Perspectives in Biology and Medicine

STUDIES IN GROWTH ALBERT SZENT-CYÖRGYI* Cancer is a ghastly disease which causes endless human suffering. This places the biologist who happens to drift into cancer research in a peculiar position. Ifhe sees a ray ofhope ofa cure or a better understanding, it is his moral obligation to pursue his work till its final success or failure. He may feel compelled to publish prematurely, hoping to find support and open his line for others. This he is especially likely to do ifhe knows cancer, not only from statistics, but ifthis specter has knocked at his own door. You will have noticed that what I am doing is to start my talk with an apology, apologizing, also, in the name ofmy associates, A. Hegyeli and J. A. McLaughlin, for the premature nature and many shortcomings of our communication, hoping to elicit from you a lenientjudgment. I will put before you the whole story ofmy research. There is one point which I want you to note, especially. This story has many sharp turns, and if I still pursue my cancer research hopefully, I owe it to the great freedom with which the National Institutes of Health and the National Science Foundation allowed me to use my grants. My story starts with muscle, which, for many years, was my preoccupation . The thymus gland, somehow, seemed to be involved in the function of muscle, since, in one of its most common diseases, myasthenia, the thymus seems to be overbearing. My fate became sealed when a friend donated to me a herd ofmyotonic goats. Myotonia, similarly to myasthenia , is a "degenerative disease," the word "degenerative" meaning simply that we do not understand it, what it is and why it is. Myotonia is the only degenerative disease ofman which has its exact pair in animals, afflicting * Institute for Muscle Research at the Marine Biological Laboratory, Woods Hole, Massachusetts . Thislecture was given at the 2jth Anniversary Celebration ofThe Squibb Institute for Medical Research, New Brunswick, NewJersey, October loth, 1963. The underlying research was supported by the National Institutes of Health, Grant No. GM-10383, and the National Science Foundation, Grant No. G-5835. 279 goats. What made myotonia interesting to me is the fact that its symptoms are exactly the mirror image, the opposite, ofthe symptoms ofmyasthenia . So ifin myasthenia there is too much ofa hormone, produced by the thymus, there must be too little ofit in myotonia and, consequently, the myotonic symptoms should be cured by injections ofthat hormone. This should have made myotonic goats the test animal par excellence for my hypothetic hormone. It was thus that I started injecting thymus extracts into these goats. But work on goats at a marine biological laboratory is connected with major difficulties, one being that goats do not smell exactly like the sea. I had to find a different approach. According to my theories, my hypothetic hormone had to be involved in energy transfer, and substances involved in energy transfer could be expected to be colored or fluorescent. So I felt rather encouraged whenI discovered in my thymus extract an intensely yellow substance, never seen before. The substance was isolated and found to be the metal complex ofan oxidation product of ascorbic acid which could have no possible biological significance. Beaten back on the color line, I started hunting for fluorescent substances and soon discovered a substance in my extract which, ifilluminated with near-ultraviolet, showed a splendid fluorescence. It was present in traces only. The isolation ofthis substance in crystals was the only brilliant piece ofchemical work I ever produced. The crystals were sent for the analysis oftheir constitution to Merck & Company, whose report was expected with great excitement. I did not have to wait long for it. It told me that what I isolated was a substance which I extracted from my rubber tubing. This failure made me throw all theories overboard and I reasoned thus: Growth is, in a way, the integral ofall functions; ifanything goes wrong anywhere, growth goes wrong. So I asked whether thymus extracts influenced growth? But growth is a slow process. To have answers, possibly fast, I had to take a rapid growth. The most rapidly growing mammalian tissue is...