On August 7, 2019, Kary Banks Mullis died at the age of 74. Kary was a good friend. In 1983, he had a revolutionary idea for a cyclic process to exponentially amplify small quantities of DNA. After being separated at high temperature, two strands of DNA could then be copied using a DNA polymerase, primed by short oligonucleotides. In a series of painstaking experiments carried out manually, Kary determined the conditions needed for the process to work. The technique he developed, known as the polymerase chain reaction (PCR), became an instant hit. Eventually, the method was automated so that a segment of DNA could be copied more than a billion times in an hour or two. Molecular and genetic analyses that required large amounts of DNA became considerably easier as a result. Kary’s employer at the time, Cetus Corporation, made a great deal of money when it sold the technology to several buyers. Sadly, Kary was only paid a pittance by Cetus for his pioneering work.
In the articles that have been published since his death, much has been made of Kary’s eccentricities. He has often been portrayed as a wayward genius who enjoyed surfing, drugs, and wild women. Certainly, the word “quirky” scarcely does him justice. Kary had an agile mind that frequently wandered off in unexpected directions, and a conversation with him could be both an exhilarating and exhausting experience.
I knew him in a somewhat different context, and it is that side of Kary that I describe here. In 1983, I was a consultant for New England Biolabs (NEB), where I now work. When we first heard about PCR, our immediate reaction was that sales of restriction enzymes might be negatively affected because it was now possible to clone DNA without using NEB’s products. Upon reflection, we realized that our fears were ill-founded. The development of PCR meant that much more DNA would now be available to researchers, and that larger quantities of restriction enzymes would be needed to cleave it. When he discovered the PCR, Kary had used a mesophilic DNA polymerase isolated from Escherichia coli. He soon realized that the thermostable Taq DNA polymerase—originally isolated from Thermus aquaticus, an organism discovered in a hot spring at Yellowstone National Park—was much more suitable. Kary and Cetus bought Taq polymerase from NEB until a patent was issued and we were forced to stop selling it. We then turned our attention to another heat-stable polymerase, known as Vent DNA polymerase, which is produced by Thermococcus litoralis, an organism found in deep-sea hydrothermal vents. This work, in turn, led to the inadvertent discovery of the first heat stable intein.
In the years following Kary’s PCR breakthrough, our paths crossed on several occasions and we became good friends. I loved his rebellious nature. It was often remarked that Kary might one day win a Nobel Prize for his work on PCR, and when I learned that I had been awarded the 1993 Nobel Prize in Physiology or Medicine, one of my first thoughts was that this might be the year when Kary would win it too. Not long after, he was announced as the winner of the 1993 Nobel Prize in Chemistry. We spent a magical 10 days in Stockholm celebrating our wins in grand fashion. The Swedes know how to throw a party, and in Kary they found a willing collaborator. At one point during our stay, Kary had to be rescued from the clutches of the police, who wanted to arrest him for shining a laser pointer down from above onto unsuspecting pedestrians. Little did he know, a criminal in Stockholm had been doing just that for weeks on end and the police were desperate to make an arrest. It was only after the intervention of the management at the Grand Hôtel that they were able to prevent Kary from being taken into custody.
After our trip to Stockholm, Kary and I often found ourselves attending the same meetings. When we met up with him at these gatherings, my wife, Jean, and I were invariably introduced to Kary’s latest girlfriend. It was on one of these occasions that he introduced us to Nancy Cosgrove, whom both Jean and I immediately liked very much. We tried to warn her about Kary’s flightiness, but she was not easily deterred. It soon became clear that something special was happening. We were delighted when they married in 1997. Kary benefited enormously from Nancy’s love and common sense.
Over the years, Kary made a number of attempts at becoming an entrepreneur, one of which involved following up on a clever idea to fight influenza and other infections by altering the immune system. This led to the creation of a startup named Altermune, which Kary founded in 2004. Some years later, the company’s main focus switched to cancer research, much to Kary’s disappointment.
One last memory is from a trip to Kazakhstan, where Kary, Nancy, Jean, and I spent some very happy times together. We were taken aback by the unabashedly lavish architecture of the capital, Astana, as it was known then, and we marveled at the capacity of our hosts to consume vast amounts of alcohol.
Kary was born in Lenoir, North Carolina, in 1944. As a teenager, he discovered the joy that fireworks can bring to a creative mind. He fell in love with science, and chemistry in particular. Kary completed his undergraduate studies at the Georgia Institute of Technology in 1966. From there, he enrolled at the University of California at Berkeley, becoming a doctoral student of Joe Neilands. In 1972, Kary was awarded a PhD in biochemistry. In the fall of 1979, he joined Cetus Corporation, where he worked until 1986. Kary is survived by his wife, Nancy; three children, Louise, Christopher, and Jeremy; and two grandchildren.1
