- Email: [email protected]
Remembering Austin L. Hughes
Infection, Genetics and Evolution 40 (2016) 262–265
Contents lists available at ScienceDirect
Infection, Genetics and Evolution journal homepage: www.elsevier.com/locate/meegid
Remembering Austin L. Hughes
Keywords: Austin L. Hughes Major histocompatibility complex Molecular evolution Next-generation sequencing Neutral theory Obituary Positive selection
Dear Editor,
Over tea in a New York November seems an odd place to weep for you, straight Catholic man. Your most honest of intellects and most awkward of greetings —a look up, a nod—are needed now, my guide and muse. How could you bow? I am unfit to tell the brilliance you knew. The clack of a 1 train your parting knell, a gesture too quick. The last words too few. Dr. Austin L. Hughes. [—C. W. N., 2 November 2015]
http://dx.doi.org/10.1016/j.meegid.2016.02.030 1567-1348/© 2016 Elsevier B.V. All rights reserved.
Dr. Austin L. Hughes, esteemed evolutionary biologist, husband, father, and teacher, passed away on 31 October 2015. Like so many early deaths in his field, including those of Motoo Kimura and Takeo Maruyama, the 66-year-old University of South Carolina Distinguished Professor succumbed to an unexpected heart attack, leaving those under his tutelage floundering. Hughes' expertise covered multiple languages—Welsh, French, Latin, Greek, Italian, and English—and a host of disciplines from philosophy to matrix algebra. He produced an enormous body of work in his own profession, including the books Evolution and Human Kinship (Hughes, 1988) and Adaptive Evolution of Genes and Genomes (Hughes, 1999), as well as over 300 peerreviewed studies. Hughes became a member of the American Association for the Advancement of Science in 2010, owing largely to his work on the evolution of genes encoding the major histocompatibility complex (MHC). While a postdoctoral researcher with Masatoshi Nei, he used the recently published structure of the MHC molecule (Bjorkman et al., 1987) to support the hypothesis that overdominant positive selection (i.e., heterozygote advantage) maintains the high polymorphism observed at these loci (Hughes and Nei, 1988). Subsequent work confirmed his conclusions (Hughes and Yeager, 1998), and his focus quickly expanded to the role of selection in shaping the genomes of pathogens. His last article in these pages discusses an approach for such studies using pooled next-generation sequencing (NGS) variant data from viruses (Nelson and Hughes, 2015). Hughes made several other major contributions to evolutionary theory. For example, his work on gene duplication stressed the ancestral multi-functionality of duplicated genes which later experience sub-functionalization (Hughes, 1994), and he demonstrated a preponderance of gene family loss in the evolution of animals (Hughes and Friedman, 2004). He also criticized the use of inappropriate statistical tests for detecting positive selection (Hughes, 2007) and, as a proponent of the nearly neutral theory (Hughes, 2008), he argued that phenotypic plasticity plays a central role in adaptive evolution (Hughes, 2012a). Regardless of complexity, there seemed to be no dataset from which he could not extract conceptual generalities and meaningful patterns. A full review of his scientific work is in preparation elsewhere. Beyond science, Hughes had penned a book on philosophy, a sample of which can be found in his essay “The Folly of Scientism” (Hughes, 2012b). He was a staunch opponent of those who treat religion and science as incompatible (Hughes, 2015). He was also writing a new work on environmental ethics, and published several essays on society, philosophy, and ethics (e.g., Hughes, 2013). Although he was quite shy on a personal level—a quality often misinterpreted as ego—things changed when the focus was science. In lab meetings, he would visibly metamorphose into a creature of childlike alacrity, streaming ideas and opinions that revealed his true nature: a gleeful mind, an incisive wit, a learned jokester. He was an incredible advisor, at once responsive, creative, and selfless. Some could be offended by his candor, but his simplicity and straightforwardness were some of his greatest qualities. They also made for elegance in his writing, if awkwardness in his interactions.
263
Besides family, including Andrea Hughes (his wife of six years) and his children and grandchildren, Hughes also deeply impacted those he mentored in science. These include seven Ph.D. students, three M.S. students, seven postdoctoral researchers, and many more undergraduates and high schoolers. Thus, while I knew Hughes for about five years and have contributed a personal memoir elsewhere (Nelson, 2015), I had only begun to appreciate his rich scholarship and shy personality. It therefore seems fitting to remember him with the words of some of his other students, colleagues, and friends, many of whom knew him for decades. Although important individuals are not represented here (e.g., Masatoshi Nei was unable to comment due to severe health concerns and Charles P. Poole, Jr. passed the day after Hughes), these reflections help to paint the memory of a man who touched hearts as profoundly as he did minds. The broad swathe of personalities included—scientists and philosophers, atheists and theists, young and old—is a testament to the truly liberal nature of his personality and thought. It is impossible to exaggerate the importance of Austin Hughes' fundamental contributions to molecular evolutionary theory and practice. He was a prolific researcher whose work covered such disparate topics as coevolution, phylogenetics, repetitive DNA, and more recently the application of population genetics to clinical research. Austin had an incredibly sharp mind, an imitable scientific intuition, and an abundance of impatience for bad science, faulty logic, and demagoguery. Debunking unwarranted generalizations and “accepted” theories was one of his fortes. His writing was crystal clear; I wish he had written a manual of writing style for scientists. He was also fluent in the Welsh language (Cymraeg) and wrote both poetry and prose in this ancient tongue. His untimely death deprived me of a friend and colleague; science was deprived of a great biologist who knew living systems inside and out at all levels, from the molecular to ecological. I'll miss you, Austin. Gorffwys mewn hedd. [—Dan Graur, University of Houston] I first met Austin in Houston when he was a fellow at the University of Texas. It was an exciting time for those studying molecular evolution and immunogenetics, as Drs. Hughes and Nei had recently published important papers on the MHC loci. I was lucky enough to take part in their work as a graduate student. Austin was a man with a sense of humor, and his words helped me to live in a foreign land as a non-native speaker. The unexpected loss shocked me and those who know him. We once again thank him for being a role model for young scientists; no one can replace him. [—Tatsuya Ota, SOKENDAI, Japan] Austin Hughes was a thinker, a theorist, and a highly original scientist. Trained as an ecologist, he started to pursue molecular evolution in his postdoctoral years and soon became a leader in the field. Anyone who had a conversation with him would have been impressed by his critical thinking and broad knowledge. His passing is a big loss for science. [—Wen-Hsiung Li, University of Chicago; National Academy of Sciences, USA; Academia Sinica, Taiwan] Dr. Austin L. Hughes' work on the MHC was the first of many subsequent attempts to discover adaptive evolution at the level of protein structure and function. He conducted this research with Dr. Masatoshi Nei, with whom I have had a long-lasting debate on issues such as the near-neutrality of molecular evolution. After Dr. Hughes moved to South Carolina, he performed many relevant analyses, finding that many genome data indeed show the prevalence of slightly deleterious mutations, supporting near neutrality.
I have always been much impressed by his work, and grateful for his fair presentation. [—Tomoko Ohta, National Institute of Genetics, Japan; National Academy of Sciences, USA] I first met Dr. Austin Hughes in the late 1990s at a symposium on molecular evolution in Mishima, Japan. He was one of the invited speakers, yet when the welcome party commenced, he did not show up. I went to his hotel room and asked him to join us. He replied, “I was not invited to the party.” It was my oversight—but even without invitation, other invited speakers had thought it natural to attend. I think that this episode reveals Austin's sincere and straightforward attitude toward everything. Besides MHC work, he is known as a staunch opponent of the two-round genome duplication hypothesis in the vertebrate common ancestor. Even if his conclusions were sometimes different from what I believe, I always respected his papers because of his clear logic and thorough analysis. I regret his sudden and early death. [—Naruya Saitou, National Institute of Genetics; SOKENDAI; University of Tokyo, Japan] I remember Austin fondly—an unusual individual to say the least. He held deep religious convictions and yet was a rigorous scientist. I would call Austin, talk to him about whatever subject, and he would come up with some form of analysis. He was a rare scientist who bridged both biology and computing; his passing is such a loss to the field. It's not that his relationship with my lab members was always plain sailing. His intolerance of naïve graduate students was legendary! I would ask them, with a smile on my face, to talk to Austin about their ideas. Almost always, they would be back in my office, despondent and demoralized! But once they got to know Austin, their disposition would change. I never, ever, had a single issue with Austin. He was always ready and excited to help with new analyses, and entertaining to talk to—really a wonderful colleague and friend. [—David I. Watkins, University of Miami] I feel lucky and honored to have known and collaborated with Austin Hughes for over ten years. In the early 2000s, we made some puzzling findings, showing that certain specificities of MHC molecules were coming up repeatedly in rather different animal species. When we tried to establish whether this was due to common ancestry or convergent evolution, we could not find a way out—that is, until Austin came into the picture. By doing the analysis “his way”, which was “the right way”, he showed us that in fact both convergent evolution and common ancestry were at play. That was a remarkably simple, brilliant and unexpected explanation for a complex problem. I appreciated him so much. [—Alessandro Sette, La Jolla Institute for Allergy & Immunology] We were fortunate to meet Austin Hughes 20 years ago when he helped us understand the molecular evolution of MHC introns in primates. Austin was one of the most brilliant scientists we ever met. His insight into and explanations for our seemingly complex questions were simple but precise. After a long gap, we had just reconnected this year to work on the population genetics of HLA and other immune response genes. His sudden death came as a shock. We will miss him immensely, his down to earth personality, and his brilliant and creative mind. [—Soo Young Yang & Nezih Cereb, HistoGenetics LLC]
Austin Hughes was a valued collaborator and friend, distinguished by his incisive understanding of quantitative evolutionary biology.
264
We leaned heavily on Austin and his students to apply statistical rigor to increasingly large and complex datasets, such as new data for the thousands to millions of closely related viral variants circulating in the same host. With so many variants, how can we distinguish authentic variants from experimental noise? Austin developed a robust statistical approach to answer this thorny question (Becker et al., 2012). We understood because Austin was also a masterful communicator, his writing at once eloquent, flowing, and precise. More personally, we remember a time he visited us when our son was a toddler. He told us of his family and was warm and caring with ours. We aspire to successfully blend professional accomplishment with devotion to our family as effectively as he did. [—David H. O'Connor & Shelby L. O'Connor, UW-Madison] I have known Austin for almost 15 years. Our first meeting only confirmed the impressions I had received over phone and email, namely that he was a gifted, insightful, and careful scientist, but also a kind and patient man. I owe Austin a huge debt. He was a crucial collaborator since I was a Ph.D. student, bringing critically important intellectual (and mathematical!) rigor to virtually all the studies that defined my lab's current interests in viral evolution and helping to train my students in the process. No matter how busy he was, Austin was always willing to carefully read manuscripts, grant proposal outlines, and other random musings, and promptly returned carefully considered (and no less carefully written) replies. It is no exaggeration to say that my science would not be where it is today without Austin's contributions. [—Thomas C. Friedrich, UW-Madison, Wisconsin National Primate Research Center] In the early 1990s, I was a graduate student interested in studying MHC evolution in relation to disease, and had read every one of Austin's papers on the subject. When he visited the National Cancer Institute, we immediately hit it off, and I ended up transferring to Penn State to finish my Ph.D. with him. I could talk to him about anything. We were a great team. I fondly remember our lab meetings; the entirety of my thesis was conceived over “beery lunches!” I could spend weeks analyzing data, then he might look at them for less than a minute and either observe something I hadn't or invent the next analysis that I hadn't even considered. Although he could be a harsh critic, he was always fair and kind to me, and treated me like a peer and a friend. He taught me so much; how to think, how to write. It is difficult to express the loss I feel, as I thought I would always have him in my intellectual arsenal. [—Meredith Yeager, National Cancer Institute] Austin Hughes' genius and personality were of the kind that sometimes moved me to inaction. What influenced me the most about him was that he was a devout Catholic working in molecular evolution—and yet he was not at all the sort of person one would imagine given that description. He never wielded any of the rhetorical tactics of the much-trodden debate over origins, and yet he could wither misguided arguments from all sides with clarity of thought that was so complete and compelling that he needed none of the usual bombast. Austin showed that a dichotomy in worldviews does not have to define an individual's own thoughts, and that a true scholar doesn't need the tactics of rhetoric. Working around him helped me realize that education isn't supposed to make you conquer the mountain; it is supposed to make you climb high enough to see all the mountains you will never climb. Then you start to learn. [—Jeffrey O. French, North Greenville University] Austin was a great mentor, both supportive and encouraging. After every one of our conversations I left filing away new words and
ideas. He absolutely loved what he did, and was always thinking about future studies with an enthusiasm that was indeed infectious (pun intended). He and his bits of wisdom (“…XYZ is nonsense…”) will ever remain in my memory. [—Helen Piontkivska, Kent State University] Dr. Austin L. Hughes was an amazing scientist and an enigma—the sort that one could hardly hope to come by in academia today, as he was heavily involved in both his religion and philosophy. When I met Austin, we were working on a project dealing with the Dengue virus, but I soon learned that he and I shared a tremendous interest in all things animal. Once we established this connection, our relationship changed drastically. We began working on several different behavioral studies that included an expanding number of undergraduates. He would tell us stories about his grandchildren and his wife, revealing an astonishing side of his heart that touched us all. There are still so many things I wish I could ask him now that he has passed, as he had so much life-changing knowledge to share. [—April C. H. South, University of South Carolina] I'll never forget the day I first met Dr. Hughes, almost eleven years ago. As I knocked on his office door, I couldn't help but feel that I had interrupted something important as the tapping of the keyboard ceased and he peered up at me over his glasses. I introduced myself; he nodded and looked over at a chair in his office, covered with a stack of books and papers. We cleared the chair and began the very first of many brief but productive conversations. I felt privileged to work with such a brilliant mind as a graduate student. When I heard of his passing, my first thoughts went to his family. My second thoughts were of regret, as I had been looking forward to working with him again on an upcoming project. I think of him often, and when I do, I picture him as he was the first day we met: typing away at his desk, working diligently, intent to share his scientific truths. [—Stephanie J. Irausquin, University of South Carolina]
Dr. Hughes had an unquenchable thirst for knowledge. This kept him driven and focused, a combination essential to a good scientist—and his myriad works are an enduring proof that he was a very successful one. Yet, despite his tremendous accomplishments, he remained very modest. This modesty came from a deep understanding that, notwithstanding its strengths, scientific methodology has its limitations too. It should thus come as no surprise that he was a very spiritual person. When I asked him how he managed to be a scientist when he is also spiritual, he replied, “You can be a true scientist only when you acknowledge that there is a sense of direction and purpose to life. If you are not able to recognize this higher cause, then maybe you are not a true scientist yet.” It was a wonderful gift to have had such an excellent scientist as my mentor. [—Saravanan Rajabojan, University of South Carolina]
I was rather in awe of Austin. He and his wife Andrea were present when I led a marriage preparation class at St. Joseph Church in Columbia, SC. Although he surely knew far more about the Church than I do, he bore it with patience, for which I was grateful. Similarly, when a year or so later I was invited to speak about research that destroys human embryos to a gathering that included Austin, I tried not to think about the incongruity of my talking about embryogenesis in the presence of a truly great scientist. His more philosophical work, while written for a general audience, shows as well just how learned he was in that discipline. What a tremendous resource he
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was for the University and for the Catholic community. I will miss him, his erudition, and his love of truth a great deal. [—Christopher O. Tollefsen, University of South Carolina; Witherspoon Institute] Austin Hughes was that rarest of rare birds in academia: a distinguished scientist with the soul of a humanist. At the foundation of his scientific labors was a philosophical and, indeed, theological conviction: the supreme importance of seeking and attaining truth. It was this that motivated and sustained his work. And because he was aware that this (only) rational motivation for scientific inquiry is not itself something that can be grasped by deploying scientific methods, he eschewed philosophical empiricism and scientific reductionism. He knew that non-scientific methods of inquiry are as necessary as scientific ones in the House of Intellect. For Austin, scientists and humanists were—are—not inhabitants of “two cultures,” much less “cultures in conflict”; they are, rather, friends and collaborators in the comprehensive project of truth seeking. [—Robert P. George, Princeton University]
Acknowledgments This obituary was written by C.W.N. with the support of NSF Graduate Research Fellowship DGE-0929297. References Becker, E.A., Burns, C.M., León, E.J., Rajabojan, S., Friedman, R., Friedrich, T.C., O'Connor, S.L., Hughes, A.L., 2012. Experimental analysis of sources of error in evolutionary
studies based on Roche/454 pyrosequencing of viral genomes. Genome Biol. Evol. 4 (4), 457–465. Bjorkman, P.J., Saper, M.A., Samraoui, B., Bennett, W.S., Strominger, J.L., Wiley, D.C., 1987. Structure of the human class I histocompatibility antigen, HLA-A2. Nature 329 (6139), 506–512. Hughes, A.L., 1988. Evolution and Human Kinship. Oxford University Press, New York. Hughes, A.L., 1994. The evolution of functionally novel proteins after gene duplication. Proc. R. Soc. Lond. B 256 (1346), 119–124. Hughes, A.L., 1999. Adaptive Evolution of Genes and Genomes. Oxford University Press, New York. Hughes, A.L., 2007. Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level. Heredity 99 (4), 364–373. Hughes, A.L., 2008. Near-neutrality: the leading edge of the neutral theory of molecular evolution. Ann. N. Y. Acad. Sci. 1133, 162–179. Hughes, A.L., 2012a. Evolution of adaptive phenotypic traits without positive Darwinian selection. Heredity 108 (4), 347–353. Hughes, A.L., 2012b. The folly of scientism. The New Atlantis. 37, pp. 32–50. Hughes, A.L., 2013. Me, my genome, and 23andMe. The New Atlantis. 40, pp. 3–18. Hughes, A.L., 2015. Faith, fact, and false dichotomies. The New Atlantis. 45, pp. 111–117. Hughes, A.L., Friedman, R., 2004. Shedding genomic ballast: extensive parallel loss of ancestral gene families in animals. J. Mol. Evol. 59 (6), 827–833. Hughes, A.L., Nei, M., 1988. Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 335 (6185), 167–170. Hughes, A.L., Yeager, M., 1998. Natural selection at major histocompatibility complex loci of vertebrates. Annu. Rev. Genet. 32, 415–435. Nelson, C.W., 2015. The humble scientist. The New Atlantis. 47, pp. 98–102. Nelson, C.W., Hughes, A.L., 2015. Within-host nucleotide diversity of virus populations: insights from next-generation sequencing. Infect. Genet. Evol. 30, 1–7.
Chase W. Nelson Department of Biological Sciences, University of South Carolina, 715 Sumter St., Columbia, SC 29208, USA E-mail address: [email protected]. 22 February 2016 Available online 11 March 2016
Contents lists available at ScienceDirect
Infection, Genetics and Evolution journal homepage: www.elsevier.com/locate/meegid
Remembering Austin L. Hughes
Keywords: Austin L. Hughes Major histocompatibility complex Molecular evolution Next-generation sequencing Neutral theory Obituary Positive selection
Dear Editor,
Over tea in a New York November seems an odd place to weep for you, straight Catholic man. Your most honest of intellects and most awkward of greetings —a look up, a nod—are needed now, my guide and muse. How could you bow? I am unfit to tell the brilliance you knew. The clack of a 1 train your parting knell, a gesture too quick. The last words too few. Dr. Austin L. Hughes. [—C. W. N., 2 November 2015]
http://dx.doi.org/10.1016/j.meegid.2016.02.030 1567-1348/© 2016 Elsevier B.V. All rights reserved.
Dr. Austin L. Hughes, esteemed evolutionary biologist, husband, father, and teacher, passed away on 31 October 2015. Like so many early deaths in his field, including those of Motoo Kimura and Takeo Maruyama, the 66-year-old University of South Carolina Distinguished Professor succumbed to an unexpected heart attack, leaving those under his tutelage floundering. Hughes' expertise covered multiple languages—Welsh, French, Latin, Greek, Italian, and English—and a host of disciplines from philosophy to matrix algebra. He produced an enormous body of work in his own profession, including the books Evolution and Human Kinship (Hughes, 1988) and Adaptive Evolution of Genes and Genomes (Hughes, 1999), as well as over 300 peerreviewed studies. Hughes became a member of the American Association for the Advancement of Science in 2010, owing largely to his work on the evolution of genes encoding the major histocompatibility complex (MHC). While a postdoctoral researcher with Masatoshi Nei, he used the recently published structure of the MHC molecule (Bjorkman et al., 1987) to support the hypothesis that overdominant positive selection (i.e., heterozygote advantage) maintains the high polymorphism observed at these loci (Hughes and Nei, 1988). Subsequent work confirmed his conclusions (Hughes and Yeager, 1998), and his focus quickly expanded to the role of selection in shaping the genomes of pathogens. His last article in these pages discusses an approach for such studies using pooled next-generation sequencing (NGS) variant data from viruses (Nelson and Hughes, 2015). Hughes made several other major contributions to evolutionary theory. For example, his work on gene duplication stressed the ancestral multi-functionality of duplicated genes which later experience sub-functionalization (Hughes, 1994), and he demonstrated a preponderance of gene family loss in the evolution of animals (Hughes and Friedman, 2004). He also criticized the use of inappropriate statistical tests for detecting positive selection (Hughes, 2007) and, as a proponent of the nearly neutral theory (Hughes, 2008), he argued that phenotypic plasticity plays a central role in adaptive evolution (Hughes, 2012a). Regardless of complexity, there seemed to be no dataset from which he could not extract conceptual generalities and meaningful patterns. A full review of his scientific work is in preparation elsewhere. Beyond science, Hughes had penned a book on philosophy, a sample of which can be found in his essay “The Folly of Scientism” (Hughes, 2012b). He was a staunch opponent of those who treat religion and science as incompatible (Hughes, 2015). He was also writing a new work on environmental ethics, and published several essays on society, philosophy, and ethics (e.g., Hughes, 2013). Although he was quite shy on a personal level—a quality often misinterpreted as ego—things changed when the focus was science. In lab meetings, he would visibly metamorphose into a creature of childlike alacrity, streaming ideas and opinions that revealed his true nature: a gleeful mind, an incisive wit, a learned jokester. He was an incredible advisor, at once responsive, creative, and selfless. Some could be offended by his candor, but his simplicity and straightforwardness were some of his greatest qualities. They also made for elegance in his writing, if awkwardness in his interactions.
263
Besides family, including Andrea Hughes (his wife of six years) and his children and grandchildren, Hughes also deeply impacted those he mentored in science. These include seven Ph.D. students, three M.S. students, seven postdoctoral researchers, and many more undergraduates and high schoolers. Thus, while I knew Hughes for about five years and have contributed a personal memoir elsewhere (Nelson, 2015), I had only begun to appreciate his rich scholarship and shy personality. It therefore seems fitting to remember him with the words of some of his other students, colleagues, and friends, many of whom knew him for decades. Although important individuals are not represented here (e.g., Masatoshi Nei was unable to comment due to severe health concerns and Charles P. Poole, Jr. passed the day after Hughes), these reflections help to paint the memory of a man who touched hearts as profoundly as he did minds. The broad swathe of personalities included—scientists and philosophers, atheists and theists, young and old—is a testament to the truly liberal nature of his personality and thought. It is impossible to exaggerate the importance of Austin Hughes' fundamental contributions to molecular evolutionary theory and practice. He was a prolific researcher whose work covered such disparate topics as coevolution, phylogenetics, repetitive DNA, and more recently the application of population genetics to clinical research. Austin had an incredibly sharp mind, an imitable scientific intuition, and an abundance of impatience for bad science, faulty logic, and demagoguery. Debunking unwarranted generalizations and “accepted” theories was one of his fortes. His writing was crystal clear; I wish he had written a manual of writing style for scientists. He was also fluent in the Welsh language (Cymraeg) and wrote both poetry and prose in this ancient tongue. His untimely death deprived me of a friend and colleague; science was deprived of a great biologist who knew living systems inside and out at all levels, from the molecular to ecological. I'll miss you, Austin. Gorffwys mewn hedd. [—Dan Graur, University of Houston] I first met Austin in Houston when he was a fellow at the University of Texas. It was an exciting time for those studying molecular evolution and immunogenetics, as Drs. Hughes and Nei had recently published important papers on the MHC loci. I was lucky enough to take part in their work as a graduate student. Austin was a man with a sense of humor, and his words helped me to live in a foreign land as a non-native speaker. The unexpected loss shocked me and those who know him. We once again thank him for being a role model for young scientists; no one can replace him. [—Tatsuya Ota, SOKENDAI, Japan] Austin Hughes was a thinker, a theorist, and a highly original scientist. Trained as an ecologist, he started to pursue molecular evolution in his postdoctoral years and soon became a leader in the field. Anyone who had a conversation with him would have been impressed by his critical thinking and broad knowledge. His passing is a big loss for science. [—Wen-Hsiung Li, University of Chicago; National Academy of Sciences, USA; Academia Sinica, Taiwan] Dr. Austin L. Hughes' work on the MHC was the first of many subsequent attempts to discover adaptive evolution at the level of protein structure and function. He conducted this research with Dr. Masatoshi Nei, with whom I have had a long-lasting debate on issues such as the near-neutrality of molecular evolution. After Dr. Hughes moved to South Carolina, he performed many relevant analyses, finding that many genome data indeed show the prevalence of slightly deleterious mutations, supporting near neutrality.
I have always been much impressed by his work, and grateful for his fair presentation. [—Tomoko Ohta, National Institute of Genetics, Japan; National Academy of Sciences, USA] I first met Dr. Austin Hughes in the late 1990s at a symposium on molecular evolution in Mishima, Japan. He was one of the invited speakers, yet when the welcome party commenced, he did not show up. I went to his hotel room and asked him to join us. He replied, “I was not invited to the party.” It was my oversight—but even without invitation, other invited speakers had thought it natural to attend. I think that this episode reveals Austin's sincere and straightforward attitude toward everything. Besides MHC work, he is known as a staunch opponent of the two-round genome duplication hypothesis in the vertebrate common ancestor. Even if his conclusions were sometimes different from what I believe, I always respected his papers because of his clear logic and thorough analysis. I regret his sudden and early death. [—Naruya Saitou, National Institute of Genetics; SOKENDAI; University of Tokyo, Japan] I remember Austin fondly—an unusual individual to say the least. He held deep religious convictions and yet was a rigorous scientist. I would call Austin, talk to him about whatever subject, and he would come up with some form of analysis. He was a rare scientist who bridged both biology and computing; his passing is such a loss to the field. It's not that his relationship with my lab members was always plain sailing. His intolerance of naïve graduate students was legendary! I would ask them, with a smile on my face, to talk to Austin about their ideas. Almost always, they would be back in my office, despondent and demoralized! But once they got to know Austin, their disposition would change. I never, ever, had a single issue with Austin. He was always ready and excited to help with new analyses, and entertaining to talk to—really a wonderful colleague and friend. [—David I. Watkins, University of Miami] I feel lucky and honored to have known and collaborated with Austin Hughes for over ten years. In the early 2000s, we made some puzzling findings, showing that certain specificities of MHC molecules were coming up repeatedly in rather different animal species. When we tried to establish whether this was due to common ancestry or convergent evolution, we could not find a way out—that is, until Austin came into the picture. By doing the analysis “his way”, which was “the right way”, he showed us that in fact both convergent evolution and common ancestry were at play. That was a remarkably simple, brilliant and unexpected explanation for a complex problem. I appreciated him so much. [—Alessandro Sette, La Jolla Institute for Allergy & Immunology] We were fortunate to meet Austin Hughes 20 years ago when he helped us understand the molecular evolution of MHC introns in primates. Austin was one of the most brilliant scientists we ever met. His insight into and explanations for our seemingly complex questions were simple but precise. After a long gap, we had just reconnected this year to work on the population genetics of HLA and other immune response genes. His sudden death came as a shock. We will miss him immensely, his down to earth personality, and his brilliant and creative mind. [—Soo Young Yang & Nezih Cereb, HistoGenetics LLC]
Austin Hughes was a valued collaborator and friend, distinguished by his incisive understanding of quantitative evolutionary biology.
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We leaned heavily on Austin and his students to apply statistical rigor to increasingly large and complex datasets, such as new data for the thousands to millions of closely related viral variants circulating in the same host. With so many variants, how can we distinguish authentic variants from experimental noise? Austin developed a robust statistical approach to answer this thorny question (Becker et al., 2012). We understood because Austin was also a masterful communicator, his writing at once eloquent, flowing, and precise. More personally, we remember a time he visited us when our son was a toddler. He told us of his family and was warm and caring with ours. We aspire to successfully blend professional accomplishment with devotion to our family as effectively as he did. [—David H. O'Connor & Shelby L. O'Connor, UW-Madison] I have known Austin for almost 15 years. Our first meeting only confirmed the impressions I had received over phone and email, namely that he was a gifted, insightful, and careful scientist, but also a kind and patient man. I owe Austin a huge debt. He was a crucial collaborator since I was a Ph.D. student, bringing critically important intellectual (and mathematical!) rigor to virtually all the studies that defined my lab's current interests in viral evolution and helping to train my students in the process. No matter how busy he was, Austin was always willing to carefully read manuscripts, grant proposal outlines, and other random musings, and promptly returned carefully considered (and no less carefully written) replies. It is no exaggeration to say that my science would not be where it is today without Austin's contributions. [—Thomas C. Friedrich, UW-Madison, Wisconsin National Primate Research Center] In the early 1990s, I was a graduate student interested in studying MHC evolution in relation to disease, and had read every one of Austin's papers on the subject. When he visited the National Cancer Institute, we immediately hit it off, and I ended up transferring to Penn State to finish my Ph.D. with him. I could talk to him about anything. We were a great team. I fondly remember our lab meetings; the entirety of my thesis was conceived over “beery lunches!” I could spend weeks analyzing data, then he might look at them for less than a minute and either observe something I hadn't or invent the next analysis that I hadn't even considered. Although he could be a harsh critic, he was always fair and kind to me, and treated me like a peer and a friend. He taught me so much; how to think, how to write. It is difficult to express the loss I feel, as I thought I would always have him in my intellectual arsenal. [—Meredith Yeager, National Cancer Institute] Austin Hughes' genius and personality were of the kind that sometimes moved me to inaction. What influenced me the most about him was that he was a devout Catholic working in molecular evolution—and yet he was not at all the sort of person one would imagine given that description. He never wielded any of the rhetorical tactics of the much-trodden debate over origins, and yet he could wither misguided arguments from all sides with clarity of thought that was so complete and compelling that he needed none of the usual bombast. Austin showed that a dichotomy in worldviews does not have to define an individual's own thoughts, and that a true scholar doesn't need the tactics of rhetoric. Working around him helped me realize that education isn't supposed to make you conquer the mountain; it is supposed to make you climb high enough to see all the mountains you will never climb. Then you start to learn. [—Jeffrey O. French, North Greenville University] Austin was a great mentor, both supportive and encouraging. After every one of our conversations I left filing away new words and
ideas. He absolutely loved what he did, and was always thinking about future studies with an enthusiasm that was indeed infectious (pun intended). He and his bits of wisdom (“…XYZ is nonsense…”) will ever remain in my memory. [—Helen Piontkivska, Kent State University] Dr. Austin L. Hughes was an amazing scientist and an enigma—the sort that one could hardly hope to come by in academia today, as he was heavily involved in both his religion and philosophy. When I met Austin, we were working on a project dealing with the Dengue virus, but I soon learned that he and I shared a tremendous interest in all things animal. Once we established this connection, our relationship changed drastically. We began working on several different behavioral studies that included an expanding number of undergraduates. He would tell us stories about his grandchildren and his wife, revealing an astonishing side of his heart that touched us all. There are still so many things I wish I could ask him now that he has passed, as he had so much life-changing knowledge to share. [—April C. H. South, University of South Carolina] I'll never forget the day I first met Dr. Hughes, almost eleven years ago. As I knocked on his office door, I couldn't help but feel that I had interrupted something important as the tapping of the keyboard ceased and he peered up at me over his glasses. I introduced myself; he nodded and looked over at a chair in his office, covered with a stack of books and papers. We cleared the chair and began the very first of many brief but productive conversations. I felt privileged to work with such a brilliant mind as a graduate student. When I heard of his passing, my first thoughts went to his family. My second thoughts were of regret, as I had been looking forward to working with him again on an upcoming project. I think of him often, and when I do, I picture him as he was the first day we met: typing away at his desk, working diligently, intent to share his scientific truths. [—Stephanie J. Irausquin, University of South Carolina]
Dr. Hughes had an unquenchable thirst for knowledge. This kept him driven and focused, a combination essential to a good scientist—and his myriad works are an enduring proof that he was a very successful one. Yet, despite his tremendous accomplishments, he remained very modest. This modesty came from a deep understanding that, notwithstanding its strengths, scientific methodology has its limitations too. It should thus come as no surprise that he was a very spiritual person. When I asked him how he managed to be a scientist when he is also spiritual, he replied, “You can be a true scientist only when you acknowledge that there is a sense of direction and purpose to life. If you are not able to recognize this higher cause, then maybe you are not a true scientist yet.” It was a wonderful gift to have had such an excellent scientist as my mentor. [—Saravanan Rajabojan, University of South Carolina]
I was rather in awe of Austin. He and his wife Andrea were present when I led a marriage preparation class at St. Joseph Church in Columbia, SC. Although he surely knew far more about the Church than I do, he bore it with patience, for which I was grateful. Similarly, when a year or so later I was invited to speak about research that destroys human embryos to a gathering that included Austin, I tried not to think about the incongruity of my talking about embryogenesis in the presence of a truly great scientist. His more philosophical work, while written for a general audience, shows as well just how learned he was in that discipline. What a tremendous resource he
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was for the University and for the Catholic community. I will miss him, his erudition, and his love of truth a great deal. [—Christopher O. Tollefsen, University of South Carolina; Witherspoon Institute] Austin Hughes was that rarest of rare birds in academia: a distinguished scientist with the soul of a humanist. At the foundation of his scientific labors was a philosophical and, indeed, theological conviction: the supreme importance of seeking and attaining truth. It was this that motivated and sustained his work. And because he was aware that this (only) rational motivation for scientific inquiry is not itself something that can be grasped by deploying scientific methods, he eschewed philosophical empiricism and scientific reductionism. He knew that non-scientific methods of inquiry are as necessary as scientific ones in the House of Intellect. For Austin, scientists and humanists were—are—not inhabitants of “two cultures,” much less “cultures in conflict”; they are, rather, friends and collaborators in the comprehensive project of truth seeking. [—Robert P. George, Princeton University]
Acknowledgments This obituary was written by C.W.N. with the support of NSF Graduate Research Fellowship DGE-0929297. References Becker, E.A., Burns, C.M., León, E.J., Rajabojan, S., Friedman, R., Friedrich, T.C., O'Connor, S.L., Hughes, A.L., 2012. Experimental analysis of sources of error in evolutionary
studies based on Roche/454 pyrosequencing of viral genomes. Genome Biol. Evol. 4 (4), 457–465. Bjorkman, P.J., Saper, M.A., Samraoui, B., Bennett, W.S., Strominger, J.L., Wiley, D.C., 1987. Structure of the human class I histocompatibility antigen, HLA-A2. Nature 329 (6139), 506–512. Hughes, A.L., 1988. Evolution and Human Kinship. Oxford University Press, New York. Hughes, A.L., 1994. The evolution of functionally novel proteins after gene duplication. Proc. R. Soc. Lond. B 256 (1346), 119–124. Hughes, A.L., 1999. Adaptive Evolution of Genes and Genomes. Oxford University Press, New York. Hughes, A.L., 2007. Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level. Heredity 99 (4), 364–373. Hughes, A.L., 2008. Near-neutrality: the leading edge of the neutral theory of molecular evolution. Ann. N. Y. Acad. Sci. 1133, 162–179. Hughes, A.L., 2012a. Evolution of adaptive phenotypic traits without positive Darwinian selection. Heredity 108 (4), 347–353. Hughes, A.L., 2012b. The folly of scientism. The New Atlantis. 37, pp. 32–50. Hughes, A.L., 2013. Me, my genome, and 23andMe. The New Atlantis. 40, pp. 3–18. Hughes, A.L., 2015. Faith, fact, and false dichotomies. The New Atlantis. 45, pp. 111–117. Hughes, A.L., Friedman, R., 2004. Shedding genomic ballast: extensive parallel loss of ancestral gene families in animals. J. Mol. Evol. 59 (6), 827–833. Hughes, A.L., Nei, M., 1988. Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 335 (6185), 167–170. Hughes, A.L., Yeager, M., 1998. Natural selection at major histocompatibility complex loci of vertebrates. Annu. Rev. Genet. 32, 415–435. Nelson, C.W., 2015. The humble scientist. The New Atlantis. 47, pp. 98–102. Nelson, C.W., Hughes, A.L., 2015. Within-host nucleotide diversity of virus populations: insights from next-generation sequencing. Infect. Genet. Evol. 30, 1–7.
Chase W. Nelson Department of Biological Sciences, University of South Carolina, 715 Sumter St., Columbia, SC 29208, USA E-mail address: [email protected]. 22 February 2016 Available online 11 March 2016