Neurovirologist Richard T. Johnson, 84

Viral Infections of the Nervous SystemJohns Hopkins Neurovirologist Richard T. Johnson has died, and his obituary at Hub provides a good summary of his career. He had an important influence on my work early in my career.

The first edition of Dr. Johnson’s book, Viral Infections of the Nervous System, was published in 1982 – the year I began my laboratory at Columbia University. I was interested in studying poliovirus pathogenesis, so I immediately purchased the book (which I still have to this day – that’s a photo of it in the upper left). It served as an important resource and source of inspiration for many years, whether for writing grants, review articles, or thinking about viruses and their interaction with the central nervous system.

I always liked his sentence on page 5, under ‘Origins of Virology’: Virology as a discipline began in botany, not in medicine.

For me the most valuable chapter was ‘Pathogenesis of CNS Infections’ in which Johnson discussed how viruses move into and within that system. Many of the pages in that chapter are underlined and marked with comments (see photo below).

The blood-brain barrierYears later, when I was writing Principles of Virology, many of the concepts that I learned from Dr. Johnson made their way into that book. Dr. Johnson supplied me with an electron micrograph of the blood-brain barrier for use in our textbook.

A testimony to the value of this book for me is how many questions it raised, rather than answered. It truly influenced my thinking about poliovirus pathogenesis, for which I am very grateful to Dr. Johnson.

Aaron J. Shatkin, 77

Aaron J ShatkinAaron J. Shatkin was well known for his work on reoviruses beginning in the 1960s in his laboratory at the Roche Institute of Molecular Biology in Nutley, NJ and then at Rutgers University. He was among the first to appreciate that virus particles contained many different enzymes, such as RNA polymerase and poly(A) polymerase, that could be readily purified and used to study aspects of the viral replication cycle. His studies of reovirus mRNAs revealed an unusual methylated, blocked 5′-terminal structure, m-7G(5′)ppp(5′)G-MpCp-. He found that the 5′-terminal G of reovirus mRNAs made in purified virions or in infected cells was linked to the second G via a 5′-5′ chemical linkage, not the typical 5′-3′ linkage found in nucleic acids. This structure, soon to be called the cap, was subsequently found on many other viral and cellular mRNAs. His laboratory found that the cap is required for efficient translation of mRNA and also for mRNA stability. His discovery of a protein that binds the cap, now called eIF4E, lead to our understanding of how ribosomes are recruited to mRNAs to initiate protein synthesis. In recent years he became interested in the enzymatic machinery in cells that is responsible for synthesis of the cap structure, the capping enzyme. He studied the role of the capping enzyme in the nematode C. elegans and, in one of his last papers, solved the structure of the protein.

I have very good memories of Aaron: in 1979 I interviewed for a postdoctoral position in his laboratory at the Roche Institute (during my seminar I also met Ann Skalka with whom I co-authored a virology textbook many years later). Aaron was the first to offer me a postdoctoral position. I recall him being extremely kind and genuinely interested in my career. When I told him I was also interested in David Baltimore’s laboratory, he quipped ‘You’ll be lucky to even talk to him’; but he had a smile on his face. I was lucky to obtain a position in the Baltimore lab, and when I called Aaron to tell him, he was extremely gracious and congratulatory.

Over the years I met Aaron on many occasions; he was always friendly and cheerful and we often had long scientific conversations. When I moved to Scotch Plains, NJ in 1989 I was surprised to find that Aaron lived just around the corner, less than a mile away. I often saw him jogging by my home on Saturday mornings. Once I pointed him out to my older son: ‘that is the man who discovered the cap on mRNAs!’ My son had just studied the mRNA cap in high school biology so he knew what I meant. After that he often told his friends that the cap-discoverer lived near him in NJ.

Cooper Island rally

Several years ago, when our town wanted to build a home on a nearby small island of land, residents organized a rally to protest the development. It was called ‘Save Cooper Road Island‘ and Aaron and his wife Joan came to lend their support! You can see me with Aaron in photographs of the event (In the photo at left, he is to my left, wearing khaki pants, a dark jacket, and white cap; I am holding a sign, and Joan is to my right).

Just over a year ago he interrupted one of his runs to come by and tell me that his wife had passed away. ‘It’s a bummer’, he said, ‘I have to do all the cooking and cleaning by myself’. I asked him when he was going to retire, and he said now that his wife had died, he would probably keep working as long as he lived. Which he did.

Aaron was a terrific person and scientist. I will miss watching him jog by, telling people that my neighbor discovered the mRNA cap, and thinking about him as I drive past his home. I had planned for years to organize a dinner with him and my Ph.D. mentor, Peter Palese (Peter did a postdoctoral fellowship at the Roche Institute while Aaron was there and knew him well). I also planned to interview Aaron for TWiV. Now I can’t do either. I really should learn not to put off doing important things.


On the Death of Aaron J. Shatkin

Aaron J. Shatkin Ph.D. Obituary

Photos from a presentation (pdf)

Robert A. Weisberg, 1937-2011

weisbergRobert A. Weisberg was a Scientist Emeritus at NCI until the time of his death on 1 September 2011. Previously he was Chief of Microbial Genetics at NICHHD, a position he retired from in 2008. He was a pioneer in the study of the bacteriophage lambda. His research lead to seminal contributions about how bacteriophage lambda integrates into the E. coli chromosome. His laboratory produced the first library of cloned genes, using lambda transducing phages. Weisberg’s work was a combination of biochemical and genetic approaches, and he was an expert in both disciplines.

My colleague Max Gottesman was a good friend of Weisberg and writes:

Bob was a wonderful colleague; he shared freely his innovative ideas with others, had no issues with authorship, and welcomed the success of others – in short, a model citizen/scientist. He leaves behind a substantial scientific legacy that taken together established lambda as a model system for the study of recombination and gene control and an important tool for bacterial genetics. And those who knew him personally feel that he enriched their lives, and that an era has ended with his passing.

Weisberg’s recent review, co-authored with Gottesman, Little lambda, who made thee?, is an excellent review of the virus and its contribution to the field of molecular biology.

Bernard F. Erlanger, 88

erlangerWe note the passing of Bernard F. Erlanger, Ph.D., Professor Emeritus of Microbiology & Immunology at Columbia University Medical Center. Bernie, as he was known to his colleagues, joined our department in 1952 after earning his Ph.D. in biochemistry at Columbia University in 1951, and remained a member of the department until he passed away on September 8, 2011. Dr. Erlanger served as director of the department’s graduate program for many years, then as Acting and Deputy Chair of the department, and was also the Chair of the Science & Technology Policy Committee at Columbia.

Dr. Erlanger had a distinguished career as a biochemist and immunologist, and his research interests were very broad. They included developing receptor specific antibodies using an auto-anti-idiotypic strategy, studying nucleic acid structure and conformation, investigating microtubule assembly, and developing antibodies to carbon nanotubules and fullerenes. He was an active inventor with over a dozen scientific patents, including patents for the creation and delivery of specific antibodies, detection of HIV, and treatment of HIV and sickle cell disease. Dr. Erlanger was the recipient of many scientific awards and honors throughout his career, including a Fulbright Scholarship, a Guggenheim Fellowship, and the Townsend Harris Medal.

Frank Fenner, MD, 1914-2010

Australian virologist Frank Fenner, MD was born in Ballarat, Victoria in 1914. He earned a Doctor of Medicine in 1942 at the University of Adelaide, and from 1940 – 1946 he worked on the malaria parasite in Egypt and Papua New Guinea as an officer in the Australian Army Medical Corps. He subsequently began studying the pathogenesis of mousepox virus at the Walter and Eliza Hall Institute of Medical Research in Melbourne. Later he was appointed Professor of Microbiology at the John Curtin School of Medical Research at the Australian National University, where he continued his work on viruses, including myxoma virus. His interest in the balance between virus virulence and host resistance was put to practical use in an effort to control Australia’s rabbit plague through the introduction of myxoma virus.

Dr. Fenner was a co-author of The Biology of Animal Viruses, first published in 1968. I still have my paperback ‘student’s edition’ which served as my virology bible during my years as a Ph.D. student. Later, when I was developing virology lectures for medical and graduate students, I relied on this book heavily. From the introduction:

During the last twenty years virology has developed into an independent science. It is now growing so rapidly that two new journals of virology were launched this year. Four major works on viruses of vertebrate animals have been published recently….However, none of these books deals in a comprehensive way with the broader biological principles of animal virology, which is the aim of this two-volume work.

The idea of presenting virology as a series of principles, not simply a list of viruses, was novel, and inspired us during the writing of Principles of Virology many years later.

Fenner’s classic studies on mousepox pathogenesis were the first to demonstrate how disseminated viral infections develop from local multiplication to primary and secondary viremia. In the case of mousepox, after local multiplication in the foot, the host response leads to swelling at the site of inoculation; after viremia, the host response to replication in the skin results in a rash. The figure at left depicting these events is included in Principles of Virology, because the findings serve as a paradigm for many other viral infections.

Fenner was also well known for his work on rabbitpox. European rabbits were introduced into Australia for hunting in 1859, and lacking natural predators, they reproduced to plague proportions. The rabbitpoxvirus, myxoma virus, was released in Australia in the 1950s in an attempt to rid the continent of these rabbits. In the first year, the infection killed the rabbits with a 99.8% mortality rate. By the second year the mortality dropped to 25%, and subsequently the rate of killing was lower than the reproductive rate of the rabbits, ending any hope for 100% eradication of the animals. The most important lesson from this incident is that the original idea to eliminate rabbits with a lethal virus was flawed, because powerful selective forces that could not be controlled or anticipated were at work. Fenner published a series of journal articles from 1950-1964 which carefully documented the changes in the virus and the host that occurred during this incident.

For more information on Dr. Fenner, see his interview from June of 2010 in The Australian, and a summary of his career at the Australian National University.

Fenner F (2010). Deliberate introduction of the European rabbit, Oryctolagus cuniculus, into Australia. Revue scientifique et technique (International Office of Epizootics), 29 (1), 103-11 PMID: 20617651

FENNER F, & WOODROOFE GM (1965). CHANGES IN THE VIRULENCE AND ANTIGENIC STRUCTURE OF STRAINS OF MYOMA VIRUS RECOVERED FROM AUSTRALIAN WILD RABBITS BETWEEN 1950 AND 1964. The Australian journal of experimental biology and medical science, 43, 359-70 PMID: 14343496

Robert M. Chanock, MD, 1924-2010

From the Washington Post:

Dr. ROBERT M. CHANOCK (Age 86) On July 30, 2010 of Bethesda, MD. He was a resident in the Washington area for over 50 years, a distinguished scientist at the National Institute of Health. He received many awards and was a member of the National Academy of Sciences. He received his undergrad and medical degrees at the University of Chicago where he also received an honorary doctorate degree.

Chanock received his MD in 1947 from the University of Chicago, and after clinical training in pediatrics (note the bowtie), joined Albert Sabin at the University of Cincinnati where he studied arthropod-borne viruses. After a stint in the US Army, he rejoined Sabin’s laboratory in 1954 as an independent investigator. Sabin advised him to work on something other than poliomyelitis, to establish his own scientific identity. He decided to study an ongoing outbreak of croup in Cincinnati children and isolated a new virus, subsequently called human parainfluenza virus type 2. This discovery ensured that he would study respiratory viruses for the rest of his career.

His move to the Laboratory of Infectious Diseases, National Institutes of Health in 1957 was the last of his career but lead to his most productive years. Together with Robert Huebner he developed an effective adenovirus vaccine which was used by the military. He discovered four additional human parainfluenza viruses, but his most important finding was the isolation of respiratory syncytial virus, the most common viral cause of serious lower respiratory tract disease in infants and young children. Under his leadership, the Laboratory of Infectious Diseases began to study other important human viruses, including gastroenteritis viruses (e.g. Norwalk virus) and hepatitis viruses.

I was fortunate to interact with Dr. Chanock early in my career, at scientific meetings and during visits to the NIH. My main recollection was that he was always enthusiastic and supportive. His first question upon seeing me was always ‘how’s the work with polio?’ Since his early years with Albert Sabin he had always followed basic research on poliovirus with great interest. Sabin had a significant positive influence on Chanock’s career and his view of viruses – in fact, Sabin considered Chanock his ‘scientific son’. It is therefore fitting that the last award bestowed upon Chanock was the Albert B. Sabin Gold Medal in 1995, for his work in the field of vaccinology, particularly the control of respiratory diseases.

Update: Washington Post story

LIGON, B. (1998). Robert M. Chanock, MD: A living legend in the war against viruses Seminars in Pediatric Infectious Diseases, 9 (3), 258-269 DOI: 10.1016/S1045-1870(98)80040-X