The Code of Codes: Scientific and Social Issues in the Human Genome Project
Mapping the Code: The Human Genome Project and the Choices of Modern Science
Genethics: The Ethics of Engineering Life
Mapping and Sequencing the Human Genome
Genome: The Story of the Most Astonishing Scientific Adventure of Our TimeThe Attempt to Map All the Genes in the Human Body
Exons, Introns, and Talking Genes: The Science Behind the Human Genome Project
DNA Technology in Forensic Science
FETISH…An inanimate object worshipped by savages on account of its supposed inherent magical powers, or as being animated by a spirit. (OED)
Scientists are public figures, and like other public figures with a sense of their own importance, they self-consciously compare themselves and their work to past monuments of culture and history. Modern biology, especially molecular biology, has undergone two such episodes of preening before the glass of history. The first, characteristic of a newly developing field that promises to solve important problems that have long resisted the methods of an older tradition, has used the metaphor of revolution. Tocqueville observed that when the bourgeois monarchy was overthrown on February 24, 1848, the Deputies compared themselves consciously to the “Girondins” and the “Montagnards” of the National Convention of 1793.
The men of the first Revolution were living in every mind, their deeds and words present to every memory. All that I saw that day bore the visible impress of those recollections; it seemed to me throughout as though they were engaged in acting the French Revolution rather than continuing it.
The romance of being a revolutionary had infected scientists long before Thomas Kuhn made Scientific Revolution the shibboleth of progressive knowledge. Many of the founders of molecular biology began as physicists, steeped in the lore of the quantum mechanical revolution of the 1920s. The Rousseau of molecular biology was Erwin Schrödinger, the inventor of the quantum wave equation, whose What is Life? was the ideological manifesto of the new biology. Molecular biology’s Robespierre was Max Delbruck, a student of Schrödinger, who created a political apparatus called the Phage Group, which carried out the experimental program. A history of the Phage Group written by its early participants and rich in the consciousness of a revolutionary tradition was produced twenty-five years ago.1
The molecular biological revolution has not had its Thermidor, but on the contrary it has ascended to the state of an unchallenged orthodoxy. The self-image of its practitioners and the source of their metaphors have changed accordingly, to reflect their perception of transcendent truth and unassailable power. Molecular biology is now a religion, and molecular biologists are its prophets. Scientists now speak of the “Central Dogma” of molecular biology, and Walter Gilbert’s contribution to the collection The Code of Codes is entitled “A Vision of the Grail.” In their preface, Daniel Kevles and Leroy Hood take the metaphor with straight faces and no quotation marks:
The search for the biological grail has been going on since the turn of the century, but it has now entered its culminating phase with the recent creation of the human genome project, the ultimate goal of which is the acquisition of all the details of our genome…. It will transform our capacities to predict what we may become….
Unquestionably, the connotations of power and fear associated with the holy grail accompany the genome project, its biological counterpart…. Undoubtedly, it will affect the way much of biology is pursued in the twenty-first century. Whatever the shape of that effect, the quest for the biological grail will, sooner or later, achieve its end, and we believe that it is not too early to begin thinking about how to control the power so as to diminish—better yet, abolish—the legitimate social and scientific fears.
It is a sure sign of their alienation from revealed religion that a scientific community with a high concentration of Eastern European Jews and atheists has chosen for its central metaphor the most mystery-laden object of medieval Christianity.
As there were legends of the Saint Graal of Perceval, Gawain, and Galahad, so there is a legend of the Grail of Gilbert. It seems that each cell of my body (and yours) contains in its nucleus two copies of a very long molecule called deoxyribonucleic acid (DNA). One of these copies came to me from my father and one from my mother, brought together in the union of sperm and egg. This very long molecule is differentiated along its length into segments of separate function called genes, and the set of all these genes is called, collectively, my genome.
What I am, the differences between me and other human beings, and the similarities among human beings that distinguish them from, say, chimpanzees, are determined by the exact chemical composition of the DNA making up my genes. In the words of a popular bard of the legend, genes “have created us body and mind.”2 So when we know exactly what the genes look like we will know what it is to be human, and we will also know why some of us read The New York Review while others cannot get beyond The New York Post. “Genetic variations in the genome, various combinations of different possible genes…create the infinite variety that we see among individual members of a species,” according to Joel Davis in Mapping the Code. Success or failure, health or disease, madness or sanity, our ability to take it or leave it alone—all are determined, or at the very least are strongly influenced, by our genes.
The substance of which the genes are made must have two properties. First, if the millions of cells of my body all contain copies of molecules that were originally present only once in the sperm and once in the egg with which my life began, and if, in turn, I have been able to pass copies to the millions of sperm cells that I have produced, then the DNA molecule must have the power of self-reproduction. Second, if the DNA of the genes is the efficient cause of my properties as a living being, of which I am the result, then DNA must have the power of self-action. That is, it must be an active molecule that imposes specific form on a previously undifferentiated fertilized egg, according to a scheme that is dictated by the internal structure of DNA itself.
Because this self-producing, self-acting molecule is the ground of our being, “precious DNA” must be guarded by a “magic shield” against the “hurricane of forces” that threaten it from the outside, according to Christopher Wills, by which he means the bombardment by the other chemically active molecules of the cell that may destroy the DNA. It is not idly that DNA is called the Grail. Like that mystic bowl, DNA is said to be regularly self-renewing, providing its possessors with sustenance “sans serjant et sans seneschal,” and shielded by its own Knights Templar from hostile forces.
How is it that a mere molecule can have both the power of self-reproduction and self-action, being the cause of itself and the cause of all the other things? DNA is composed of basic units, the nucleotides, of which there are four kinds, adenine, cystosine, guanine, and thymine (A, C, G, and T), and these are strung one after another in a long linear sequence which makes a DNA molecule. So one bit of DNA might have the sequence of units…CAAATTGC…and another the sequence…TATCGCTA,…and so on. A typical gene might consist of 10,000 basic units, and since there are four different possibilities for each position in the string, the number of different possible kinds of genes is a great deal larger than what is usually called “astronomically large.” (It would be represented as a 1 followed by 6,020 zeros.) The DNA string is like a code with four different letters whose arrangements in messages thousands of letters long are of infinite variety. Only a small fraction of the possible messages can specify the form and content of a functioning organism, but that is still an astronomically large number.
The DNA messages specify the organism by specifying the makeup of the proteins of which organisms are made. A particular DNA sequence makes a particular protein according to a set of decoding rules and manufacturing processes that are well understood. Part of the DNA code determines exactly which protein will be made. A protein is a long string of basic units called amino acids, of which there are twenty different kinds. The DNA code is read in groups of three consecutive nucleotides, and to each of the triplets AAA, AAC, GCT, TAT, etc., there corresponds one of the amino acids. Since there are sixty-four possible triplets and only twenty amino acids, more than one triplet matches the same amino acid (the code is “redundant”). Another part of the DNA determines when in development and where in the organism the manufacture of a given protein will be “turned on” or “turned off.” By turning genes on and off in the different parts of the developing organism at different times, the DNA “creates” the living being, “body and mind.”
But how does the DNA recreate itself? By its own dual and self-complementary structure (as the blood of Christ is said to be renewed in the Grail by the dove of the Holy Ghost). The string of nucleic acids in DNA that carries the message of protein production is accompanied by another string helically entwined with it and bound to it in a chemical embrace. This DNA Doppelgänger is matched nucleotide by nucleotide with the message strand in a complementary fashion. Each A in the message is matched by a T on the complementary strand, each C by a G, each A by a C, and each T by an A. (See the upper part of the illustration on the opposite page.)
Reproduction of DNA is, ironically, an uncoupling of the mated strands, followed by a building up of a new complementary strand on each of the parental strings. (See the lower part of the figure.) So the self-reproduction of DNA is explained by its dual, complementary structure, and its creative power by its linear differentiation.
The problem with this story is that although it is correct in its detailed molecular description, it is wrong in what it claims to explain. First, DNA is not self-reproducing, second, it makes nothing, and third, organisms are not determined by it.
DNA is a dead molecule, among the most nonreactive, chemically inert molecules in the living world. That is why it can be recovered in good enough shape to determine its sequence from mummies, from mastodons frozen tens of thousands of years ago, and even, under the right circumstances, from twenty-million-year-old fossil plants. The forensic use of DNA for linking alleged criminals with victims depends upon recovering undegraded molecules from scrapings of long-dried blood and skin. DNA has no power to reproduce itself. Rather it is produced out of elementary materials by a complex cellular machinery of proteins. While it is often said that DNA produces proteins, in fact proteins (enzymes) produce DNA. The newly manufactured DNA is certainly a copy of the old, and the dual structure of the DNA molecule provides a complementary template on which the copying process works. The process of copying a photograph includes the production of a complementary negative which is then printed, but we do not describe the Eastman Kodak factory as a place of self-reproduction.
Phage and the Origins of Molecular Biology, edited by J. Cairn, G.S. Stent, and J.D. Watson (Cold Spring Harbor Laboratory of Quantitative Biology, 1966).↩
Richard Dawkins in The Selfish Gene (Oxford University Press, 1976), p. 21.↩