07-07-2025
Robert Holton dies at 81; his potent chemo drug saved lives
He called the technique, which produced the medication in high amounts, the metal alkoxide process. He licensed his methodology to Bristol Myers Squibb, which became the first pharmaceutical company to manufacture Taxol. Generic versions are sold under the name paclitaxel.
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'There was a worldwide race underway to synthesize it,' Dr. Jeff Boyd, chief scientific officer for the Northwell Health Cancer Institute in Manhasset, N.Y., said in an interview. 'Many groups were working on it because what was needed was a cheap and readily obtainable source of the drug. He was the first to achieve total organic synthesis.'
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Dr. Holton completed the artificially made compound Dec. 9, 1993, beating dozens of competitors. Although scientists at the Scripps Research Institute in La Jolla, Calif., announced that they had also succeeded in synthesizing the drug, Dr. Holton's team was the first to publish details of its methods in a scientific journal.
Before Dr. Holton's achievement, not only did three yews per patient have to die — because the bark where the anticancer alkaloid was first isolated had to be fully stripped — but the forests where they grew also stood to lose the bulk of these conifers.
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Yew trees as a source for cancer treatment first came to scientific attention in the early 1960s. The US government began an extensive search for powerful anticancer compounds lurking in the leaves, twigs, roots, and bark of plants nationwide.
It wasn't until 1970, after nearly a decade of research, that two scientists at the Research Triangle Institute in North Carolina isolated the potent alkaloid in the bark of a Washington state yew tree. Dr. Holton started his drug synthesis research in 1989.
To avoid depleting the species of yew that is native to the western United States, especially the Pacific Northwest, Dr. Holton turned to the more abundant European variety as another source of the medication. Instead of utilizing the bark, he was able to isolate the alkaloid from twigs and needles, foregoing the need to kill the tree. Once he was able to fabricate the medication in a lab, it was no longer necessary to collect any part of the tree for drug production.
'I have always been drawn to difficult problems, and synthesizing Taxol was a big one,' Dr. Holton said in 2018 during remarks at the annual meeting of the National Academy of Inventors in Washington, D.C. He was elected an academy fellow that year. 'Seeing the drug's success in treating so many patients has been an incredibly gratifying experience.'
The National Cancer Institute estimates that more than 1 million patients have been treated with Taxol. It was approved by the Food and Drug Administration in 1992 for ovarian cancer and, in 1994, for advanced breast cancer. The chemo agent is also used for the treatment of lung cancer and Kaposi's sarcoma, among other malignancies, Boyd said.
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'Dr. Holton's extraordinary contributions to science saved countless lives,' Richard McCullough, the president of Florida State University who is a chemist, said in a statement. 'Most scientists dream of having that kind of impact.'
In 1994, The New York Times called Dr. Holton's synthesis of Taxol 'arguably the most important drug cobbled together by human hands.' The article also noted 'the cutthroat competition' to synthesize what everyone believed was destined to become a multibillion-dollar medication. In 1999, Bristol Myers Squibb earned $1.5 billion from sales of the drug.
'It's one of the most commonly used cancer drugs,' said Boyd, who is also the director of the Institute of Cancer Research at the Feinstein Institutes for Medical Research in Manhasset.
Through licensing deals, Florida State University has earned more than $350 million in royalties associated with Dr. Holton's methodology, according to the university.
Of that total, about $140 million went to Dr. Holton. The university announced in 2018 that royalties stemming from the drug synthesis technology are 'the most royalty income from any university-licensed technology in the United States.'
Robert Anthony Holton was born Jan. 26, 1944, in Fayetteville, N.C., the only child of Aaron T. Holton and Marion (Downing) Holton. His father, who served in World War II, was a decorated US Navy veteran and worked as a salesperson after the war.
After his father died in 1959, when Robert was 15, he and his mother moved to Charlotte where he attended secondary school and where she worked as a high school mathematics teacher. In 1962, he enrolled at the University of North Carolina in Chapel Hill where he majored in chemistry and met his first wife, Juanita Bird. They moved in 1966 to Tallahassee, where he began work on a doctoral degree in chemistry at Florida State University. The couple divorced in the early 1980s.
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After a postdoctoral fellowship at Stanford University, Dr. Holton taught chemistry at Purdue University and Virginia Tech. He returned to Florida State in 1985 as a faculty member.
In 1999, Florida State named him a distinguished research professor, and in 2007 the Florida Academy of Sciences awarded him a medal for his scientific contributions. He was inducted into the Florida Inventors Hall of Fame in 2015 and retired from the university in 2023.
'He was very creative and was also a scientist that focused on really hard problems in chemistry,' Sam Huckaba, dean of the College of Arts and Sciences at Florida State University, said in an interview. 'It took that kind of drive to crack the synthesis of Taxol.'
He added that Dr. Holton's work brought national attention to Florida State's chemistry department, as did the research of his second wife, Dr. Marie Krafft, also a professor of chemistry. She died in 2014.
Dr. Holton is survived by three sons: Robert and David Holton, from his first marriage, and Paul Holton, from his second.
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