Calling it a career pinnacle in some ways, University of Houston professor Richard Willson said he was extremely satisfied when he was notified that he was the recipient of the Alan S. Michaels Award in the Recovery of Biological Products for 2021 from the American Chemical Society Biochemical Technology Division.
“The award is given only every other year, worldwide, and there have been only eight winners before me,” he said. “I know or knew all of them, and have great respect for each of them. It is particularly satisfying to be included among their number.”
The award is named for Michaels, who also has a lecture series in his honor at MIT. He was a pioneer in the application of chemical engineering principles to bioengineering, according to MIT. Willson, the Huffington-Woestemeyer Professor of Chemical and Biomolecular Engineering, Biomedical Engineering and Biochemical & Biophysical Sciences, noted that he knew Michaels.
“Alan Michaels was actually for a little while a member of my Ph.D. thesis committee, which gives this award a special significance to me,” Willson said. “I also saw him at the Recovery of Biological Products conference where he was a leading figure. He was a very sharp investigator, something of a visionary in seeing what was coming in the future, and also a successful entrepreneur who started a company called Amicon, which stood for Alan Michaels company. I have used many of their products, so this has a certain homecoming feeling for me.”
Willson's work has deep roots, with the field of recovery of biological products starting around products like alcohol, acetone and antibiotics. For example, penicillin was originally more valuable than gold, and has to be isolated from fermentation broth. Willson noted that for most of his career, the main challenge has been purifying novel medicines made possible by recombinant DNA technology.
“When I was a student, there was a real possibility the world would run out of insulin for diabetics,” he said, as he explained one medical application. “Human insulin was made chemically from pig insulin from pig pancreases, and there was a simple extrapolation that there soon would be more diabetics than pigs. Molecular biologists figured out how to teach microorganisms like bacteria and yeast how to make human proteins like genuine human insulin, but this was demonstrated only at tiny scale, making very small amounts of product.”
Willson added that this was a problem that needed an engineering mindset.
“There was a need for engineers to think about production of these emerging pharmaceutical products like insulin, and then human growth hormone, and then clotting factors for hemophiliacs, and then novel vaccines, and then enzyme replacement therapies, and then lots of monoclonal antibodies for diseases like cancer and rheumatoid arthritis and blindness due to macular degeneration and even now migraines, and most recently messenger RNA as a vaccine and emerging as a drug.”
According to Willson, engineers and biologists had to come together to work at the solution with a multi-disciplinary approach.
“The problem was that the biochemists and molecular biologists did not think in terms of developing scalable processes, but the engineers mostly didn't think about these kinds of molecules,” he said. “I wandered into this field thinking it was interesting and might turn out to be important, and it certainly did. I received the Presidential Young Investigator award for work on the fundamentals of protein chromatography, and I continue 30 years later to enjoy doing research in downstream processing, which is the more modern term for recovery of biological products.”
Willson was quick to credit the environment at UH with much of his research and professional success, as well as his past and current colleagues and mentors.
“I am grateful to Dan Luss, the transformative, long-time chair of chemical engineering, who hired me to work in a field that was seen as promising but very different from what most of the department did,” he said. “It was an act of faith for which I am grateful.”
Willson earned his doctorate at MIT in 1988, which was also fundamental for his later work.
“I was greatly influenced by my instructors and lab mates, notably professor Charles Cooney and professor Robert Reid of MIT, who gave me the desire to study biotechnological processes from a quantitative physical chemistry point of view,” he said. “I give a lot of credit to Jonathan King of the department of biology at MIT, who hired me as a postdoc directly from the chemical engineering department. This was a great act of heresy at the time, since I think no engineer had ever gone to that department. It was a terrific learning opportunity for me, where under the mostly-gentle guidance of people like his senior postdoc Peter Previlege, now on the faculty at the University of Alabama at Birmingham, I got my first real exposure to protein purification, starting from a very low base of applicable knowledge.”
He added, “I also want to acknowledge my grad school classmate Max Follettie who taught me recombinant DNA at a time when that was a very unusual thing for chemical engineers to be studying. Mike Benidek, an accomplished microbial molecular geneticist, was a great collaborator all the time he was at UH, and we are now talking science again while he is provost of a university in Qatar. George Fox, the most famous molecular biologist who is really an engineer, was a great collaborator for many years and got me interested originally in nucleic acids and their purification, leading among other things to my giving a seminar on how to purify RNA to the few employees of Moderna back in 2012, and serving on their technical advisory board.”
“There is one more person I must credit – My collaborator professor Christy Landes, formerly of UH and now at Rice. With her expertise in single-molecule spectroscopy we were able to perform some truly groundbreaking observations of the chromatography of single protein molecules.”
However, Willson said the most important factor in his success were the hard-working students he had helping with his research.
“After the first few years, they actually did all of the work, including indulging some fanciful but bad ideas on my part, and engaging in shared exploration of new spaces that gave a distinctive character to our work,” he said.
In the future, Willson said his research group would continue its work on bioseparations, also known as downstream processing and the recovery of biological products.
“Some of our new projects respond to the extraordinary growth in the importance of antibodies as pharmaceuticals, including about half of the top 10 drugs in the world,” he said. “Sales of therapeutic monoclonal antibodies now exceed the sales of Chevron and are approaching those of Exxon. We also are quite interested in the emerging information-driven manufacturing processes using process analytical technology, in which quality of products is monitored close to or even during their processing instead of inspected in later.”
Willson said he was also interested in tracking the progress of Luminostics, Inc., an early-stage startup founded by two students from his lab.
“We have taken some of our experience in chromatography and applied it to lateral flow chromatography diagnostics, the format of the home pregnancy test,” he said “Luminostics now has about 70 employees and is FDA-authorised with a COVID-19 diagnostic based originally on a glowing star I took off my young daughter’s ceiling, after years of excellent, hard and shrewd work on Andrew and Bala’s parts. We also are working now on a much earlier-stage chromatographic diagnostic with support from the NIH Rapid Acceleration of Diagnostics program.”