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Charles Janeway, Jr Charles Janeway, Jr. Polly Matzinger J Clin Invest. 2003;112(1):2-2. https://doi.org/10.1172/JCI119978. Obituary Charlie Janeway passed away on April 12, 2003 and with him went a good chunk of immunological creativity. Because several tributes relating to his official accomplishments have already been written, I will focus on the man and scientist as I knew him. Charlie and I met in 1977 in Cambridge, when I was a graduate student visiting a friend and he was a young assistant professor at Yale. Having just read a paper of his in the April edition of Nature, and having decided (with the arrogance of a third-year grad student) that it was wrong, I asked him if it had been an April fool’s joke. Without batting an eye, and ignoring my rudeness, Charlie asked me why I thought that. The three of us then spent the next few hours in a pub discussing that paper (which turned out to be right, of course) and many other aspects of immunology, Charlie treating me throughout as an equal despite the differences in our immunological knowledge. This was one of his great features. He loved students and treated us, if we were capable, as colleagues without ever hinting that we should hold our tongues and not argue with the “adults”. As well as being a great teacher, Charlie was a pioneer in several immunological fields, tackling problems that mattered, rather […] Find the latest version: https://jci.me/119978/pdf OBITUARY Charles Janeway, Jr. those that were simply fashionable. receptors (PRRs) that recognized For example, his group was the first evolutionarily conserved molecules to ask whether less antigen might be on infectious nonself organisms. In needed for thymic tolerance than for effect, he said that the immune sys- peripheral activation; i.e., does the tem’s default state is off and that it immune system have a built-in safe- can be turned on by bacteria. ty margin for self-tolerance? He and Then, in the coup that caused the his postdoc, Alexander Rudensky, immunological community to final- were the first to biochemically char- ly take notice, Charlie and Ruslan acterize peptides from MHC class II. Medzitoff found the PRRs. They He and Mark Mamula were the first studied Drosophila, arguing that the to show that B cells were involved in PRRs ought to be evolutionarily “epitope spreading,” a phenomonon ancient. Using the fruit fly’s innate that has since been studied by sever- immune sensor, Toll, they found the al groups working in autoimmunity. mammalian Toll-like receptors As importantly, Charlie had an (TLRs), which are now studied by amazing intuition and an ear for labs around the world. Charlie’s apparently bizarre phenomena on PRRs had come of age. the margins of immunology, coupled When I asked him (in my now older Charlie Janeway passed away on with the ability to bring them to cen- and “wiser” mode as his ever-chal- April 12, 2003 and with him went a ter stage. Long before superantigens, lenging colleague) how his model good chunk of immunological cre- for example, became a popular sub- explained autoimmunity or immune ativity. Because several tributes ject, Charlie studied them and sug- responses to tumors or transplants relating to his official accomplish- gested that a superantigen acted as a (which are not usually covered in bac- ments have already been written, I “hook” to glue T cell receptors to teria), Charlie answered that I need- will focus on the man and scientist MHC molecules, a suggestion that n’t worry because we hadn’t evolved as I knew him. other labs later showed to be true. to deal with these things. Trans- Charlie and I met in 1977 in Cam- But of course, Charlie will most be plants, after all, were a modern inven- bridge, when I was a graduate stu- remembered for his championing of tion, and tumors and autoimmunity dent visiting a friend and he was a the innate immune system as the killed us late in life, after procreation, young assistant professor at Yale. controller of immunity. At a time and thus were not subject to evolu- Having just read a paper of his in the when most labs were interested only tionary pressure. April edition of Nature, and having in antigen recognition, believing As usual, I disagree with Charlie. A decided (with the arrogance of a that this controlled immune model of immunity must explain third-year grad student) that it was responses, Charlie looked around transplants, tumors, and autoimmu- wrong, I asked him if it had been an and asked a very basic question. nity in order to be complete. And I April fool’s joke. Without batting an “Why,” he asked, “was the mere for- wonder sometimes if the TLRs really eye, and ignoring my rudeness, Char- eignness of a protein not enough to evolved to see bacteria or if the bacte- lie asked me why I thought that. The elicit immunity? Why did we need to ria evolved to see the TLRs. However, three of us then spent the next few add adjuvant (noxious substances the disagreement, and the discussions hours in a pub discussing that paper like mineral oil, mycobacteria, or we had, honed both of our thoughts. (which turned out to be right, of aluminum hydroxide) in order to There are few scientists like Charlie, course) and many other aspects of get a decent response to a vaccine?” with enough self-confidence to argue immunology, Charlie treating me The self-nonself model neither pre- heatedly with a colleague who has put throughout as an equal despite the dicted nor explained the need for out an opposing model . and then differences in our immunological adjuvant. Charlie gnawed at this go dancing with her. Charlie and I knowledge. This was one of his great problem (which he called the danced a lot, argued a lot, and had a features. He loved students and “immunologists’ dirty little secret”) wonderful time doing it. I will treated us, if we were capable, as col- for years, slowly coming to an remember him as one of the most leagues without ever hinting that we important understanding that exciting, decent, and thoughtful should hold our tongues and not caused a major switch in immuno- immunologists on the planet. argue with the “adults”. logical thinking. He decided that As well as being a great teacher, immune responses could not occur Charlie was a pioneer in several unless antigen-presenting cells were Polly Matzinger immunological fields, tackling prob- first activated, and that they were Ghost Lab, LCMI, NIAID, NIH lems that mattered, rather than activated via pattern recognition [email protected] 2 The Journal of Clinical Investigation | July 2003 | Volume 112 | Number 1.
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