Chapter 6, Note 31. Youth And Viruses

Another interesting aspect of the changes induced in viruses by lipoids with an alcoholic polar group, especially sterols, is the relationship to age of the host. The great amount of insaponifiable fraction present in youth— which appears to be capable, in itself, of increasing virus virulence—has been discussed previously.

In an experiment, smallpox vaccine was inoculated in groups of very young, adult and old rabbits. The young animals reacted much more intensively than did the adults, with confluent pustulae; in the old animals, only a few small pustulae appeared. After several passages in animals of the same age, we tested the virus on mouse skin and found the virulence increased by each passage in young rabbits. On the other hand, virulence was decreased by passage in old animals, becoming negative with the fourth passage. After the third passage, virus obtained from young rabbits induced a strong response in mice, while no pustulae were obtained with virus from old animals. The latter was still able to induce some response in young mice, but only few small pustulae. The virus obtained from the third passage in young rabbits induced a frank response even in old mice. This indicates that opposite changes in virus virulence are induced simply by passage through young and old animals.

This experiment appears especially interesting in connection with childhood colds. It is known that children catch colds frequently and that this susceptibility disappears as they approach puberty. From a pathogenic point of view, it is an interesting fact, however, that older siblings, parents, and even grandparents are still infected if the cold comes from a child in the family. The virus itself seems to be changed by passage through the child so that it becomes virulent not only for teenagers and parents but for older people, all of whom previously may have been free of colds for years.

Chapter 6, Note 32. Changes In The Viruses Induced By Lipids

The effect of lipids upon viruses seems not to consist exclusively in an alteration of the host's response but also includes a change in the viruses' virulence. We have noted previously the big difference in the response of the skin of an animal when, prior to inoculation with smallpox virus, a lipoid with a positive or negative polar group was injected subcutaneously. The lipoid with a positive polar group induces an exaggerated response; the lipoid with a negative polar group, a reduced one.

We used viruses obtained from both types of lesions for inoculations in new animals. Viruses from lesions in which the response had been exaggerated produced again an exaggerated response, while those obtained from a small pustule induced a reduced response. The effect, in one or the other direction, was enhanced by successive passages on skin pretreated by subcutaneous injections. The changes in virulence also were confirmed in mice tests.

The importance of this experiment lies in the fact that, by treatment of the host with members of one or the other group of lipoids, we can obtain a desired increase or decrease in virus virulence. In several other experiments, we found the method applicable to other viruses, generally making the virus more or less virulent even for intracerebral inoculation. Interesting changes are produced by the polyunsaturated fatty acids and the alcohols obtained from these acids by changing the carboxyl into a primary alcohol through treatment with lithium aluminum hydride. Especially effective influences are obtained using acid lipidic fractions of refractive species in order to reduce the virulence, or insaponifiable fractions of especially sensitive species or of chicken embryos to enhance virulence. Treatment of the host with lipoacid preparations, repeated for several passages of the virus, has reduced virulence to the point where the virus no longer is pathogenic. This treatment seems to provide a method for reducing virulence and obtaining nonpathogenic live virus vaccines.