Medicine's Unsung Heroes

Posted 31 May 2017 By Max Sherman

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This article introduces readers to Boyd Woodruff, a legend in the field of microbiology, and discusses his groundbreaking achievements in antibiotic development and Merck's research laboratories.

Introduction

Most or all of us who work in the pharmaceutical industry know about Alexander Fleming and that in 1929, he astutely recognized the organism responsible for penicillin. We also are likely acquainted with Selman Waksman, the scientist who discovered streptomycin in 1944. Waksman was a Rutgers professor whose research into organic substances and their decomposition promoted the discovery of a number of antibiotics.1 Both Fleming and Waksman won Nobel prizes for medicine or physiology. However, I would venture that not many can identify Boyd Woodruff even though he was a legend in the field of microbiology and played a pivotal role in Merck's research laboratories at the dawn of the antibiotic era. His groundbreaking work enabled fellow scientists to harvest an arsenal of lifesaving antibiotics from ordinary dirt. He was instrumental in introducing a fermentation process to increase the production of penicillin; a means to produce Vitamins B12, C and riboflavin; a treatment for a rare cancer called Wilms tumor using actinomycin a chemotherapy medication; a pneumonia vaccine; statins and a drug (avermectin) to treat river blindness.2 His early method to isolate streptothricin was used to discover streptomycin. Moreover, he was the author or co-author of numerous papers, an elected member of the National Academy of Sciences and the founding editor of the journal Applied Microbiology.3 Few if any pharmaceutical researchers can match his body of work and contributions to medicine.

More About Woodruff

Boyd Woodruff was born in Southern New Jersey on 22 July 1917. He attended Bridgeton High School in New Jersey before attending Rutgers University where he received a bachelor's degree in soil chemistry, followed by a PhD from the same school in soil microbiology. His advisor was Selman Waksman. Waksman's course on soil microbiology that combined chemistry with biology was instrumental in Woodruff's career choice.

Woodruff was the first of Waksman's graduate students at the Department of Soil Microbiology to work on antibiotic research. He began the project in 1939. While there, he lived with other students above a chicken house and Woodruff earned money selling eggs. His career had an ignominious, albeit unusual beginning. One of his first projects was trying to discover the minimum temperature needed to kill all of the harmful bacteria in human feces so that they could be safely used for compost in China. (He literally started from the bottom.) Because human feces were not used that way in America, he studied a combination of horse dung, horse urine and straw to see how the mixture worked. After that, he moved on to study Potato Scab disease caused by an actinomycete (Streptomyces scabies).4 When Rene Dubos, one of Waksman's students, discovered tyrothricin from a soil microorganism that would kill pathogens, Woodruff was given the assignment to isolate other Streptomyces and search for other antibiotics.

Much of Woodruff's early successes were derived from a planned experiment growing Escherichia coli in increasing amounts to garden soil. He noted that after several months none of the organisms were present. They were being killed off by one or more species of actinomycetes in the soil. One of which, Actinomyces griseus (later named Streptomyces griseus), produced a red chemical substance apparently responsible for the killings. Subsequent testing isolated the active agent, actinomycin. Fortunately unlike penicillin, actinomycin was easy to extract and purify. The name was chosen because it was the most active antibiotic ever discovered. However, the drug was extremely toxic. A number of years later it was found to have anti-tumor properties. It turned out to be a cure for one childhood type of kidney cancer, Wilm's disease. Prior to actinomycin, Wilm's disease was one hundred percent fatal. Now treated with the drug, it yields a ninety percent success rate.5

Woodruff's work with actinomycin led to the discovery of many other antibiotics from the Streptomyces group. In 1942, Woodruff isolated and purified streptothricin, which prevents the proliferation of Mycobacterium tuberculosis, but it also was toxic for human use. Two years later, Waksman, Albert Schatz and Elizabeth Bugie, isolated the first aminoglycoside, streptomycin, from S. griseus. Merck immediately began manufacturing streptomycin with Woodruff's help. Woodruff had been sent to Merck to help develop new means to produce penicillin and he continued to work there.6 After streptomycin, Woodruff began working on an antipernicious anemia factor, a substance in liver extract. Through his involvement in an extraction technique, the process was able to isolate and crystallize pure vitamin B12.7

Woodruff also was involved in the process to manufacture avermectins, a class of drugs isolated from soil samples the contained Streptomyces avermectinius. The organism was found originally on a golf course in Japan. A series of avermectins are used to treat parasitic roundworm infections in human patients and heartworms in dogs. It also is a drug used to prevent river blindness, a major disease in Africa.8

Final Thoughts

Woodruff passed away on 19 January 2017 at the age of 99. A few months later, another little recognized hero, Lloyd Conover, also died. He was 93. Conover was a chemist whose breakthrough invention of tetracycline, led to a whole new approach to developing such drugs.9 He received his BA degree from Amherst College and his PhD from the University of Rochester. Conover started his research at Pfizer in 1950, when companies were racing to find new antibiotics and was the first chemist to elucidate then chemically alter the structures of oxytetracycline and chlortetracycline, two naturally occurring antibiotics.10 He was almost solely responsible for tetracycline's remarkable commercial success. Conover spent his entire career at Pfizer and he went on to help invent pyrantel and morantel, used to treat parasitic worm infections. He rose through the ranks to become senior vice president for agricultural products research and development.11

A recent editorial in the Wall Street Journal mentioned the growing threat of bacteria that can resist all or nearly all antibiotics.12 Today, microbes appear to be outpacing science's capacity to develop new human defenses. New antibiotics are desperately needed as are scientists like Boyd Woodruff and Lloyd Conover—individuals who spend their lives searching for new ways to discover and develop life-saving drugs.

References

  1. Gordon, K. "Selman Waksman and the Discovery of Streptomycin." Mitchell Lane Publishers, Hockessin, Delaware, 2003.
  2. Roberts, S. "H. Boyd Woodruff, Microbiologist who Paved way for Antibiotics, Dies at 99. New York Times, 3 February 2017.
  3. Merck Honors Research Microbiologist H. Boyd Woodruff, PhD. Merck News. http://www.merck.com/about/featured-stories/H-Boyd-Woodruff.html. Accessed 26 May 2017.
  4. Pringle, P. "Experiment Eleven. Dark Secrets Behind the Discovery of a Wonder Drug." Bloomsbury USA, New York, 2012
  5. Rutgers Oral History Archives. http://oralhistory.rutgers.edu/interviewees/1337-woodruff-h-boyd. Accessed 26 May 2017.
  6. Op cit 4.
  7. 1940s Antibiotics and Isotopes. The Pharmaceutical Century.  http://www3.uah.es/farmamol/The%20Pharmaceutical%20Century/Ch3.html. Accessed 26 May 2017.
  8. Molecules of the Week. Avermectins and Ivermectins. 2 November 2015. American Chemical Society. https://acs.org/content/acs/en/molecule-of-the-week/archive/a/avermectins-ivermectins.html. Accessed 26 May 2017.
  9. Conover, L.H. "Discovering Tetracycline. Research Management. 1984; Vol 27, Issue 5:17-22.
  10. Ibid.
  11. Gellene, D. "Lloyd Conover, Inventor of Groundbreaking Antibiotic, Dies at 93. New York Times, 12 March 2017.
  12. The Superbug Dirty Dozen. Editorial, Wall Street Journal. March 2017.

About the Author

Max Sherman is a retired regulatory professional. He has contributed to Regulatory Focus for more than a decade 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 Medical Device Validation Handbook" published in 2015. He can be contacted at maxsherman339@gmail.com.

Cite as: Sherman, M. "Medicine's Unsung Heroes" Regulatory Focus. May 2017. Regulatory Affairs Professionals Society.

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