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Four Gone, but not Forgotten

Posted 09 July 2018 | By Max Sherman 

Four Gone, but not Forgotten

This article discusses the lives and work of four important scientists who have passed on and who are in danger of passing out of the important annals of medical history if not appropriately remembered. The author frames this discussion with opinions about the importance of knowing about and giving credit to research “heroes” no longer with us as well as noting the importance of their discoveries and contributions, most of which created the foundations for today’s medical advances and new therapies.

Introduction

Although I have no hard data, it is my contention that the younger generation lacks knowledge about or interest in the history of medicine or the heroes that preceded us in our profession. To me, this is troubling. While teaching, I have frequently mentioned a number of notables and rarely did anyone in the class have a clue as to who they were or about their accomplishments. Three such individuals—Stanley Falkow, John Sulston and Jens Skou—died this year. Their deaths occurred without the fanfare to which they were entitled. Although he passed away many years ago, of the four, Otto Warburg, belatedly recognized as the “father” of seminal cancer research, was recently in the news. Because we all should know more about the history and the important people who lived in the past and made contributions that should not be forgotten, this article will provide brief biographical sketches of these four forgotten heroes and highlight their important work.

Stanley Falkow (1934-2018)

Falkow was born in Albany, NY in 1934. His father, born in Kiev, was a shoe salesman, and his mother ran a shop selling corsets. The family moved to Newport, RI when Falkow was nine years old. He attributed his interest in science to the book Microbe Hunters by Paul de Kruif (1890-1971), a bacteriologist and pathologist.1 The book featured Louis Pasteur and Robert Koch, both world renowned bacteriologists.

After Falkow earned an undergraduate degree at the University of Maine be began working as a hospital microbiologist in the 1950s and joining Brown University graduate school in 1957. At Brown, he was quickly drawn toward the emerging field of bacterial genetics and earned his doctoral degree. During the 1960s, he worked on several studies demonstrating how bacteria could swap genetic material, molecular structures now referred to as “plasmids,” genetic structures in a cell that can reproduce independently of the chromosomes. He later was a researcher at Georgetown University and the University of Washington.2 During those years, he demonstrated how the bacteria that can cause gonorrhea could acquire resistance to antibiotics. He also identified a subtype of Escherichia coli responsible for some types of life-threatening diarrhea, prevalent in developing countries. Starting in the 1970s, Falkow warned that the use of antibiotics in animal feeds could spur resistance to medications and damage human health.3 While others fretted about the dangers of bacteria, he pointed out their benefits as well, such as bolstering defenses against diseases. He suggested that eradicating one microbe might cure an ailment, yet that eradication may pave the way for another. In 1981, he accepted the position of chairman of Stanford's Department of Medical Microbiology. At Stanford, he focused on the mechanisms by which organisms cause disease. His primary interest were bacterial pathogens including Yersinia, Helicobacter, Bordetella, Salmonella, Neisseria, and Edwardsiella.

In addition to his research contributions, Falkow was known for his dedication to educating future generations of scientists. He contributed to numerous textbooks and public lecture series on microbiology and also was well known for generously redirecting praise away from himself and toward those with whom he worked.

John Sulston (1942-2018)

Sulston was born in Buckingshire, UK. He received his bachelor’s degree in natural sciences in 1963 and his doctorate in chemistry in 1966 from the University of Cambridge. He was renowned for his strong work ethic and was happiest working in the laboratory where he developed a number of freezing, drying and handling techniques. His findings on genetics, along with Sydney Brenner and H. Robert Horvitz, helped prepare the scientific world for the project of mapping the human genome and won them the Nobel Prize for physiology in 2002.4 Sulston described their work (modestly) as the ability to read the language of evolution. To fully understand the significance of their groundbreaking work, it is necessary to know more about the makeup of the human genome, the complete set of human genes, packaged in 23 separate pairs of chromosomes. Of these, 22 pairs are numbered in approximate order of size, from the largest (number one), to the smallest (number 22), while the remaining pair consists of sex chromosomes: two large X chromosomes in women, one X and one small Y in men. One set of the genome comes from the mother and one from the father. Each set includes the same 30 to 80 thousand genes on the same 23 chromosomes.5 The chromosomes are located in the nucleus of each of the 100 trillion cells found in the human body. Inside the nucleus are two complete sets of the human genome, except in egg cells and sperm cells, which have one copy each, and red blood cells which have none.

Sulston, often described as a visionary biologist with a deep social conscience, was instrumental in keeping the human genome in the public domain. He was vehemently opposed to allowing a private company to sequence the genome for profit, thereby and preventing free and open access to this important information for the benefit of the scientific community and everyone else. His efforts in this cause were described in his book “The Common Thread.”6

Jens Christian Skou (1918-2018)

Skou was born to a wealthy family of timber and coal merchants on 8 October 1918 in Lemvig, in western Denmark. At 15, he left for boarding school, finishing his studies in 1937. He decided to become a physician and began his studies at the University of Copenhagen. He earned his medical degree in 1944 and took residency at a hospital in northern Denmark. He joined Aarhus University in 1947 to conduct research as a graduate student and his interest in anesthetics led to research in membrane physiology, cell biology, enzymes and ion transport.7 His doctoral thesis was completed in 1951, but by then he had become engrossed in research.

He was the first to discover the sodium-potassium pump in cell membranes. The sodium-potassium pump is an enzyme that moves ions across the cell membrane and regulates the amount of sodium and potassium inside cells. This movement is the basis for many of the body functions, including muscle contractions and digestion. The most spectacular use is in the transmission of nerve signals. Nerve axons deplete themselves of sodium ions, then use special channels to allow ions to rush back in during a nerve impulse. The sodium-potassium pump serves to keep the axon ready for the next signal. Adenosine triphosphate, which the body uses to generate energy, powers the pump. Dr. Skou's findings formed the cornerstone of our present day understanding of how the body works and scientists have since studied the pump for the role it plays in a variety of diseases.8

He earned a Nobel Prize for chemistry in 1997 for his exceptional work in cellular biology and maintained his spirit throughout the years. His final scientific article was published in the Journal of Psychiatric Research in 2015, the year he turned 96.

Otto Warburg (1883-1970)

Otto Warburg was born on 8 October 1883, in Germany. His father, Emil Warburg, was a famous physicist. Otto studied chemistry and was awarded a Doctor of Chemistry degree in 1906. He then studied medicine and obtained the Doctor of Medicine degree in 1911. He served with distinction in the Prussian Guard in World War I. It is interesting to note that when Warburg enlisted in the army, Albert Einstein sent him a letter urging him to come home for the sake of science.

Warburg's early research was in botany, studying the assimilation of carbon dioxide in plants.9 He later went on to study the metabolism of tumors and the chemical constituent of oxygen transfer during fermentation. For his discovery of the nature and mode of action of the respiratory enzyme, he won the Nobel Prize in 1931. He was considered for the award on at least two other occasions. This Nobel Prize winning discovery opened up new research in the fields of cellular metabolism and respiration. He subsequently demonstrated for the first time how cancerous cells live and develop, even in the absence of oxygen. At the time, this research was hailed as a major breakthrough in understanding cancer, but was largely neglected through the years and unpublished in textbooks. It should be noted that Warburg's work was conducted in Germany, despite the fact that Warburg was Jewish, an indication of how important cancer research was in that country. Cancer was more prevalent in Germany than in almost any other nation and while he was working in the laboratory, other members of his faith were being persecuted or awaiting death in Nazi concentration camps.

Through the years, it became more obvious that cancer cells were hungry for glucose. His discovery, later named the "Warburg effect," has been found to occur in up to 80 percent of cancers. It is so fundamental to most cancers that Positron Emission Tomography (PET) scans, which have emerged as an important tool in diagnosing cancer, works simply by revealing the places in the body where cells are consuming extra glucose. In many cases, the more glucose a tumor consumes, the worse the cancer prognosis.10

Final Thoughts

When I had the opportunity to interview job candidates, I frequently asked about their interests outside of work. Were they curious? What books did they read? Through the years, I found those individuals with an abiding interest in history were frequently the best qualified for the job at-hand. According to one author, history allows an individual to learn from great men and women who successfully worked through moral dilemmas by virtue of their courage and diligence. An excellent summary about the reasons to study history is available on the American Historical Association's website.11

References

  1. De Kruif P. “Microbe Hunters.” New York, Harcourt, Brace and Co. 1926.
  2. Hagerty J R. “Microbiologist Defended the Value of Bugs Within us.” New York Times. 19-20May 2018.
  3. Offord C. “Stanley Falkow, Father of Molecular Microbial Pathogenesis, Dies.” The Scientist Magazine. 9 May 2018.
  4. Hagerty J R. “Exhaustive Study of a Worm Ended in Nobel Prize.” New York Times. 17-18 March 2018.
  5. Sulston J E, et al. “The Common Thread: A Story of Science, Politics, Ethics and the Human Genome.” Washington DC, Joseph Henry Press. 2002.
  6. Ibid.
  7. Thomas K. “Jens Christian Skou, Nobel Winner for Chemistry, Dies at 99.” New York Times. 1 June 2018.
  8. Skou J C. “The Identification of the Sodium-Potassium Pump.” Nobel Lecture. 8 December 1997.
  9. Nobel Lectures, Physiology or Medicine, Elsevier Publishing Company, Amsterdam, 1965.
  10. Vander Heiden M G, et al. “Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation.” Science. 22 May 2009; 324(5930): 1029-1033.
  11. American Historical Association website. https://www.historians.org/about-aha-and-membership/aha-history-and-archives/historical-archives/why-study-history-(1998). Accessed 14 June 2018.

About the Author

Max Sherman is a retired regulatory professional. He has contributed to Regulatory Focus for more than two decades and is the author of the recently published book entitled "Eclectic Science and Regulatory Compliance: Stories for the Curious." The book contains 36 essays, most of which appeared in Regulatory Focus. In 2012, RAPS published "From Alzheimer's to Zebrafish: Eclectic Science and Regulatory Stories." He is also the editor of the first (2015) and second (2018) editions of "The Medical Device Validation Handbook." He may be contacted at maxsherman339@gmail.com.

Cite as: Sherman M. “Four Gone, but not Forgotten.” Regulatory Focus. July 2018. Regulatory Affairs Professionals Society.


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