Joseph A. Sonnabend (1933-2021): Pioneering interferon researcher turned AIDS activist

Front row, from left to right: Robert Friedman, Sam Baron and Joseph Sonnabend in 1964 attending the First International Symposium on Interferon in Smolenice, Czechoslovakia

Robert M. Friedman1 and Jan Vilcek2

1Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814 [email protected]

2Depoartment of Microbiology, NYU Grossman School of Medicine, New York, NY 10016 [email protected]

Joseph Sonnabend, a physician, virologist, and multi-talented individual, who participated in pioneering studies on virus replication and on the mechanism of action of interferon died in London on January 24, 2021. He will, however, be best remembered for his activism and contributions to research during the early stages of the AIDS epidemic. His career in general was certainly anything but conventional. 

Joseph was born in South Africa but growing up in what is now Zimbabwe, where his Russian-born mother was a practicing physician. His father, a sociologist, was an active Zionist.  Joseph lived in a highly cultured atmosphere that endowed him with a love for art and classical music. Throughout his life he played the piano and the organ. He studied medicine at the University of Witwatersrand in Johannesburg, South Africa, and was trained in infectious diseases at The Royal College of Physicians in Edinburgh. He became attracted to virology and interferon research and, in 1961, joined the laboratory group of Alick Isaacs, co-author with Jean Lindenmann of the first description of interferon (1), at the National Institute for Medical Research in London. While working at the NIMR, Joseph contributed to early research on the mechanism of interferon action, establishing that cellular protein synthesis was necessary to its antiviral effect (ref 2, 3).  At the time, this was an important finding suggesting that interferon’s antiviral action was mediated by newly induced cellular proteins, a fact amply documented in subsequent studies. He also contributed to early research on the mechanism of interferon’s inhibition of the replication of arboviruses and poxviruses (4,5).

At the time that Isaacs suffered a severe cerebral hemorrhage in 1964, Joseph contributed significantly to his attempts to keep up his research. Upon Isaacs’ death in 1967, Joseph decided to move to the US to assume a position in the Medicine Department of SUNY Downstate Medical School in Brooklyn, NY. He later transferred to the Microbiology Department of the Mt. Sinai Medical School in New York City, where he participated in research on the purification of interferons.

Upon moving to New York, Joseph’s original aim was to continue to focus on interferon research. Yet, he was drawn to his original medical specialty of infectious diseases, and in 1977 he established a medical practice in the Greenwich Village neighborhood of New York City. Many of his patients suffered from infectious diseases, especially sexually transmitted infections. These turned out to be among some of the earliest AIDS patients in the US. Among this group, Joseph was highly appreciated for his efforts to treat their multiple clinical problems, including Kaposi’s sarcoma and Pneumocystis pneumonia. Once AIDS had been recognized as a major health problem in the early 1980s, Joseph became fully focused on treating patients with AIDS and understanding its etiology and pathogenesis. (This was in the days when AIDS was still referred to as “gay-related immunodeficiency” or GRID. It was not known until 1983 that AIDS is caused by the retrovirus, HIV, nor was it clear at the time that it is a contagious, infectious disease.)  Joseph was devoted to his patients, often not billing them for office visits or house calls.  He is credited with saving many lives of AIDS patients by treating their Pneumocystis pneumonia with widely available sulfa drugs. Joseph contributed significantly to our understanding of the nature of AIDS. With Stuart Schlossman he found that seriously ill AIDS patients have a marked reversal of their CD4/CD8 ratio and that the loss of CD4 helper T cells accounts for the profound immunodeficiency suffered by these patients (6). Interestingly, Joseph was slow to accept the notion that AIDS is caused by HIV, persisting for some time in his belief that there are multiple factors contributing to its etiology.

Joseph also came up with the idea to look for the presence of interferon in the blood of AIDS patients. He collected blood samples from his patients and invited the co-authors of this obituary to determine if they contained interferon activity. This collaboration led to the discovery that most AIDS patients have in their blood demonstrable levels of an acid-labile form of interferon-alpha (7), a finding corroborated by many subsequent studies. Curiously, the original rationale to look for the presence of interferon in the blood of AIDS patients was not that AIDS is a virus-caused disease—a fact that was not yet known at the time. Rather, it was hypothesized in those days that the underlying cause of AIDS may be some kind of an immune disturbance, and earlier studies showed that the blood of patients with autoimmune diseases, such as systemic lupus erythematosus, contained interferon-alpha (8).

Inspired by his clinical and research experience with AIDS, Joseph became an outspoken advocate for safe sex for gay men. Together with Mathilde Krim he helped to establish the Foundation for AIDS Research, AmFAR, a leading organization devoted to research and treatment of AIDS.

Joseph spent the last fifteen years of life in London, devoting some of his creative energy to the composition of computer music. One of his compositions was recently performed on the BBC3 music channel.

Acknowledgment. This obituary is also appearing in the Journal of Interferon and Cytokine Research.

References

  1. Isaacs, A, and Lindenmann, J, Virus interference. I. The interferon. Proc. Roy. Soc. B 147, 258-267, 1957.
  2. Friedman, RM and Sonnabend, JA, Inhibition of interferon action by p-fluorophenylalanine, Nature 203:366-7, 1964.
  3. Friedman, RM and Sonnabend, JA, Inhibition of interferon action by puromycin, J Immunol. 95, 696-703, 1965.
  4. Friedman, RM and Sonnabend, JA,  Inhibition by interferon of production of double-stranded Semliki forest virus ribonucleic acid. Nature 206, 532, 1965.
  5. Friedman, RM, Sonnabend, JA, and McDevitt, H, Interferon inhibition of cytoplasmic DNA accumulation in vaccinia virus infection. A radioautographic study. Proc. Soc. Exp. Biol. Med. 119, 551-553, 1965.
  6. Wallace JI, Coral FS, Rimm IJ, Lane H, Levine H, Reinherz EL, Schlossman SF, and Sonnabend J, T- cell ratios in homosexuals. (Letter) Lancet, Vol. I, p. 908, 1982.
  7. DeStefano E, Friedman RM, Friedman-Kien AE, Goedert JJ, Henriksen D, Preble OT, Sonnabend JA, and Vilcek J, Acid-labile human leukocyte interferon in homosexual men with Kaposi’s sarcoma and lymphadenopathy. J Infect Dis 146, 451-9, 1982
  8. Preble OT, Black RJ, Friedman RM, Klippel JH, and Vilcek J, Systemic lupus erythematosus: presence in human serum of an unusual acid-labile leukocyte interferon. Science 216, 429-31, 1982.