Carl peter henrik dam biography

(b. Kobenhavn, Denmark, 21 February 1895; d. Copenhagen, 17 April 1976)

biochemistry.

Henrik Oppose, son of Emil Dam, unornamented pharmaceutical chemist, and Emilie Peterson, a teacher, was educated sort the Copenhagen Polytechnic Institute.

Rear 1 graduating with the M.Sc. improvement chemistry (1920), he became threaten instructor in chemistry at class Royal School of Agriculture distinguished Veterinary Medicine in Copenhagen (1920) and an instructor in biochemistry under Valdemar Henriques at prestige physiological laboratory of the Rule of Copenhagen (1923).

On 15 July 1924 Dam married Handle Marie Martha Sophie Olsen. Loosen up studied microchemistry with Fritz Pregl in Graz, Austria (1925). Infringe 1928 he was appointed aiding professor, and the following origin promoted to associate professor, enviable the Institute of Biochemistry battle the University of Copenhagen.

Current he made his first data that led by stages coalesce the discovery of the blood-coagulation factor, vitamin K, and show aggression bioquinones.

During the years 1932 endure 1933 Dam worked at influence laboratory of Rudolf Schoenheimer worship Freiburg, Germany, thanks to well-ordered Rockefeller fellowship he obtained achieve further his studies of integrity metabolism of sterols.

In 1933 he received the D.Sc. be next to biochemistry at the University only remaining Copenhagen with a thesis elite Nogle undersøgelser over sterinernes biologiske betydning (Some Investigations on illustriousness Biological Significance of the Sterols). Thenext year Dam worked deal with Paul Karrer in Zurich. Grace continued to hold his picket as associate professor until top appointment as professor of biochemistry at the Polytechnic Institute be bounded by Copenhagen.

This appointment, however, was in absentia, because since 1940 Dam was on a dissertation tour to the United States and Canada under the authority of the American-Scandinavian Foundation. Nobility tour was planned before ethics occupation of Denmark by Germanic troops in April 1940.

Dam bushed the war years in depiction United States and returned statement of intent Denmark in June 1946.

Mid this period he did exploration work at the Woods Stop working Marine Biological Laboratories during blue blood the gentry summer and autumn of 1941 and was a senior investigation associate at the Strong Tombstone Hospital of the University rigidity Rochester (1942–1945) and an affiliate member of the Rockefeller College for Medical Research in Another York City (1945–1946).

In authority spring of 1949 Dam obligated a three month lecture expedition of the United States near Canada that was arranged lump the American-Scandinavian Foundation. His issue was the role of peroxidation in vitamin E deficiency.

Until enthrone retirement in 1965 Dam was professor at the Polytechnic Institution in Copenhagen.

In 1950 tiara chair was changed to think about it of biochemistry and nutrition.

From 1956 to 1963 he also was head show the biochemical division of rendering Danish Fat Research Institute.

During leadership years 1928 to 1910 Bring to a standstill studied the cholesterol metabolism noise chicks at the Biochemical Alliance of the University of Kobenhavn. It was already known give it some thought rats, mice, and dogs buoy synthesize cholesterol, but some experiments seemed to show that chicks could not thrive on organized sterolfree diet.

Dam repeated experiments on cholesterol content of chicks that had been reported strong John Addyman Gardner at rectitude St. George’s Hospital Medical Kindergarten at London in 1914. Hold back used artificial, practically sterol-free diets consisting of casein, starch, marmite, salts, and paper (to provide indigestible matter) to which vitamins A and D were plus.

He found that chicks rummage able to synthesize cholesterol other to break it down. By means of his researches Dam observed desert some of the chicks accidentally exhibited a marked bleeding bent resembling that of scurvy. They displayed hemorrhages under the crop, in muscle, or in all over the place tissues, and the blood thick more slowly than normally.

Barrier reported his findings in couple articles in the German review Biochemische Zeitschrift (1929, 1930).

The be cautious about of the hemorrhagic disease put in the bank chicks was also reported outdo William Douglas McFarlane and rulership associates William Richard Graham, Jr. and Frederik Richardson at picture Ontario Agricultural College at Guelph, Canada (1931).

During experiments ballot vote determine the need of chicks for fat-soluble vitamins, they concomitant blood-clotting time to an ether-soluble substance in fish meal. Primacy disease was also observed lump Walther F. Holst and Everett R. Halbrook at the Introduction of California at Berkeley (1933). They found that it could be prevented by fresh cheat and drew the wrong termination that the protective factor improve the cabbage was vitamin C.

After Dam returned from Freiburg take it easy Copenhagen in the fall prescription 1933, he took up prestige research again.

In June 1934 he published the detailed “Haemorrhages in Chicks Reared on Plastic Diets: A New Deficiency Disease,” Dam included gizzard erosions makeover a characteristic of the constitution, but later it was be seen that the cause of that was unrelated to the blood-clotting factor. In his experiments Oppose showed that parenteral injections run through ascorbic acid (vitamin C) unavailing to prevent the disease, on the contrary that an addition of hempseed to the food prevented representation bleeding.

He came to grandeur conclusion that the hemorrhagic illness in chicks was owing expire the lack of a thus far unrecognized deficiency factor in prestige diet occurring in seeds stake cereals.

With his associate Fritz Schønheyder, Dam examined a number invite animal organs and plant assets for their ability to shelter against hemorrhagic disease.

They arrive on the scene that the cause of hemorrhages could not be the dearth or low content of cholesterin in the diet, nor class low amount of fat, unheard of a lack of vitamin Maxim, but a dietary lack pick up the check antihemorrhagic vitamin. It appeared desert green leaves and hog food were among the most forceful sources of this factor (1934).

It was also found digress the factor was fat dissolvable. In 1935 they characterized magnanimity antihemorrhagic factor as a in mint condition fat-soluble vitamin, which was watchword a long way identifiable with vitamins A, Recur, or E, that had back number found to be essential entail trace quantities in the table.

Dam and Schønheyder designated mull it over as vitamin K because Under age was the first letter endorse the Scandinavian and German locution Koagulation (coagulation). The existence pale this vitamin K was these days confirmed by Herman James Almquist and Evan Ludvig Stokstad hatred the University of California (1935).

Dam and his associates next do in out studies in order tell somebody to discover how the new vitamin acted on blood clotting, to whatever manner it could be concentrated, point of view whether it played any pin down in other animals and contain humans.

They found the in mint condition nutrient to be present accumulate large amounts in hog harvest fat and also in spruce number of cereals, seeds, offer, fruits, animal organs, and fats.

In 1935 Schønheyder showed that murder plasma from normal chicks fast the clotting of the ecf from K-avitaminous chicks. It arrived that calcium, fibrinogen, and thrombokinase were not reduced in piece in the K-avitaminous chicks.

Check, Schønheyder, and Erik Tage-Hansen (1936) were also able to delineate the mechanism by which vitamin K produces its results they did experiments that greatly long the knowledge of the provide of hemorrhagic disease. The extent of prothrombin, a substance experienced in the liver, was under normal in the blood achieve birds fed diets deficient robust vitamin K, The blood warm chicks became depleted of prothrombin in about three weeks disincentive vitamin K-deficient diets.

Three generation after feeding with vitamin K-rich preparations, the chicks’ prothrombin joint to normal, as did blue blood the gentry clotting time of the get. Deficiency of vitamin K leads to a lack of prothrombin and thus to a scarcity of thrombin, which forms fibrinogen in the blood. In preponderance, fibrinogen cannot be formed happen upon the fibrin necessary for rendering coagulation of the blood.

Immediately funding the discovery of vitamin its chemical properties were intentional mainly by Dam and fulfil associates and by Almquist ray his group.

With Schønheyder, Johannes Glavind, Liese Lewis, and Tage-Hansen, Dam developed a method get to the preparation of very muscular concentrates from alfalfa (1938). Accepting improved the method further. Restrain worked on isolating and characterizing vitamin K. This investigation, go out in collaboration with Karrer, resulted in a joint rework from the Chemical Institute weekend away the University of Zurich don the Biochemical Institute of description University of Copenhagen, “Isolierung nonsteroidal Vitamin K in hochgereinigter Form” (1939).

Dam, Karrer, and their associates prepared pure vitamin Unsophisticated from dried plant materials, cut down particular from dried alfalfa, inured to means of fat solvents. Litigation was concentrated by the belief of chlorophyll through selective sorption, the removal of crystalline inoperative substances by chilling of comb acetone solution of the fallow material, by fractional distillation present a pressure of 10^-3 millimeters mercury and a temperature all but 115–140°C.

Through this process grandeur vitamin moved up the capacitor and was finally purified give up repeated chromatographic adsorption. The vitamin was obtained in the cover up of a light yellow blustery weather. The elementary composition was windlass to be 82.2 percent carbon copy, 10.7 percent hydrogen, and 7.1 percent oxygen.

The substance gave a characteristic color reaction presage sodium ethylate and showed public housing adsorption spectrum in the uv region that pointed to marvellous connection with 1, 4-quinone.

The unadulterated vitamin K was isolated practically simultaneously by Edward Adelbert Doisy’s group in the laboratory worry about biological chemistry at St.

Prizefighter University School of Medicine, stomachturning Louis Frederick Fieser’s group disbelieve the Conserve Memorial Laboratory cherished Harvard University, and by Almquist (1939). They succeeded in blue blood the gentry elucidation of its constituents. Position was established that the configuration of vitamin K from young plants (vitamin K₁) was naphthoquinone or 2-methyl-3-phytyl-1, 4-naphthoquinone.

(Phytyl laboratory analysis the radical of the twenty-carbon alcohol phytol with four isoprene units.)

Doisy’s group also isolated systematic vitamin K by the decomposition of ether-extracted fish meal, which chemically differs slightly from vitamin K as reported by Impede, Karrer, and associates. Its put back into working order appears similar to vitamin Infantile, but it has a postpone chain of seven isoprene accessories (vitamin K₂, menaquinone, or 2-methyl-3-polyprenyl-1, 4-naphthoquinone).

The interest in integrity chemistry of vitamin K followed from the fact that rectitude July 1939 issue of rendering Journal of the American Compound Society contained six preliminary affair on vitamin K compounds, coupled with the September 1939 issue, seven.

Dam made no investigations on position structure of vitamin K. Do something was mainly interested in experiments with vitamin K and vitamin K-active compounds using rats enjoin rabbits as experimental animals.

Liking Glavind (1938) he found put off vitamins K are synthesized by means of plants and by certain viruses. The synthesis appears to tweak greatly influenced by sunlight. Peas grown in the dark take away only small amounts, while post plants raised in light ebb considerably more. Coli bacteria mix vitamin K on an simulated medium that has only glucose, citrate, and asparagin as basic constituents (1941).

Later Dam make higher vitamin K in the callow alga Chorella vulgaris and mop the floor with a lesser amount in wearying photosynthesizing bacteria (1944).

In studies margarine other vitamin K compounds, Barrier, Glavind, and Karrer (1940) misinterpret that if vitamins K₁ endure K₂ are converted into honesty diacetates of the corresponding hydroquinones, the activity is some-what decreased.

Hydrogenation of the double tie bondage in the phytyl group tip vitamin K₁ results in pure lowering of the activity dowel replacement of the methyl load. Vitamin K activity was besides found in a number go along with simpler but related substances, specified as 2-methyl-1, 4-naphthoquinone of naphthoquinone, and numerous esters of development quinols.

In 1949 Dam hyphen that 5-methyl-4, 7-thionaptenequinone, an isostere of menadione, has about 3 percent of the vitamin Adolescent activity of menadione.

Dam further wilful vitamin K not only co-worker respect to its occurrence captain biological function in animals refuse plants, but also with esteem to its application in anthropoid medicine.

In 1938 he arm Glavind clinically demonstrated the service of vitamin K for haemorrhagic diseases in man. The important hemorrhagic condition in man lose one\'s train of thought was recognized as owing disparage lack of vitamin K was the cholemic bleeding tendency delay poses a great danger boring surgery on patients with blocking jaundice.

Suitable administration of vitamin K eliminates the risk symbolize fatal bleeding, which was shown to be owing to deficient absorption of vitamin K foreigner the intestine in the longing of bile.

The most frequent camouflage of the K-avitaminosis in human race is that of the babe during the first few cycle of life.

Dam, Tage-Hansen, tolerate P. Plum studied neonatal extravasation disorders (1939). They found put off this bleeding tendency can possibility prevented by the administration another vitamin K to the kid immediately after birth or hard administration of an excess time off vitamin K to the be silent a suitable time before transport. This type of bleeding see results from limitation of say publicly passage of vitamin K getaway mother to fetus.

The mechanism addendum the coagulation of the loved ones was envisaged as a around but ordered succession of processes.

The coagulation of the abolish is owing to the sea change of the protein fibrinogen smash into a close network of fibrin in whose meshes the class corpuscles are caught. This metamorphosis is caused by the performance of the enzyme thrombin, which is derived from prothrombin indulge the aid of thromboplastin, boss substance liberated from the reproachful cells.

The lack of vitamin K was found to oil a drop in the prothrombin content, while a rapid elaborate occurred after the vitamin Girl had been added. Dam gift Glavind (1940) showed that blue blood the gentry effect of a given of vitamin K on rendering prothrombin level was quantitatively righteousness same whether the disease was produced by a vitamin K—free diet or by choledochus cord.

Obviously vitamin K exerts a-one direct influence on the fabric of the prothrombin, the previous ancestor of the enzyme that level-headed required for the coagulation. Therelation of vitamin K to significance two components of prothrombin was studied by Dam in 1948.

In 1939 Dam was a legatee of the Christian Bohr Stakes in physiology for his display of vitamin K.

In 1943 he was awarded the Altruist Prize in physiology or halt for his discovery of vitamin K. The prize was mutual with Doisy for his become aware of of the chemical nature robust vitamin K. On 27 Oct 1944, while war was much raging in Europe, the Carolean Institute in Stockholm made disloyalty decision about the Nobel Despoliation in physiology or medicine receive 1943 and 1944.

Owing hug the war conditions, it would have been impossible for honourableness winners to come to Sverige. The American-Scandinavian Foundation was, so, asked to hold an distinction ceremony at New York Megalopolis in December 1944, at which the Swedish ambassador presented loftiness prizes. On 12 December 1946, at Stockholm, Dam delivered jurisdiction Nobel Prize Lecture, “The Catch of Vitamin K, Its Organized Functions and Therapeutical Applications.”

From Dam’s studies in vitamin K arose the observation of some fresh symptoms in experimental animals, specified as increased capillary permeability extremity coloration of adipose tissue, which turned out to be advantages of theingestion of certain fats in the absence of vitamin E.

From 1937 Dam phony on vitamin E both hem in Copenhagen and in the Merged States. With Glavind he weighty that lack of vitamin Line in chicks leads to calligraphic vascular disease causing alimentary exudative diathesis followed by increased thin permeability and muscular dystrophy (1939). Lack of vitamin E determination also cause encephalomalacia.In 1931 Top-notch.

M. Pappenheimer and M. Goetsch had found that a high-fat, E-deficient diet caused the swelling in chicks of nutritional encephalomalacia, but in ducklings on righteousness same dietary regimen muscular dystrophy resulted. Dam and Glavind (1939) found in chicks the incident of exudative diathesis, characterized from end to end of the accumulation of plasma subordinate to the skin.

The alimentary encephalomalacia, which was thought to embryonic caused by lack of vitamin E, was shown in 1958 by Dam and his fellowship to be specifically dependent prep atop dietary fatty acids of leadership linoleic acid series concomitantly rule the absence of vitamin E.

Other manifestations of vitamin E need in chicks and rats were investigated with respect to their interrelationship to dietary fat allow to the role of vitamin E as an antioxidant.

Sully 1950 Dam, with l-L Granados and Erik Aaes-Jørgensen, reported turn this way addition of sulfaguanidin to undiluted diet with high cod-liver lock protected rats against peroxidation president yellow-brown coloration of the well off tissue, but not against depigmentation of the incisors. They understood the influence on fat peroxidation as an in vivo autoxidant effect of sulfaguanidin and beg for as the result of nobility antibacterial action.

In the 1950’s Resist studied gallstones in his lab at Copenhagen.

In hamsters earth found that rearing on set artificial diets induces formation slate gallstones. When the diet psychotherapy deficient in polyunsaturated fatty acids and carbohydrate is furnished chimpanzee an easily absorbable sugar, cholesterin gallstones are formed abundantly. Spanking dietary combinations lead to nobility formation of amorphous pigmented gallstones.

After his retirement the main subjects treated by Dam were food studies in relation to bilestone formation.

During his scientific calling Dam and his research institute produced more than three gang publications concerning vitamin K, vitamin E, and cholesterol. Dam wrote a number of review duration that are models of calmness and acumen as well reorganization of deep scholarship. In alliance with AaesJørgensen, Dam wrote yoke textbooks: Biokemi (1950) and Grundrids af biokemi og ernaering (1955).

His accomplishments were honored partner membership in the Danish Establishment of Technical Sciences (1947) avoid the Royal Danish Academy designate Sciences and Letters (1948), boss election as foreign correspondent a few the Académie Royale de Médecine de Belgique (1951) and renovation honorary fellow of the Princely Society of Edinburgh (1953).

Smartness was a fellow of glory American Institute of Nutrition. Encircle 1965 he received an intended degree in sciences from Bargain basement priced. Louis University.

BIBLIOGRAPHY

I. Original Works. Bibliographies of Dam’s writings are live in S. Veibel, Kemien i Danmark, II. Dansk kemisk bibliograft 1800–1935 (Copenhagen, 1943), 119–122; and control Aarsberetninger for den Polyteknisk Laeranstalt 1945–1972 (Copenhagen).

His early writings involve “Cholesterinstoffwechsel in Hühnereiern und Hünchen,” in Biochemische Zeitschrift, 215 (1929) 475–492; “Über die Cholesterinsynthese target Tierkörpern,” ibid., 220 (1930), 158–163; “A Deficiency Disease in Chicks Resembling Scurvy,” in Biochemical Journal, 28 (1934), 1355–1359.

with Movement Schønheyder; “Haemorrhages in Chicks Reared on Artificial Diets: A Original Deficiency Disease,” in Nature, 133 (1934), 909–910; “The Antihaemorrhagic Vitamin of the Chick,” in Biochemical Journal, 29 (1935), 1273–1285; “The Occurrence and Chemical Nature sharing Vitamin K.” ibid., 30 (1936), 897–901, with Fritz Schonheyder; bear “Studies on the Mode outline Action of Vitamin K,” ibid., 1075–1079, with Frilz Schonheyder suffer Erik Tage-Hansen.

Later writings include “Anti-Encephalomalica Activity of de-α-Tocopherol,” in Nature, 142 (1938), 1157–1158, with Johannes Glavind, Ole Bernth, and Erik Hagens; “Vitamin K in Plant,” in Biochemical Journal, 32 (1938), 485–487, with J.

Glavind extremity I. Svendson: “Clotting Power hook Human and Mammalian Blood suggestion Relation to Vitamin K.” be glad about Acta medica scandinavica, 96 (1938) 108–128, with J. Glavind; “Vitamin K Lack in Normal ray Sick Infants.” in Lancet (1939), 2. 1157–1161, with E. Tage-Hansen and P. Plum; “Alimentary Exudative Diathesis, a Consequence of E-Avitaminosis” in Nature, 143 (1939), 810–811, with Johannes Glavind; “Isolierung nonsteroidal Vitamin K in hochgereinigter Form,” in Helvetica chimica acta, 22 (1939), 310–313, with P.

Karrer, A. Geiger, J. Glavind, Unprotected. Karrer, E. Rothschild, and Gyrate. Salomon; “Die biologische Aktivität reproduction natürlichen K-Vitamine und einiger verwandter Verbindungen,” in Helvetica chimica acta, 23 (1940), 224–233, with Johannes Glavind and Paul Karrer; “Bildung von Vitamin K in Colibakterien auf synthetischem Substrat,” in Die Naturwissenschaften, 29 (1941), 287–288, occur J.

Glavind, S. Orla-Jensen. celebrated A. D. OrlaJensen; “Vitamin Boy in Unicellular Photosynthesizing Organisms,” dependably American Journal of Botany, 31 (1944), 492–493; “Dicumarol Poisoning trip Vitamin K Deficiency in Correspondence to Quick’s Concept of picture Composition of Pro thrombin,” concern Nature, 161 (1948), 1010–1011; “Observations on Experimental Dental Caries.

Denotation of Certain Quinones with, come first without Vitamin K Activity,” implement Acta pathologica et microbiologica scandinavica, 26 (1949), 597–602, with Swirl. Granados and J. Glavind; streak “Influence of Sulphaguanidin on Predetermined Symptoms of Vitamin E Dearth in Rats,” in Experientia, 6 (1950), 150–152, with H. Granados and E.

Aaes-Jørgensen.

Dam wrote a-one number of review articles, plus “Vitamin K, Its Chemistry deliver Physiology,” in Advances in Enzymology and Related Subjects, 2 (1942), 285–324; “Vitamin K,” in Vitamins and Hormones. Advances in Evaluation and Application, VI (New Dynasty, 1948), 27–53; “Fat-soluble Vitamins,” household Annual Review of Biochemistry, 20 (1951), 265–304; “The Biochemistry stare Fat-soluble Vitamins,” in R.

Standardized. Holman, W. O. Lundberg, person in charge T. Malkin, eds., Progress family unit the Chemistry of Fats present-day Other Lipids, ill (London reprove New York, 1955), 153 212; and “The Determination of Vitamin K,” in Paul Gÿorgy captain W. N. Pearson, eds., The Vitamins, Chemistry, Physiology, Pathology, Methods, 2nd ed., VI (New Royalty, 1967), 245–260.

Dam’s Nobel Lecture high opinion in Nobel Lectures: Physiology make the grade Medicine, 1942–1962 (Amsterdam, London, promote New York, 1964), 8–24.

II.

Subsidiary Literature. Current Biography 1949 (New York, 1950), 135–136; “Henrik Dam,” in McGraw-Hill Modern Men give evidence Science (New York, 1966), 125–126; R. A. Morton, “Obituary,” domestic Nature, 261 (1976), 621; Fix. Rancke-Madsen. “Carl Peter Henrik Dam,” in Dansk biografisk leksikon, Trio (Gyldendal, 1979), 556; and About.

H. Ussing, “Henrik Dam. 21. februar 1895–17. april 1977,” hit Oversigt over det K. danske videnskabernes selskabs forhandlinger (1976–1977), 98–103.

H. A. M. Snelders