Storm-driven: Maud Slye and her dancing mice
Maud Slye. Photo by Helen Balfour Morrison, Library of Congress - Public Domain
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Born in Minneapolis, Minnesota, in 1879, Maud didn't initially set out to answer the question 'is cancer inherited?' In fact, she almost didn’t even make it through her undergraduate science degree at all.
At the time, few scholarships were available for women, and her family couldn’t afford to pay for her to go to university. So as a student, she combined a full academic load with working long hours to pay for her tuition and board. It eventually led her to the point of a nervous breakdown, and she had to take a break from her studies to recover.
When she eventually made it through her degree, she found a job as a psychology teacher - work that introduced her to the fields of genetics and psychiatry. The topics fascinated her, and in 1908 she ditched the teaching gig and took up a position as a graduate assistant with Charles Whitman, Professor of Zoology at the University of Chicago.
Drawing on her experience in psychiatric problems and her growing interest in genetics, she decided to investigate the inheritance of so-called ‘nervous abnormalities’.
She chose Japanese waltzing mice for her study - animals with an inherited neurological disorder that causes them to whirl and spin in circles like dancers - planning to cross-breed them with regular white mice and observe the results. Her experiment was a bit like what Mendel did with his peas, but with dancing mice instead of coloured flowers.
She purchased the mice with her own money, including buying several from Massachusetts mouse breeder Abbie Lathrop, the ‘mother of all mice’, who we talked about in episode 7 of our first series, Supermodels of science.
Maud’s project had no funding for an assistant or expenses, so she worked 18 hours a day caring for hundreds of mice.
She also had to paid for their bedding straw and grain with her meagre stipend, often going without food herself. Outside of the laboratory, Maud was a keen poet, often reflecting on her dedication to science in her poems:
“I work alone now, and my treasure is only in my work.”
As her research trundled on (the breeding cycle of mice can’t be hurried, after all), Maud became interested in the work of a pathologist called Leo Loeb, who was studying the incidence of cancer and wanted to know why the disease seemed more common in certain communities.
Loeb studied thyroid cancer in mice and eye cancer in cattle - a species I assume he didn’t have to keep in his laboratory or care for in his spare time…
Loeb suspected that the cancers were hereditary, but proving it would require a carefully controlled breeding program. Luckily for him, the basic components of such a study were already sitting in Maud’s laboratory. Intrigued by Loeb’s ideas, Maud decided to switch the focus of her research from figuring out the inheritance of waltzing in her to studying the hereditary patterns of cancer instead.
Just as she had crossed her dancing mice with their more stable counterparts, Maud would begin breeding cancerous with non-cancerous mice and watch what happened in their offspring. Of course, the research would require thousands of matings and years of study, but Maud was undaunted by the scale of the project and soon began in earnest.
Eventually, one of her mice spontaneously developed breast cancer, then another, and more after that. It wasn't long before she had her first litter of mice born to one of these affected mothers. But Maud knew that this was just the beginning; it would take more matings, more data, and, most importantly, more money to get to an answer.
Maud took one of the baby mice to the department head, declaring, "Here is the material to determine whether or not cancer is inherited." I like to think that maybe he was sipping his morning coffee at the moment Maud presented him with this naked, squirming baby mouse.
In any case, the department head was not impressed, telling her,
"That question was settled long ago, cancer is not inherited.”
Mansplaining at its finest. But Maud wouldn’t be dismissed so easily, so she moved on to the head of the pathology department, Dr. Ludvig Hektoen, and carefully explained her proposed study to him. Perhaps this was more convincing than an unexpected meeting with a baby mouse, and he listened patiently. Hektoen gave her permission to pursue her research and promised to apply for funding from the university.
In the meantime, Maud worked around the clock caring for her cancerous mice. Scrubbing cages, feeding them, compiling data, and conducting autopsies. Cleanliness of the mice cages was a top priority because an infectious disease could quickly wipe out all her work.
As her mice multiplied, so did her workload. She kept on working for months, wondering if any funding would ever come. Later, when she was asked about this period of her life, she described herself as 'hanging on by her teeth'.
As to what might have kept her going, we can look to one of her poems, where she talks about her compulsion to understand the workings of nature, saying,
‘I pace the world because I am storm-driven,
By this compelling of creation.’
Then in 1911 she got the break she had been hoping for: a staff position at the newly formed Sprague Memorial Institute at the university.
Along with the job, Maud got a real laboratory and a raise that meant she could finally work in relative comfort. But there still wasn’t enough money for an assistant, so she continued to care for her mice single-handedly.
Maud devoted herself to the animals, even taking them with her on a cross-country journey when she travelled to visit her mother's sickbed. Slowly but surely, people became interested in what this ‘cancer mouse lady’ was doing with all the squeaking creatures in her laboratory.
One day, Maud had a visitor - a woman named Miss Harriet Holmes. Holmes was a trained pathologist of independent means, who listened intently as Maud explained her experiments. She was amazed that Maud had kept the mice all by herself and offered to fill the position of laboratory assistant.
Maud explained that there was no money for such a job, and she would not be able to pay her. But Holmes responded that she had her own money and wanted to be useful, so she would volunteer to work for free. Together they soldiered on with their breeding program.
After years of research and thousands of delicate mouse autopsies, Maud wrote her first report detailing the life history of a litter of six mice: three males, and three females. Two of the males died of breast cancer, and a third male was cancer-free. One female died from lung cancer, one was alive but had mammary tumours, and the third female was cancer-free. In total, four of the six mice in the litter developed cancer.
Maud used this family to support her suggestion that cancer had hereditary factors. What’s more, Maud excluded the idea that an infection was causing the disease by mating non-cancerous mice in the soiled cages of cancerous mice. The offspring were cancer-free.
On May 5th, 1913, she presented her results at a meeting of the American Society for Cancer Research. Whether they believed that cancer was inherited or not - and many refused to accept Maud's conclusions because they didn't think her work in mice was applicable to humans - the scientists in the audience were all impressed by the scale of her project.
Maud accepted professional challenges and criticism of her research and continued working to provide more evidence for the inheritability of cancer. Other researchers were also investigating the causes of the disease, with several scientists showing they could induce cancer in animals with various types of irritation.
Parasites in rats and tar painted on the ears of rabbits both successfully produced tumours. Maud’s opponents quickly leapt on the work. If cancer was inherited, how could worms or tar cause the disease?
Maud stressed what she had been saying all along, that cancers only appeared in susceptible individuals, and inheritance was a factor in the disease, but she did not believe that it was the only one.
As she continued her work, Maud fought off repeated attempts to discredit her, and the attacks got increasingly personal. One researcher who opposed her views even supposedly told a group of physicians from the Columbus Academy of Medicine that she had refused to show her data when requested, breaking down and crying at the request. It was a charge that infuriated Maud, leading to a storm of angry letters between all the parties involved.
Despite the onslaught, Maud soldiered on with her research. Gradually, the reputation of her work grew, though it remained controversial. In a poem, she reflected on her feelings about her work:
“The robin does not wait
To ask if you like his song;
He sings because he must.”
Maud’s work continued to yield results. In line with Mendel's first law of heredity, Maud found that if a cancerous mouse mated with a cancer-free mouse, the offspring would be cancer-free, but the disease would reappear in the next generation of mice.
She concluded that cancer resistance was a dominant trait, and cancer susceptibility was recessive. She suggested that the recessive cancer susceptibility was responsible for the disease, suddenly appearing in families that had previously been cancer-free.
In her laboratory, Maud could introduce or eradicate cancer from families of mice by selective breeding. She was convinced that choosing the right mate was key to avoiding the disease, not only in mice but in people too.
And this is where things get more than a little dark, because right around this time the hot topic in genetics was… you guessed it, eugenics.
Maud often suggested eliminating cancer from human populations by selective breeding, once saying,
"If we had records for human beings comparable to those for mice, we could stamp out cancer in a generation…. At present, we take no account at all of the laws of heredity in the making of human young. Do not worry about romance. Romance will take care of itself. But knowledge can be applied even to romance.”
Perhaps unsurprisingly, Maud never married or had any children. Instead, she dedicated her whole life to her research, continuing to analyse her data even after her retirement in 1945.
Over the course of her 37-year research career, she raised and tracked around 150,000 mice. Her work earned her a gold medal from the American Medical Society in 1914 and from the American Radiological Association in 1922. She was also awarded the Ricketts Prize from the University of Chicago in 1915 and an honorary doctorate from Brown University in 1937.
She was even nominated for a Nobel prize in 1923, though she didn’t win. Perhaps she was too controversial for that one.
Maud died in 1954, leaving behind a massive volume of work. We now know that the hereditary aspects of cancer are much more complicated than she suggested. Still, her work was vital in establishing heredity as an essential aspect of cancer research.
Today, people with a strong family history of the disease can receive genetic testing, with increased monitoring and treatments available for those carrying gene variations that increase cancer susceptibility.
As for Maud and her mice? Although they are now largely forgotten, I don’t believe that she would mind, because the legacy of her devotion to research lives on. In her own poetic words:
“This is the work that I was set to do
And could it seem
For a transcendent dream
I could forsake to see it finished through.”
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