Karl Paul Link
Encyclopedia
Karl Paul Gerhard Link was an American
biochemist
best known for his discovery of the anticoagulant
warfarin
.
to a Lutheran
minister of German
descent as one of ten children. He was schooled locally, and attended the University of Wisconsin–Madison
, 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
. He briefly worked with carbohydrate chemist Sir James Irvine
at the University of St Andrews
in Scotland and from 1926 with Fritz Pregl
, inventor of microchemistry and Nobel Laureate. Finally he spent several months with organic chemist and future Nobel laureate Paul Karrer
in the latter's lab in Zurich
; during this period Link suffered from tuberculosis
, requiring recuperation in Davos
. Around this time he may have acquired his taste for dressing eccentrically.
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 in 1930; they were to have three sons.
, 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
-related compound—and synthetised and tested it; it turned out to be dicumarol (3,3'-methylenebis-(4 hydroxycoumarin)).
Dicumarol was subjected to clinical trials in Wisconsin General Hospital and the Mayo Clinic
. It was for several years the most popular oral anticoagulant.
Warfarin
, one of the several compounds synthesised as part of the coumarin research, was patented in 1945 with the Wisconsin Alumni Research Foundation
, Link and researchers Stahlmann and Ikawa jointly owning the patent. Initially marketed as rat poison
, warfarin would later, in the 1950s, become the second most important anticoagulant for clinical use (after heparin
).
in 1946. He received several awards for his work, including the 1955 Albert Lasker Award for Basic Medical Research
and the 1960 Albert Lasker Award for Clinical Medical Research
. He remained closely involved in the biochemistry of warfarin and related compounds.
His work in later years was hampered by poor health (tuberculosis). Nevertheless he remained a full professor until 1971, when he retired. He was a lifelong pioneer of liberal
causes, and his wife was active in the pacifist movement.
Link died from heart failure in 1978.
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
biochemist
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
best known for his discovery of the anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
.
Training and early career
He was born in LaPorte, IndianaLaPorte, Indiana
La Porte is a city in La Porte County, Indiana, United States, of which it is the county seat. Its population was 22,053 at the 2010 census. It is one of the two principal cities of the Michigan City-La Porte, Indiana Metropolitan Statistical Area, which is included in the...
to a Lutheran
Lutheranism
Lutheranism is a major branch of Western Christianity that identifies with the theology of Martin Luther, a German reformer. Luther's efforts to reform the theology and practice of the church launched the Protestant Reformation...
minister of German
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
descent as one of ten children. He was schooled locally, and attended the University of Wisconsin–Madison
University of Wisconsin–Madison
The University of Wisconsin–Madison is a public research university located in Madison, Wisconsin, United States. Founded in 1848, UW–Madison is the flagship campus of the University of Wisconsin System. It became a land-grant institution in 1866...
, 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
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
. He briefly worked with carbohydrate chemist Sir James Irvine
James Irvine (chemist)
Sir James Colquhoun Irvine KBE FRS FRSE FEIS was a Scottish organic chemist and Principal and Vice-Chancellor of the University of St Andrews from 1921 until his death...
at the University of St Andrews
University of St Andrews
The University of St Andrews, informally referred to as "St Andrews", is the oldest university in Scotland and the third oldest in the English-speaking world after Oxford and Cambridge. The university is situated in the town of St Andrews, Fife, on the east coast of Scotland. It was founded between...
in Scotland and from 1926 with Fritz Pregl
Fritz Pregl
Fritz Pregl , was an Austrian chemist and physician from a mixed Slovene-German-speaking background...
, inventor of microchemistry and Nobel Laureate. Finally he spent several months with organic chemist and future Nobel laureate Paul Karrer
Paul Karrer
Paul Karrer was a Swiss organic chemist best known for his research on vitamins. He and Walter Haworth won the Nobel Prize for Chemistry in 1937.-Early years:...
in the latter's lab in Zurich
Zürich
Zurich is the largest city in Switzerland and the capital of the canton of Zurich. It is located in central Switzerland at the northwestern tip of Lake Zurich...
; during this period Link suffered from tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
, requiring recuperation in Davos
Davos
Davos is a municipality in the district of Prättigau/Davos in the canton of Graubünden, Switzerland. It has a permanent population of 11,248 . Davos is located on the Landwasser River, in the Swiss Alps, between the Plessur and Albula Range...
. Around this time he may have acquired his taste for dressing eccentrically.
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 in 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 clotCoagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
, 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
Coumarin is a fragrant chemical compound in the benzopyrone chemical class, found in many plants, notably in high concentration in the tonka bean , vanilla grass , sweet woodruff , mullein , sweet grass , cassia cinnamon and sweet clover...
-related compound—and synthetised and tested it; it turned out to be dicumarol (3,3'-methylenebis-(4 hydroxycoumarin)).
Dicumarol was subjected to clinical trials in Wisconsin General Hospital and the Mayo Clinic
Mayo Clinic
Mayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...
. It was for several years the most popular oral anticoagulant.
Warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
, one of the several compounds synthesised as part of the coumarin research, was patented in 1945 with the Wisconsin Alumni Research Foundation
Wisconsin Alumni Research Foundation
The Wisconsin Alumni Research Foundation is the nonprofit technology transfer office of the University of Wisconsin–Madison. It is a significant source of research support, independent of federal grants...
, Link and researchers Stahlmann and Ikawa jointly owning the patent. Initially marketed as rat poison
Rat poison
Rodenticides are a category of pest control chemicals intended to kill rodents.Single feed baits are chemicals sufficiently dangerous that the first dose is sufficient to kill....
, warfarin would later, in the 1950s, become the second most important anticoagulant for clinical use (after heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
).
Later years
Link was elected to the National Academy of SciencesUnited States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
in 1946. He received several awards for his work, including the 1955 Albert Lasker Award for Basic Medical Research
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 the understanding, diagnosis, prevention, treatment, and cure of disease...
and the 1960 Albert Lasker Award for Clinical Medical Research
Albert Lasker Award for Clinical Medical Research
Lasker~DeBakey Clinical Medical Research Award is awarded by the Lasker Foundation for the understanding, diagnosis, prevention, treatment, and cure of disease. The award was renamed in 2008 in honor of Michael E. DeBakey...
. He remained closely involved in the biochemistry of warfarin and related compounds.
His work in later years was hampered by poor health (tuberculosis). Nevertheless he remained a full professor until 1971, when he retired. He was a lifelong pioneer of liberal
Liberalism
Liberalism is the belief in the importance of liberty and equal rights. Liberals espouse a wide array of views depending on their understanding of these principles, but generally, liberals support ideas such as constitutionalism, liberal democracy, free and fair elections, human rights,...
causes, and his wife was active in the pacifist movement.
Link died from heart failure in 1978.
Source
- Burris RH. "Karl Paul Link". In: Biographical Memoirs: v. 64. National Academy Press, 1994. ISBN 0-309-04978-4.