Interferon Revisited
The cost of the interferon used in the Common Cold Unit experiment—administered as a nasal spray—was nearly $3,000 per subject tested. Promising though the test results were for progress against colds, Merigan and others experimenting with interferon turned their attention to the substance’s value in combating chronic and life-threatening diseases associated with the immune system such as chronic hepatitis, rabies and cancer.
Cold sufferers, however, need not give up on interferon, for a great deal is being done to get around its scarcity and lower its cost. Three strategies are in the experimental stage. It may be possible to find artificial substances that mimic the effects of interferon. When scientists learn more about the nature of a cell’s interferon receptors and the internal mechanisms that take direction from them, they may be able to create a compound that, like interferon, will switch on a healthy cell’s receptors and make it produce antiviral proteins. Or the antiviral proteins themselves may be synthesized or imitated.
More productive has been a second approach: the creation of agents known as interferon inducers. They are substances that stimulate the body to make extra amounts of its own interferon—but in the absence of infection. Several such inducers have been found as a result of a deeper understanding of the natural actions of the immune system.
The cell’s natural production of interferon, it turns out, is stimulated by the internal components of a virus, the nucleic-acid compounds that make up the virus’s heredity- controlling ribonucleic and deoxyribonucleic acids—RNA and DNA. In the late 1960s scientists at the Merck Institute for Therapeutic Research in West Point, Pennsylvania, synthesized an RNA-like molecule that proved to be a very potent inducer of interferon production in the test tube, and in animals and humans as well. However, this synthetic, which they named poly 1:C, turned out to have some dangerous side effects. So, unfortunately, did several other synthetics with similar powers.
Another promising strategy for making the body produce interferon also involves inducers, but in compounds derived from natural rather than synthetic sources. These so-called biological inducers act like viruses in stimulating interferon production but lack viruses’ virulence and contagion. One is endotoxin, a substance in bacterial cell walls that has been found to stimulate interferon production in many types of animal cells. Endotoxin also is poisonous, but some less harmful bacterial product artificially seeded in the respiratory tract of a human cold sufferer could set off a release of booster doses of interferon and antiviral proteins. Similar promise as a biological inducer is shown by the mycoplasmas, cells that resemble—but are smaller than—bacteria.
But the likeliest route to cheap and plentiful interferon seems to lie on the frontiers of genetic engineering in the controversial field known as recombinant DNA technology, or gene splicing. It offers a way to make pure human interferon in vats, milking the priceless elixir from specially bred bacteria, This goal was achieved experimentally in 1979, when a group of scientists led by Dr. Charles Weissmann, Professor of Molecular Biology at the University of Zurich, succeeded in synthesizing human interferon outside the body, using something other than human cells.
The scientists isolated the group of nucleic acids—the gene—in human DNA that is responsible for producing interferon in the human body. In a delicate process of biological cut-and-paste, they then spliced this portion of human DNA into the DNA molecule of Escherichia co/i, a common species of bacteria found in the intestines. The subtly modified Escherichia co/i grows readily in culture mediums, its recombined DNA molecule producing a protein essentially like human interferon. Though differing somewhat in molecular make-up from interferon, the laboratory product possesses many of the genetic original’s antiviral characteristics.
Even in its imperfect state, gene-spliced interferon seems to have a number of major advantages over its current natural and induced counterparts. Once in production, it will be a good deal less expensive than interferon extracted from human blood (Escherichia co/i is cheap labor). It is also safer than induced interferon, because no foreign catalyst comes into play. And it can be manufactured on what amounts to an industrial assembly line, in large quantities.
