Honoring one of the greatest antibiotic researchers… H. Boyd Woodruff

Boyd Woodruff was the son of an East Coast farmer whose ground-breaking research served as a lynch pin for fellow scientists to be able to harvest a plethora of lifesaving antibiotics from every day soil.

Known simply as Boyd, he loved to read and explore the world around him. However, it was not until he was a senior in high school and had to take chemistry that he discovered his true passion in life. From that point on, his goal was to be a chemist.

Upon graduation from high school, he was accepted into the microbiology program at Rutgers University, where he lived above the chicken coops on campus and did work in the poultry office building.

Throughout his time as an undergraduate, he developed an interest in biology, since at that time, the study of biology was not well defined and largely experimental.

However, once he took a class on soil microbiology, he realized that biology is simply chemistry, and that what happens in biology is a result of chemical reactions that occur in the body. This realization allowed him to fully embrace biology, and as a result microbiology, without leaving his desire to still be a chemist.

After finishing his undergraduate at Rutgers, he enrolled in the Rutgers Graduate program as a microbiologist, where he studied under Dr. Selman Waksman, a Nobel Prize winner for the discovery of H Boyd Woodruff was one of the first to isolate an antibiotic from bacteria living in soil. He is seen here in 1940 with his mentor Selman Waksman (left) at Rutgers University. Waksman was known to say “Out of the earth shall come thy salvation!” Streptomycin. Shortly after Boyd had completed four months of graduate work, an Oxford graduate had been able to purify Penicillin sufficiently to show it could kill pathogenic bacteria in mice that had been injected with bacteria and cure the mice. Dr. Waksman then assigned Boyd to do the same experimentation as the person who came up with the method that the British had perfected for Penicillin but to do it with his favorite organism, Actinomyces, a genus of the Actinobacteria class of bacteria known for soil ecology and producing enzymes useful in the formation of compost. At that point, the rest of Boyd’s graduate school assignments were working only with antibiotics. Boyd then began to work with Streptomyces to find an antibiotic that is better than penicillin. Streptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae, found predominately in soil and decaying vegetation. A Gram positive spore-former, they are known for their distinct “earthy” odor.

Within two months, Boyd and Waksman had their first antibiotic, Actinomycin, which was found to be one of the most potent antibiotics. However, it was also discovered to be extremely toxic. Though it was not practically valuable at that point, Boyd had come up with a purified antibiotic that was crystallized by Merck. This was important news, and from that day on, Rutgers University became known for its work with antibiotics, and Boyd and Waksman gained a critical and mutually beneficial relationship with Merck.

After the success of purifying Actinomycin, Boyd began to do additional work to find an antibiotic that would be active against Gram-negative infections. After experimenting on infected guinea pigs, Boyd came up with Streptothricin that showed a very broad spectrum of activity beyond what Penicillin could do, including activity against Gram-negative infections. Merck began building a factory for this new antibiotic, but it was found to be too toxic for final use in humans. It would cure the infection, but the human kidneys would be damaged so much that most patients would have died from the toxicity of the antibiotic.

Six months before Boyd graduated from the Rutgers University graduate program, he became involved with the Penicillin project at Merck. Prior to the beginning of this project, Merck had a project to create citric acid from a microorganism other than Aspergillus niger on a sugar solution, which converted the sugar to citric acid, a secret process that was exclusive to Pfizer. This resulted in contacting Rutgers University and Dr. Waksman. Dr. Waksman and a graduate student discovered a brown microorganism that created good yields of citric acid under submerged conditions.

This spurred Merck to try to produce Penicillin under submerged conditions at the Merck facility. Through some ingenuity and experimentation, the research lab assigned to experiment the feasibility attempted to grow penicillin on corn steep liquor instead of proteins. This increased the yield tenfold, and Merck officially accepted the project to create penicillin.

In January of 1942, Boyd left Rutgers and went to work for Merck, the pharmaceutical giant, where he would eventually oversee the introduction of other antibiotics, vitamins B12 and C, and riboflavin; a treatment for a rare cancer called Wilms tumor; a pneumonia vaccine; and a drug used to treat river blindness.

Three months later, in March of 1942, Anne Sheafe Miller, the wife of a professor at Yale University, became the first person cured by penicillin. After the penicillin project wrapped up, another Rutgers student discovered Streptomycin using Boyd’s earlier research and experiments regarding Streptothricin. Streptomycin was purified in the exact same way as Streptothricin, allowing Merck to utilize the factory that they had initially built for Streptothricin, leading to the finishing of the new factory.

After Streptomycin, Tom Wood, a chemist at Merck decided to work on an antipernicious anemia factor, a substance in liver extract that will overcome pernicious anemia. Wood approached Boyd soliciting help due to the difficulties encountered in trying to isolate and purify this substance from liver extract since the only way to tell if there is an active substance is to find a human patient and have it tested and animal testing was not an option. Wood and Boyd collaborated and were able to take some mold cultures Boyd had growing in his lab and utilize the same technique as on the liver extract. Using color as a guide, Wood found one of the molds produced a product that was more active than what he could get from liver extract. These harvested red crystals from the cultures were pure vitamin B12. Though two other companies were working on the antipernicious anemia factor and found solutions shortly after the harvesting of vitamin B12, Merck got the full patent rights since they were first to provide a solution.

Boyd’s next step was to license the processes for penicillin, streptomycin and vitamin B12 to ten countries around the world, resulting in agreements to share research for ten years. This resulted in a new research lab in Spain for antibiotic discovery and a new facility associated with a university in Japan where Boyd spent the last ten years of his career.

Actinomycin, initially thought to be of no practical value, was studied by a German scientist who thought that its toxicity may prove valuable in fighting tumors. Scientists at SloanKettering discovered that Actinomycin proved to be 90% successful in curing a rare type of childhood kidney cancer called Wilms Disease, a disease that proved to be 100% fatal within 1-2 years. Because of Actinomycin, the first antibiotic reported to be able to halt cancer, the several hundred children each year that contract this disease now had a cure.

A product that was discovered his lab in Japan that was shared with Merck under the production agreement is a heartburn medication known as Pepcid. Another product is Avermectin, used for worms in farm and domestic animals, is also given away free in Africa by Merck to prevent river blindness. Avermectin was one of the two thousand unusual microorganisms from Japan’s collection and was found on a golf course. Japan also contributed discoveries for the treatment of urinary tract infections, ulcers, parasitic diseases, and a vaccine for the prevention of chicken pox.

Boyd became the founding editor of Applied Microbiology, a publication by the American Microbiological Society. Nominated because of his expertise and the numerous papers that he had written and co-authored about antibiotics, Applied Microbiology eventually became the most profitable journal the society has ever published.

In 1998, Boyd was elected to the National Academy of Sciences. He also was granted an honorary membership in the American Society for Microbiology, the Society for Actinomycetes in Japan, and the Kitasato Institute in Japan.

In 2004, he was inducted into the Rutgers University Hall of Distinguished alumni.

In addition to Dr. Woodruff’s many awards, a bacterium, Seleniivibrio woodruffii — isolated from sludge in a New Jersey wastewater treatment plant — was named in his honor.

Dr. H. Boyd Woodruff passed away on January 19, 2017, at the age of 99 years old. The results of his work are still relevant and fundamental for the rise of antibiotic discovery, and he will certainly be missed for his persistence and spirit of innovation.

By Tara Brown, Technical Representative at Hardy Diagnostics

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