History of Interferon

In 1957, Isaacs and Lindenmann identified interferon as a secreted factor produced by chicken egg chorioallantoic membrane fragments infected with heat-inactivated influenza virus. When used to treat membrane fragments in culture not previously exposed to virus, the secreted factor, now known as interferon, was able to transfer a virus-resistant state and thus to interfere with subsequent influenza virus replication. This discovery led to the expectation that viral diseases could be treated.

Interest beyond the field of virology occured during the early 1960s when workers began to define the substance’s growth inhibitory and immune activation properties. It was clear that interferon could modulate a number of cellular functions including cell growth and differentiation and the immune response, in addition to affecting virus multiplication. Nonetheless, the potential of interferon as an antiviral agent has been central to the tremendous progress that has been made in elucidating the interferon system.

Because this species-specific molecule was difficult to produce, the field languished until production methods were devised. The most significant of these techniques was developed in Finland, and during the 1960s and early 1970s, reports of antiviral and antitumor activity in laboratory animals and humans stirred up the field.

Enthusiasm intensified when two groups successfully cloned IFN-a and brought the purified protein to the clinic in 1981. Within 3 years, between 1979 and 1982, several groups announced the molecular cloning of cDNAs coding for IFN-a, -b and –g. For the first time, IFNs could be defined on a molecular basis rather than as biological activities.