Karl Paul Link
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Karl Paul Gerhard Link (31 January 1901 – 21 November 1978) was an American
biochemist Biochemists are scientists who are trained in biochemistry. They study chemical processes and chemical transformations in living organisms. Biochemists study DNA, proteins and cell parts. The word "biochemist" is a portmanteau of "biological ch ...
best known for his discovery of the
anticoagulant Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where t ...
warfarin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent st ...
.


Training and early career

He was born in
LaPorte, Indiana La Porte (French for "The Door") is a city in LaPorte County, Indiana, United States, of which it is the county seat. Its population was estimated to be 21,341 in 2022. It is one of the two principal cities of the Michigan City-La Porte, India ...
to a
Lutheran Lutheranism is one of the largest branches of Protestantism, identifying primarily with the theology of Martin Luther, the 16th-century German monk and reformer whose efforts to reform the theology and practice of the Catholic Church launched ...
minister of
German German(s) may refer to: * Germany (of or related to) **Germania (historical use) * Germans, citizens of Germany, people of German ancestry, or native speakers of the German language ** For citizens of Germany, see also German nationality law **Ge ...
descent as one of ten children. He was schooled locally, and attended the
University of Wisconsin–Madison A university () is an institution of higher (or tertiary) education and research which awards academic degrees in several academic disciplines. Universities typically offer both undergraduate and postgraduate programs. In the United Stat ...
, where he studied agricultural chemistry at the College of Agriculture from 1918 to 1925, obtaining an MS in 1923 and a PhD in 1925. He was then chosen by the national Education Board for a postdoctoral scholarship, and relocated to
Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...
. He briefly worked with carbohydrate chemist
Sir James Irvine Sir James Colquhoun Irvine KBE JP PhD (Leipzig) DL DSc BSc FRS FRSE FEIS (9 May 1877 – 12 June 1952) was a British organic chemist and Principal and Vice-Chancellor of the University of St Andrews from 1921 until his death. As a research ch ...
at the
University of St Andrews (Aien aristeuein) , motto_lang = grc , mottoeng = Ever to ExcelorEver to be the Best , established = , type = Public research university Ancient university , endowment ...
in Scotland and from 1926 in Graz, Austria with Fritz Pregl, inventor of microchemistry and Nobel Laureate. Finally he spent several months with organic chemist and future Nobel laureate
Paul Karrer Paul may refer to: *Paul (given name), a given name (includes a list of people with that name) * Paul (surname), a list of people People Christianity *Paul the Apostle (AD c.5–c.64/65), also known as Saul of Tarsus or Saint Paul, early Chri ...
in the latter's lab in Zurich; during this period Link suffered from
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, ...
, requiring recuperation in
Davos , neighboring_municipalities= Arosa, Bergün/Bravuogn, Klosters-Serneus, Langwies, S-chanf, Susch , twintowns = } Davos (, ; or ; rm, ; archaic it, Tavate) is an Alps, Alpine resort town and a Municipalities of Switzerland, muni ...
. After his return from Europe, he acquired his taste for dressing eccentrically, as he was often seen in large bow ties, flannel shirts, and sometimes a cape. He was offered an assistant professorship at the University of Wisconsin–Madison in 1927, and was promoted to associate professor in 1928. He worked initially on plant carbohydrates and resistance to disease. He married Elizabeth Feldman on September 20, 1930; they were to have three sons.


Anticoagulants

In the subsequent years, most of his research focused on plant carbohydrates. However, the most fruitful period began when Ed Carson, a Wisconsin farmer, attracted Link's attention to "sweet clover disease", described in 1924 by veterinarian Frank Schofield. In this condition, cows bled to death after consuming hay made from spoilt sweet clover. Carson's stock had been affected, and he brought a dead cow, blood that would not
clot A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cr ...
, and 100 pounds of sweet clover hay. Under the direction of Link, PhD students Harold Campbell, Ralph Overman, Charles Huebner, and Mark Stahmann crystallised the putative poison—a
coumarin Coumarin () or 2''H''-chromen-2-one is an aromatic organic chemical compound with formula . Its molecule can be described as a benzene molecule with two adjacent hydrogen atoms replaced by a lactone-like chain , forming a second six-membered h ...
-related compound—and synthetised and tested it; it turned out to be
dicoumarol Dicoumarol ( INN) or dicumarol (USAN) is a naturally occurring anticoagulant drug that depletes stores of vitamin K (similar to warfarin, a drug that dicoumarol inspired). It is also used in biochemical experiments as an inhibitor of reductases. ...
(3,3'-methylenebis-(4 hydroxycoumarin)). Dicoumarol was subjected to clinical trials in
Wisconsin General Hospital UW Health University Hospital (UW Health, University of Wisconsin Hospital and Clinics or UWHC) is a 515-bed academic regional referral center with 127 outpatient clinics, located on the western edge of the University of Wisconsin–Madison's camp ...
and the
Mayo Clinic The Mayo Clinic () is a nonprofit American academic medical center focused on integrated health care, education, and research. It employs over 4,500 physicians and scientists, along with another 58,400 administrative and allied health staf ...
. It was for several years the most popularly prescribed oral anticoagulant.
Warfarin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent st ...
, one of the several compounds synthesised as part of the coumarin research, was patented in 1945. The patent was assigned to the Wisconsin Alumni Research Foundation (WARF), for which reason it was given the name Warfarin. Link and researchers Stahmann and Ikawa jointly owning the patent. Initially marketed as
rat poison Rodenticides are chemicals made and sold for the purpose of killing rodents. While commonly referred to as "rat poison", rodenticides are also used to kill mice, squirrels, groundhog, woodchucks, chipmunks, porcupines, nutria, beavers, and voles ...
, warfarin would later, in the 1950s, become the second most important anticoagulant for clinical use (after
heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treat ...
).


Later years

Link was elected to the
National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, 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 Nat ...
in 1946. He received several awards for his work, including the 1955
Albert Lasker Award for Basic Medical Research The Albert Lasker Award for Basic Medical Research is one of the prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Medicine; almost 50 ...
and the 1960
Albert Lasker Award for Clinical Medical Research Lasker-DeBakey Clinical Medical Research Award is one of four annual awards presented by the Lasker Foundation. The Lasker-DeBakey award is given to honor outstanding work for the understanding, diagnosis, prevention, treatment, and cure of diseas ...
. He remained closely involved in the biochemistry of warfarin and related compounds. His work in later years was hampered by poor health (tuberculosis) as he was then relocated to Lake View sanatorium, and upon his return was never able to fully regain his momentum in research. Nevertheless, he remained a full professor until 1971, when he retired. He was a lifelong pioneer of
liberal Liberal or liberalism may refer to: Politics * a supporter of liberalism ** Liberalism by country * an adherent of a Liberal Party * Liberalism (international relations) * Sexually liberal feminism * Social liberalism Arts, entertainment and m ...
causes, and his wife was active in the pacifist movement. Link died from
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
on November 21, 1978.


Bibliography

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References

{{DEFAULTSORT:Link, Karl Paul 1901 births 1978 deaths American biochemists American Lutherans People from La Porte, Indiana Recipients of the Albert Lasker Award for Basic Medical Research Recipients of the Lasker-DeBakey Clinical Medical Research Award University of Wisconsin–Madison College of Agricultural and Life Sciences alumni Members of the United States National Academy of Sciences 20th-century Lutherans