Dr. Frank Schabel, a virologist, arrived at Southern Research in 1951 after working for the Chicago Health Department, where he studied the patterns, causes and effects of polio, and at the U.S. Army’s infectious disease laboratories at Camp Detrick in Frederick, Maryland, during World War II.
While much of Schabel’s work at Southern Research was related to the cancer research program, he retained a deep interest in virus research and bacteriology programs and recruited virologists, cell biologists and bacteriologists to the organization.
Early virus research focused on the evaluation of potential antiviral agents against a wide range of pathogenic viruses, particularly those known to cause cancers in mice, chickens and hamsters. Early studies were also conducted with the herpesviruses, poxviruses, acute upper respiratory disease viruses, and the mosquito-borne viruses such as Yellow Fever virus.
Sponsors of this work included the NIH, the U.S. Army, and Parke, Davis & Co., a pharmaceutical company that became a longstanding partner.
Schabel, who arrived at Southern Research in 1951 as a virologist, had become a key member of Dr. Howard Skipper’s cancer research team. According to Skipper, Schabel was one of a few who believed in the potential of chemotherapy for virus diseases in the 1950s.
Schabel, working with pharmaceutical company Parke Davis, was instrumental in the discovery and development of the first agent proved useful for systemic treatment of a virus disease — Arabinosyl Adenine or Ara-A.
The agent reduced the mortality of herpes encephalitis infections in man from approximately 85 percent to less than 15 percent in the first few years of clinical trials, and it was approved by the U. S. Food and Drug Administration in 1976. Much of the preclinical research work on this drug in cell culture and in animal models was conducted at Southern Research.
The antiviral drug was also effective against human herpesviruses and varicella-zoster, the virus that causes chicken pox.
In 1986, Southern Research’s Microbiology-Virology department began work under a five-year, $8.8 million contract from the U.S. Army to study the potential antiviral activity of compounds against exotic RNA viruses. That positioned the department perfectly for a separate $1.1 million contract that same year from the National Institutes of Health and the Army to evaluate compounds for the treatment of AIDS.
The organization has been involved in AIDS research ever since.
As part of the NIH/Army contract, Southern Research tested approximately 1,500 compounds a year, making it the only laboratory outside of the NIH actively evaluating AIDS compounds on a large scale. Southern Research also set out to develop a more effective assay method for large-scale screens.
The anti-HIV drug evaluation work at Southern Research eventually expanded to the testing of all synthetic chemical compounds submitted to the U.S. government for screening against the virus, approximately 20,000 compound-tests per year for a decade. Many of the active anti-HIV drugs came through this screen over the years, including Carbovir.
An interest-free loan from Southern Research made possible 1988’s International Conference on Antiviral Research (ICAR) in Williamsburg, Virginia, the first conference officially held by the newly organized International Society for Antiviral Research (ISAR).
Southern Research’s Dr. William Shannon incorporated ISAR in Birmingham as a non-profit organization.The conference was a major success, and ISAR is currently in its third decade of operation, still strongly supported by Southern Research.
Shannon served as one of ISAR’s co-founders and its first treasurer from 1988 to 1994. Dr. Jack Secrist, head of Drug Discovery and later president of Southern Research, also served as ISAR’s treasurer from 1994 to 2003 and as its president from 2004 to 2006.
The facility in Maryland’s second largest city enabled to Southern Research to have a presence close to many of its key government sponsors when operations started there in late 1990. Over the years, the Frederick lab has become home to a major portion of the organization’s infectious disease research program.
Dr. Peter Canonico, previously with the U.S. Army Medical Research Institute for Infectious Diseases, was the facility’s first director.
The Frederick lab was deeply involved in Southern Research’s effort to screen compounds that could be effective against HIV and other viral infections.
The High-Throughput Screen (HTS) Center, which can scan thousands of compounds for biological activity, begins operation at Southern Research in 2003. Screens ramped up to more than 500,000 compounds in 2005. Between 2006 and 2014, the average topped 3 million compounds screened each year.
The HTS system uses specialized automation equipment and high density microtiter screening plates to test a large number of chemical compounds in a short period of time. Screening of 30,000 to 100,000 compounds per day is common.
Southern Research’s earliest HTS campaign stemmed from the SARS coronavirus outbreak in 2003 when the National Institutes of Health asked the organization to look for compounds that could be used as antiviral drugs for the emerging disease.
Southern Research has gained international recognition for its ability to test hundreds of thousands of compounds using infectious pathogens such as avian influenza (bird flu), seasonal influenza, tuberculosis, and eventually the hemorrhagic fever pathogens Ebola virus and Nipah virus, among others.
Southern Research was awarded a seven-year contract of up to $22 million to support research that could contribute to the cure of HIV disease.
Under this 2015 contract, Southern Research will develop and standardize assays, or screens, that measure what is known as “latent reservoirs” of HIV.
HIV replication can be effectively suppressed in infected patients with antiretroviral therapy, which reduces the level of HIV in the blood to an undetectable level. However, HIV stays hidden within these infected blood cells – latent reservoirs – and a reactivated cell can begin to produce HIV again.
The National Institute of Allergy and Infectious Diseases awarded the grant to Southern Research to support the HIV cure initiative.
The organization’s research to combat the harmful effects of the Zika virus was expanded with a contract from the National Institute of Allergic and Infectious Diseases (NIAID) and the National Institutes of Health (NIH) to develop a non-human primate model of Zika infection for product evaluation.
The model will serve as a resource to accelerate research into possible vaccines or therapeutics for Zika disease.
“Southern Research has a long history of pivotal work on infectious diseases,including mosquito-borne illnesses such as dengue, chikungunya, and West Nile Virus,” President and CEO Art Tipton said.
Earlier in 2016, Southern Research scientists developed a unique antiviral assay that can be used by researchers worldwide to detect the Zika virus in infected cell cultures. Scientists also launched experiments to better understand the course of the infection in Cynomolgus macaque, a model previously used in dengue studies.
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