Research: New Defense Against Viruses

As protection against the dozens of viruses that attack him throughout his lifetime, man has two major natural defenses: antibodies and a mysterious substance called interferon. Most antibodies give lifetime immunity, but the body takes days or weeks to make them, and each type of antibody is effective against only one type of virus. The body makes interferon faster, within a few hours of exposure, but still not fast enough to keep many invading viruses from multiplying in millions of cells and causing severe illness. It is effective against the whole catalogue of viruses, but its protection may last only two or three weeks. Nevertheless, researchers believed that if they could help the system produce interferon even before exposure, they could prevent many viral invasions from ever becoming established and causing illness.

Last week a team at the Merck Institute for Therapeutic Research reported that it has succeeded in doing this in mice and rabbits, and is ready to try to extend the method to man. Chief of the investigators is Dr. Maurice R. Hilleman, already famed for his work in developing a mumps vaccine (TIME, July 1, 1966) and Enders measles vaccine. The first of his group’s reports appeared under the prestige imprint of the Proceedings of the National Academy of Sciences.

Forearmed Cells. Interferon is a protein discovered ten years ago in Britain. Many if not all of the body’s cells can make it. When the infective core of a virus particle invades a cell, that cell is usually doomed; its biochemical factory will soon be taken over by the virus and begin making new virus particles or parts of them. But before this happens, some cells produce interferon and pass this on through the bloodstream. Thus forearmed, other cells can then ward off attacks by the next generation of virus particles.

Dr. Hilleman’s group reasoned that since it seems to be the nucleic acid in the virus’ core that provokes natural interferon output, something like a harmless form of nucleic acid might stimulate the increased production they were seeking. They tested helenine, extracted from a mold related to those that make penicillin and already known to have antiviral properties (though no one then knew why). Extraordinarily complex extraction procedures yielded a pure ribonucleic acid (RNA). But this was no ordinary RNA, such as occurs in the cores of many viruses in molecules of single strands. This proved to be a double-stranded form. The lab team called it Hel-RNA.

When the researchers injected Hel-RNA into mice and then gave the animals a second injection of a normally fatal dose of an encephalitis virus, 73% of the animals survived, as against only 3% of unprotected mice. The score was still better when the RNA preparation was put into the animals’ noses and they were exposed to a pneumonia virus: 90% survived, whereas every one of the unprotected comparison group of mice died.

Promising Prospects. The Merck virologists tried other kinds of nucleic acid: single-stranded RNA, doublestranded deoxyribonucleic acid (DNA), and substances containing proteins. None worked. Then they took two groups of nucleic acid components. Alone, neither of these had worked, but when they were combined in what turned out to be a multi-stranded RNA, the protective effect for infected mice was about the same as that conferred by HeL-RNA.

Finally, the researchers took reovirus-3, a common cause of respiratory and intestinal infections in man and remark able because its RNA core is normally double-stranded. Unlike the whole vi rus, the purified RNA extracted from it did not cause infections, but it stimulated interferon production within an hour in cells grown in the test tube. The process usually requires five hours with the whole virus.

Though it will take years to translate the Merck group’s findings into everyday medical practice, the prospects are promising. Previously, they had appeared dim because man normally produces so little interferon. And interferon from one species is of little or no use in another, so there was no chance of “growing” it in animals for later use in man. But now it seems virtu ally certain that man can be stimulated to produce it by a periodic intake of a harmless form of RNA, either injected or even more convenient, by means of an inhaler. Though the maximum effect may last only two or three weeks, that would be long enough to protect other members of a family when one of them starts spreading cold germs around the house. And interferon might be still more valuable against flu.