist, and monk, cross-pollinated peas with white and violet flowers. The results were astonishing: rather than produce a mixed pink or mauve variant, the experiment favored violet flowers. Clearly, a set of traits was favored, which Mendel dubbed dominant traits. He called the traits which had not been inherited recessive. Mendel further observed that recessive traits made an appearance in the second generation of hybrid peas. He posited that when a plant inherits a dominant and a recessive trait, it exhibits the dominant trait. However, recessive-recessive plants show the recessive trait, such as white flowers. Unlike Darwin’s well-publicized theory, Mendel’s work received little attention at the time and was rediscovered only in 1900, when it became the basis of the concept of the unit of heredity, dubbed the “gene” by Danish botanist Wilhelm Johannsen in 1905.

What carries genes from one generation to another? The idea of proteins as carriers was ditched in favor of nucleic acids, molecules that live in the nucleuses of living cells. Composed of sugars, phosphates, and four substances called bases arranged in chains, nucleic acids come in two varieties: ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). DNA is essentially like RNA, but with an oxygen atom missing. That DNA was the repository of genes was shown by biochemist Oswald Avery and his team in 1944. However, the exact mechanism by which DNA carried and transferred genes was explained by James Watson and Francis Crick in the 1950s.

James Watson was only 15 when he entered the University of Chicago to study ornithology. In college Watson’s focus shifted to the gene, and he ultimately enrolled for a PhD in genetics at Indiana University, home to the future Nobel Prize winner Hermann Muller and the brilliant Salvador Luria.

Under Luria, Watson studied viruses. These “tiny packets” of genetic material are essentially lifeless till they invade living cells and hijack their machinery to multiply. The focus of Watson’s study was bacteriophages, or viruses that “eat” bacteria. While studying the structure of viruses, Watson discovered the work of molecular biochemist Maurice Wilkins (King’s College, London). Wilkins used techniques called crystallography and X-ray diffraction to figure out the structure of molecules. He took a liquid saturated with these molecules, allowed it to cool down till the molecules formed into crystals, purified the crystals, then shone an X-ray on them from different angles. The shadows cast by the crystals under X-ray helped Wilkins figure out their structure. Since Watson knew genes could crystallize, Wilkins’s methods suggested their structure too could be determined.

By 1951, Watson was a postdoctoral student in chemistry in Cambridge’s Cavendish lab, where he met biochemical theorist Francis Crick, “forming one of history’s most powerful bond between two scientists” (34). Brash and energetic like Watson, Crick too was intrigued by the structure of the gene. However, unlike Watson, Crick was wary about using crystallography to study the gene because this would mean intruding on Wilkins’s territory.

Meanwhile, Wilkins himself was locked in a power struggle with the brilliant Rosalind Franklin. Franklin had studied crystallography in France and hoped to lead the team studying DNA at King’s College, but she was relegated to a junior colleague, a fate no doubt fueled by the sexism of the time. Franklin’s lecture on her findings on studying DNA under X-ray was attended by Watson at King’s College in 1951. Aided by Franklin’s data, Watson and Crick surmised that DNA consisted of two, three, or four strands twisted in a helix. In the model of DNA they drew and later shared with Wilkins and Franklin, three strands twisted in a helix, the attached bases jutting outward like a backbone.

Franklin dismissed the structure on two counts. One, her data did not suggest DNA had a helical structure, and two, the twisting backbones had to be on the inside rather than the outside of the structure. Though she was wrong on the first count, her second objection would turn out to be completely valid.

As the race to find the structure of DNA heated up, Wilkins did something sneaky: He secretly showed the Cambridge men pictures of a “wet form of DNA” Franklin had taken days before. One of these, now known as Photo 51, conformed to Watson and Crick’s helical structure, and confirmed Franklin’s hypothesis about the bases being inside the helix.

Though Watson and Crick had not stolen Franklin’s work, they appropriated her data without permission. Using their own extensive research and Franklin’s findings, they suggested DNA had two sugar-phosphate strands that twisted and spiraled into a double helix. The two helices were joined ladder-like, by rungs of the four bases of DNA: adenine, thymine, guanine, and cytosine, now known by the letters A, T, G, and C. Adenine naturally attracted thymine, while guanine would attract cytosine. This natural A-T G-C propensity meant that when the two strands split apart, they could replicate perfectly, since each half-rung attracted its natural partner. Watson and Crick published their path-breaking findings in 1953 and were awarded the Nobel Prize in 1962, along with Wilkins. Franklin was not eligible for the award since she had died in 1958, at age 37.

Above everything else, Watson’s The Double Helix taught Doudna that science could be exciting. Watson, Crick, and Franklin’s story presented the labor of science as thrilling detective work, a perspective that would inform Doudna’s career for life. Her childhood wonder for nature and a growing desire to discover the workings of things at a molecular level made Doudna sure she wanted to study chemistry in college. However, others, like her high school guidance counselor, were more skeptical. His assertion that girls “don’t do” science hurt Doudna but also strengthened her resolve to prove him wrong. She was soon accepted in the chemistry program at Pomona College in California.

Graduate school at Harvard found Doudna in the lab of Spanish chemist Roberto Koulter, who assigned her to study how bacteria made molecules toxic to other bacteria. To clone or make an exact DNA copy of bacteria as part of the process, Doudna persisted with an unconventional method about which Koulter was skeptical. When Doudna succeeded, Koulter was surprised but supportive. Her confidence buoyed, Doudna eventually decided to do her dissertation work with Jack Szostak, a biologist who was studying DNA in yeast. One of the aspects of Szostak’s intelligence which appealed to Doudna was his ability to make surprising interdisciplinary connections. In Szostak’s lab Doudna utilized the prodigious efficiency of yeast cells in integrating strands of DNA into their own genetic makeup. Doudna engineered DNA strands that ended in a sequence that matched a sequence in the DNA of yeast. She then applied tiny electric shocks to yeast cells, opening little passageways in the cellular walls that let in the engineered DNA. Thus, Doudna had created a tool to edit the DNA of yeast.