living process or a specific cell. Just as a real microscope permits examination of the structural details of cells, isotopes permit examination of the chemical activities of molecules, atoms, and ions as they react within cells. (Neither optical nor electron microscopes are powerful enough for us to see anything as small as a molecule clearly.)

DNA SYNTHESIS: THE AUTOBIOGRAPHY OF CELLS

Here, surely, is the prime substance of life itself.

Isaac Asimov

The many characteristic features of each living species, its complex architecture, its particular behavior patterns, the ingenious modifications of structure and function that enable it to compete and survive—all these must pass, figuratively speaking, through the eye of an ultramicroscopic needle before they are brought together as a new, individual organism. The thread that passes through the eye of this needle is a strand of the filamentous molecule, deoxyribonucleic acid (DNA). Let us now outline the research that led to these conclusions.

DNA in Somatic and Germinal Cells

One of the fundamental laws of modern biology—which states that the DNA content of somatic cells is constant for any given species—was first set forth in a research report of 1948. This finding means that in any given species, such as a mouse or a man, all cells except the germinal cells contain the same amount of DNA. Germinal cells, that is, the sperm cells of the male semen and the female egg, contain exactly half the amount of DNA of the somatic cells. This must be the case, since DNA is the hereditary material, and each individual’s heredity is shaped half by his father and half by his mother. One ten-trillionth of an ounce of DNA from a father and one ten-trillionth of an ounce of DNA from the mother together contain all the specifications to produce a new human being.

A large amount of DNA must be manufactured by an individual organism as it develops from a fertilized egg (one single cell) to an adult containing several million cells. For instance, a mouse cell contains about 7 picograms of DNA (one picogram is one millionth of a microgram, or one millionth of one millionth of a gram). A whole mouse contains in its body approximately 25 milligrams (25 thousandths of a gram) of DNA, and all this DNA was synthesized by the cells as the mouse grew to adulthood. Since the amount of DNA per cell remains constant and since each cell divides into two cells, it is apparent that each new cell receives the amount of DNA characteristic of that species.

Once we realize that a cell that is making new DNA (as most cells do) must divide to keep the amount of DNA per cell constant, it follows that a cell that is making DNA is one that is soon destined to divide. If we can now mark newly made DNA with a radioactive isotope, we can actually mark and thus identify cells that are preparing to divide. The task can be divided into two parts: (1) to label the newly made DNA and (2) to detect the newly made, labeled DNA.

Replication of DNA

Figure 11 is a diagram showing the essential structure of the large DNA molecule. According to the Watson-Crick model,[7] the molecule consists of two strands of smaller molecules twisted around each other to form a double helix. Each strand consists of a sequence of the smaller molecules linked linearly to each other. These smaller molecules are called nucleotides, and each consists of three still smaller molecules, a sugar (deoxyribose), phosphoric acid, and a nitrogen base. Each nucleotide and its nearest neighbor are linked together (between the sugar of one and the phosphoric acid of the neighbor). This leaves the nitrogen base free to attach itself, through hydrogen bonding, to another nitrogen base in the opposite strand of the helix.

In the DNA of higher organisms, there are only four types of nitrogen bases: adenine, guanine, thymine, and cytosine. Adenine in either strand of the helix pairs only with thymine in the opposite strand, and vice versa, and guanine pairs only with cytosine, and vice versa, so that each strand is complementary in structure to the other strand (see Figure 12). The full structure resembles a long twisted ladder, with the sugar and phosphate molecules of the nucleotides forming the uprights and the linked nitrogen bases forming the rungs. Each upright strand is essentially a mirror image of the other, although the two ends of any one rung are dissimilar.

Figure 11 Diagrammatic structure of the DNA molecule as proposed by the Watson-Crick model.

When DNA is replicated, or copied, as the organism grows, the two nucleotide strands separate from each other by disjoining the rungs at the point where the bases meet, and each strand then makes a new and similarly complementary strand. The result is two double-stranded DNA molecules, each of which is identical to the parent molecule and contains the same genetic material. When the cell divides, each of the two daughter cells gets one of the new double strands; each new cell thus always has the same amount of DNA and the same genetic material as the parent cell.

(All that has been said so far about DNA replication depends upon an assumption that the DNA molecule is in some way untwisted to allow separation of two helical strands, but there is no compelling reason to believe that such an untwisting does indeed take place, nor do we know, if the untwisting does take place, how it is accomplished. Much that has been said in the last few paragraphs is therefore purely speculative. It is, however, based on sound observation and is a more logical explanation than others that have been advanced.)

Figure 12 The pairing of the nucleotide bases that make up DNA.

Figure 13 The DNA molecule and how it replicates. (a) The constituent submolecules. (b) Assembly of subunits in complete DNA molecule. (c) “Unzipping” of the double nucleotide strand. (d) and (e) The forming of a new strand by each individual strand. (f) DNA molecule in twisted double-strand configuration.

Adapted from Viruses and the Nature of Life, Wendell M. Stanley and Evans C. Valens, E. P. Dutton & Co., Inc., 1961, with permission.

Labeling DNA with a Radioactive Isotope

Of the four bases in DNA, three are also found in the other nucleic acid, RNA; but the fourth, thymine, is found only in DNA. Therefore, if thymine could be labeled and introduced into a number of cells, including a cell in which DNA is being formed, we would specifically label the newly synthesized DNA, since