Maud Slye. (ACC.90-105 Science Service Records, 1920s–70s, Smithsonian Institution Archives)

Storm driven

Researcher Maud Slye’s (EX 1899) contentious career helped open the field of cancer genetics.

On an April 1937 Newsweek cover, Maud Slye watched over her mice. Slye, EX 1899, hovered as two white rodents peered over the open door of a metal cage, ready to leap out. Inside the issue, a two-page spread chronicled the UChicago pathologist’s 30-year effort to study cancer susceptibility in 140,000 mice.

In the accompanying photos Slye, with strong features, cropped hair, and ever-present lab coat, works in the three-story Hyde Park greystone where she maintained endless rows of caged mice, performed breeding experiments and autopsies, and kept copious records. The research led to her highly controversial conviction that cancer was hereditary and could be bred out of the human population. “Had such a notion originated in the mind of a lesser person,” wrote Newsweek, “the story would have died after one day.”

Born in Minneapolis in 1869, Slye was raised in Des Moines and Marshalltown, Iowa, by educated parents of modest financial means; her mother hoped she’d become an artist or an author, but Slye wanted to study science. She chose to do so at the College, where she arrived in the fall of 1895 with $40 to her name.

Slye carried a full course load while supporting herself by working as a secretary to President William Rainey Harper. According to several sources, the relentless pace led to a nervous breakdown, and in 1897 she moved to Woods Hole, Massachusetts, to live with relatives. Later Slye transferred to Brown, which granted her a bachelor’s degree in 1899. After teaching psychology at Rhode Island State Normal School, Slye returned to the University of Chicago in 1907 as a graduate student and assistant to zoologist Charles O. Whitman.

In Rhode Island, Slye had become interested in genetics. Now she spent $6 on a half dozen Japanese waltzing mice, so named because, unable to move in a straight line due to a nervous disorder, they whirl in small circles instead. Breeding the mice, she launched a study on the inheritance of such disorders.

Never earning a graduate degree, Slye gained prominence as a pathologist once she focused on cancer. Her interest in the disease’s inheritability was sparked by a young researcher named Leo Loeb, who had noted the prevalence of eye cancer in a group of cattle at the Union Stock Yards, all from the same ranch in Wyoming. A link between cancer and genes had been proposed but not yet established; some researchers still subscribed to the “germ theory,” which viewed the disease as a contagious infection caused by microbes. Observing that cancerous tumors were common in mice, Slye began breeding her animals to see whether the tumors were related to heredity.

She initially struggled to fund her long-term study. But in 1911, when the Sprague Memorial Institute for “the investigation of the cause of disease” was established in Chicago, the research director, H. Gideon Wells, PhD 1903, took an interest in Slye’s work and gave her generous funding. Becoming director of UChicago’s cancer laboratory in 1919, Slye was promoted to associate professor in 1926. She presented her findings widely, winning a gold medal from the American Medical Association in 1914, among other prizes.

Cancer, according to Slye’s interpretation of her data, was a Mendelian recessive trait, like albinism or cystic fibrosis. The inheritance process would work much as it does for CF: every person inherits two cystic fibrosis transmembrane conductance regulator genes, one from each parent. Children who inherit two faulty CFTR genes develop CF; those who inherit one faulty gene are carriers who never develop the disease but can pass the gene on to their offspring. Differing from the CF or other Mendelian models, however, was Slye’s argument that genes were only half the story in cancer and that irritation needed to occur at a given site for the disease to emerge.

One of the first to embark on a long-term study of the link between cancer and genetics, Slye produced evidence damning to the germ theory. Placing cancerous mice with those she deemed genetically immune, Slye confirmed that the latter remained cancer-free in spite of exposure to the former. And she pointed out in a 1926 paper that the tumors did not produce symptoms consistent with viral or bacterial infections, such as hindered reproduction. Cancer in her mice never interfered with reproduction unless it was in the reproductive organs; in fact, reproduction slowed tumor growth.

By incorporating irritation into her theory of Mendelian inheritance, Slye helped pave the way for modern-day cancer studies that stress interactions between genes and outside aggravators. Although it’s now widely thought that only a small percentage of cancers are directly inherited, much research is dedicated to how environmental factors can alter genes and ultimately cause cancer—an idea that Slye explored tangentially.

As her work gained recognition, the media took notice. Newspapers and magazines heralded her scholarship and marveled at Slye’s dedication, noting that she worked tirelessly, moving back and forth between the laboratory at 5825 Drexel Avenue and her home across the street. When she traveled to California to visit her ailing mother, she rented a boxcar and took her mice along, wrote Newsweek. The Chicago Tribune reported that her first extended research break was in 1936, when she went to Europe as a delegate to the International Congress for the Control of Cancer.

Slye never married, although she was rumored to have had a love affair with a male artist. Her recreation was writing poetry. A 1944 Tribune article described how Slye spent much of her time away from the lab writing verse. She published about 700 of her poems in two Stratford volumes, 1934’s Songs and Solaces and 1936’s I in the Wind. Frequently alluding to nature, the poems spoke to her consuming scientific commitment: “I pace the world because I am storm-driven / By this compelling of creation.”

Slye’s pacing was not always welcome. Often associated with eugenics, she was outspoken that a bureau of human statistics should be created to breed cancer out of the human population. “At present we take no account at all of the laws of heredity in the making of human young,” she said in a 1938 Chicago-area talk. “Do not worry about romance. Romance will take care of itself. But knowledge can be applied even to romance.”

Not so fast, thought some of Slye’s fellow pathologists. Almost all of them were male, and some were cutting in their critiques. Columbia University’s Francis Wood questioned whether Slye’s hereditary findings in mice could be applied to humans and further noted that he was unable to replicate her results in white rats. In the fall of 1926, Slye discovered that during a meeting of the Columbus Academy of Medicine, surgeon André Crotti had publicly relayed a story apparently told to him by Wood: When Wood’s “representative” visited Slye’s lab and asked to see her records, she burst into tears and refused to share them.

Outraged, Slye began a blistering correspondence with the two men, insisting that the story had “not the slightest foundation in fact behind it.” Crotti was apologetic; Wood was dismissive, writing to Crotti, “Don’t feel embarrassed in the least concerning your remarks regarding Miss Slye. She is always indignant with me, but it seems to me that indignation has very little to do with scientific facts.”

Also facing criticism from genetics researcher Clarence C. Little that her own data suggested a more complex relationship between genetics and cancer than a single-gene Mendelian recessive trait, Slye eventually modified her theory to incorporate three genes: one that determined cancer’s location; a second, its type; and a third, its degree of malignancy. Time would prove that both Slye and Little had failed to perceive the actual complexity of genes’ role in cancer, still not fully unraveled.

After taking mandatory retirement from the University in 1944, Slye spent her remaining years compiling data before suffering a fatal heart attack on September 17, 1954. Since her death, she’s been credited with playing a pivotal role in disproving the contagion hypothesis and with helping open wide the field of genetic cancer research. But she might be remembered best for her conviction to live, unapologetically, in the single-minded service of discovery. As she wrote: “The robin does not wait / To ask if you like his song; / He sings because he must.”