Fifty Years with Interferons

In 1981 Sidney Pestka and colleagues at Roche purified recombinant human leukocyte interferon from bacteria setting the stage for its structure elucidation.

COURTESY OF SIDNEY PESTKA / PBL BIOMEDICAL LABORATORIES

In 1957, Alick Isaacs and Jean Lindenmann, both at the National Institute for Medical Research in London, set out to understand why inactivated influenza virus could induce interference in cells and tissues, preventing infection by "live" virus.

That the inactivated viruses physically blocked infection seemed unlikely. So, the two incubated chorio-allatoic membranes from chicken eggs with heat-inactivated influenza. They then washed the membranes and tried to infect them with normal virus. An interfering agent produced in response to the inactive virus seemed to be protecting both incubated membranes and fresh membranes placed in the fluids from incubated membranes. "To distinguish it from the heated influenza virus," the authors wrote, "we have called the newly released interfering agent, 'interferon.'" ¹

Interferon was thought to apply strictly to viruses, but subsequent research showed that interferon could inhibit intracellular bacteria and tumorigenesis. Because interferon is secreted in minute amounts, it took nearly 20 years to isolate and purify the protein. In 1977, a group of researchers purified type I interferon by alternating a crude mixture between normal- and reverse-phase chromatography 80,000 times. Interferon now has several applications beyond virus inhibition; while its initial promise of cancer prevention never panned out, two pegylated interferons are commercially available for treating Hepatitis C, and recombinant IFN-β is used for treating relapsing forms of multiple sclerosis.

The discovery of a family of interferon transcription factors in 1988, ² launched a long chain of research, some of which dealt with innate and adaptive immune responses, as well as with type I interferon gene activation. More recently, interferon has been shown to be activated by double- and single-stranded RNA in a variety of cell types. And just last month, researchers discovered a new component to the interferon activation pathway, the IKK-ε kinase. ³