Philip Showalter Hench

Philip Showalter Hench was born on February 28, 1896, in Pittsburgh, Pennsylvania, the son of Jacob Bixler Hench and Clara Showalter. He attended local local schools and then Lafayette College, graduating in 1916. After graduation he enlisted in the U. S. Army Medical Corps. and was transfered to the reserves so that he could finish his medical training. In 1920 he received his doctorate in medicine from the University of Pittsburgh and he did an internship at St. Francis Hospital. After his internship he became a fellow at the Mayo Foundation, the graduate school of the University of Minnesota's School of Medicine. In 1923 he became an assistant in the Mayo Clinic's Department of Rheumatic Diseases, and three years later he became the director. Between 1928 and 1929 he studied abroad at Freiburg University and the von Muller Clinic in Munich. He was appointed instructor for the Mayo Foundation in 1928, assistant professor in 1932, associate professor in 1935 and professor of medicine in 1947.

During the 1920s the cause of rheumatoid arthritis had yet to be discovered and it was thought to be an infectious disease. One of Hench's patients with the disease, a sixty-nine year old doctor had started to improve the day after he became jaundiced. The jaundice passed in 4 weeks, but the improvement lasted for seven months. Hench documented patients with similar improvements following jaundice and noted the the improvement occurred no matter the cause of the jaundice and he had found that the greater the jaundice the greater the improvement. By 1938 he had collected a further 31 cases in which patients with rheumatoid arthritis who had improved following jaundice and he had also found improvements in pregnant and post-surgical patients and patients suffering from infections. Hench attributed the improvements to a unknown substance he called "Substance X", which he was unable to isolate.

A break came when, after realizing that patients who have been in surgery have their adrenal glands stimulated, Hench turned his attention to the adrenals to find the substance. Hench collaborated with Edward Kendall, a professor physiological chemistry at the Mayo Clinic. Kendall was a prolific researcher, who during the 1930s was deeply involved in adrenal gland research. Kendall had isolated a number of compounds from the adrenal glands of cattle that showed biological activity. By 1941 Hench and Kendall, hypothesized that one of these substances, "Compound E", which was shown to preserve life in adrenaectomized animals, might be substance X. However they were unable to test their hypothesis because of the war and lack of Compound E.

During World War II, Hench became the Chief of the Medical Service and Director of the U.S. Army's Rheumatism Center. At that time the U. S. Government became interested in adrenal research due to rumors that Luftwaffe pilots were able to fly at altitudes of over 40,000 feet due to injections of adrenal extracts, and intelligence reports that Germany was buying large numbers of cattle adrenal glands from Argentina. With this interest National Research Council set up a committee to share research involving adrenal hormones and it was decided that due to the scarcity of adrenal hormones available from natural sources, they must look to synthetic sources. It took until 1944 for Compound E to be synthesized and then only in amounts too small for the synthesis to be commercially viable.

In April 1948 Merck, the company who had completed the synthesis, convened a conference of endocrinologists who were interested in Compound E and split the 9 grams of the compound that they had up among the participants. Hench attempted to get some of this for his patients with rheumatoid arthritis, but he was unable to get any. Hench persisted and in September 1948 he was able to get 5 grams of Compound E from Merck. For his first patient Hench chose "Ms. Gardner", a 29-year old with severe, erosive rheumatoid arthritis. She had been an inpatient at the Mayo Clinic for 2 months, refusing to be discharged until she felt better. Using an initial dose of 50 milligrams, which was followed with four daily injections of 100 milligrams, the patient showed improvement and was able to walk out of the hospital after this treatment. Hench continued his teatments on another 14 patient over the following months and all showed improvement. Hench shared his results at the weekly meeting of the Mayo Clinic scientific staff on April 13, 1949. The meeting was packed and the presentation, which included a dramatic "before and after" film, was followed by a standing ovation. Word of the breakthrough quickly leaked to the scientific press. Hench renamed "Compound E" cortisone, the name it bears today.

In 1950 Hench, Kendall and Tadeus Reichstein, a Swiss chemist who had collaborated with Hench and Kendall in their research, were awarded the Nobel Prize for Medicine and Physiology for "their discoveries relating to the hormones of the adrenal cortex, their structure and biological effects". Hench also won the Lasker award in 1949. He retired in 1957 and in his retirement worked with the Nobel Foundation to set up the Nobel Conferences, high level conferences that deal with the implications of scientific advance.

Hench died on March 30, 1965.

References:

Lloyd, M.; "Philip Showalter Hench, 1896-1965"; Rheumatology (2002) 41:582-584

Bowden, Mary Ellen; Pharmaceutical Achievers: The Human Face of Pharmaceutical Research
; Chemical Heritage Association; 2005

Philip Showalter Hench Nobel Prize biography

August Paul von Wassermann

August Paul von Wassermann was born on February 21, 1866, in Bamberg Germany. He was the son of a Bavarian court banker Angelo Wassermann (who was elevated to hereditary nobility in 1910) and Dora Bauer. He attended the Gymnasium at Bamberg and studied medicine at the Universities of Erlangen, Vienna, and Munich. He graduated with his medical degree from the University of Strasbourg in 1888.

He joined Robert Koch's newly established Institute for Infectious Diseases in 1891 as an unpaid assistant under Bernhard Proskauer. In 1893 he became a temporary assistant working on the problems related to cholera. In 1895 he became the inspecting physician at the Institute's control station for diphtheria. In 1902 he became the director of the clinical division of the Institute. In 1913 he left the Institute to become the director of the department of experimental therapy at the Kaiser Wilhelm Institute, a position he held until his death.

Wassermann was quick to understand the importance of the young science of bacteriology and he made the acquaintance of Paul Ehrlich of whom he became a pupil and colleague. After 1900 he became interested in complement, which was still being investigated. Complement is series of serum proteins that functions as a part of the immune system which, in concert with antibodies, attach to invading bacteria to cause lysis and phagocytosis (see here for the Wikipedia article on the complement system). Starting in 1901 Wassermann unsuccessfully worked to develop a complement based test to diagnose tuberculosis. Later, in 1906, working with Albert Neisser, he developed a complement based test to detect antibodies to the causative agent for syphilis. This test, known as the Wassermann test, was widely used to diagnose syphilis, was developed only one year after the discovery of the causative agent by Fritz Richard Schaudinn and Paul Erich Hoffmann.

During World War I, Wassermann's research was curtailed and eventually suspended completely. During the war he served as a hygienist and bacteriologist, supervising epidemic control on the eastern front. In 1924 he began to suffer from Bright's disease, which took his life on March 16, 1925.

References:

Firkin, Barry G. and Whitworth Judith A.; "Wasserman Test" in Dictionary of Medical Eponyms, Second Edition, Paperback; Informa Healthcare, 2001

"World of Microbiology and Immunology: Von Wassermann, August Paul (1866-1925)"; found at enotes.com

"August Paul von Wassermann" at whonamedit.com

"A First Cure for Syphlis" at the Magnus Hirschfield Archive for Sexology, hosted at www2.hu-berlin.de

Willem Johan Kolff

Willem Johan Kolff was born on February 14, 1911 in Leyden, Holland. Kolff was the son of Jacob Kolff who was the director of Tuberculosis Sanatorium at Beekbergen where Willem spent a great deal of his childhood. Following in his father's footsteps Kolff decided on a medical career and he studied medicine at the University of Leiden, graduating with a medical degree in 1938. He earned a Ph.D. in Medicine from the University of Groningen in 1946.

During World War II Kolff practiced medicine in Kampen, Ovreyssel in the eastern part of the Netherlands. During the war he was active in the resistance and was able to save more than 800 from Nazi labor camps by hiding them in his hospital. In 1940 he set up first blood bank in Europe in the hospital. After watching a patient of his die of temporary kidney failure he was inspired to experiment with using sausage casing to remove impurities from blood. The sausage casing functions as a semi-permeable membrane, permeable to small molecules like urea, but impermeable to larger proteins and blood cells. The first artificial kidney he tried out on patients consisted of fifty feet of sausage casing wrapped around a wooden drum set into salt solution. During dialysis the drum was rotated to remove impurities. To get blood back into the patient Kolff used a part from Ford engine water pump.

The first fifteen patients that the machine was used on died. Later Kolff used anti-coagulants in conjunction with the machine and in 1945 a woman who had gone into a coma from kidney failure was saved by the machine. In 1947 Kolff sent his machine to Mount Sinai Hospital in New York and he began talking with American physicians about artificial organs. Eventually the machine underwent improvements that allowed it to be used on terminal kidney failure patients awaiting transplants, not just patients with temporary kidney failure.

Kolff emigrated to the United States in 1950 becoming the head of the Department of Artificial Organs at the Cleveland Clinic in Cleveland, Ohio. Faced with rebuilding after the war the government of the Netherlands was not able to devote much funding to medical research and Kolff found the environment for medical research in America better. At the Cleveland Clinic Kolff continued his work on artificial organs including artificial heart and lungs. In 1957 Kolff implanted an artificial heart into an animal.

In 1967 Kolff moved to the University of Utah where he became the director of the Institute of Biomechanical Engineering. In Utah he continued his work on artificial organs including artificial eyes and ears. In 1986 Dr. Richard Jarvik implanted an artificial heart into a human patient. The artificial heart used, the Jarvik-7, was based on principals developed by Kolff.

Kolff, in addition to being hailed as the father of artificial organs, received numerous awards including 13 honorary doctorates and the Lasker Award in 2002. He was the first person living in the United States to be made Commander of the Order of Oranje-Nassau by Queen Juliana of the Netherlands. Kolff retired in 1986 on his 75th birthday, but continued, part time his work on artificial organs including the wearable artificial lung.

Kolff died on February 11, 2009.

References:

Davies, Sven T.; "Willem J. Kolff"; at Utah History (media.utah.edu)

Blakeslee, Sandrah; "Willem J. Kolff, at 97; Dutch inventor of artificial heart and organs"; New York Times, Feb. 16, 2009; found at boston.com

"Kolff, Willem Johan [1911-2009]" at New Netherlands Project (nnp.org)

Willem Johan Kolff Wikipedia Entry

Sir William Huggins

Sir William Huggins was born on February 7, 1824 in London, the only surviving child of a silk mercer and his wife. He received his only formal education at the City of London School. Afterwards he continued his studies of mathematics, classics, and modern languages under private tutors. During his university years he worked in the shop of his father. An independent learner he devoted much of his spare time to the study of chemistry and physics, collecting apparatus by which he conducted experiments. For several years he devoted himself to the microscopical study of plant and animal physiology and he was appointed to the Microscopical Society in 1852.

In the mid 1850's his parents sold their business and in 1856 Huggins built an observatory at his residence in at Upper Tulse Hill in Lambeth, London. His first observations were of double stars and he made detailed drawings of Mars, Jupiter, and Saturn. On September 7, 1857 Huggins married Margaret Murray of Dublin, Ireland. Twenty four years his junior, Margaret was an avid astronomer and photographer in her own right. With their marriage the couple began a collaboration that lasted until William's Death. Evidence of the couple's collaboration include a change from William's terse notebook entries to Margaret's more detailed write-ups and a switch to the use of photography to record observations. Starting in 1862 he began working with chemist William A. Miller of Kings College, London taking the stellar spectra of Sirius which they reported to the Royal Society in 1863.

Although Huggins was not the first to study the spectra of astronomical objects, he was the first to employ an apparatus by which the spectral lines could be compared with the spectral lines of chemical elements. As he wrote, "The observatory became meeting place where terrestrial chemistry was brought into direct touch with celestial chemistry." In 1864 he was the first to observe the spectra of nebula when he observed the planetary nebula of Draco. He was surprised that he saw only the spectral lines of gaseous elements and this eventually allowed him to be the first to distinguish the difference between nebula and galaxies in which the other spectral lines of the non-gaseous elements found in stars could be observed.

In 1865 Huggins was elected to the Royal Society and in 1866 he received one of their gold medals. In 1867 the Royal Astronomical Society awarded him a gold medal jointly with Dr. Miller. Starting in 1875 he extended the range of his spectra, observing into the ultra-violet range of the spectrum. For this research and research into the motion of stars he received a second gold medal from the Royal Society, which also awarded him the Rumford medal in 1880. He received a second gold medal from the Royal Astronomical Society in 1885. He was awarded the Bruce Medal by the Astronomical Society of the Pacific in 1904. He served as president of the Royal Society from 1900 to 1905.

Huggins died on May 13, 1910.

References:

Becker, Barbara J.; "Dispelling the Myth of the Able Assistant: Margaret and William Huggins at Work in the Tulse Hill Observatory" (1992); available online at eee.uci.edu

Plarr, Victor; "Huggins, Sir William"; in Men and Women of the Time: a Dictionary of Contemporaries 15th edition; George Routledge and Sons; 1899

von Geldern, Otto; "Address to the Retiring President of the Society, in Awarding the Bruce Medal to Sir William Huggins"; Journal of the Astronomical Society of the Pacific; (1904)16:49-62

"Sir William Huggins" Nature (1910) 83:342-343