Giant Molecules: the Machinery of Inheritance (Jun, 1938)
Giant Molecules: the Machinery of Inheritance
How Genetics, Youthful Science of Inheritance, Has produced Billions of Dollars of Wealth . . . Big Things that Boil Down to the Minutest Controls.
By BARCLAY MOON NEWMAN
THE remarkable discoveries in the youthful science of inheritance, genetics, have been applied to animal and plant breeding throughout civilization—and with almost incredible success. As regards the United States alone, during the past 30 years, even a conservative estimate of the cash value of the practical application of genetic findings would have to run into billions of dollars. Far greater yields of grains, fruits, vegetables, and cotton; far higher quality both in domestic plants and domestic animals of every description and their products, including milk, meat, eggs, and wool; increased and sometimes perfect resistance to disease; entirely new commercial varieties; and the lessening of the chances of famine: all these are in this story of science.
Thus, seemingly pure research into the machinery of inheritance has made possible stupendous progress in agriculture. This machinery works by controlling the development of the billions of cells, the tiny bits of living material or protoplasm which make up our bodies. Not only do certain cells develop into eye tissues or brain tissue under the influence of heredity’s mechanism, but also each special group of cells submits to even more precise regulation: frequently so precise that you may inherit a startlingly exact copy of your father’s nose, or mouth, or of your mother’s brain, perhaps with its peculiar sort of “nervousness.”
WE did not derive all our practically countless cells directly from our parents. Each parent provides only one cell. These two unite to form the first stage of our existence, the one-celled embryo. This tiny cell, multiplying by continued cell division, finally produces the fully mature body.
We are made up of billions of cells, and so, of course, as we recall, they are microscopic. Yet, small as they are, only a tiny fraction of each protoplasmic bit is involved in inheritance. If we could focus a fine microscope upon the single cell provided by one parent, and if this microscope were very powerful, we would discover, down near the limit of visibility, objects shaped like worms and called chromosomes. These chromosomes are made up of much smaller objects, the genes. At this point even the keenest microscope fails us—and scientists are not quite certain whether they can observe individual genes or, at best, clusters of genes. Nevertheless, all the evidence goes to prove that these minutest genes are the controllers of inheritance. And they have turned out to be giant molecules, each with some specific role to play in the development of color of hair, hardness of teeth, or some other of the thousands of characteristics which we inherit.
The science of genetics took its rise as late as the beginning of this century. That is, the first real approach to the understanding of the mechanism of heredity followed the discovery that practically the sole significant material which parents transmit to their offspring is the substance chromatin, the material of which all the wormlike chromosomes are made. It was found that chromatin makes up the chief portion of the sperm cell, the sex cell from the male. And in the case of the egg cell, the sex cell from the female, there appears to be little else but chromatin and reserve food. Hence, was it not logical to assume that chromatin contained the whole machinery for regulation of the offspring’s development of its parents’ characteristics?
The opening up of an entirely novel field of research placed the basic meaning of chromatin beyond any question. The highest honors for leadership in this field belong to Dr. T. H. Morgan, of the California Institution of Technology, who received the 1933 Nobel award in Medicine for his outstanding labors. The lowly vinegar fly, Drosophila melanogaster (“black-stomached fruit-lover”), has been in a major way the organism experimented with—though biologists have not neglected to check their results by ferreting out the secrets of wasps, barley, corn, wheat, primroses, jimpson weed, and many other living things. In this new branch of science, not only the chromosomes have been exhaustively investigated, but even the ultra-microscopic units out of which these wormlike rods are constructed. Modern scientific probing has penetrated down from the microscopically visible rods of chromatin to their constituent particles, the genes, whose measurements are in terms of a few hundred-thousandths of an inch.
More than 25,000,000 vinegar gnats have been examined. Excellent reasons lie behind this magnitudinous study. A human generation appears about every 25 years; the fruit-loving gnat reproduces in 12 days. Moreover, these gnats are readily raised by the tens of thousands in milk bottles in the laboratory. They have only four pairs of chromosomes, and it is not difficult to distinguish between the individual rods. Best of all, the vinegar fly has many heritable characteristics which are easily recognized: form of body, color, shape of wings; color of eyes; number and types of bristles; susceptibility to disease; and length of life. Finally, Morgan was awarded a Nobel prize in Medicine—because the laws of inheritance which apply to the fruit fly apply also to man. Like the fruit fly’s body shape, human feeblemindedness, short-fingeredness, and color blindness show up, generation after generation, in response to the manner in which heredity’s machinery operates throughout the animal and plant kingdoms.
MORGAN went far beyond merely proving that a given chromosome bears the determinants (genes) for a given characteristic, such as eye-color. By delicate and difficult technique, he demonstrated that a given determinant is located in a given region of a chromosome. Astoundingly, he was ultimately able to construct accurate maps of the chromosomal positions of the various physical bases of definite features of the species; that is, maps of gene locations. Tens of thousands of breedings have attested the accuracy of his chromosome mapping. Genes once had existence in theory alone. Today their existence is an established fact.
Now we are certain that behind susceptibility or resistance to disease in wheat or potato; production of milk with a high content of butter fat; liability to hog cholera; record egg-laying—-behind these characteristics and many another valuable financially, lies the gene as the fundamental unit, out of which the machinery of inheritance is constructed.
Once bio-scientists became satisfied that the gene is a real, physical unit, they sought its structure, its properties, and its arrangement in the chromosomes. Their findings have been amazing, not merely to themselves, but to physicists and chemists as well.
Compounded of a million atoms yoked in a bafflingly intricate design, the gene is gigantic among molecules. Though of course as a molecule it is (probably) invisible even beneath the most powerful lenses, its dimensions are for a molecule actually tremendous: somewhere near a ten-thousandth of an inch in length, and some fraction of this measure in diameter.
The chemical classification of this super-molecule seems to be with the proteins, which are exceedingly complex compounds of carbon, hydrogen, oxygen, nitrogen, often sulfur, phosphorus, and other elements, and which are assumed to be the truly essential molecules of life. Certainly, no live material without protein is known—or supposed to exist. Examples of proteins are hemoglobin, the pigment which gives red blood corpuscles their color; albumin, the main constituent of egg-white; and the milk protein, casein. The ultra-microscopic virus of mosaic disease of tobacco is another protein, recently obtained in bulk as glassy, needlelike crystals, each made up of countless molecules. These too are super-molecules—also with many an uncanny property of the gene.
The genes are strung end to end to form wisps, called chromonemas, and these fine threads are bound together to produce a chromosome. The machinery of inheritance therefore is no more and no less than a vast and stupendously intricate system of chemical systems—the basis of whose chemistry is the particle, the gene, a super-compound.
IN cell division, chromosomes are seen to reproduce themselves. The gene, the foundation of the chromosome’s architecture, must do likewise. Or, rather, genes, by their individual multiplication, construct new chromosomes. Here is an almost unbelievable, a wholly novel, ability of a molecule: to create its like out of the lesser molecules of a suitable surrounding medium. Only in the gigantic virus protein have we discovered such a remarkable property—almost incredible to the physical scientist, who is used to far simpler aggregations of atoms.
For an approach to this problem of self-creation, or autosynthesis, we must consider the enzyme, also believed to be a formidable protein, though not so accomplished a one as the gene. Digestive ferments, such as trypsin of pancreatic juice, stimulate and regulate the breaking up of complex compounds into simpler molecules, known as amino acids, which the body can then assimilate. This disintegration can be reversed, however: an enzyme under appropriate conditions works backward—builds up amino acids into proteins (or unites them into protein-like compounds). If a super-enzyme had the power to fashion not simply great molecules out of small ones, but moreover great molecules precisely like itself, would we not have autosynthesis, as in the gene? And so it is thought that a clearer idea of the workings of enzymes may give us a better grasp of the self-production of giant molecules, like the genes, the cogs in heredity’s mechanism.
In the first 25,000,000 fruit gnats studied, about 500 heritable changes in eye-color, length of life, susceptibility to germs, showed up. Such heritable modifications of the ancestral characteristics are mutations. For example, every so often a young gnat, offspring of red-eyed ancestors, is born with the mutation, white eyes. Man has made valuable use of natural mutants like the seedless orange and rust-resistant wheat.
How do the genes, linked by the thousands to make chromonemas, cooperate to change a microscopic, one-celled embryo into a billion-celled man —and even a man very closely resembling his parents? We must assume that the genes have the ability not only to reproduce themselves, but, still more like super-enzymes, to start, regulate, modify, and terminate the biochemical reactions which, all together, mean life— and growth of many diverse tissues and organs and organ systems into a body astonishingly similar to that of the preceding generation. Incomparable abilities!
We have to speculate that the gene, as a super-enzyme, causes a bafflingly complex chain of chemical processes in the protoplasm in which the chromosomes swim. And this chain must include the production of innumerable stimulators and regulators; that is, enzymes, every one with its kingdom of biochemistry to supervise and keep harmonious.
Far from halting his labors in despair at the vastness of such chemical systems, the embryologist has persisted in his attack upon these deepest mysteries of vital existence. Thus, recently, he has been able to exhibit the presence, in the developing animal, of substances called organizers, which promise to turn out to be super-enzymes, given substance and activity through the agency of the genes.
IN 1900, Dr. Hans Spemann, now of the University of Freiburg, Germany, began a laborious series of researches upon the embryology of amphibians, including newts and salamanders. He cut newt eggs and young embryos into pieces, and observed the development of these pieces with a view toward finding the stages at which special determiners of particular kinds of tissues appear—or might appear. He transplanted bits from an early embryo to certain definite sections of more fully developed embryos, to watch the effects of possible early-appearing or late-appearing super-enzymes, or organizers. In the course of these experiments, from one embryo he took tissue which would normally produce the spinal cord of the young animal, and transplanted this tissue into another embryo. A spinal cord came into being in the second animal where one would not ordinarily be formed. Hence, the transplanted cells must manufacture organizers which stimulate surrounding cells to change into a particular kind of structure: a spinal cord, in this case.
Spemann’s work established the fact that an organizer determines whether a group of cells becomes spinal cord or becomes skin, or some other sort of tissue; and that such activators bring about the growth of organs each in its own proper place and each with its own proper functions. His achievement won him a Nobel award in 1935.
The transformation of the single-celled offspring into smoothly functioning adult, with billions of cells, must involve many a super-molecule, the delight of the biologist and the confusion of the physical scientist.