“Is public health becoming illiberal?,” asked Katelyn Jetelina last week. I assumed it would be a classic case of Betteridge’s Law &ndash…
The First Century of Women in Vaccine Science: 1940s-1960s (Part 2)
This is the second post in a series highlighting outstanding women in vaccine science or immunology related to vaccine development in the 20th century. And there are some milestones for women in immunology more generally, too. The odds have historically been dramatically stacked against women gaining access to science education and research careers, though, and if they did get through, against getting credit for their contributions – and then against being celebrated, too. All of which makes those who did achieve important breakthroughs and prominence all the more impressive.
1942: Katherine McDermott co-published a landmark study on an adjuvant – a vaccine ingredient used to strengthen immune response
This entry is all but blank – and so represents the invisible contributions made by so many, especially those from others than white men.
I cannot find anything online about McDermott, other than that she is a co-author of this 1942 paper with Jules Freund, a celebrated immunologist. The paper has been listed as a major landmark in immunology.
1948: In her PhD dissertation, Astrid Fagraeus showed that antibodies are produced by plasma B cells in lymphoid tissue – one of the major breakthroughs in immunology
Correction to the Twitter thread above: the last photo was incorrectly used published as Fagraeus. In fact, that photo is Swedish medical professor Nanna Svartz. I’m grateful to Gunilla Källenius who knew Fagraeus and pointed this out.
Astrid Fagraeus (later Fagraeus-Wallbom) (1913-1997) was born in Stockholm, in a well-to-do family: her father was a consul-general, and, I think, a banker. She graduated from the Karolinska Institute in 1943 and earned her doctorate for her groundbreaking work on antibodies in 1948.
In 1947, she published a paper in Nature showing that at the same time as antibodies were being produced, plasma cells were building up in rabbit spleens. With a series of experiments in her doctoral work, she showed that antibodies were secreted by plasma cells. Plasma cells are formed from B-cells. Understanding this critical part of the immune system was a major step forward for immunology. Fagraeus was awarded the Swedish Society of Medicine’s Jubilee Prize in 1950 as a result, and the North Star (a royal honor).
Fagraeus had to move to the U.S. for a while, because there weren’t opportunities in immunology in Sweden when she graduated. However, she in 1953 she headed a department at a national laboratory and in 1965 became Sweden’s first Professor of Immunology, at the Karolinska.
In 1952, she was one of a 10-person team who started work on a polio vaccine. Sweden was one of the countries hard hit by that virus. Their team disagreed with Jonas Salk about how to adequately and safely inactivate the virus for vaccines. His vaccine crossed the finish line first, but in 1955 a batch of inadequately inactivated Salk vaccine caused over 200 cases of polio in the U.S., and caused a major backlash against the vaccine. So Sweden started to use the local vaccine – Fagraeus writes her point of view of the Swedish polio vaccine story here. There were 3 doses in the initial course: the first 2 were a month or 2 apart, then the third was a year later. A fourth and final shot was recommended 4-5 years later. Polio appeared again in Sweden in 1961 and in 1976 in unvaxed people, but didn’t break out widely in the community.
A lab at Karolinska is named after Fagraeus. “Research was her joy” said her colleagues in an obituary. She was still publishing in her 70s. She died aged 83.
1949: Isabel Morgan and colleagues showed there were 3 serotypes of polio and a vaccine would have to protect against them all – she went on to complete the first preclinical test of inactivated polio vaccine
When Eleanor Roosevelt dedicated the Infantile Paralysis Hall of Fame in 1958 (pictured below), only 1 woman scientist was honored: Isabel Morgan.
Isabel Merrick Morgan (1911-1996) was born in New Bedford, Massachusetts, the eldest of 4 children of famous biologist parents. Her mother was Lilian Vaughan Morgan, who contributed to the science of Drosophila genetics, and, among other achievements, co-founded the Children’s School of Science at Woods Hole. Her father was Thomas Hunt Morgan, an evolutionary biologist and geneticist who was awarded the Nobel Prize in Physiology and Medicine in 1933.
Morgan graduated from Stanford, gained a Masters in bacteriology from Cornell University, and was awarded her PhD from the University of Pennsylvania in 1940. She worked at the Rockefeller before joining David Bodian’s polio laboratory at Johns Hopkins. Their critical breakthrough was identifying that there were multiple strains of poliovirus, publishing a trio of papers in 1949, including one by Morgan on her experiments, and the paper by Bodian, Morgan, and Howe grouping 14 strains into 3 immunological types. Previous vaccines had inactivated only a single type: all had failed.
Morgan went on to test a killed-virus polio vaccine in animals, showing it needed boosters, and experimenting with the method of killing the virus that Salk later used, as well as adjuvants. She was thought to be well ahead of Salk, and likely to have been the first to succeed at a polio vaccine. Success depended greatly on her breakthrough, as well as Dorothy Horstmann’s (see below). However, she left Johns Hopkins and polio research in 1949. There were 2 contributors: she had ethical concerns about testing an inactivated virus vaccine in humans, and she got married (to a man who had a child with a disability). No one at Johns Hopkins continued her work, so it was over to Salk.
Morgan moved to Westchester County in New York, and worked for the County. After her stepson died in an accident in 1960, she gained a degree in biostatistics from Columbia University, and worked as a consultant for the Sloan Kettering Cancer Institute in New York City.
1952: Dorothy Horstmann upended views of how polio developed and was transmitted, putting scientists onto a path towards polio vaccine
Dorothy Horstmann (1911-2001) was born in Spokane, Washington, but grew up in San Francisco, dreaming of becoming a doctor. She’d go on ward rounds with a physician friend of the family. Horstmann graduated as an M.D. from the University of California San Francisco, and applied for a residency at Vanderbilt Hospital in Nashville. But the Chief of Medicine there had a “no women” policy and rejected her. She was considering private practice when the Chief forgot that Dr Horstmann was a woman and invited her to the program a few months later. His secretary would later tell Horstmann that when he realized what he’d done, he “all but went into shock”. After that year, she went to Yale, where she spent most of her career – in 1961 she became the first woman tenured professor in Yale’s School of Medicine, and in 1969, the first to be awarded an endowed chair.
In 1942, when she joined Yale’s polio unit, experts believed that polio infected the brain via the nasal passages. They investigated 5 polio outbreaks in 1943 and 1944, taking samples from throat swabs, washings from the mouth and throat, feces, and blood from patients and contacts. Most of the fecal samples were positive for the virus, but not so much for the oral and throat swabs, which is where conventional wisdom suggested it would be. So they thought it must be gastrointestinal – but how did it get in the brain?
During an outbreak in 1943, Horstmann took blood samples from all 111 people with admitted to Yale Hospital with suspected polio. Only 1 tested positive – a 9-year-old girl with mild symptoms who didn’t end up with paralysis – and that would ordinarily be dismissed as an oddity. All the other 110 patients already had more advanced disease. Horstmann wondered if it was possible that the virus appeared in the blood briefly before the person got very sick. So she infected lab animals in the usual way, and took blood samples every day. The virus appeared in the blood a few days after exposure, and before the onset of paralysis symptoms. Everyone had failed to detect it in the blood because they’d been testing too late the whole time: antibodies kick it out of the bloodstream. When she published her paper on these experiments in 1952, and it was soon replicated by David Bodian (Isabel Morgan’s colleague), the understanding of polio shifted. This opened the way to oral polio vaccine – antibodies could destroy the virus before it entered the nervous system.
Horstmann later worked on the rubella vaccine. She was elected to the National Academy in 1975, and for a time, her portrait was the only one of a woman hanging on the walls of Yale’s School of Medicine. She retired in 1982, and died of complications of Alzheimer disease aged 89.
1955-1960: Rosalyn Sussman Yalow and a colleague developed the radioimmunoassay, a very sensitive test that could detect smaller antigens than had ever been seen before – for which she was awarded the Nobel Prize in 1977
Rosalyn Sussman Yalow (1921-2011) was born in the Bronx, New York. Her parents hadn’t finished high school, and they weren’t well off: her mother wanted her to become a teacher, though. However, Sussman wanted to be a physicist. She worked as a secretary to pay her way through her education. Sussman earned her PhD in nuclear physics during World War 2 – it was awarded in 1945 – but was nevertheless the only woman in the 400-member department at the University of Illinois at Urbana-Champaign, and she was the first woman to teach in engineering there.
After World War 2, she also began collaborating with the Veterans Administration to establish research programs involving radioactive substances. That’s where she developed the radioimmunoassay (RIA) with Solomon Berson. It’s a technique using radioisotope tracing to measure miniscule substances in blood and other fluids. It was first used to measure insulin levels.
She was 29 when she started work with Berson on the RIA, and they spent 2 years developing it. They attached radioactive iodine to insulin molecules and injected the radioactive-tagged insulin, including in themselves. It’s used for an enormous range of measurements and research. Despite the enormous value of the invention, she and Berson refused to patent it. She became the first American woman to win a Nobel Prize in science, and only the sixth woman overall – and the second to win in Physiology or Medicine. (Berson had died, and Nobels are only awarded to living people.)
The VA had a policy that women had to leave when they became pregnant: Sussman Yalow ignored it, and continued to work. Sussman Yalow went on to be a professor in the School of Medicine at Mount Sinai. The Nobel Prize website has a great photo gallery of her life.
1966: Teruko Ishizaka and her husband described how the antibody Immunoglobulin E (IgE) works
Teruko Ishizaka (1926-2019) was born into a prominent family in Yamagata, Japan – her father was a lawyer. She graduated in medicine from the Tokyo Women’s Medical School in 1949, and earned her PhD from the University of Tokyo in 1955. She met Kimishige Ishizaka when they were both medical students in a lab at the University of Tokyo, and they married in 1949. They worked on anaphylaxis together, and in 1957 began postdoctoral studies at Caltech, then Johns Hopkins, and returned to Japan’s National Institutes of Health.
In 1962, they were recruited to the Children’s Asthma Research Institute and Hospital in Denver. That’s where they identified the antibody protein, Immunoglobulin E (IgE), publishing the results with another colleague in 1966. Researchers in Sweden had separately identified IgE too, and they published a joint paper in 1969. IgE is key to allergic reactions, including to vaccines.
In 1970 the couple moved to Johns Hopkins, and then to San Diego in 1989 where he became the director of the new La Jolla Institute for Allergy and Immunology. That year, she published results of experiments on mast cells, and for that work, along with her whole body of research, she was awarded the Behring Kitasato Prize – the first female Japanese scientist honored with that award. The couple were honored with multiple awards internationally.
The couple retired in 1996, returning to live in her hometown, Yamagata. They both lived to 92: he died in 2018, and she in 2019.
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