Laurence Corash, a hematologist at the University of California, San Francisco, started hearing reports in the early 1980s that demand for the antibiotic pentamidine was skyrocketing. The drug was used to treat pneumocystosis, a severe pneumonia caused by a yeast-like fungus that typically gained a foothold by exploiting the weakened immune systems of very old or severely malnourished people.
Some of Corash’s hemophilia patients, who were otherwise healthy, started contracting the fungal disease and taking pentamidine to combat the infection. Searching for a cause for this trend, Corash realized that his patients had one thing in common: they were getting injections of a concentrated blood extract called factor VIII to help their blood clot. It dawned upon the physician that something in the factor VIII preparations might be destroying his patients’ immune systems.
By 1984, Corash realized that the newly characterized HIV virus was the causative agent. “It was a very sad and gut-wrenching experience to have to sit down with people and say, ‘You got this disease from the products I gave you, and I don’t have a treatment for you,’” Corash says. “To see 300 people get HIV infections from the treatments that you give them is a very disturbing thing.”
So when researchers at Advanced Genetics Research Institute (AGRI), a Berkeley, California, veterinary pharmaceutical company, called Corash to help them run routine blood tests on a new vaccine against the feline leukemia virus, he wondered whether the agent used to inactivate the virus for the vaccine, a defensive chemical produced by plants called a psoralen, might also inactivate HIV, and so protect his hemophilia patients from acquiring the disease from factor VIII preparations. The AGRI scientists realized that psoralens, which prevented DNA and RNA replication in most viruses and bacteria, could conceivably wipe out any pathogens in blood products like factor VIII without harming the patient, because the plasma from which factor VIII is derived does not contain any cells or nuclei to be damaged by the treatment.
The vaccine’s virus-inactivating agent, a chemical called 8-methoxypsoralen, normally drifts harmlessly in and out of cells and nestles inside nucleic acid helices. But when the psoralen molecule is hit with UV light, two photons bind the ends of the molecule, one to each strand of the DNA, and “tie the strands together,” preventing replication, says John Hearst, a founder of AGRI and a molecular biologist at the University of California, Berkeley, who studied some of the first synthetic psoralen compounds in the 1970s. Carl Hanson, who was then a postdoctoral student in Hearst’s lab, discovered that the cross-linking worked in both RNA and DNA, and reasoned that it could thus prevent bacteria, viruses, and eukaryotic cells from replicating.
“Using drugs that target DNA and RNA was very innovative as a concept,” says Richard Benjamin, chief medical officer for the American Red Cross. Several members of Hearst’s lab began meeting for coffee at Oliveto Restaurant near Berkeley to brainstorm ways of using psoralens to develop blood-cleaning products, says Hanson, who is now at the California Department of Public Health.
To show that the approach could actually prevent the transmission of disease, Corash and collaborator Harvey Alter of the National Institutes of Health mixed concentrated factor VIII preparations with hepatitis B and C viruses, added psoralens, and then shone UV light on the preparations. Healthy chimpanzees transfused with the treated factor VIII and other psoralen-cleaned concentrates were disease-free months later.
The group formed a startup called Steritech and began synthesizing psoralen compounds that could inactivate viruses and bacteria more quickly. Their original product took 8 hours to clean a few hundred milliliters of blood; by the end of 1993, newer variants could clean the same amount of blood in less than 3 minutes.
Steritech (renamed Cerus in 1997) would go on to develop pathogen-inactivation products to scrub red blood cells, plasma, and platelets of HIV and several other viruses and bacteria. The technology is currently used in parts of Europe and Asia to clean blood supplies of dozens of pathogens such as SARS, MRSA, and HIV, and is currently under FDA regulatory review. When more than one-third of the population on the French island of Réunion in the Indian Ocean was infected with a rare arthritis-causing virus called Chikungunya, France hired Cerus to sterilize the entire blood supply on the tiny Indian Ocean outpost.