Monday, Nov. 15, 1937

Macro-Molecules

Five years ago Dr. Wendell Meredith Stanley, an organic chemist trained at the University of Illinois and in Germany, went to work in the new laboratories of the Rockefeller Institute at Princeton. His objective was to find out what viruses are. Last week at a biophysics meeting in Philadelphia (sponsored by the American Institute of Physics and the University of them as Pennsylvania) he "mysterious was still purveyors of referring disease'' to but he was able to tell much more about them than he or any man knew five years ago, to describe the results which he and his co-workers have obtained in recent months.

Late in the 19th Century a Russian named Iwanowski demonstrated the existence of an infectious something smaller than bacteria by passing a solution from diseased tobacco plants through a Chamberland filter. In time it was found that many animal and human diseases were also due to such viruses: rabies, distemper, foot-and-mouth disease, encephalitis, poliomyelitis, measles, yellow fever, certain tumors, common colds. At Princeton Dr. Stanley grew acres of tobacco plants, infected them with the disease known as tobacco mosaic, ground up their wizened leaves, extracted their juices. This liquid was highly infectious to normal plants. But the deadly principle could not be cultured like a bacterium. Dr. Stanley found that it could be digested -- that is, destroyed -- by certain enzymes such as pepsin. This was important. Pepsin digests only proteins. Finally, using an ammonium compound which nudges proteins out of solution, Dr. Stanley isolated the virus as white crystals. When diluted 100,000,000 times, the crystals were still able to infect plants.

In Sweden, Nobel Laureate The Svedberg had designed an ultracentrifuge -- a machine which separates heavy molecules from light ones, inferentially measuring their molecular weights, by whirling them at enormous speeds. In this ultracentrifuge the molecular weight of the Stanley crystals was found to be about 17,000,000 units (17,000,000 times as heavy as a hydrogen atom).

The virus, found to contain carbon, hydrogen, nitrogen and oxygen like thousands of organic compounds, could now be contemplated as a huge protein molecule --a "macro-molecule." Was it alive or not alive? No known living thing is crystalline in form. It would be fantastic to imagine a crystalline pig. Yet the virus showed the ability to reproduce itself in great quantities when stimulated by contact with a plant. Thus the Princeton chemist had discovered an apparent bridge between living and nonliving matter. This was a discovery of Nobel Prize calibre.

But the latest discoveries have gone even further. Other plant viruses resisted the chemical method of separation. Dr. Ralph Wyckoff, however, designed an air-driven centrifuge, which now serves not only to measure molecular weights but to perform the first separation of viruses.

The next step was to try animal viruses. If these viruses could also be revealed as protein molecules, the eventual possibility of treating virus diseases by chemicals having a selective action on the molecules would be greatly enlarged. Dr. Joseph Beard isolated a virus from, papillomas (warts) in rabbits which appeared to be a giant molecule weighing 20,000,000 units. Dr. Carl TenBroeck centrifuged extracts of horse tissue diseased by encephalitis (sleeping sickness), obtained macro-molecules weighing 25,000,000 units. Finally, it was learned that virus proteins may change so that they cause different disease symptoms from those expected. This is something like the appearance of mutations--abrupt hereditary alterations--in animals and plants. It is another link between viruses and living organisms.

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