Four decades ago, Frederick made it possible to implement the first blood test for HIV

Frederick has long been a hub for discovery, innovation, and advancements in HIV/AIDS research. 

The expertise of a Frederick team studying cancer-causing viruses led to the development of the first successful blood test for the human immunodeficiency virus in 1985 as the team’s large-scale virus production provided the needed basis for the tests. 

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“I picked [the flasks of virus cells] up in April of 1984, and by March of 1985, there were FDA-approved assays--That’s 11 months,” said Larry Arthur, Ph.D., who led the team. “That is probably as fast of getting some kind of approval as you could possibly imagine." 

In April 1984, Larry and his team at the Frederick Cancer Research Facility, an early predecessor to the Frederick National Laboratory, used two flasks of HIV-infected cells to quickly manufacture thousands of liters of the substance —a feat few groups at the time could achieve.  

This virus production facilitated both NCI research and the development of an FDA-approved blood test for HIV, which would become a critical tool in reducing transmission via transfusions. 

The team at the Frederick Cancer Research Facility, now the AIDS and Cancer Virus Program at the FNL, was one of the few groups with the expertise and capability to address the large-scale viral production at the time.  

Forty years later, the AIDS and Cancer Virus Program continues to advance HIV research with investigator-initiated research and to leverage its expertise for extramural investigators through unique technical services. 

The program is built on a legacy of innovative HIV research and talented, collaborative teams, which can be traced back to this critical need for virus production in an emerging infectious disease outbreak. 

The right group in a crisis 

Thousands of people were dead. 

They had succumbed to unusual infections, rare cancers, and a variety of other maladies but had one thing in common: acquired immunodeficiency syndrome or AIDS, an immune dysfunction that had made them vulnerable to these diseases.  

America was in the throes of a crisis from a disease first identified in 1981. Approximately half of the people diagnosed with AIDS had already died, and diagnoses were mounting. 

Growing evidence showed HIV could be transmitted by blood and blood products—and that the virus had entered America’s blood supply through donors who unknowingly were infected with this virus.Sadly, nearly half of Americans with hemophilia, a group that depended on transfusions of the purified plasma product coagulation factor 8, had acquired HIV by spring 1984. 

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It was amid these conditions that the National Cancer Institute asked the Frederick Cancer Research Facility for help. 

NCI virologists were studying HIV, the virus that causes AIDS, in a biological interrogation for information that might help curb the pandemic. They needed massive quantities of the virus to do this work, far more than the Institute had on hand.  

Others in the research community also needed large quantities of the virus. The National Institutes of Health was poised to award contracts to five companies to adapt or develop a blood test for HIV. Such research and development would also require large amounts of virus, and the burgeoning crisis wouldn’t wait for the companies to set up their own manufacturing pipelines. 

NCI scientists saw the Frederick Cancer Research Facility, which was part of the NCI AIDS Task Force established in 1983, had the prowess to produce the required amount. 

The team was prepared: It specialized in high-stakes viral production. The scientists worked in biosafety level 3 laboratories, which were innovated and retrofitted for the task, and had spent the last few years producing HTLV-I, the first discovered human retrovirus (the same category of virus as HIV), for NCI studies.   

High risk, high reward 

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The Frederick Cancer Research Facility team completed a 12-liter pilot lot of virus production by the end of May, just seven weeks after they received the two flasks of cells. The team produced 100 liters of virus-infected cells for each of the five companies that needed access to this product by the end of the summer.  

Each batch would have filled half of a 55-gallon drum had it not been concentrated down, said Arthur, who retired in 2011 as CEO of SAIC-Frederick, predecessor to Leidos Biomedical Research, operator of the Frederick National Laboratory. 

“The idea was with that amount they could go into production immediately,” Arthur said. 

The team produced purified HIV-1 for NCI throughout 1984. They completed 80 lots from 6,820 liters of cell culture by the end of the year, an average of one 85-liter lot every two workdays, said Julian Bess Jr., who was a member of the team and is currently a scientist in the AIDS and Cancer Virus Program. 

All of this virus was immediately and securely shipped to NCI’s researchers in Bethesda for a grand total of 34 billion infectious doses.  

This fast-paced effort came with great potential risk to the team. The manufacturing process required pumping and concentrating large amounts of HIV and infected cells, with the team frequently handling containers with the virus.  

At various points the material was centrifuged, with the potential for a spill or aerosolization risk if the centrifuge leaked. It demanded careful mitigation through safety controls. 

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The work was so controlled that the staff signed a logbook before entering the laboratory to provide a record of who to monitor in case of a leak or exposure. They donned full-body protective suits. For certain procedures, they swapped out their safety glasses, bonnets, and masks for a helmet connected to a plumbed-in air supply. Then, they opened the door, stepped inside, and got to work. 

“We knew that HIV could be transmitted by bodily fluids, but we didn’t know if it could be transmitted via aerosols while working with the large quantities we would be producing,” Bess said. 

Despite these high risks, their large quantity production was among the first of Frederick’s many major contributions to AIDS research. 

In March 1985, the FDA granted licenses for HIV blood tests to two of the five contracted companies that had used the purified virus manufactured by the Frederick Cancer Research Facility.  

The scientific and medical communities took some time to determine when to deploy the test and how to do so while protecting the privacy of people living with AIDS. However, it wasn’t long before the test began to make a difference. Combined with other measures, it would throttle HIV transmission via transfusion from a tidal wave to a trickle over the next few years. 

Retrofitting the space to achieve the mission 

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The biosafety level 3 (BSL-3) facilities in Building 560 on Fort Detrick’s campus were as special as the work conducted in them. They were run-of-the-mill laboratories retrofitted for this viral production purpose—designed and built out by the facility’s own maintenance teams. 

Architects, engineers, and tradespeople working on the Frederick campus visited Building 560 and spoke with members of Arthur’s team to ascertain the intricacies of creating a high-containment space.  

They constructed showers and locker rooms from the ground up. In the laboratories themselves, they built sheetrock walls around the many pipes and conduits that ran along the ceiling, ensuring that no contamination could enter. Every crack and gap was meticulously sealed. 

It was the reverse of how such a project would typically be done, where existing pipes would already be hidden and holes for the utilities would be bored into the existing structure. But it was what Frederick staff often had to contend with—and an innovative solution characteristic of the facility. 

“I’m enormously thankful for everything the maintenance team did for us,” Bess said. “They helped keep us safe. They were intimately involved with getting a BSL-3 laboratory validated.” 

Unsung heroes

The following individuals worked in the laboratory at the Frederick Cancer Research Facility and were responsible for the large-scale virus production effort.