A girl from Queens
Judith Graham was born on June 1, 1919, in Queens, New York City, into a Jewish family. Her mother, Nellie Baron Graham, was a schoolteacher, and her father, Leon Graham, was a stockbroker. She grew up in the borough, graduated from Jamaica High School and won a place at the University of Chicago, then one of the most demanding universities in the country for a young scientist.
At Chicago she studied physics and was elected to Phi Beta Kappa and to Sigma Xi, the scientific honour society. In 1938, in her junior year, she married Ithiel de Sola Pool, a fellow student who would become a well-known political scientist. The couple had two sons, Jonathan Robert, born in 1942, and Jeremy David, born in 1945.
A physicist inside a muscle fibre
Pool went on to graduate work at Chicago, where she worked as an assistant in her department, and taught physics at Hobart College in Geneva, New York, while she wrote her dissertation. Her doctoral research, with the physiologist Ralph W. Gerard, was on the electrophysiology of muscle. Together they measured the electrical potential across the membrane of a single isolated muscle fibre, a delicate experiment that required inserting a fine electrode into one cell. The Jewish Women’s Archive notes that the techniques she developed for measuring the electric potential of a single muscle fibre came to be used all over the world.
Raising two small boys while finishing a doctorate was not easy, and she left the graduate programme for a time when her sons were born. She completed her Ph.D. in 1946. It was a hard-won degree for a woman of her generation, and it gave her the physicist’s habit of measuring things precisely that would serve her well in an entirely different field.
Stanford and the problem of hemophilia
In 1949 the family moved to California, and Pool began a relationship with Stanford that lasted the rest of her life. In 1950 she became a research associate at the Stanford Research Institute. In 1953 she joined the Stanford School of Medicine as a research fellow, funded by a Bank of America-Giannini Foundation grant for hemophilia research. That same year she and her husband divorced.
Hemophilia A is an inherited bleeding disorder, mostly affecting boys and men, in which the blood lacks enough of a clotting protein called factor VIII, also known as antihemophilic factor. Without it, small injuries can bleed for days, and bleeding into joints and muscles causes crippling pain and damage. In the early 1950s the only way to replace the missing protein was to give whole blood or plasma. Factor VIII is present in plasma only in small amounts, so patients needed large volumes of fluid, often in hospital, and it was difficult to give enough to stop a serious bleed or to make surgery safe.
Pool turned her precise laboratory methods to blood coagulation. She published her first paper on the subject in 1954 and spent the next decade studying how factor VIII could be measured, extracted and preserved. In 1958 and 1959 she spent a year in Oslo, Norway, on a Fulbright research fellowship.
The discovery in the cold
Pool’s key observation was that factor VIII could be concentrated simply by temperature. When frozen plasma is thawed slowly in the cold, just above freezing, a small amount of material stays solid and settles out. Pool and her colleagues found that this cold-insoluble precipitate held much of the plasma’s factor VIII. Collected and resuspended in a small volume of plasma, it delivered far more clotting factor in far less fluid than plasma itself.
She reported the finding with E. J. Hershgold and A. R. Pappenhagen in the journal Nature in July 1964, in a paper titled “High-potency antihaemophilic factor concentrate prepared from cryoglobulin precipitate.” The product became known as cryoprecipitate. In December 1965 she and A. E. Shannon described in the New England Journal of Medicine how to make high-potency concentrates in a closed-bag system, the same sterile plastic bags blood banks already used.
That practical step was what made the discovery change lives. Cryoprecipitate needed no special factory equipment. Any blood bank could prepare it, freeze it in its plastic bag and store it for up to a year. It was made from the plasma of a single donor or a few donors, and it could be given quickly in a small volume. It was first approved in the United States in 1971, under the name Cryoprecipitated AHF.
How it changed hemophilia care
For people with hemophilia A, cryoprecipitate was the first treatment that really worked beyond whole blood and plasma. Doctors could now give enough factor VIII to stop a bleed promptly, and to prepare patients for operations, including elective surgery that had previously been too dangerous. Because it was concentrated and could be stored frozen, treatment could move out of the hospital ward: as the Jewish Women’s Archive puts it, hemophiliacs could be treated with more ease than ever before, at home or in any hospital or medical facility. The Hemophilia Alliance describes it as the treatment that rapidly became the preferred choice for acute bleeding episodes in hemophilia A.
Her method also laid the groundwork for what came next. Purified factor concentrates, and later genetically engineered factor VIII, have since replaced cryoprecipitate as the standard hemophilia treatment in countries that can afford them. But cryoprecipitate is still routinely stocked by hospital blood banks. Today it is used mainly to replace fibrinogen, another clotting protein it contains, in patients with massive bleeding after trauma, surgery or childbirth, and it remains a fallback for hemophilia and von Willebrand disease wherever concentrates are not available. The preparation Pool devised in the 1960s is still made in essentially the same way: plasma thawed slowly in the cold, the precipitate collected and refrozen.
Rising without the usual ladder
Pool’s career was unusual. She became a senior research associate in 1956 and a senior scientist in 1970, and in 1972 Stanford made her a full professor without her ever passing through the lower professorial ranks. She was invited to lecture at institutions and congresses around the world, including the Paul M. Aggeler Memorial Lecture in 1974.
She served on the national scientific advisory committees of the National Institutes of Health and the American Red Cross Blood Program, on the medical and scientific advisory committees of the National Hemophilia Foundation and the World Federation of Hemophilia, and on the editorial boards of the journals Transfusion and the American Journal of Hematology. Besides cryoprecipitate she made other contributions on the extraction, preservation and survival of proteins. She received the Murray Thelin Award of the National Hemophilia Foundation in 1968, the Elizabeth Blackwell Award from Hobart and William Smith Colleges in 1973 and the Professional Achievement Award of the University of Chicago in 1975.
Opening doors for women in science
In her final years Pool put much of her energy into a cause she had lived personally: opportunity for women in science. She wrote articles on the subject, founded and chaired the Professional Women of Stanford University Medical Center, and in 1971 became a founding member and co-president, with Neena Schwartz, of the Association for Women in Science. She served on its steering committee in 1972 and 1973. The organisation grew into a national voice for women researchers.
Her personal life was full and sometimes difficult. In 1964, twenty years after her second son, she had a daughter, Lorna. In 1972 she married Maurice Sokolow, a professor of medicine at the University of California, San Francisco; they divorced in 1975.
Jewish roots
Pool was born into a Jewish family in New York at a time when the city’s public high schools and its striving middle class were sending a generation of Jewish children into science and medicine. Like many children of that world, she went from a city public high school to a leading university and into a profession that had few places for women. She is included in the Jewish Women’s Archive’s encyclopedia of notable American Jewish women. The sources do not record how she practised Judaism or how she saw her own Jewish identity, and this profile does not claim more than they say.
An early death and a lasting gift
Judith Graham Pool died of a brain tumour on July 13, 1975, in Palo Alto, California, at the age of 56. She worked almost to the end: in the year of her death the journal Transfusion published her paper “Cryoprecipitate quality and supply,” still concerned with making her product better and more widely available. At the time of her death she was widely respected in hematology. The National Hemophilia Foundation, which had launched a research fellowship programme in 1972, renamed it the Judith Graham Pool Research Fellowship in her honour. Generations of young scientists studying hemophilia and other bleeding disorders have since trained as Judith Graham Pool fellows.
Her legacy is measured in ordinary days. Before cryoprecipitate, a boy with severe hemophilia could expect long hospital stays, crippled joints and the constant risk of a fatal bleed. After it, families could keep treatment in the freezer, doctors could operate, and children could go to school. The simple observation that a precious protein falls out of plasma in the cold opened the way to the modern era of hemophilia care.
Sources & further reading
Judith Graham Pool, Jewish Women’s Archive Encyclopedia · Judith Graham Pool, Wikipedia · Pool JG, Hershgold EJ, Pappenhagen AR. High-potency antihaemophilic factor concentrate prepared from cryoglobulin precipitate. Nature 1964 (PubMed) · Pool JG, Shannon AE. Production of high-potency concentrates of antihemophilic globulin in a closed-bag system. NEJM 1965 (PubMed) · 1964: Judith Pool discovers a simple way to make cryoprecipitates, Hemophilia Alliance · Cryoprecipitate, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
A life of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.