George Hoyt Whipple
Biography of George Hoyt Whipple
In 1934 George Hoyt Whipple, George Richards Minot (1885-1950) and William Parry Murphy (1892-1987) received the Nobel Prize in Physiology or Medicine "for their discoveries concerning liver therapy in cases of anaemia".
George Hoyt Whipple was born in Ashland, New Hampshire. His grandfather, Solomon Mason Whipple (1820-1884), had been a practitioner and an active proponent of better medical education. Also his father, Ashley Cooper Whipple (1852-1880), was educated as a physician but died of pneumonia at the early age of 28 years, when George was only two years old.. His wife, Frances Anna Hoyt Whipple (1857-1904), was then pregnant and in July 1880 gave birth to a daughter who was named Ashley after her father.
The father’s premature death left the family in a difficult economical situation. The two children were brought up by their mother and their maternal grandmother Frances Moody Hoyt. Thanks to the efforts of the two women and their own hard work, George and Ashley were able to continue their education and preparation for college at Phillips Andover Academy. After graduating from Phillips Academy, Whipple entered Yale College, where he took his A.B. degree in 1900. As an undergraduate there, Whipple distinguished himself not only as an outstanding student of the sciences, but also as a prize-winning gymnast and oarsman
In order to improve the family economy and raise money to pay for his planned medical education, Whipple subsequently worked for one year as a teacher of the natural sciences at Dr. Holbrook's Military School in Ossining, New York. Here he also served as an athletic coach.
A student at Johns Hopkins
From early childhood George Whipple had been convinced that he was going to devote his life to medicine. With his thorough basic education and good marks he could expect to be admitted anywhere. The most reputable insitution in medical education at the time was the Johns Hopkins Medical School in Baltimore. This faculty had been established as recently as in 1893, but soon had attracted distinguished teachers and created a fruitful research climate. In this he was significantly influenced by his mother, who had learned about the university's outstanding teachers. Hopkins was the only medical school in the United States that requiered a bachelor's degree and a knowledge of Greek, Latin, French and German for admission.
The dean of the university was William Henry Welch (1850-1934), professor of pathology and at that time considered the foremost medical researcher in the U.S. Other great names at the faculty were William Osler (1840-1919) and Harvey Williams Cushing (1869-1939). In his first year at Hopkins, Whipple's training in physiological chemistry at Yale Qualified him to apply for a student teaching assistantship in John Jacob Abel's (1857-1938) Depeartment of Physiological Chemistry. His performance in his first year anatomy course was outstanding enough to win him a second-year appointment as a student instructor in anatomy. During that year Whipple's training was dominated by his introduction to pathology.
Young physician goes to science
Whipple graduated in medicine from Johns Hopkins in 1905. Standing fourth in his class of fifty-four students. At that time he had planned to specialise in pediatrics, but was offered a position as assistant under professor Welch. He was soon fascinated by pathology and sought a second year's appointment from Welch. Professor Welch’s saying : "...... another year of pathology, and he is anchored to it", was proved right.
In 1907, after two years of assistantship, Whipple embarked on his career as a pathologist and was encouraged to undertake research in descriptive and experimental pathology. Thus he never fulfilled his mother’s wish of seeing her son a general practitioner. On the other hand, however, she had ample reeason to enjoy her son’s brilliant career in research.
Doctor in Panama - researcher in Germany
In 1907, with the encouragement of Welch, Whipple went to the Gorgas Hospital in Panama to work for a year as a pathologist with Samuel Taylor Darling (1872-1925), the resident pathologist, and General William Crawford Gorgas (1854-1920). Whipple's main researches were concerned with anaemia and the physiology and pathology of the liver. He worked on anaemia caused by parasitic infections and especially on the lesions found in the intestinal tract in people suffering from these infections. He also studied the histology of the tissues in patients suffering from blackwater fever.
The salary for the work in Panama allowed him to travel to Europe before returning to Hopkins. He spent several months at Heidelberg in the laboratories of Ludolf Krehl (1861-1937) and Paul Morawitz (1879-1939). There he saw a first-class European laboratory in action, and participated briefly in some studies involving the experimental production of anaemia in rabbits.
A prize winner in Austria
Upon his return to Hopkins in 1909, Whipple began work on the pathologic disturbance of function such as that associated with acute chloroform poisoning and liver injury in the dog. Early interest in the pathogenesis of jaundice led him to submit an Essay on the Pathogenesis of Icterus in the blind competition for the Warren Triennial Prize of the Massachusetts General Hospital. Whipple was declared the winner of the prize in April 1910. This immensely pleased his department chairman Welch and added considerably to Whipple's growing renown. Soon thereafter he was offered professorships at the University of Pennsylvania and the University of California schools of medicine. He chose to turn them down and in 1911 was appointed an associate professor of pathology at Hopkins.
Whipple spent the spring and summer of 1911 in Vienna in the laboratory of Professor Hans Horst Meyer (1853-1939). There he learned how to produce the experimental porto-caval shunt in the dog known as the Eck fistula. The Russian physiologist Nikolai Vladimirovich Eck (1849–1917) introduced this technique in 1877 in order to study liver function. Using this technique in later years Whipple was able to study the effects of totally diverting the portal vein of blood flow on a number of hepatic functions in the dog.
Liver studies with Hooper
During the period 1907 to 1914 Whipple's research interests shifted from studies primarily concerned with histopathologic anatomy to problems in which altered functions could be studied with the tools of biochemistry and physiology.
During the last several years at Hopkins, he collaborated with Charles W. Hooper on a long series of studies in dogs on the origin and excretion of bile pigment and on the icterus as one manifestation of impaired hepatic function. They found that the liver cells had an almost limitless power of regeneration. He then became interested in jaundice, which is always associated with chloroform poisoning and injury to the liver. He studied the route by which the bile pigments pass into the blood and thus produce jaundice of various parts of the body and he found that the lympathic system was of little importance in transporting them.
Bile and blood
Whipples studies of bile pigments led to his interest in the body’s production of the oxygen-carrying haemoglobin, which also plays an important part in the production of bile pigment.
He later showed that histiocytes broke red cells down into bilirubin and bile pigments and by exclusion of the liver that histiocytes in other organs could also do this. He demonstrated that fibrinogen was made in the liver and proposed the term Thalassaemia for Cooley's anaemia. He also conducted experiments on artificial anaemia (1923-1925) demonstrating that iron is the strongest inorganic factor involved in the production of red blood cells. This work was done in collaboration with Charles W. Hooper.
His studies were briefly interrupted in the spring of 1914 when Whipple, at age thirty-four, married Katherine Ball Waring of Charleston, South Carolina. They had one son George Hoyt (born 1917), and one daughter Barbara (born 1921) and got seven grandchildren. In 1914 he also accepted an offer to become professor of experimental medicine and head of the newly established George Williams Hooper Foundation for Medical Research at the University of California School of Medicine in San Francisco. This Hooper family had no connection to the family of Whipple's colleague Charles W. Hooper
Over to California
Charles W. Hooper accompanied Whipple in the move from Hopkins to San Francisco. In spite of the many difficulties, they managed to establish a totally new laboratory where Whipple continued his research on bile pigment metabolism. This work culminated in a series of twelve publications between 1915 and 1917.
In the course of studying bile pigment metabolism and recognizing that blood red cells were the major normal source of bilirubin, Whipple and Hooper studied the effects of acute haemorrhagic anaemia and diet composition on bilirubin excretion and shifted the emphasis of their research to the study of the regeneration of red cells in simple anaemia.
Whipple was dean of the medical school in San Francisco during the years 1920 and 1921.
Over to Rochester
In 1921, Whipple, was offered the position of professor and dean of the School of Medicine and Dentistry at a university then planned in Rochester, New York. One of the men behind the initiative was George Eastman (1854-1932), the film magnate who had the headquarter if his corporation in this city.
With his research program in full swing, Whipple was reluctant to leave California, but he was finally won over as the offer was a rare opportunity to create a medical school from the ground up, with a full-time faculty in a physical setting conductive to easy exchange between clinical and preclinical disciplines.
Due to Eastman’s enormous contribution the university was able to receive its first students in 1925. Whipple, now also proving himself a skilled administrator, built the university into a reputable school, contributing importantly with his own lectures and seminaries. He served as dean and professor of pathology until his retirement in 1955, aged 77. However, he continued lecturing and giving seminaries until the beginning of the 1960s, when he was more than 80 years old. In the midst of his busy retirement he also found time to write a short autobiography in which he wrote "I would be remembered as a teacher".
The work leading to his description of the disease that bears his name, commenced in the pathological institute at Johns Hopkins University Medical School on May 9, 1907. Whipple conducted an autopsy on a 36 year old physician who had been a missionary in Turkey, domiciled in Constantinople. He had returned home to the U.S. due to a disease characterised by painful arthritis in multiple joints, gradual loss of weight and strength, abdominal pains and diarrhoea.
Based on his findings, Whipple incorrectly concluded that the condition arose from an abnormality of fat metabolism; hence, he coined the term “intestinal lipodystrophy”. Similar pathological findings were reported by William Henry Allchin (1846-1922) and Richard Grainger Hebb (1848-1918) at the Westminster Hospital in London in 1895 under the name “lymphangiectasis intestini.” This similarity went unnoticed until 1961, during an organising of the collection of unusual pathological findings at the Westminster Hospital. A. D. Morgan then reviewed the original tissue blocks, restained the sections, and demonstrated PAS (para-aminosalicylic acid)-positive macrophages.
Liver to the Nobel banquet
In 1920 Whipple began studies on the effects of various foodstuffs on blood regeneration. His research technician Frieda Robscheit-Robbins arrived in Rochester in December 1922 with forty of her special strain of dogs. Their experimental model was to bleed dogs to make them anaemic, and then to feed them diets that were restricted to food from one particular organ, for instance kidney, liver, brain, etc. Using this approach he found that liver was the most effective, followed by kidney and then muscle.
In 1925 they published the first of what was to become a series of eighteen papers on "Blood Regeneration in Severe Anemia". That report, clearly establishing the superior potency of fed liver in promoting the regeneration of haemoglobin of the anaemic dog, caught the attention of George Richards Minot (1885-1950) in Boston; he and William Parry Murphy (1892-1987) were preoccupied with the treatment of humans afflicted with pernicious anaemia for which there was at the time no cure. In a relatively short time they were able to demonstrate conclusively that a diet containing large amounts of raw or cooked beef liver produced phenomenal sustained remissions of pernicious anaemia. The effectiveness of liver feeding in the successful treatment of pernicious anaemia was soon widely confirmed and recognized internationally.
Between 1925 and 1930 Whipple and Robscheit-Robbins published a total of twenty-one papers describing the use of the standard anaemic dog to test a lengthy array of foods of animal and vegetable origin.
Their work culminated in Whipple, Minot, and Murphy sharing the Nobel prize in physiology or medicine in 1934. Although a modest man who did not enjoy being the centre of attention, it is obvious that the journey to Stockholm with his wife Katharine was one of the great moments in his life. His mother, Anna Whipple, cancelled her subscription to the reputable newspaper Boston Transcript, because she meant that it gave too much of the credit to Minot. During the Nobel dinner in Stockholm, Katharina Whipple was King Gustaf VI Adolph's partner. Upon his returning home Whipple showed his generosity by sharing a part of the prize money with his assistant over many years, Frieda Saur Robscheit-Robbins (1893-1973). His mother, too, received a substantial slump of money in recognition for her sacrifice.
Whipple's later years in Rochester were dominated to total commitment and devotion to his work as dean, as department head, as teacher of pathology and as medical researcher. He continued to use the standard anaemic dog to explore several questions bearing on the metabolism and synthesis of haemoglobin. In 1934 William B. Hawkins and Whipple used bile fistula dogs to determine the average life span of the red blood cell in the dog. They did that by timing the large increase in bile pigment that occurred at about 124 days after the acute massive regeneration of red cells in response to the massive haemolysis induced by the administration of phenylhydrazine.
A man of honours
Among the many honours and distinctions Whipple received are honorary doctorates of several American Universities as well as of the Universities of Athens and Glasgow; the Popular Science Monthly Gold Medal and Annual Award in 1930 (with Dr. Minot), and the William Wood Gerhard Gold Medal of the Pathological Society of Philadelphia, in 1934.
He was a Trustee of the Rockefeller Foundation, a Corresponding Member of the Association of Physicians in Vienna and of the Royal Society of Physicians in Budapest, and of the European Society of Haematology, as well as a Foreign Corresponding Member of the British Medical Association. He was an Honorary Member of the Pathological Society of Great Britain and Ireland, and of the American Philosophical Society and the Society of Experimental Biology and Medicine. He was, from 1936-1953, a member of the Board of Scientific Directors of the Rockefeller Institute, a member of the Board of Trustees of this Foundation from 1939-1953, Vice-Chairman of its Board of Trustees from 1953-1960, and in 1960 he was appointed Trustee Emeritus.
The old man and the sea
Whipple resigned as professor of pathology and dean of the school of medicine and retired two years later, aged 77. He had grown up in a landscape of wild nature that early woke the interest in hunting and fishing in the young George. He maintained these interests all through his life and, due to his vitality, was able to enjoy them even at very advanced ages. As a retiree he spent sustained periods of time every year in Florida with big game fishing, a pleasure he reluctantly gave up.
However, in 1962 two invitations to Washington forced him to cancel his trip to Florida. First he was to receive a high medical honour, second he and his wife with other Nobel prize laureates were invited to a gala dinner at the White House by president George F. Kennedy. Whipple immediately made it clear that he could not refuse the award, but said no thanks to the White House dinner, as it would cost one week of fishing, and that was out of the question.
He died in Rochester on February 1, 1976, aged 97.
- "I would be remembered as a teacher"
I cannot recall a single instance where Whipple spoke in praise of his own work or ideas.
Leon L. Miller
"This report with its unequivocal emphasis on liver feeding is the most important single paper as regards George H. Whipple's world reputation as a scientist, in the whole of his immense lifetime list of more than 300 publications."
G. W. Corner, Whipple's biographer, on the second paper (1925) by Whipple and Robscheit-Robbins on "Blood Regeneration in Severe Anemia".
"Of the three prize winners, it was Whipple who first occupied himself with the investigations for which the prize is now awarded . . . Whipple's experiments were planned exceedingly well, and carried out very accurately, and consequently their results can lay claim to absolute reliability. These investigations and results of Whipple's gave Minot and Murphy the idea to see whether favourable resuots might also be obtained in the case of pernicious anaemia, an anaemia of quite different type, by making use of the foods of the kind that Whipple had found to yield favourable results in his experiments regarding anaemia from loss of blood."
Professor I. Holmgren, speaking for the Nobel Prize award committee.