Research and career
In the early 1980s, Corey worked with Nobel Prize-winning biochemist and pharmacologist Dr. Gertrude Elion to demonstrate that an antiviral that was selective and specific for a viral-specified enzyme could be safely and effectively administered to control a chronic viral infection (herpes simplex virus type 2 or HSV-2). Corey first conceived of, demonstrated the core concepts and directed line association between quantitative viral load reduction and clinical benefit using topical, intravenous and oral formulations of acyclovir in classic studies performed between 1980 and 1984.[1][2][3] Acyclovir was the first antiviral drug to get rapid approval from the FDA, and it was Corey's studies that defined its use in genital herpes. These studies led to the licensure for acyclovir in a wide variety of infections such as HSV-1, HSV-2 and varicella chickenpox virus, including the first use of an antiviral for daily long term use. Acyclovir and its derivatives valacyclovir and famciclovir are the most prescribed antivirals in the world: over 400 million people have HSV-2 infection. These early studies prompted the subsequent successful involvement of the pharmaceutical and medical sciences communities to develop effective antiviral therapy for HIV and Hepatitis B.
In 1987, Corey directed the NIH supported AIDS Clinical Trials Group (ACTG), which was established to test antivirals to HIV-1, and conducted pivotal clinical trials demonstrating the use of the antiretroviral drug AZT to reduce maternal-fetal transmission of HIV and the usefulness of combinations of antiretrovirals to prolong survival from HIV.[4] During this time, that laboratory demonstrated that HIV circulated in plasma well before the development of AIDS.[5] The ACTG subsequently demonstrated that the initiation of therapy early during asymptomatic stages of HIV infection reduced progression to HIV[6] and that combinations of antiretrovirals (3>2>1 drug) were critical to the control of HIV replication and management; the result being that HIV control has enabled life expectancy to increase globally.[7] Triple combination therapy with two nucleosides and a protease inhibitor demonstrated a marked reduction in viral load, increase in CD4+ T-cell count and lowering of activation markers with the addition of the protease inhibitor.[8] The ACTG was the first to lead the integration of community members into clinical research activities.[9]
In the mid-1990s, Corey increasingly focused his work in the area of vaccine development, and in 1998 worked with the US National Institute of Allergy and Infectious Diseases to develop a global clinical trials group to speed the development of HIV vaccines. In 2002, Corey became the major driver in conceiving of the Global HIV Vaccine Enterprise. The Enterprise is one of the few scientific programs that is overseen by leaders of the major industrialized countries of the world.
One of Corey's major scientific initiatives has been to study and develop better therapy for the treatment and prevention of infectious disease associated cancers such as Kaposi sarcoma and Burkitt lymphoma.[10] In the mid-2000s, Corey launched a partnership between Fred Hutchinson Cancer Research Center and the Uganda Cancer Institute.[11] On July 30, 2010, Dr. Corey was named the fourth president of the Fred Hutchinson Cancer Research Center.[12] One of his major initiatives was to increase the strength of the Fred Hutch's translational research programs and its commitment to bring better therapies and preventions for cancer to the developing world. In May 2015, the Fred Hutch/UCI partnership led to the opening of the first comprehensive cancer center jointly constructed by US and African institutions in sub-Saharan Africa: the UCI-Fred Hutch Cancer Centre.[13] In 2013, as an outgrowth of his work in T-cell immunology, Corey became a cofounder of Juno Therapeutics, a company devoted to using genetically engineered T cells to fight cancer.[14]
Corey's early research dealt with herpes simplex viruses, and he headed several landmark studies defining the disease and leading the licensure of acyclovir and valacyclovir for its treatment.[15][16] This included a study to reduce acquisition among sexual partners. Between 1988 and 1998, Corey published a series of key studies showing the association between infection with HSV-2 and HIV-1.[17][18] These studies led to pilot and large sale clinical trials of anti-HSV-2 therapy to reduce HIV acquisition and transmission.[19] In 2000, Corey conducted the first discordant couple study using antiviral therapy for HSV-2. His publication in 2004 on reduction of transmission of HSV-2 was the first to demonstrate that antivirals could reduce transmission of infections to others (treatment as prevention),[20] a concept subsequently utilized by the HPTN 052 protocol team using continuous ART to reduce transmission of HIV to discordant couples. This latter approach is one of the current cornerstones of public health practices for reducing the morbidity and potentially the transmission of HIV-I.[21]
More recently, his research group has shown the importance of the mucosal immune system in controlling HSV reactivation, leading to current momentum to try to develop novel vaccines for treating genital herpes. Previously, the scientific consensus for HSV-2 pathogenesis was that virus reactivation was infrequent and determined by virus-neuronal interactions at the ganglion level and that most reactivations resulted in genital lesions.
Corey has been a central figure in the field of HIV vaccine development.[22] The HIV Vaccine Trials Network (HVTN) now includes investigators on five continents spanning more than 30 cities[23] and is leading the research for phase 1–3 clinical trials of candidate HIV vaccines globally. The HVTN as of 2018 is conducting 4 large scale efficacy trials in North America, South America and several countries in sub-Saharan Africa. On December 01, 2015 the work of Corey and HTVN scientists pursuing a vaccine to potentially halt HIV and AIDS was highlighted in an HBO/VICE special report titled "Countdown to Zero."[24]
Honors
Corey was a member of the editorial board of the New England Journal of Medicine. He is a fellow of the Infectious Diseases Society of America and a member of the American Epidemiological Society, American Society for Clinical Investigation, and the Association of American Physicians. In addition, he is the recipient of the Pan American Society's Clinical Virology Award, the American Sexually Transmitted Diseases Association's Parran Award, and the University of Michigan Medical School's Distinguished Alumnus Award.[25] In 2008, he was elected to the National Academy of Medicine and in 2012 elected a Member of the American Academy of Arts and Sciences. He has published over 900 scientific publications and editorials (as of 2018).
