Williams Reveals Insect Hormone Controls Growth

A hormone which controls growth has been discovered by Carroll M. Williams, professor of Biology. The discovery was par of five year series of experiments which has done much toward the understanding of cancer.

Williams discussed his work last night before the Joint Session of the Federation of American Societies for Experimental Biology in Cleveland, in an address analyzing the normal growth mechanism.

Williams and his associates discovered a "growth and differentiation hormone, the role of the cytochrome system, and the relation between the two."

An understanding of the part that this hormone and the cytochrome system play in the normal growth mechanism is important Williams said, since, "Aberration in the normal growth mechanism must necessarily underlie . . . cancer.

In the address, one of three invitation lectures, Williams said he used insects rather than other animals because he "could observe in their metamorphosis events which in the other animals are usually restricted to early and frequently inaccessible stages of embryonic development."

In addition to greater accessibility, conclusions reached about the basic growth mechanisms of insects give information that applies to other forms of life, including humans, because all organisms are thought to share the same processes in growth and differentiation.

Williams discovered that growth in insects is controlled by a "growth and differentiation hormone," and that growth at any state is impossible without this compound.

The hormone is secreted by a pair of prothoracic glands in the body of the insect. In the vertebrate, this action seems, to be paralleled by the growth hormone secreted by the pituitary land.

The prothoracic glands secrete the "growth and differentiation hormone" only when stimulated by the "brain hormone" which is secreted by 26 nerve cells in the brain. This discovery led to the first step in the understanding of the growth pattern: growth in ultimately controlled in the brain.

Male Sex Cells Develop

Having discovered the prothoracic or "growth and differentiation hormone," Williams and Edmond Schmidt next devised a test for it. Then found that the presence of the hormone in a tissue culture would cause the male sex cells to develop into sperm cells.

When primitive sex cells were placed in tubes containing the blood of a growing insect, the sex cells immediately elongated and transformed into spermatoza. Blood at this stage contains the hormone.

On the other hand, when sex cells were placed in the blood of the dormant pupa--where the hormone is absent, and where the animal is not growth--the sex cells underwent no change.

This is the first test for the presence of the hormone, and it is the first instance of the production of spermatoza in tissue culture. The test also showed that growth at all stages in the life history required the "growth and differentiation hormone."

Directing the Formation

After discussing what the hormone did, how to test for it, and its chemical nature, Williams reported on the manner in which the hormone acted; it directs the formation of an enzyme known as cytochrome.

All air-breathing animals, including humans, have cytochrome systems (a gourd of three iron-containing enzymes related to hemoglobin) in their body cells. These systems provide the basic means by which all animals utilize oxygen in the tissue.

In insects, Williams, and Howard Schneiderman found that the cytochrome enzymes are not synthesized unless the prothoracic hormone is present and that growth and differentiation is absolutely dependent on the function of the cytochrome system. In the absence of the hormone there is no cytochrome, and in the absence of the cytochrome, there is no growth.

Since this enzyme system occurs in all animals, and since in insects in controls growth, it seems likely that it also plays a crucial role in the growth of all animals.

Blocking the System

In the last section of his address, Williams said that there were three proofs of this theory of cytochrome controlled growth. The basic idea in all was to use various agents to block the cytochrome system selectively, that is, to affect the cytochrome system without harming the other parts of the animal.

It was found that high pressures of carbon monoxide will block the action of cytochrome, by combining with it and forming a combination compound which does not have the power to handle oxygen.

The blocking by CO is reversed by light. By pinpointing light on a particular areas, growth was immediately resumed in that area, while the unilluminated parts continued to lie dormant.

Another way to block the cytochrome is to use purified diphtheria toxin. Diphtheria toxin is a protein excreted by diphtheria bacilli, and is a part of the bacterium's cytochrome b, which in turn is an enzyme in that bacterium's cytochrome system.

The diphtheria toxin a cytochrome enzyme, gets into the human body and is mistakenly incorporated into its cytochrome system--the cytochromes of all animals are related but not identical.

The human cytochrome can't function properly, and since no oxygen can then be utilized, there is no growth. When this happens, the human dies.

Proof Positive?

Proof of this theory was again found in insects. At the non-growing stage when the cytochrome system is absent (the pupal stage), the insect was found to be wholly resistant to diphtheria toxin. But at other stages, when cytochrome is present, the toxin caused an immediate cessation of growth and ultimately caused death.

Imidazole and certain other organic chemicals attack the cytochrome in a third way. These chemicals combine with all the available sources of iron and thus prevent the formation of cytochrome. This block also causes the immediate cessation of growth.

These studies have therefore demonstrated several ways in which the growth mechanism can be disassociated from the maintenance mechanism by he action of chemicals whose biochemical target within the living cell is the cytochrome system.

Significance to Cancer

Such chemicals appear to be of great interest since they may lead to suitable non-toxic substance to block malignant growth.

Williams is interested in normal growth, because "the understanding of normal growth mechanisms is necessary for the rational understanding of that aberration of the normal process which produces malignant diseases such as tumors and cancers.

He adds that "When we completely understand the normal growth mechanisms and its hormonal control, then we will have the basic facts for understanding the abnormal, since the problem of hormones is right at the center of the cancer problem.CARROLL M. WILLIAMS, professor of Biology; "Malignant growth is a much simpler proposition than normal growth; the transition involves the loss of the normal controlling mechanism."