Dr. Donald Sharp Fredrickson (born 1924)

Fredrickson was born in Canon 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, but completed his studies at the University of Michigan after being transferred there by the army. During a cycling trip in the Netherlands he met his future wife, Priscilla Eekhof, and they married two years later. They would have two sons.^[1]

Between 1949 and 1952 he worked as a resident and subsequently as a fellow in internal medicine at the Peter Bent Brigham Hospital (now part of Brigham and Women's Hospital) in Boston. Much of his published work from this period is in the field of endocrinology. Subsequently he spent a year in the laboratory of Ivan Frantz, a cholesterol biochemist, at Massachusetts General Hospital.^[1]

Lipid research[edit]

In 1953 he took up a post at the National Heart Institute, part of the National Institutes of Health in Bethesda, Maryland. Initially, he worked with protein chemist and Nobel laureate Christian B. Anfinsen, and subsequently (with Daniel Steinberg) developed an interest in the metabolism of cholesterol and lipoproteins, as well as related medical conditions such as Niemann-Pick disease. His group identified Tangier disease (HDL deficiency)^[2] and cholesteryl ester storage disease, two inborn errors of cholesterol metabolism. He played a prime role in the identification of several apolipoproteins (proteins that characterise the nature of a blood lipid particle): APOA2, APOC1, APOC2 and APOC3.^[1]

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.^[3] It was adopted as the mondial standard by the World Health Organization in 1972.^[1] His group also conducted the first trials of pharmacological cholesterol reduction in the prevention and treatment of cardiovascular disease.^[1]

Textbooks[edit]

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.^[1][4]

Directorships[edit]

Fredrickson at NIH in 1976

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, a task he commenced on 1975-06-01.^[1]

One of the main issues that occupied him was the controversy over research involving recombinant DNA. 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.^[1] 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.^[1] The recombinant DNA controversy was the subject of a book published by Fredrickson in 2001.^[5]

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.^[1]

Later years[edit]

Fredrickson returned to the NIH, resuming work on lipid diseases and writing for the National Library of Medicine. He participated in the genetic elucidation of Tangier disease, which he had himself described in the 1960s.^[1][6]

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.^[1]

He was found dead, face-down, in his swimming pool in 2002. He is buried in Leiden, the Netherlands.^[1]

His papers are held at the National Library of Medicine in Bethesda, Maryland.^[7]

References[edit]

^
Jump up to:
^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ Wyngaarden JB. "Donald Sharp Fredrickson". In Biographical Memoirs. National Academy of Sciences 2006;87:164-179. ISBN 0-309-09579-4. Fulltext. Reprinted from Proc Am Phil Soc 2004;148(3):382-393. PDF Archived September 27, 2007, at the Wayback Machine.
^ Fredrickson DS, Altrocchi PH, Avioli LV, Goodman DS, Goodman HC. Tangier disease. Ann Intern Med 1961;55:1016-1031.
^ Fredrickson, DS; Levy, RI; Lees, RS (1967). "Fat transport in lipoproteins--an integrated approach to mechanisms and disorders". The New England Journal of Medicine. 276 (1): 34–42 contd. doi:10.1056/NEJM196701052760107. PMID 5333081.
^ Stanbury JB, Wyngaarden JB, Fredrickson DS (Eds). The Metabolic Basis of Inherited Disease. New York, Toronto, and London: McGraw-Hill, 1960.
^ Fredrickson DS. The Recombinant DNA Controversy: A Memoir, Science, Politics, and the Public Interest 1974-1981. ASM press, 2001. ISBN 1-55581-222-8.
^ Remaley, AT; Rust, S; Rosier, M; Knapper, C; Naudin, L; Broccardo, C; Peterson, KM; Koch, C; et al. (1999). "Human ATP-binding cassette transporter 1 (ABC1): genomic organization and identification of the genetic defect in the original Tangier disease kindred". Proceedings of the National Academy of Sciences of the United States of America. 96 (22): 12685–90. doi:10.1073/pnas.96.22.12685. PMC 23050. PMID 10535983.
^ "Donald S. Fredrickson Papers 1910-2002 (bulk 1960-1999)". National Library of Medicine.

External links[edit]

The Donald S. Fredrickson Papers, Profiles in Science, National Library of Medicine

1969 - Dr. Fredrickson and Dr. Ernst Klenk at a symposium on phospholipid

See Dr. Ernst Klenk (born 1896) / Source : [HG00BP][GDrive] / NOTES : "Abstract: Ernst Klenk, chair of physiologische chemie at the University of Cologne, Donald Fredrickson, of the National Heart Institute (NHI), and Willi Stoffel, docent of physiologische chemie at the University of Cologne, are seated at a table with wine glasses and a flower center piece." ; Copyright: The National Library of Medicine believes this item to be in the public domain."

1994 - Long-time friend of Fauci ?

1994-02-15-nytimes-scientist-at-work-fauci.pdf

https://www.nytimes.com/1994/02/15/science/scientist-at-work-anthony-s-fauci-consummate-politician-on-the-aids-front.html

SCIENTIST AT WORK: Anthony S. Fauci; Consummate Politician On the AIDS Front

By Natalie Angier

Feb. 15, 1994

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IF everyone in the world were like Dr. Anthony S. Fauci, there would be no need for Prozac. By any sensible reckoning, the man should be wilting around the edges. He has been at the center of the AIDS tornado since the epidemic began, serving as the director of the National Institute for Allergy and Infectious Diseases and the Government's Office of AIDS Research, which together oversee much of the AIDS-related research carried out around the nation.

Apart from his official credentials, he has been the most visible and quotable spokesman on every medical, epidemiological and social aspect of the disease, the de facto AIDS czar until the appointment last year of Kristine Gebbie as the czar de jure to the President.

The institute that Dr. Fauci runs at the National Institutes of Health not only controls about 40 percent of the Federal budget designated for AIDS, but also the money for studies of all the other infectious diseases afflicting the nation's citizenry, from tuberculosis to hanta virus infections. In addition, Dr. Fauci runs a laboratory on the Bethesda campus that does basic research on how the human immunodeficiency virus gradually disassembles the immune system, studies that lately have yielded insights into AIDS and buffed his luster as something more than a superbureaucrat.

Even among scientists, where work addicts are commonplace, Dr. Fauci, 53, is renowned as a truly hard worker. This is the bookend refrain for any discussion about him, an emphasis first and last on how astonishing it is that he manages to work 16 hours a day, day after day, year after year.

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And he is working on a plague for which, scientific revelations about the virus notwithstanding, there have been depressingly few advances to help human patients. There is no vaccine in sight. There are no new drugs in the pipeline, and the antiviral drugs that do exist, like AZT, DDI and DDC, have been shown to be of questionable benefit in prolonging life.

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The epidemic continues to spread relentlessly across the globe. It has killed 210,000 people in the United States alone and eviscerated entire subcultures, including the arts community, which gives depth and resonance to the rest of the population. It is a new disease that has turned the world old overnight.

Dr. Fauci has been bounced around by activists in the AIDS community, denounced one day, embraced as comrade and hero the next. Most recently, activists have put his pride and ego to the test by persuading Congress that the Office of AIDS Research should be removed from his jurisdiction and given a full-time director of its own, who is expected to be named any day now.

Yet Dr. Fauci looks the same as he has looked for years, a compact, meticulous, supremely confident, unflappable bullet of a man, at once compassionate and hard-driving, gentle and ferocious. The man with the natty suits, hearty handshake and resilient Brooklyn accent.

Doesn't he ever doubt himself, or his ability to make a real dent in the disease? Doesn't he ever get tired or depressed or demoralized, or just overwhelmed by it all?

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"If you're asking whether I have fears, pain and anxieties, yes, of course I do," he said. "That's a natural human thing. But do you mean, have I ever let them interfere with my responsibilities, or get in the way of my work? No."

Not once? Not one single lapse?

"Never," he said firmly. "I have the self-discipline not to let that happen." As though to make a point about his purposefulness, he jumps up from the couch where he had been sitting in his office and strides over to his desk. Two of the walls in the large room are covered practically to the ceiling with his plaques and awards and degrees real and honorary.

"To take on what I take on, you have to be very organized and energetic," he said. "I have made enormous sacrifices in my family and personal life. But I don't want to be praised or pitied for this. I do it because this is what I want to do." Optimistic About AIDS Treatment

He is religiously organized, his day blocked out in chunks for his administrative duties, his rounds to see AIDS patients in the research hospital at the institutes, his lab meetings, his discussions with scientists in his group. He runs seven miles every lunch hour regardless of the brutality of the weather. He sets aside every Saturday evening and all day Sunday for his family, a commitment that is essential if he is to see his three young daughters while they are awake.

And perhaps his is the attitude that must prevail in the plague years: not robotic, because robots break down, but calmly obsessive and matter-of-fact. His pragmatism may be his strongest suit, the impulse that ultimately overrides what some say is his sensitivity and a tendency to take things personally. When told that Harold Varmus, the new head of the N.I.H., had described him as "running his institute with an iron fist," Dr. Fauci made a point of asking every subordinate he encountered that evening whether the description was accurate. Most giggled nervously and said variations of, well, yes, but you're always fair.

Dr. Fauci is a man of many opinions, the most essential of which are scientific ones. And it is in the scientific arena that he is most optimistic, although cautiously so. "We've been on a roller-coaster ride for years, from great enthusiasm to despair," he said. "Recently, there was a sense that the sky was falling, when it became clear that giving people AZT early in the course of the disease doesn't give significant benefit.

"But despite the feeling of a roller- coaster ride," he added, "the science will march ahead to the time when we'll have an enduring solution or a therapeutic intervention. And it all will be based on a step-by-step understanding of the immune pathogenesis" that is the hallmark of AIDS.

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Dr. Fauci has lately devoted most of his attention to dissecting those steps. In widely praised work published last year, Dr. Fauci and his colleagues reported that the human immunodeficiency virus never really lies latent in the body, but rather is sequestered in the lymph nodes, where it disturbs many threads of the body's densely interwoven immune system. It overexcites some immune signaling pathways, while eluding the detection of others. And though the main target of the virus appears to be the famed helper T-cells, or CD-4 cells, which it can infiltrate and kill, the virus also ends up stimulating the response of other immune cells so inappropriately that they eventually collapse from overwork or confusion.

He proposes that one possible approach to treating infection with H.I.V. is not to focus on clearing every last viral particle from the body, but rather to figure out exactly how the immune system comes unstrung, and then replace or compensate for those signaling pathways thrown out of whack. For example, he and his colleagues have learned that AIDS patients suffer from a defect in the arousal of an immune signaling molecule called interleukin-2. In trials now under way, they are giving patients IL-2 in carefully calibrated doses designed to recapitulate the activity of a normal immune system. They have found that the patients' T-cell counts improve with the treatment, but they now must determine whether that rise in cell number translates into an improvement in symptoms of the disease; for example, whether the interleukin treatment causes Kaposi's sarcoma lesions to shrink.

Dr. Fauci and his colleagues are also studying the immune systems of 10 people who are members of a small and fortunate minority: they have been infected with H.I.V. for 12 years or longer, yet they have not progressed to showing any symptoms of AIDS. "We think the real clues to the disease are with these people," said Dr. Fauci. "What is it about them that's different? The architecture of their lymphoid tissue appears to be preserved compared to those who progress, and we're trying to see what is responsible for that preservation." 'A Consummate Politician'

Dr. Fauci's current fixation on his science is what keeps him from getting excessively rankled by recent struggles over who will have the greatest hand in shaping the course of AIDS research. The new legislation that reorganized the Office of AIDS Research was whisked through Congress last spring so easily that even the activists who had promoted the change were surprised. Under the plan, the office has been turned into a strong force within the N.I.H., one with more personnel and power than it had under Dr. Fauci's rule. Whoever is chosen as director will coordinate the entire $1.3 billion budget for AIDS research, keeping track of all AIDS-related programs and clinical trials that currently are run by 21 different institutes at the N.I.H.

Dr. Fauci and many other scientists had vigorously opposed the reorganization of the Office of AIDS Research, arguing, among other things, that it would emphasize a trend toward excessively targeted science at the expense of untethered basic research.

Dr. Fauci soft-pedals the degree to which his pride has been wounded, but friends and colleagues said they sensed his frustration. "It might be a relief for him to get some of the pressure off his back," said Dr. Donald Frederickson, a former director of the N.I.H. and one of Dr. Fauci's old friends. "It's enough to do to run his own institute, and his lab is now going full steam. But nobody likes to be downgraded from the position of national importance that he's had."

Those who know Dr. Fauci said there is no chance he will fade into the scenery. "His role will change, but anybody coming into the office would be a fool not to take advantage of Tony's leadership skills," said Derek Hodel of the AIDS Action Council, a Washington-based lobbying group for AIDS organizations. "He's a consummate politician and a fine scientist, and it's clear he's going to continue to play a central role in AIDS research."

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Dr. Fauci, say friends and co-workers, has always been like a child's punching bag, which can be pushed over but will always pop back up for more. For the first eight years of his directorship at the allergy and infectious diseases institute, he worked under Republican Administrations reluctant to focus their attention on AIDS. He has been the repeated target of activists furious at what they perceived to be bureaucratic indifference and timidity -- and he has also been their greatest friend.

"I call him murderer or hero, depending on the week," said Larry Kramer, a playwright, journalist and the most resilient bullhorn of all activists. "It's been such a complicated relationship." That complexity was reflected in Mr. Kramer's latest play, "The Destiny of Me," in which Dr. Fauci is portrayed, with scant attempt at disguise, as Dr. Anthony della Vida, or Dr. Life, a chipper physician-researcher who accepts descriptions of himself as "a son of a bitch of Hitler" and a "scientific fraud" from his churlish AIDS patient -- modeled after Mr. Kramer -- yet who tries with equal fortitude to keep that patient alive. Dr. Fauci attended the play's opening. Assailed and Beloved by Activists

"I've worked with Dr. Fauci for years, and during that time we've have a combination adversarial and collaborative relationship," said Mr. Hodel. He and other activists give Dr. Fauci tremendous credit for lending his support several years ago to the idea of a parallel track, of allowing experimental drugs to be made available to AIDS patients even as the compounds are tested in clinical trials. They also appreciate that he has spoken out against mandatory H.I.V. testing of health care workers, and has opposed barring immigrants who carry the virus. They said he has been willing to listen to members of the AIDS community and to persuade grudging researchers and pharmaceutical companies that they should do the same.

Yet for every cheer there is a hiss. Some activists recall bitterly that during the Reagan and Bush Administrations Dr. Fauci defended research budgets that they thought were dreadfully inadequate. Some say he is a great scientist but a poor administrator; others insist that he is too smooth a bureaucrat to make any scientific headway. Scientists also have criticized Dr. Fauci for capitulating to the demands of activists too readily.

And through it all, Dr. Fauci accepts the criticisms, and he accepts that someone must absorb the anger and terror that AIDS has spawned, so why not somebody of strong vertebrae who was raised on the streets of Bensonhurst? "I was on a C-Span program a couple of months ago with Tony, and I attacked him for the entire hour," said Mr. Kramer. "He called me up afterwards and said he thought the program went very well. I said, 'How can you say that? I did nothing but yell at you.' He said, 'You don't realize that you can say things I can't. It doesn't mean I don't agree with you.' "

Dr. Fauci claims he does not take the intermittent blasts personally. "That's the activist mode," he said. "When there's a disagreement their tendency is to trash somebody. But I know that when Larry Kramer says the reason we're all in so much trouble is because of Tony Fauci, he's too smart to believe that.

"I don't want them to change or compromise that mode," he added, "as long as they don't ask me to change my opinions."

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"I'm totally obsessed by this problem," said Dr. Fauci. "I'm going to finish this job." That is why he turned down an offer to take over the entire National Institutes of Health several years ago, he said, and that is why he does not mind ceding control over the Office of AIDS Research now.

"I think Tony believes he will find a cure for AIDS," said Mr. Hodel. "I hope he's right. And I hope a lot of other people are given the opportunity to believe that as well."