From his office window in the Shelby Biomedical Research Building, John F. Kearney, Ph.D., Distinguished Professor and Endowed Professor in Immunology in the Department of Microbiology, has a view to the ever-changing UAB campus. Just up the street, a multi-year renovation of the McCallum Basic Health Sciences Building wrapped up in January. On a roughly perpendicular line a block away, the final exterior details are being added to the Altec/Styslinger Genomic Medicine and Data Sciences Building.
These are just two of the latest in a long line of research facilities that have sprung up at UAB since Kearney first arrived sight unseen from Australia in 1973, with a young family and a tea chest filled with specialized scientific tools. Kearney had earned a bachelor’s degree in dentistry at the University of Adelaide and later a Ph.D. in dental research from the University of Melbourne. Knowing he needed a postdoc position, his mentor suggested he apply for a job in Birmingham with UAB’s Harold M. Fullmer, DDS, director of its Institute of Dental Research. A few years before, Fullmer had come to the University of Adelaide on a sabbatical as a visiting faculty member.
Kearney turned out to have some unusual skills that were just what the growing UAB research enterprise needed. While he was at the University of Melbourne, he had become a regular at the Walter and Eliza Hall Institute, just across the street, which was one of the world’s leading immunology research centers and had produced 1960 Nobel Prize winner Frank Macfarlane Burnet. “I would go to all their seminars and one of their guys taught me how to do thoracic duct cannulations in mice, which was how you could access the purest source of B lymphocytes at the time,” Kearney said.
“A whole series of lucky events”
Kearney’s letter intrigued Fullmer and UAB star immunologists Max Cooper, M.D., and Alexander “Sandy” Lawton, M.D. “Life is a whole series of lucky events,” Kearney said. “I think the main reason Max and Sandy wanted to hire me was because I could do this technically difficult surgical technique. And then Harold never asked me to do any dental research — I spent all my time working with Sandy and Max during my postdoc.”
Kearney in his UAB lab. Photo courtesy UAB ArchivesB lymphocytes, or B cells, are the antibody-producing arm of the immune system. They were the subject of Kearney’s doctoral research and, more than 50 years later, are still producing questions to keep him busy in his lab. He was awarded the Dean’s Award for Excellence in mentorship in 2010. In 2013, Kearney was selected to give the UAB Distinguished Faculty Lecture, the academic medical center’s highest honor. In 2016, he earned a career award from the American Association of Immunologists for his outstanding contributions to the field of B cell research. He was awarded the Dean’s Award for Research, Senior Faculty in 2018. He is a 2018 Fellow of the American Association for the Advancement of Science and in 2023 was named a Distinguished Fellow by the American Association of Immunologists. He has written more than 245 articles in peer-reviewed publications and some 25 book chapters.
Kearney will be honored for his five decades of service to UAB during the annual Service Awards Program reception on April 8 in the Hill Student Center. (The first years at UAB do not count toward his official service time, because he was an international fellow, Kearney explains. “But I will have actually been here 52 years in May.”)
Sheer stubbornness
Many of Kearney’s colleagues were, like himself, transplants from elsewhere, many from overseas. “These people came because they saw the opportunity here,” he said. “There was an openness to collaboration and new ideas.”
“It was back-breaking work, but I kept at it out of sheer stubbornness. I did about 600. And eventually, to our delight, we found one that did not make its own antibody.”
If new ideas were in short supply, smart young researchers such as Kearney were sent out to get them. That is how he ended up on a sabbatical year at the University of Cologne in Germany with his young family in 1978, in the lab of noted immunologist Klaus Rajewsky, Ph.D. Rajewsky was working on hybridoma technology — a combination of B cells and myeloma cancer cells that could generate an endless supply of an antibody, which was a critical step if you were going to make them into a drug. Hybridomas had been demonstrated in 1975 by Drs. Georges Kohler and César Milstein, who won a Nobel Prize for the work in 1984. These “monoclonal antibodies” clearly had potential to create revolutionary therapies against cancer, autoimmune diseases and more. But Kohler and Milstein’s hybridomas did not create “pure” monoclonal antibodies, because the cancer cell partners produced their own, non-specific antibodies that contaminated the end result.
Rajewsky’s lab was trying different techniques to overcome this problem. Kearney went ahead with his own method. “People thought this was foolhardy,” he recalled several years ago; but he went at it by brute force, growing hundreds of clones of the mother cancer cell line and then checking to see if any of these had mutated to lose their ability to produce antibodies.
"Nobody else would have done it that way because it was so tedious and unlikely to succeed,” Kearney said. “It was back-breaking work, but I kept at it out of sheer stubbornness. I did about 600. And eventually, to our delight, we found one that did not make its own antibody.”
In many ways, that encapsulates Kearney’s experience in science: a willingness to try new things, even if others think them foolhardy or unlikely to succeed. “Nine out of 10 of the things you try won’t work, but then you get that one,” Kearney said.
One to $412 billion
Kearney’s cell line, known as P3X63Ag8.653, “became famous worldwide instantaneously,” recalled Rajewsky in nominating Kearney for the UAB Distinguished Faculty Lecture. Today, Kearney’s paper describing the breakthrough has been cited more than 2,330 times. The presence of noted B cell researchers such as Kearney and Cooper and many others led a colleague at another university to tell Kearney that UAB actually stood for “the University of the Almighty B cell.”
According to the UABRF, agreements for Kearney’s materials have generated more than $5 million of revenue — and more than $2 million of that has been generated in the past five years alone.
Kearney’s cell line “became so useful and easy to use that it became widespread in the academic community, and the individuals who started looking into this for therapeutic purposes, most of that community started using this cell line that John had made,” said Flavius Martin, M.D., who was a postdoctoral fellow in Kearney’s lab in the 1990s and is now executive vice president of Research at Gilead Sciences. “Over a few years, that technology evolved; but in many ways, the work John did in Germany really helped the field explode.”
The first monoclonal antibody was approved by the U.S. Food and Drug Administration in 1986. In 2013, global sales of monoclonal antibody drugs had reached nearly $75 billion. Ten years later, that number had surpassed $218 billion, and by 2029, the market is projected to reach $412 billion.
Kearney’s own antibody producing cell lines — research tools important to study proteins and cells and contribute to the understanding of disease and treatments in many areas of biomedical research — are licensed to companies by the UAB Research Foundation, and they continue to generate a substantial stream of income for the institution. According to the UABRF, agreements for Kearney’s materials have generated more than $5 million of revenue — and more than $2 million of that has been generated in the past five years alone.
“That is probably the best part of this job”
Kearney has trained nearly 50 graduate students and postdoctoral fellows. “I’ve had good students,” he said. “That is probably the best part of this job. I really enjoyed working with them and seeing them mature. And I don’t know of any who dropped out of science.” In addition to Martin, many of Kearney’s other trainees can be found in leading positions in academia and industry, including Stewart New, Ph.D., who heads the in vivo antibody discovery team at leading biotech company InCyte, and Linda Hendershot, Ph.D., who recently retired after a distinguished career as a professor of tumor cell biology at St. Jude Children’s Research Hospital in Memphis.
Kearney is not ready to stop doing science yet. His most recent project, spearheaded by his colleague Microbiology Associate Professor Rodney King, Ph.D., is to study the effects of human aging on B cell diversity. “We’ve put in a new grant to understand why, as people get older, their B cells get less diverse,” Kearney said. “Perhaps it is because exposure to antigens over a lifetime causes certain clones to dominate and impact the aging process. So it will be really interesting to find out if there is such a link.”