Life Science Historical Sketches from the Blue Ridge Institute for Medical Research

The first article is an obituary, articles 2-6 are book reviews, and articles 7 and 8 are about the science of biological and medical research. To download the pdf, click on the article number.

1. Roskoski, Robert Jr. (1987) Fritz Lipmann (1899-1986): An Appreciation. Trends in Biochemical Sciences 12, 136-138. Fritz Lipmann was arguably one of the three most influential biochemists of the 20th century (along with Otto Warburg and Hans Krebs). He received the Nobel Prize in Medicine or Physiology is 1953 for his discovery of coenzyme A. He also formulated the concept of the high-energy, or energy-rich, bond.

2. Roskoski, Robert Jr. (1994) Hans Krebs: Architect of Intermediary Metabolism 1933-1937 (Vol II) by Frederic L Holmes. Trends in Biochemical Sciences 19, 254-265. Hans Krebs was arguably one of the three most influential biochemists of the 20th century (along with Otto Warburg and Fritz Lipmann). He received the Nobel Prize in Medicine or Physiology for his discovery of the citric acid cycle, more commonly known as the Krebs cycle, the most famous metabolic pathway in biochemistry.

3. Roskoski, Robert Jr. (2002) Nature's Robots: A History of Proteins by Tanford, C. and Reynolds, J. Biochem. Mol. Biol. Educ. 30, 343-345. A review of a book that includes many pioneer protein chemists including Emil Fischer, Linus Pauling, James Sumner, John Northrop, Stanford Moore, William Stein, and Max Perutz, all Nobel Laureates. The article begins on the bottom of the first page.

4. Roskoski, Robert Jr. (2002) Meselson, Stahl, and the Replication of DNA: A History of the "Most Beautiful Experiment in Biology" by Frederic Holmes, Biochem. Mol. Biol. Educ. 30, 431-432. Horace Judson, a chronicler of biochemistry and molecular biology, dubbed the Meselson and Stahl experiment as the most beautiful experiment of all. The review provides information on Linus Pauling, Richard Feynman, Max Delbrück, and George Beadle, all Nobel Laureates who worked at Caltech. The article begins on the bottom of the first page.

5. Roskoski, Robert Jr. (2004) Wandering in the Gardens of the Mind: Peter Mitchell and the Making of Glynn by John Prebble and Bruce Weber, Biochem. Mol. Biol. Educ. 32, 64-65. Peter Mitchell was a pioneer in bioenergetics and Nobel Laureate (1978). His ideas were so revolutionary that scientists took more than a decade to accept them. The review also provides information on the person and his forgetory (the opposite of memory). Some 10 years after Mitchell's divorce from his first wife, Eileen, he attended the wedding of their daughter, and he notice a woman who looked familiar. He asked whether he knew her, and she replied "Yes, I was your first wife!"

The Mitchell Chemiosmotic Hypothesis was not accepted by the majority of the scientific community in the early 1970s. In 1972 I asked Fritz Lipmann what he thought of the hypothesis. Lipmann was an acknowledged expert of bioenergetics, and indeed was one of its founders. Lipmann formulated the concept of the so-called energy-rich bond, denoted by the swiggle (~). Lipmann was also known for his scientific acumen and his intuition. He said the he thought it was correct because it was general. In 1973 I asked Hans Krebs what he thought of the Mitchell Hypothesis. He thought that it was probably wrong because it was too general. He stated that one of the positive aspects of the Mitchell Hypothesis that it was stimulating considerable first-rate research. We see how experts can interpret the same information and reach opposite conclusions. In retrospect we see that Lipmann was closer to the mark.

6. Roskoski, Robert Jr. (2004) George Beadle, an Uncommon Farmer: the Emergence of Genetics in the 20^th Century by Paul Berg and Maxine Singer, Cold Spring Harbor Laboratory Press, 2003. 383 pp. ISBN 0-87969-688-5, Heredity 93, 516-517. George Beadle, who was reared on a farm near Wahoo, Nebraska, had early ideas on gene function. The review also provides insight on Barbara McClintock and Max Delbrück and Beadle's administration of the Caltech Department of Biology and the University of Chicago. Beadle, Delbrück, and McClintock were Nobel Laureates.

7. Krebs, Hans A. (1967) The making of a scientist. Nature 215, 1441-1445. This article traces the scientific genealogy of Otto Warburg, Hans Krebs, and Fritz Lipmann from Berthollet, Gay-Lussac, Liebig, Kekulé, von Baeyer, and Emil Fischer. One of the attributes that a successful scientist learns from a mentor is hard work. Kekulé, the famous scientist who discovered the structure of benzene, remarked that Liebig told him, "If you wish to be a chemist you must be willing to work so hard as to ruin your health. He who is not prepared to do this will not get far in chemistry nowadays". Kekulé added that, "For many years four, or sometimes even three, hours of sleep were enough for me". Krebs states that Kekulé went a bit too far, something with which we can all agree. The article begins on the bottom of the first page.

8. Huggins, Charles B. (1965) The Business of discovery in the medical sciences. Journal of the American Medical Association 194, 153-157. In this article Huggins provides some rules for research and discovery in the biological/medical sciences. He also describes his training and work at the University of Chicago. The first citation in this article is to Claude Bernard's "An Introduction to the Study of Experimental Medicine." Claude Bernard was the father of physiological research. Although Bernard's book was written in the 19th century, its outlook is modern except that Bernard eschewed the use of statistics in physiological research. I asked Hans Krebs about the non-use of statistics in biomedical research. He replied that for Bernard, when you chopped off the head of a rat, it was dead. A statistical analysis was unnecessary.

Huggins, who was a urological surgeon, performed early work on the interrelationship of hormones and cancer for which he received the Nobel Prize in Medicine or Physiology in 1966. He spent 1930 in several laboratories in Europe and was impressed by the work of Otto Warburg. Huggins and Warburg were both notable scientists and eccentrics. Huggins, for example, never wore an overcoat, even on the coldest Chicago winter days. He walked home in snow storms in his sports jacket. Like Fritz Lipmann and Albert Einstein, Huggins never learned to drive a car. Huggins did not believe that people should have "routine" chest x-rays because he thought that this radiation, although minimal, might produce cancer. However, he smoked cigarettes despite the knowledge that this practice promoted lung cancer. When asked why he smoked, Huggins replied "human frailty." While caring for patients in the operating room, his surgical mask sometimes would slip below his nose. However, for self preservation, the operating room nurses knew better than to point this out to him. Also unusual for a surgeon, he was prone to bite his fingernails.

Huggins manipulated many wealthy patients into giving him luxury watches, which he kept in a desk drawer and rarely wore. While on rounds, he would take his watch off and put it in his pocket. After walking into a wealthy patient's room with his entourage, he would feel their radial artery and take the arm of a resident and use his watch to measure the pulse rate. The patient and his or her family were lead to believe that Dr. Huggins was in need of a timepiece. When many of these patients were discharged, Dr. Huggins would be presented with a fine Swiss watch. He would graciously thank them for the unexpected gift. (In the 1950s a Rolex that cost about $100 now costs several thousand dollars.) In the old days upon discharge from the hospital, many grateful patients presented faculty and house staff with home-grown fruits, home-grown vegetables, or home-made baked goods. Rarely would patients give expensive gifts such as the watches presented to Dr. Huggins.

Huggins was very efficient with his time and avoided activities that he deemed non-productive. It was thus surprising that he regularly attended University of Chicago School of Medicine commencements. As a distinguished faculty member he sat prominently on the chancel, or stage, of the Rockefeller Chapel during these proceedings. He wore one of the many colorful academic robes that he collected while receiving his numerous honorary degrees. It is unclear whether he ever wore the same robe more than once at these commencements. In keeping with the notion of time efficiency, Huggins avoided committee work like the plague.

Huggins was an experimentalist and spent his entire scientific life at the bench, even after he received the Nobel Prize. Although he had ample technical help, he insisted on performing his own experiments. He himself cleaned up the rat excretia that followed his injections or operations. One of his aphorisms was "With blood on my hands I can discover; seated at my desk I have no chance."

Huggins shared the Nobel Prize with Peyton Rous, who discovered a virus that produces cancer in chickens. Huggins has written that Rous was a hero of his, but this was disingenuous. If a seminar speaker or lecturer began to discuss the possible role of viruses in producing cancer, Huggins could not tolerate such a notion and would quietly leave the room. Huggins was known for his prescient quips and aphorisms; for examples, click here.

Commentary by Robert Roskoski Jr.

Making a discovery is such a wonderful thing. It's like falling in love and getting to the top of the mountain all in one. � Max Perutz

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Updated 18 December 2010