When Sir John Gurdon was awarded the 2012 Nobel Prize in Physiology and Medicine for his discovery that nuclei of mature cells can be induced to produce all of an organism’s cells, it triggered some memories for Bob McKinnell, professor emeritus of genetics, cell biology and development.
Like most Nobel Prizes, this one was awarded for achievements long past. In this case, the early 1960s, when Gurdon and McKinnell were both involved in early research on nuclear transplantation and cloning.
The story really goes back to 1952, when Tom King and Bob Briggs (of what is now Fox Chase Cancer Center) shook the scientific world by successfully transplanting a living nucleus from a frog cell into an enucleated egg and producing a tadpole. A couple of years later, when McKinnell was a University of Minnesota graduate student, he encouraged his department head, Magnus Olson, to invite King to the University of Minnesota as a visiting professor. Surprisingly, Bob recalls, King accepted; and, to his delight, offered to teach a course in experimental embryology. Working as King’s assistant, Bob became well acquainted with him. When the semester was over, King invited McKinnell to work in his lab in Philadelphia.
It was a dream come true for an aspiring embryologist. Under King’s guidance, Bob learned how to make his own micro pipettes and micro needles from glass, manually remove nuclei from frog eggs, transplant them into the cytoplasm of other eggs from which nuclei had been removed, and watch them grow into tadpoles and then mature leopard frogs, which became his model organism for his entire career.
Meanwhile, in his own laboratory at Oxford University in England, John Gurdon – also inspired by the work of King and Briggs – was involved in similar research. In 1958, Gurdon cloned a frog using intact nuclei from the somatic cells of a Xenopus tadpole
In the early 1960s, the two scientists published related work on nuclear transplantation and cloning and in some cases cited each other on their papers. They often crossed paths at scientific meetings.
While Gurdon continued his research on nuclear transplantation, gaining substantial funding for his work, McKinnell, who had long been interested in cancer biology, was inspired to apply the technique to understanding cancer genetics. He finished his postdoctoral fellowship with Tom King in Philadelphia and accepted a faculty position at Tulane University.
At Tulane, McKinnell used genetic markers and transplanted a cancerous cell from a frog (kidney cancer) into cytoplasm. While the tumor cell did not grow into a cloned frog, it showed significant developmental potential. Importantly, something in the cytoplasm of the new egg switched off the tumor genes.
With funding from American Cancer Society to study cancer in frogs, McKinnell visited Minnesota frequently to collect leopard frogs for his research. Magnus Olson, then head of zoology, asked him to join the faculty in 1970. Based on his work with cancer in frogs, he wrote a successful book on cancer biology.
Just a year or two before Michael Crichton’s “Jurassic Park” was published (1990) McKinnell and lifelong colleague Marie DiBerardino (then with the Medical College of Pennsylvania) published a paper on possibility of cloning an organism from an adult blood cell transplanted into the nucleus of a donor cell. DiBerardino came up with the idea for the research and McKinnell made key contributions in carrying it out. To their surprise and delight, the blood cell-derived clone developed further than any clone with a confirmed adult nuclear donor – until Dolly, the cloned sheep. When the movie came out in 1993, Bob became a local media star for his expertise on cloning and gave numerous public talks on the subject.
Now retired, McKinnell keeps busy writing about cancer biology and keeping up on research. In this video, he talks about his pioneering work on nuclear transplantation and cloning.
— Peggy Rinard