blog by Kathleen T. Ruddy, MD

 

“My most fundamental objective is to urge a change in the perception and evaluation of familiar data.”  

 Thomas S. Kuhn

from, The Structure of Scientific Revolutions, 1962

 

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In 1908, Abbie Lathrop spent the last years of her life investigating the cause of breast cancer in mice. How did this retired schoolteacher who ran a farm in Granby, Massachusetts where she raised small animals like hamsters and, yes, mice to sell as pets develop an interest in breast cancer? The answer is:  by accident, and then by design. In so doing, this unlikely and relatively obscure woman took the very first steps that eventually led to the discovery of the breast cancer virus.

Life rewards curiosity, and this certainly seems to have been the case for Lathrop. She was the only child of two schoolteachers. When she was seventeen years old she left home to study for her teaching certificate.

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She returned a year or two later, the record isn’t exactly clear, and then began teaching too. But Lathrop developed pernicious anemia, a disease that prevents the body from absorbing the essential vitamin, B12.  In patients with pernicious anemia a host of symptoms develop which eventually leads to a progressive cascade of physical debilities that result in death, usually in middle age. As a young adult, Lathrop found it increasingly difficult to keep up with the demands of teaching and, so, she retired. When her parents died, she moved to Granby, Massachusetts and bought a chicken farm. But that operation was too strenuous and she gave it up. She decided to raise small animals to sell as pets, and this proved more profitable and manageable.

At the time, pet mice were all the rage. It was a hobby that had originated in Japan in the 1700’s and was exported, first, to China, and with the East-West trade on to England and then to New England. Mice were bred for coat color – sable was the most popular – and eye color. “Waltzers” were especially prized: they were born with an inherited abnormality of their inner ears that made them ‘dance’ around due to a lack of balance.

Lathrop did a decent business selling mice and other small animals to the locals and to customers in nearby Boston. She also had customers who found her through the many “mouse club” newspapers and conventions that were popular at the time.

 

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One day, a man from Harvard University showed up on her farm looking to buy a large quantity of mice. His name was Clarence Cook Little and he was the fourth-great grandson of Paul Revere.

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Little was a research student in the Department of Biology at Harvard University and he wanted to use mice to discover the genetic cause of cancer. He told Lathrop that he needed to purchase a large number of mice to use in his experiments, and he made it clear that he would be coming back for more. Little’s appearance wasn’t as much of a surprise as it might have been given that she had already received an inquiry from Professor Leo Loeb, a pathologist from the University of Pennsylvania, who was also interested in obtaining mice to use in his experiments.

Lathrop asked Little what, exactly, he was looking for, and he explained that he was certain that cancer was an inherited disease and he intended to be the first to discover “cancer” genes.   Lathrop told him that if he was interested in finding the cause of cancer then he might be interested in checking out some of her mice, the ones that developed breast cancer.

Little must have lit up like a Christmas tree. He took armfuls of Lathrop’s mice, the ones with breast cancer, and carried them back to Boston where he began breeding them with the goal of creating strains in which the majority developed breast cancer before they died. Although Little’s colleagues back at Harvard were utterly and vocally skeptical that he would succeed, he did. Eventually, Little created strains of mice in which as many as 90% of the animals developed breast cancer. He was sure he was getting close to discovering the genes that caused breast cancer, and he couldn’t wait to find them.

Meanwhile, Lathrop wrote a letter to Dr. Loeb asking him if he would be interested in examining her mice with breast tumors to confirm that they did, indeed, have breast cancer. Loeb wrote back immediately to say that he would be delighted to do so. When he later confirmed that Lathrop’s mice did, in fact, have breast cancer he also asked Lathrop if she would be interested in helping him conduct a series of experiments to learn more about why her mice developed breast cancer. Loeb told Lathrop that they would work as equals: he would design the experiments; she would carry them out on her farm; and they would publish the results together as co-authors. She agreed.

Over the next ten years, Lathrop and Loeb conducted a series of experiments – some involving very detailed surgical dissections on pregnant females – to discover what factors influenced the risk and progression of breast cancer in these breast cancer-prone mice. The discoveries they made together are as important today as they were 100 years ago. To wit:  Breast cancer does not occur before puberty. Pregnancy increases the risk for breast cancer. Removing the ovaries decreases the risk for breast cancer; and virtually eliminates it if the ovaries are removed before puberty. Males rarely, if ever, develop breast cancer.

While Lathrop and Loeb were carrying out their experiments, Little was beginning his own with the goal of discovering the genes that caused breast cancer in Lathrop’s mice. Unfortunately, Lathrop died in 1918 as a result of the long-term consequences of pernicious anemia. But her mice lived on in Little’s laboratory. And they live on today. Little eventually relocated his operation to the Roscoe B. Jackson Memorial Laboratory in Bar Harbor, Maine. The mice that were bred there have become the most common experimental animal model for researchers around the world who want to study breast cancer in mice and in women.

 

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He looked as hard as he could, but Little had trouble nailing those breast cancer genes. His experiments failed to follow the Laws of Inheritance as set forth by Gregor Mendel.  Cancer genes were present, absolutely. But there was something else that had an influence on those breast cancer genes. In 1936, one of Little’s research scientists, Dr. John Bittner, discovered that in addition to cancer genes, Lathrop’s mice were also infected with a breast cancer virus. Bittner found the virus in the breast milk.

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In July 2013, Professor James Holland of Mt. Sinai School of Medicine, presented 100 years of research on this breast cancer virus at the 60th Anniversary celebration of the National Institutes of Health’s Clinical Center.

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In 1995, Holland and his colleague, Professor Beatriz Pogo, had discovered a virus in humans that is 95-98% similar to the virus that causes breast cancer in mice. They named it the “human mammary tumor virus”, HMTV. Holland said he thinks it causes breast cancer in at least 40% of women. In April 2015, Holland and Pogo announced that they had found HMTV in 94% of the malignant fluids in women with Stage IV breast cancer.

The final proof isn’t in yet – but, of course, he’s “working on that.” Holland said he thinks that the virus is passed in human breast milk, just as it is in mice. His presentation  at the National Institutes of Health went on for over an hour that day (July 10, 2013) and was followed by enthusiastic applause from hundreds of scientists sitting in the audience.

And to think, it all started with a retired spinster schoolteacher who had an insatiable curiosity, plenty of chutzpah, the guts of a surgeon, and an entrepreneurial spirit. Thank you, Abbie Lathrop, for getting the ball rolling. Now, let’s see if we can take it from there, finish the job, and answer the question, Does a virus cause breast cancer in women?  

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