Eloise Giblett
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Eloise "Elo" R. Giblett (January 17, 1921 – September 16, 2009) was an American genetic scientist and hematologist who discovered the first recognized immunodeficiency disease,
adenosine deaminase deficiency Adenosine deaminase deficiency (ADA deficiency) is a metabolic disorder that causes immunodeficiency. It is caused by mutations in the ADA gene. It accounts for about 10–20% of all cases of autosomal recessive forms of severe combined immun ...
. Giblett was a professor of medicine at the
University of Washington in Seattle The University of Washington (UW and informally U-Dub or U Dub) is a public research university in Seattle, Washington, United States. Founded in 1861, the University of Washington is one of the oldest universities on the West Coast of the Unite ...
and executive director of the Puget Sound Blood Center in Seattle. The author of over 200 research papers, she also wrote an esteemed textbook on
genetic marker A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify individuals or species. It can be described as a variation (which may arise due to mutation or alteration in the genomic loci) that can ...
s, ''Genetic Markers in Human Blood'', published in 1969. She was elected to the
National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, NGO, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the ...
in 1980. Giblett discovered the first
immunodeficiency Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that aff ...
disease:
adenosine deaminase deficiency Adenosine deaminase deficiency (ADA deficiency) is a metabolic disorder that causes immunodeficiency. It is caused by mutations in the ADA gene. It accounts for about 10–20% of all cases of autosomal recessive forms of severe combined immun ...
. She identified and characterized numerous
blood group antigen A blood type (also known as a blood group) is based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glycoli ...
s (including the ‘Elo’ antigen, named after her). Her work paved the way for safe red blood cell transfusions. She also applied her understanding of red blood cell protein polymorphisms to
genetic linkage Genetic linkage is the tendency of Nucleic acid sequence, DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two Genetic marker, genetic markers that are physically near ...
analyses, was senior author on the paper that demonstrated the feasibility of unrelated marrow transplantation for
leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...
, and was an early supporter of
bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
donation.


Early life and education

Giblett was born in
Tacoma, Washington Tacoma ( ) is the county seat of Pierce County, Washington, United States. A port city, it is situated along Washington's Puget Sound, southwest of Seattle, southwest of Bellevue, Washington, Bellevue, northeast of the state capital, Olympia ...
in 1921. Her family moved to Spokane, Washington for her father's job as an insurance salesman. Giblett received her early education in Spokane and was trained in singing, dancing and the violin. Her Mother, Rose, held a secret desire that Giblett would become the next
Shirley Temple Shirley Temple Black (born Shirley Jane Temple; April 23, 1928 – February 10, 2014) was an American actress, singer, dancer, and diplomat, who was Hollywood's number-one box-office draw as a child actress from 1934 to 1938. Later, she was na ...
of the era. Giblett graduated from
Lewis and Clark High School Lewis and Clark High School is a four-year public Secondary education in the United States, secondary school in Spokane, Washington, United States. Opened in 1912, it is located at 521 W. Fourth Ave. in the Cliff/Cannon, Spokane, Cliff/Cannon ...
in 1938. She was only 16 when she earned a scholarship to
Mills College Mills College at Northeastern University in Oakland, California is part of Northeastern University's global university system. Mills College was founded as the Young Ladies Seminary in 1852 in Benicia, California; it was relocated to Oakland in ...
in Oakland, California. After two years, she transferred to the
University of Washington The University of Washington (UW and informally U-Dub or U Dub) is a public research university in Seattle, Washington, United States. Founded in 1861, the University of Washington is one of the oldest universities on the West Coast of the Uni ...
in Seattle where she earned a degree in
bacteriology Bacteriology is the branch and specialty of biology that studies the Morphology (biology), morphology, ecology, genetics and biochemistry of bacteria as well as many other aspects related to them. This subdivision of microbiology involves the iden ...
(now
microbiology Microbiology () is the branches of science, scientific study of microorganisms, those being of unicellular organism, unicellular (single-celled), multicellular organism, multicellular (consisting of complex cells), or non-cellular life, acellula ...
) in 1942. From 1944 to 1946, she served in the
Navy WAVES United States Naval Reserve (Women's Reserve), better known as the WAVES (for Women Accepted for Volunteer Emergency Service), was the women's branch of the United States Naval Reserve during World War II. It was established on July 21, 1942, ...
. Through this program, she worked as a technician at the clinical laboratory of the U.S. Naval Hospital in San Diego, California. In 1947, she returned to the University of Washington to earn her Master of Science in microbiology. Her master's thesis focused on physiology of fungi in the genus ''
Microsporum ''Microsporum'' is a genus of fungi that causes tinea capitis, tinea corporis, ringworm, and other dermatophytoses (fungal infections of the skin). ''Microsporum'' forms both macroconidia (large asexual reproductive structures) and microconid ...
''. After completing her master's degree, Giblett attended the University of Washington Medical School. One of five women in her year, she graduated first in her class in 1951. From 1951 to 1953, Giblett served as an intern, then resident in Internal Medicine, at King County Hospital (now Harborview Hospital).


Early career

In 1953, Giblett was awarded a two-year fellowship for post-doctoral research in
hematology Hematology (American and British English spelling differences#ae and oe, spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to bloo ...
. During this time, Giblett worked under
Clement Finch Clement Alfred Finch (July 4, 1915 – June 28, 2010) was an American physician specializing in hematology whose research on iron metabolism in the bloodstream at the University of Washington led to significant advancements in accurately diagnosi ...
, a renowned hematologist interested in iron metabolism. Giblett primarily assisted with his research on erythrokinetics, the dynamic study of the production and destruction of
red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...
s. In her first year working for Finch, Giblett published five papers, including a highly cited paper describing red blood cell lifetime and hemolysis. Giblett also worked with geneticist Arno Motulsky studying erythrokinetics in
splenomegaly Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulat ...
, kicking off a decades-long collaboration. After completing her fellowship, Giblett traveled to London to train under
Patrick Mollison Patrick Loudon Mollison, (17 March 1914 – 26 November 2011), was a British haematologist, described as 'the father of transfusion medicine'. Life Mollison was born on 17 March 1914, to Beatrice Marjorie, née Walker, and William Mayhew Mol ...
at the Medical Research Council's Blood Transfusion Research Unit. In this research unit, Giblett gained the laboratory experience necessary to co-direct Puget Sound Blood Center (then King County Blood Bank), a position she assumed upon her return to Seattle in 1955. Giblett remained at the Blood Center as associate director until her promotion to executive director in 1979. She retired in 1987.


Scientific discoveries

Giblett focused the majority of her career on academic research. In 1955, she was appointed Clinical Associate in Medicine at the University of Washington. Giblett's lab focused on studying blood groups, with particular attention to genetic markers in human blood. She identified several blood group antigens. Her research assisted in refuting the standard practice at the time of segregating blood donations based on the race of the donor. In 1958, Giblett began research studying polymorphisms of the human plasma proteins
haptoglobin Haptoglobin (abbreviated as Hp) is the protein that in humans is encoded by the ''HP'' gene. In blood plasma, haptoglobin binds with high affinity to ''free'' hemoglobin released from erythrocytes, and thereby inhibits its deleterious oxidativ ...
and
transferrin Transferrins are glycoproteins found in vertebrates which bind and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Iron(III), Fe3+ ions. Human transferrin is ...
using starch gel electrophoresis. As a result of her studies on genetic variation, Giblett documented the first case of a
mosaic A mosaic () is a pattern or image made of small regular or irregular pieces of colored stone, glass or ceramic, held in place by plaster/Mortar (masonry), mortar, and covering a surface. Mosaics are often used as floor and wall decoration, and ...
individual conceived from dispermic fertilization of two eggs followed by cell fusion. Giblett actively collaborated with Arno Motulsky, a fellow professor at the University of Washington. Giblett analyzed blood samples from a population study Motulsky carried out in the Congo in 1960. The resulting paper, published in 1966, described many novel genetic variants. Decades later, scientists discovered that one of these samples contained first known case of
HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...
. The viral sequence from this sample is still used to date in studies of HIV. Starting in 1971, Giblett began researching
bone marrow transplants A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, and ...
with
E. Donnall Thomas Edward Donnall "Don" Thomas (March 15, 1920 – October 20, 2012)Frederick R. Appelbaum.Perspective: E. Donnall Thomas (1920–2012) Science 338(6111):1163, 30 November 2012 was an American physician, professor emeritus at the University o ...
. Bone marrow transplantations were a pioneering technique used to treat blood cancers. At the time, if the donor and acceptor were the same sex, doctors could not confirm the success of the graft. Giblett assisted in discovering genetic markers that could confirm graft success, regardless of donor sex, using polymorphic blood proteins. Giblett eventually expanded her research into the activity of polymorphic proteins in human plasma and blood cells, leading to her famous discovery of the first immunodeficiency disease. One polymorphic protein used as a routine a genetic marker for transplants was
adenosine deaminase Adenosine deaminase (also known as adenosine aminohydrolase, or ADA) is an enzyme () involved in purine metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues. Its primary function ...
(ADA) located in red blood cells. In 1972, Giblett received samples from a patient with
severe combined immunodeficiency disease Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in diff ...
(SCID). The patient was a candidate for bone marrow transplantation from her mother; analysis of blood samples surprisingly revealed that the child exhibited no ADA activity. Giblett soon discovered a second case where ADA deficiency underlaid immune dysfunction, leading her to conclude that the two may be related. Giblett named this disease adenosine deaminase immunodeficiency, and it was recognized as the first official immunodeficiency disease. The discovery of ADA deficiency lead to a breakthrough in understanding immunodeficiency. Based on the function of ADA in purine metabolism, Giblett hypothesized that mutations in other proteins involved in
purine metabolism Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms. Biosynthesis Purines are biologically synthesized as nucleotides and in particular as ribotides, i.e. bases attached to r ...
or related
pyrimidine metabolism Pyrimidine biosynthesis occurs both in the body and through organic synthesis. ''De novo'' biosynthesis of pyrimidine ''De Novo'' biosynthesis of a pyrimidine is catalyzed by three gene products CAD, DHODH and UMPS. The first three enzymes of ...
might underlie additional forms of immune dysfunction. Her hypothesis was confirmed in 1975 upon analysis of an immunocompromised patient exhibiting normal ADA activity but defective
purine nucleoside phosphorylase Purine nucleoside phosphorylase, PNP, PNPase or inosine phosphorylase () is an enzyme that in humans is encoded by the ''NP'' gene. It catalyzes the chemical reaction :purine nucleoside + phosphate \rightleftharpoons purine + alpha-D-ribose 1-p ...
(PNP) activity. Within several years, ten more cases of immune deficiency linked to PNP mutations were described, leading to the classification of the disorder as purine nucleoside phosphorylase deficiency. Giblett's other notable discoveries include T cell immunodeficiency. Throughout her career, Giblett collaborated with some of the most notable and talented scientists of her era, including:
Oliver Smithies Oliver Smithies (23 June 1925 – 10 January 2017) was a British-American geneticist and physical biochemist. He is known for introducing starch as a medium for gel electrophoresis in 1955, and for the discovery, simultaneously with Mario Cap ...
, Alexander Bearn, James Neel,
Curt Stern Curt Stern (August 30, 1902 – October 23, 1981) was a German-born American geneticist. Life Curt Jacob Stern was born into a middle-class Jewish family in Hamburg, Germany on August 30, 1902. He was the first son of Earned S. Stern, born ...
,
Victor McKusick Victor Almon McKusick (October 21, 1921 – July 22, 2008) was an American internist and medical geneticist, and Professor of Medicine at the Johns Hopkins Hospital, Baltimore. He was a proponent of the mapping of the human genome due to its ...
,
Ernest Beutler Ernest Beutler (September 30, 1928 – October 5, 2008) was a German-born American hematologist and biomedical scientist. He made important discoveries about the causes of a number of diseases, including anemias, Gaucher disease, disorders of ...
, Stanley Gartler,
Walter Bodmer Sir Walter Fred Bodmer (born 10 January 1936) is a German-born British human geneticist. Early life Bodmer was born in Frankfurt, Germany. He was educated at Manchester Grammar School and went on to study the Mathematical Tripos at the Univ ...
, John Cairns,
David Weatherall Sir David John Weatherall (9 March 1933 – 8 December 2018) was a British physician and researcher in molecular genetics, haematology, pathology and clinical medicine. Early life and education David Weatherall was born in Liverpool.Geoff Watt ...
,
Henry Kunkel Henry George Kunkel (September 9, 1916 in Brooklyn – 15 December 1983) was an American immunologist, known for his discoveries in basic immunology research, especially his contribution to the development of clinical immunology. He has been ...
,
H. Hugh Fudenberg Herman Hugh Fudenberg (October 24, 1928March 15, 2014) was an American clinical immunologist and the sole identified member of the Neuro Immuno Therapeutics Research Foundation (NITRF). Fudenberg was a proponent of the discredited hypothesis t ...
, and Newton Morton.


AIDS crisis

In 1978, Giblett closed her research lab to direct the Puget Sound Blood Center. Soon after, in 1981,
HIV/AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...
was discovered. Infectious disease experts at the time realized that the disorder might be transmissible by blood, creating complications for blood transfusions. This discovery led to a crisis in blood banking. Giblett attempted to allay fears about the hazard of giving blood and closely followed the incidence of the disease in previously transfused patients. Before HIV could be detected in blood, Giblett developed a screening policy for blood donors at the center.


Retirement

Giblett retired from the Puget Sound Blood Center in 1987. She devoted her remaining years to playing the violin and contributing to various musical groups, playing in several string quartets. She was a co-founder of the Music Center of the Northwest, and contributed to them until she died.


Honors

In 1967, Giblett was promoted to full professor at the University of Washington. Giblett served as president of the
American Society of Human Genetics The American Society of Human Genetics (ASHG), founded in 1948, is a professional membership organization for specialists in human genetics. As of 2009, the organization had approximately 8,000 members. The society's members include researchers, ...
in 1973. She was a board member of the
American Society of Hematology The American Society of Hematology (ASH) is a professional organization representing hematologists, founded in 1958. Its annual meeting is held in December of every year and has attracted more than 30,000 attendees. The society publishes the medi ...
, the
Western Association of Physicians The Western Association of Physicians (WAP) is a regional health association of academic physician-scientists. Over the years the society has grown to a membership of several hundred, including many distinguished academicians from diverse areas of ...
and the New York Blood Center Research Advisory Committee. In 1980, Giblett was elected to the National Academy of Sciences. The following year, she became a fellow of the National Association for the Advancement of Science. In 1987, she was the first woman to receive the University of Washington Medical School Alumni Association's Distinguished Alumni Award. Upon her retirement, she was awarded emeritus status at the
University of Washington School of Medicine The University of Washington School of Medicine is the medical school of the University of Washington, a public research university in Seattle, Washington. According to ''U.S. News & World Report''s 2022 Best Graduate School rankings, University ...
and Puget Sound Blood Center.


Legacy

In 1969, Giblett published ''Genetic Markers in Human Blood'', a reference book aimed to increase the accessibility of information about biochemical variation in blood. The book was described by H. E. Sutton as "a remarkable achievement for a single individual." Giblett was a fan of science fiction literature. She is mentioned by name in Robert Heinlein's novel '' The Number of the Beast.'' In 2010, the Elo Giblett Endowed Professorship in Hematology was established at the University of Washington. This professorship was created by combining an amount of money left by Giblett to the university and an additional funding from Giblett's niece, Leslie Giblett. The first recipient of this professorship was John Harlan, MD. This professorship is intended to attract talented medical professionals in hematology and keep Giblett's legacy alive. Elo's unpublished autobiography is property of her niece, Leslie.


References


External links


Arno G. Motulsky and Stanley M. Gartler, "Eloise R. Giblett", Biographical Memoirs of the National Academy of Sciences (2017)
{{DEFAULTSORT:Giblett, Eloise 1921 births 2009 deaths Members of the United States National Academy of Sciences Scientists from Washington (state) 20th-century American women scientists American hematologists American geneticists WAVES personnel United States Navy sailors Women hematologists American women geneticists 20th-century American women physicians 20th-century American physicians 21st-century American women