VACCINE RESEARCH Volume 3, Number 4, 1994 Mary Ann Liebert, Inc, Publishers
Niels Jerne, Immunologist (1911-1994)
One of the twentieth century’s most remarkable scientists, the immunologist Niels Jerne, died of cancer on October 7, 1994.
In January 1974, I was privileged to hear Jerne give an exquisitely simple lecture on immunology to a group of scientists who were not immunologists. He had no slides and no overheads. He drew simple figures with a felt-tipped pen on the large white pages of a flip chart. There was no jargon. Here was a scientist in his sixties who did not care about impressing us. He had something to say, and he wanted to be understood. He struck me at the time as the “perfect English gentleman,” although this description may not have pleased him, because he was rumored to be not at all fond of the British and to have a particular dislike for the British scientific journal Nature. This must somehow be reconciled with the facts that he traveled on a British passport, was a Dane by birth, lived in Switzerland, and in his retirement lived in a chateau in France.
Jerne presented the talk at Manfred Eigen’s annual winter seminar at a ski resort in the Swiss Alps. Eigen is a German physical chemist who had already had a Nobel Prize for half a dozen years at that time and, in the tradition of European academics, ran his winter seminar in the style of a court, surrounded by people who were uniformly deferential to him. At the end of Jerne’s talk, Eigen thanked him and encouraged him to stay on for a few more days of relaxation in the snow. Jerne did not beat around the bush. “No, I’ve had enough of this,” he said carelessly, and we of the (then) younger generation had to laugh at the remarkable and delightful irreverence toward a Nobel Prize winner. We had never before seen anyone talk to Eigen like that.
Perhaps Jerne learned this directness partly from James Watson, the codiscoverer of the double helix. In the 1950s, Jerne and Watson were both at Caltech, and they met by chance one night at an all-night restaurant. Jerne told Watson about his new, still unpublished selective theory of antibody formation. According to Jerne, Watson, in his “characteristic way of producing a succinct, unambiguous answer to any question,” said, “It stinks.”
Jerne’s remarkable scientific career began late, in the 1950s, when he was already in his forties. Before that he had studied some physics and had obtained an M.D. degree. In 1955, he triggered a first revolution in immunology based on the concept of selection as opposed to instruction as important in antibody production. He suggested that the body makes a diversity of antibodies before being exposed to antigen, and the antigen is able to expand this population. The detailed mechanism he proposed was less than credible (provoking Watson’s succinct evaluation), however, and an improved model was soon published by David Talmadge and MacFarlane Burnet, both in 1957.
In the 1960s, Jerne and his student Al Nordin gave immunologists the hemolytic plaque assay for antibody-forming cells, which played a key role in the cellular immunology experiments of the 1970s, a decade that is regarded fondly by many as a golden age of the field. The 1970s were also Jerne’s most prolific decade. For starters, he gave us an institute, the Basel Institute for Immunology, of which he was the scientific father. (The Swiss pharmaceutical giant Hoffmann-La Roche paid for it, but scientifically it was Jerne’s creation; it was mainly he who decided which scientists would be privileged to work there.) The Basel Institute was unique in its “horizontal” structure, meaning that to a first approximation all scientists were equal and had the opportunity to work on basic science independently of any boss and of any constraints to further the commercial ends of Hoffmann-La Roche. For those of us to be so privileged, this was scientific heaven. This unusual policy made the institute impressively successful. It was subsequently home to three Nobel Prize winners, Jerne, Georges Kohler, and Susumu Tonegawa.
In the early 1970s, Jerne was the first to speculate about the way the immune system may be profoundly influenced by a set of genes called the major histocompatibility complex. This was followed by a new, rich paradigm for cellular immunology, which is still in the process of being developed, namely the network concept. He postulated that not only do antibodies use their variable (V) regions to recognize foreign substances, but that the recognition of V regions by other V regions is central to the regulation of the system. He argued that we need to understand the implications of this if we are to understand regulation and then be able to correct many immune system disorders. This revolutionary insight was the beginning of a new way of looking at the immune system and has led to a great deal of exciting experimental and theoretical research.
The network paradigm led in the late 1980s to the new ideas about how the human immunodeficiency virus causes the acquired immunodeficiency syndrome (AIDS), which my colleagues and I are vigorously researching. These ideas are leading to promising new approaches for AIDS vaccines and therapies. Network ideas potentially also have broader importance for clinical medicine. How the immune system is regulated is of central importance for understanding, treating, and eventually preventing many diseases, including allergies and autoimmune diseases, such as diabetes, multiple sclerosis, arthritis, and lupus.
Jerne spoke and wrote fluently in several languages, including at least English, German, French, Danish, and Dutch. His secondary schooling was in Holland, and he once confided that Dutch was his favorite language. His command of English was outstanding. A highly entertaining example of his writing and wit is the article, “The Natural Selection Theory of Antibody Formation; Ten Years Later,” published in a volume dedicated to Max Delbriick. The anecdotes include one on how he (a Dane) and Max Delbriick (a German) spent part of their time at Caltech correcting the grammar in American scientific texts. Anyone familiar with his writing will confirm that this is more than plausible.
An important criterion for any scientist in evaluating phenomena or ideas is that they “make sense.” When I arrived as a young house theorist in Basel, I spent a couple of sessions with Jerne, during which he would describe a new immunological phenomenon to me and would then comment, “It doesn’t make any sense, does it?” As it turns out, two of the things that “didn’t make sense” were important ingredients in the model I subsequently formulated and have continued to work on for almost 20 years. I am deeply indebted to Jerne for drawing my attention to these phenomena. The difference between Jerne and many other scientists was that he dwelt on the things that didn’t make sense, rather than sweeping them under the rug, conveniently pretending they didn’t exist. As a scientist, he passionately wanted things to make sense. It was not enough for him to be a “stamp collector” who diligently merely studies and reports phenomena. He was concerned with the bigger picture.
As a newcomer in 1975 to immunology, I suggested to Al Cunningham, an established immunologist and textbook author, that Jerne must be eager to win the Nobel Prize. Cunningham answered, “No, I think he is too sensible.” A variation on this opinion came from Ivan Lefkovits, a close friend of Jerne, who said, yes, Jeme did want to win the prize, but for only one reason, namely to prove to his sister that he could do it: she apparently had been giving him a hard time for not yet having won it.
His vindication in this respect finally arrived in 1984, and we all applauded the abundantly deserved recognition.
It was remarkable that Jerne was so productive as a scientist so late in his life. His network hypothesis was published when he was 62, and he had to wait until he was 73 years old to be awarded the big prize.
His focus was not on winning prizes but on doing good science, which is not necessarily the same thing.
Jerne has given us a lot. We must now say goodbye to a no-nonsense, say what you think sort of scientist who wanted things to make sense and contributed enormously toward them making sense.
- Geoffrey W. Hoffmann
Geoffrey Hoffmann was an Associate Professor in the Department of Physics and the Department of Microbiology and Immunology at the University of British Columbia from 1979-2009. He was a member of the Basel Institute for Immunology from 1974 to 1979.