Donald S. Fredrickson
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Donald Sharp "Don" Fredrickson (August 8, 1924 – June 7, 2002) was an American medical researcher, principally of the
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids includ ...
and
cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
metabolism, and director of
National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
and subsequently the Howard Hughes Medical Institute. Wyngaarden JB. "Donald Sharp Fredrickson". In ''Biographical Memoirs''. National Academy of Sciences 2006;87:164-179.
Fulltext
Reprinted from ''Proc Am Phil Soc'' 2004;148(3):382-393
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.


Biography

Fredrickson was born in Cañon City, Colorado. His father was a county judge and the owner of Fredrickson Brown, an independent insurance agency. After high school he commenced medical school at the
University of Colorado The University of Colorado (CU) is a system of public universities in Colorado. It consists of four institutions: University of Colorado Boulder, University of Colorado Colorado Springs, University of Colorado Denver, and the University o ...
, but completed his studies at the
University of Michigan , mottoeng = "Arts, Knowledge, Truth" , former_names = Catholepistemiad, or University of Michigania (1817–1821) , budget = $10.3 billion (2021) , endowment = $17 billion (2021)As o ...
after being transferred there by the army. During a cycling trip in
the Netherlands ) , anthem = ( en, "William of Nassau") , image_map = , map_caption = , subdivision_type = Sovereign state , subdivision_name = Kingdom of the Netherlands , established_title = Before independence , established_date = Spanish Netherl ...
he met his future wife, Priscilla Eekhof, and they married two years later. They had two sons. Between 1949 and 1952 he worked as a resident and subsequently as a fellow in internal medicine at the
Peter Bent Brigham Hospital Brigham and Women's Hospital (BWH) is the second largest teaching hospital of Harvard Medical School and the largest hospital in the Longwood Medical Area in Boston, Massachusetts. Along with Massachusetts General Hospital, it is one of the two f ...
(now part of Brigham and Women's Hospital) in Boston. Much of his published work from this period is in the field of
endocrinology Endocrinology (from '' endocrine'' + '' -ology'') is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions known as hormones. It is also concerned with the integration of developmental event ...
. Subsequently he spent a year in the laboratory of
Ivan Frantz Ivan () is a Slavic male given name, connected with the variant of the Greek name (English: John) from Hebrew meaning 'God is gracious'. It is associated worldwide with Slavic countries. The earliest person known to bear the name was Bulgari ...
, a cholesterol biochemist, at Massachusetts General Hospital.


Lipid research

In 1953 he took up a post at the
National Heart Institute The National Heart, Lung, and Blood Institute (NHLBI) is the third largest Institute of the National Institutes of Health, located in Bethesda, Maryland, United States. It is tasked with allocating about $3.6 billion in FY 2020 in tax revenue to ...
, part of the
National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
in
Bethesda, Maryland Bethesda () is an unincorporated, census-designated place in southern Montgomery County, Maryland. It is located just northwest of Washington, D.C. It takes its name from a local church, the Bethesda Meeting House (1820, rebuilt 1849), which in ...
. Initially, he worked with protein chemist and Nobel laureate
Christian B. Anfinsen Christian Boehmer Anfinsen Jr. (March 26, 1916 – May 14, 1995) was an American biochemist. He shared the 1972 Nobel Prize in Chemistry with Stanford Moore and William Howard Stein for work on ribonuclease, especially concerning the c ...
, and subsequently (with Daniel Steinberg) developed an interest in the metabolism of
cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
and
lipoprotein A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, su ...
s, as well as related medical conditions such as Niemann-Pick disease. His group identified
Tangier disease Tangier disease or hypoalphalipoproteinemia is an extremely rare inherited disorder characterized by a severe reduction in the amount of high density lipoprotein (HDL), often referred to as "good cholesterol", in the bloodstream. Worldwide, ap ...
(HDL deficiency) and
cholesteryl ester storage disease Lysosomal acid lipase deficiency (LAL deficiency or LAL-D) is an autosomal recessive inborn error of metabolism that results in the body not producing enough active lysosomal acid lipase (LAL) enzyme. This enzyme plays an important role in breakin ...
, two inborn errors of cholesterol metabolism. He played a prime role in the identification of several
apolipoprotein Apolipoproteins are proteins that bind lipids (oil-soluble substances such as fats, cholesterol and fat soluble vitamins) to form lipoproteins. They transport lipids in blood, cerebrospinal fluid and lymph. The lipid components of lipoproteins ...
s (proteins that characterise the nature of a blood lipid particle):
APOA2 Apolipoprotein A-II is a protein that in humans is encoded by the ''APOA2'' gene. Function ''APOA2'' encodes apolipoprotein A-II, (ApoA-II) which is the second most abundant protein of the high density lipoprotein particles. The protein is f ...
,
APOC1 Apolipoprotein C-I is a protein component of lipoproteins that in humans is encoded by the ''APOC1'' gene. Function The protein encoded by this gene is a member of the apolipoprotein C family. This gene is expressed primarily in the liver, a ...
,
APOC2 Apolipoprotein C-II (Apo-CII, or Apoc-II), or apolipoprotein C2 is a protein that in humans is encoded by the gene. The protein encoded by this gene is secreted in plasma where it is a component of very low density lipoproteins and chylomicrons ...
and APOC3. In 1967 Fredrickson co-authored the paper that described the classification of lipoprotein abnormalities in five types, depending on the pattern of lipoprotein electrophoresis; this became known as the
Fredrickson classification Hyperlipidemia is abnormally elevated levels of any or all lipids (fats, cholesterol, or triglycerides) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also used as an umbre ...
. It was adopted as the mondial standard by the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...
in 1972. His group also conducted the first trials of pharmacological cholesterol reduction in the prevention and treatment of cardiovascular disease.


Textbooks

From 1960 he worked, with John Stanbury and James Wyngaarden, on several editions of the encyclopedic medical textbook ''The Metabolic and Molecular Bases of Inherited Disease''.


Directorships

Apart from his work in research, Fredrickson was involved in the management of the NHI from an early stage. He was clinical director from 1960 onward and from 1966 general director of NHI. In 1974 he left the NHI (then already the National Heart and Lung Institute) to head the Institute of Medicine of the National Academy of Sciences. Nine months later he was asked by president Gerald Ford to become head of the
National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
, a task he commenced on 1975-06-01. One of the main issues that occupied him was the controversy over research involving
recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...
. Already in 1973 there had been scientists urging a ban on such research for environmental reasons. Fredrickson released a guideline that restricted release of genetically modified organisms into the environment, and called into existence a body that would advise on these matters and had to approve any NIH research involving recombinant DNA technology. Fredrickson is credited with restoring confidence in this form of research. A second controversy involved congressional control over the NIH in general. Some feel that Fredrickson's decision to resign from his position in 1981 was fuelled by these controversies. The recombinant DNA controversy was the subject of a book published by Fredrickson in 2001. After 1981 Fredrickson was scholar-in-residence at the National Academy of Sciences for two years, but in 1983 he was recruited to become the vice-president of the Howard Hughes Medical Institute, a privately run health research charity. At that stage, the institute was still the owner of the Hughes Aircraft Company, and Fredrickson participated in the negotiations that led to the sale (for $5.2 billion) to General Motors. He made substantial changes to the institute's research programme. He resigned in 1987 when the trustees of the institute discovered that there had been financial malversations under his presidency.


Later years

Fredrickson returned to the NIH, resuming work on lipid diseases and writing for the
National Library of Medicine The United States National Library of Medicine (NLM), operated by the United States federal government, is the world's largest medical library. Located in Bethesda, Maryland, the NLM is an institute within the National Institutes of Health. Its ...
. He participated in the genetic elucidation of Tangier disease, which he had himself described in the 1960s. He was a member of the National Academy of Sciences, the
American Academy of Arts and Sciences The American Academy of Arts and Sciences (abbreviation: AAA&S) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, a ...
, and the
American Philosophical Society The American Philosophical Society (APS), founded in 1743 in Philadelphia, is a scholarly organization that promotes knowledge in the sciences and humanities through research, professional meetings, publications, library resources, and communit ...
. He was personal physician to Hassan II of Morocco, and had a close personal friendship with the king until the latter's death in 1999. He was found dead, face-down, in his swimming pool in 2002. He is buried in
Leiden Leiden (; in English and archaic Dutch also Leyden) is a city and municipality in the province of South Holland, Netherlands. The municipality of Leiden has a population of 119,713, but the city forms one densely connected agglomeration wi ...
,
the Netherlands ) , anthem = ( en, "William of Nassau") , image_map = , map_caption = , subdivision_type = Sovereign state , subdivision_name = Kingdom of the Netherlands , established_title = Before independence , established_date = Spanish Netherl ...
. His papers are held at the National Library of Medicine in Bethesda, Maryland.


References


External links


The Donald S. Fredrickson Papers
Profiles in Science, National Library of Medicine
Donald S. Fredrickson Papers (1910-2002)
National Library of Medicine finding aid {{DEFAULTSORT:Fredrickson, Donald American physiologists American medical researchers 1924 births 2002 deaths University of Michigan Medical School alumni People from Cañon City, Colorado Directors of the National Institutes of Health Ford administration personnel Carter administration personnel University of Colorado alumni Members of the American Philosophical Society Members of the National Academy of Medicine