Science in Christian Perspective



The Vast Unseen and the Genetic Revolution

Gordon College
Wenham, Massachusetts 01984

Box N7776 Lyford Cay
Nassau, Bahamas

From: JASA 37 (September 1985): 132-1411

A contemporary tension exists among scientists, born out of the growing complexity of scientific explanation and the resurgence of philosophical and religious questions. It is proposed that the tension arises because of a too narrow view of truth. Even where the data seems to lend itself most readily to a deterministic view, as in molecular genetics, the system can be seen to be fraught with spectacular beauty and to be characterized by ever-increasing complexity. When seen properly as the handiwork of the Creator, as it was by renowned scientists of the early days of science, it opens to us the vast unseen of His creation.

On Seeing The Unseen

God has woven a marvelous tapestry for the eyes of his creatures to behold. But there is a sense in which we have lost a certain level of perception, a dimension of seeing, a sense of a Presence in the providential design of all that is. Michael Shallis of Oxford University notes this in a recent paper entitled "The Point of Cosmology" where he speaks of

... a change in perception occurring in the late Middle Ages. The allegorical world view was turning from a representation of man's relationship with the Creator and the cosmos to being a veil, masking reality. The real nature of things was seeming to become more material and less symbolic. Man's vision was being diverted from where the material signposts were pointing to an increasing desire to understand the real nature of the signposts.1

Yet the curious result for many who chose this focus for the search was the conclusion that there was nothing there! Nobel laureate physicist Steven Weinberg says, for example, "the more the Universe seems comprehensible, the more it also seems pointless."2

It would seem appropriate to ask what it takes to see the hand of the Creator-writing large-in everything, regardless of its degree of comprehensibility? Does it demand the eyes of faith, or is it there for anyone to see who will just allow the opportunity for reflection? C.S. Lewis argues in The Abolition of Man that our narrow approach to scientific truth threatens the very existence of mankind. He calls for a "regenerate science", with the following character:

When it explained it would not explain away. When it spoke of the parts it would remember the whole .... Its followers would not be free with the words only and merely. In a word, it would conquer nature without being at the same time conquered by her and buy knowledge at a lower cost than that of life.3

The implication of these remarks is that the scientist is faced with a choice. He may maintain a narrow, reductionist view of his science, with the risk of depersonalization, or he may broaden his view to allow for an occasional enriching glimpse of the artistic, the poetic, the religious, as he surveys the implications of his data.

The difficulty of the choice is well presented by Alan Lightman in a Science 82 article entitled "To The Dizzy Edge".

Most scientists will tell you there is a clear line between science and philosophy, between those questions that are answerable by logic and experiment and those that must forever float in the nethers of epistemology. Such is the heritage of Bacon and Galileo. Following this comfortable approach, many of our finest biologists, chemists, and physicists have nestled into numbers for the duration. And it's not surprising. In this strange and deep universe, humankind has an urgent desire to know some few things with certainty. But the philosophers will not leave us our scattered harbors. Listen to the persuasive words of Bertrand Russell, philosopher and master logician: 'The observer, when he seems to himself to be observing a stone, is really, if physics is to be believed, observing the effects of the stone upon himself.' What can we know, if not the world as it appears? And adding to our anxieties, modern science, through no fault of its own, repeatedly brings itself all the way to the dizzy edge of philosophy.

In the last few decades, science has plunged headlong after many other long-staning philosophical problems. An old debate is the question of free will versus determinism in human actions. The Heisenberg uncertainty principle in physics, stating that the trajectories of individual particles cannot be predicted precisely, has provided welcome ammunition to the free willists, while the studies of genes, DNA, and the newborn field of sociobiology surely put glee in the hearts of the determinists. And then there's the ancient controversy about whether mind is distinct from matter. I imagine the "mindbody problem" has had to take stock of recent developments in neurobiology, especially the results indicating that specific mental activities like language and emotions may be localized to specific halves of the brain. Science has not really answered any of these questions but continues to sharpen the focus.

And, no matter how far it progresses, science generates more questions than it answers. Questions that disturb. Perhaps there is in science an inevitable incompleteness, analogous to that in mathematics proved by Kurt Godel. Before Godel's proof, it was widely believed that each branch of mathematics, given sufficient axioms or rules of the game, was self-contained. In 1931 Godel rigorously demonstrated that arithmetic contains true theorems that cannot be derived from the rules of arithmetic. In a similar manner I believe there may be meaningful questions about physical reality, the territory of science, whose study is intrinsically beyond the reach of any equations or experiments.

In all these mysteries we see ourselves. Would we be so intrigued if we did not ponder why as well as how, if we did not have our Dali's and Sartre's as well as our Madame Curie's? This is surely a miracle, like the fragile balance of nuclear forces and the just-right release of the cosmic pendulum.4

And so, we plead with those who have "nestled into numbers for the duration" to look beyond the numbers to see the object, the process, the model, the phenomenon as part of a larger, more marvelous and mysterious whole. Albert Einstein, perhaps the greatest scientist who ever lived, was forever fond of contrasting his mathematics with his aesthetic view of reality. Timothy Ferris quotes him in an October Science 83 article, "I want to know how God created this world. I want to know his thoughts, the rest are details." Ferris goes on to say:

Einstein saw God as dressed in questions more than answers'. What really interests me', he told his assistant Ernst Straus, 'is whether God had any choice in the creation of the world'-and his personality was imbued with a deep sense of the mysterious. 'The most beautiful experience we can have is the mysterious,' he said. 'It is the fundamental emotion that stands at the cradle of true art and true science. Whoever does not know it is as good as dead, and his eyes are dimmed.5

We plead with those who have "nestled into numbers for the duration" to look beyond the numbers to see the object, the process, the model, the phenomenon as part of a larger, more marvelous and mysterious whole.

Similarly, K.C. Cole writes in an article entitled "The Scientific Aesthetic,"

Artists approach nature with feeling; scientists rely on logic. Art elicits emotion; science makes sense. Artists are supposed to care; scientists are supposed to think.

At least one physicist I know rejects this distinction out of hand: 'What a strange misconception has been taught to people,' he says. 'They have been taught that one cannot be disciplined enough to discover the truth unless one is indifferent to it. Actually, there is no point in looking for the truth unless what it is makes a difference.'

The history of science bears him out. Darwin, while sorting out the clues he had gathered in the Galapagos Islands that eventually led to his theory of evolution, was hardly detached. 'I am like a gambler and love a wild experiment,' he wrote. 'I am horribly afraid'. 'I trust to a sort of instinct and God knows can seldom give any reason for my remarks. All nature is perverse and will not do as I wish it. I wish I bad my old barnacles to work at, and nothing new.' The scientists who took various sides in the early days of the quantum debate were scarcely less passionate. Einstein said that if classical notions of cause and effect had to be renounced, he would rather be a cobbler or even work in a gambling casino than be a physicist. Neils Bohr called Einstein's attitude appalling, and accused him of high treason. Another major physicist, Erwin Schroedinger, said, 'If one has to stick to this damned quantum jumping, then I regret having ever been involved in this thing.' On a more positive note, Einstein spoke about the universe as a 'great, eternal riddle' that 'beckoned like a liberation.' As the late Harvard professor George Sarton wrote in the preface to his History of Science. 'There are blood and tears in geometry as well as in art.6

Cole's physicist friend is surely on the right track. What truth is makes a difference! There neither is nor should be a prohibition of the subjective, the poetic or the religious in the scientist's quest for truth. Perhaps Nobel Laureate Richard Feynman says it best in a poem quoted by K.C. Cole.

'Poets say science takes away from the beauty of the starsmere globs of gas atoms. Nothing is'mere.' I too can see the stars on a desert night, and feel them. But do I see less or more? The vastness of the heavens stretches my imagination-stuck on this carrousel, my little eye can catch one-million-year-old light .... For far more marvelous is the truth than any artists of the past imagined! Why do the poets of the present not speak of it? What men are poets who can speak of Jupiter if be were like a man, but if he is an immense spinning sphere of methane and ammonia must be silent?7

And what of religion? How have we come to the point where science and theology seem so utterly divorced from each other? One of us spoke to this question in a Yale Medical School address some years ago.

Paul Tillich once referred to this age (our culture) as'the land of broken symbols'. That break is at least partly science derived, based upon the assumption that objective scientific study would produce a complete description of all of reality and preclude any other source of truth as out-moded and irrelevant. So, the little boy would say, 'Science is material and religion is immaterial.' And so, scientists and theologians have gone their separate ways.

It was a sad parting, I feel, because each discipline had done so much for the other, It is no mistake that science came out of a Christian culture, for example. For the biblical perspective of an utterly trustworthy Creator whose universe was ordered and rational was essential to the scientists' expectation of meaningful experimentation. As Einstein later wrote, 'God who creates and is nature, is very difficult to understand but He is not arbitrary or malicious.' Then, too, to be a scientist was an honorable and worthy occupation, in contrast to the pagan idea of science: Prometheus stealing fire from the gods, who were jealous of mortal man's possession of their knowledge. Biblically, man is presented as a creature of God and his work, as part of the Divine unfolding, to have dominion over the earth, always with the proviso to love God and neighbor. So the scientist is no unwelcome interloper but a servant-son in his Father's creation. As Oxford's Charles Coulson once said, the practice of science is to be seen as a fit activity for a Sabbath afternoon.

Science, in return, has given the theologian a real world. As Walter Thorson has expressed it, 'medieval society and medieval thought were ... centered on a fundamentally religious conceptual framework with a papier-mach~ sort of physical universe which had no more meaning than a kind of 'stage prop' on which the drama of salvation was enacted.' By comparison, science 'took the secular world and the secular calling more seriously. Instead of a papier-rnache universe, God bad made a real one, and the basic inspiration for the scientific revolution was a passionate belief that, in exploring and knowing what God had given us men in creation, we would find a larger framework in which our grasp of our role and destiny-could grow and develop further.'

The challenge came in the words of Francis Bacon, 'if ... there be any humility towards the Creator, if there be any reverence for or disposition to magnify His works, if there be any charity for man ... we should approach with humility and veneration to unroll the volume of Creation.' Science thus came as an outgrowth of religious concern, not as a competitor but rather as a complementary activity, to enlarge our view of God's Creation.8

And what of the study of genes, DNA and sociobiology? Do they, as Lightman suggests, really support an impersonal deterministic philosophy? We think not. For here again, it would seem, God is weaving a tapestry of great richness, beauty and intricacy. And itl seems an ever-growing, dynamic phenomenon, this structure of truth, this "volume of Creation".                                                                                                                                                                                                                       

The Genetic Revolution

The explosive increase in our knowledge of the gene began in a very quiet little garden in an Austrian monastery in the City of Brunn in the year 1865. The experimentor was Gregor Mendel, a monk, and his ten years of work, presented at the Natural History Society of Brunn, was scarcely noticed. But what Mendel discovered was truly earthshaking-that characteristics in his pea plants such as seed color or shape, and pod color or shape, were inherited as separate entities and were expressed in either of two ways which he designated "dominant" and "recessive."

Dominance was observed in the first genetic cross. If, for example, plants with smooth seeds were crossed with plants having wrinkled seeds, then the first or " F, " generation displayed only one of the two seed shapes, that of the smooth or "dominant" character. Crossing hybrid plants led to a surprising result, the re-appearance of the "missing" or recessive characteristic                                                                  unchanged-in one quarter of the progeny. Mendel's conclusion, that there existed a fundamental unit of heredity, was expressed in his now famous paper as follows:

The constant characters that appear in the group of plants may be obtained in all the associations that are possible according to the mathematical laws of combination. Those characters which are transmitted visibly, and therefore constitute the characters of the hybrid, are termed the dominant, and those that become latent in the process are termed recessive. The expression 'recessive' has been chosen because such characters withdraw or disappear entirely in the hybrids, but nevertheless reappear unchanged in their progeny in predictable proportions, without any essential alterations. Transitional forms were not observed in any experiment.9

But an appreciation of Mendel's discoveries did not come about until 1903, when a visual basis for inheritance came about with the discovery of chromosomes as structures with properties which exactly corresponded with Mendel's units of inheritance. Chromosomes could be observed prior to cell division to be divided longitudinally into two copies, and each copy to be subsequently pulled toward opposite poles of the cell. In this way each daughter cell received one copy of each chromosome-a complete set of genetic instructions.

The non-protein components of genetic material had been the subject of a study, carried out by Friedrich Miescher in Base], in the same time period as Mendel. Miescher had studied the nuclear material from two very different sources, the sperm of the Rhine salmon and pus cells from bandages from the local hospital. Both contained a substance he called nuclei which many years later was shown to be DNA. He also described another component of the salmon sperm, a very basic protein called protamine. Protamine had the usual structure of a protein molecule, a long series of amino acids linked to each other in so-called peptide linkage, but there was a preponderance of basic amino acids-arginine, lysine and histidine.

These, then, were understood as the fundamental components of the chromosome-a variety of basic proteins called prolamines and histones and some less well characterized organic phosphorus compounds.

It is amusing to speculate on the kind of reaction Gregor Mendel might have displayed if he were suddenly thrust into our era and given a molecular biological explanation for his genetic experiments.

The genetic aspect was generally assumed to reside in the protein components, but in 1944 O.T. Avery and his collaborators, at what was then the Rockefeller Institute, demonstrated that a strain of the pneumoniacausing bacterium, Pneumococcus, could be transformed from a non-virulent to a virulent type by a non-protein component of chromosome-like material obtained from the virulent type. This substance was the highly-polymerized phosphorus-containing compound deoxyribonucleic acid (DNA). Avery's description of the isolation of this curious substance, which had somehow never been suspected of being present in Pneumococcus, reads as follows:

When alcohol reaches a concentration of about 9/1o volume there

John M. Templeton, an investment counsellor living in the Bahamas, is President of the Board of Princeton Theological Seminary. He is a trustee of the Center for Theological Inquiry at Princeton and of Buena Vista College, and a member of the International Academy of Religious Sciences and the Board of Managers of the American Bible Society. He holds degrees in economics from Yale and in law from Oxford University, as a Rhodes Scholar, as well as various honorary degrees. He is the founder of the Templeton Foundation Program of Prizes for Progress in Religion.

separates out a fibrous substance which on stirring the mixture wraps itself about the glass rod like thread on a spool and the other impurities stay behind as a granular precipitate. The fibrous material is redissolved and the process repeated several times. In short, this substance is highly reactive and on elementary analysis conforms very closely to the theoretical values of pure DNA (who could have guessed it). This type of nucleic acid has not to my knowledge been recognized in Pneurnococcus before, although it has been found in other bacteria.10

His conclusion on the induction of virulence, which is accompanied by the appearance of a new cell surface polysacebaride, is also interesting.

The inducing substance, on the basis of its chemical and physical properties, appears to be a highly polymerized and viscous form of DNA. On the other hand, the type III capsular substance, the synthesis of which is evoked by this transforming agent, consists chiefly of a normitrogenous polysaccbaride .... Thus it is evident that the inducing substance and the substance produced in turn are chemically distinct and biologically specific in their action and that both are requisite in determining the type specificity of the cells of which they form a part.11

The unique character of DNA as the conveyer of hereditary information was finally and unequivocally established in 1953 with the publication of the Watson-Crick model for DNA. The structure of DNA at once suggested its hereditary role-two helical chains in which nitrogenous bases attached to the sugar-phosphate backbone of each chain were bonded to each other by weak, so-called hydrogen bonds. The bases were of four kinds called adenine (A), guanine (G), cytosine (C), and thymine (T), and bonding was specif - ic. Each time an A appeared in one chain, a T was found opposite it. Likewise, each time a G occurred in one chain, a C was on the other. This system of complementary base-pair formation-A always opposite T and G opposite C, immediately suggested the basis of a hereditary mechanism. If the chains of nucleotides-as bases attached to their sugar-pbosphates are called-were separated and a new copy of each fashioned according to the base-pairing rules, the original molecule would be exactly reproduced. Presumably, too, the sequence of bases in the polymer was the information content of the molecule. Studies of mutation in which a single base was changed showed that the exact linear sequence was essential for proper functioning of the gene.

The story of how Watson and Crick arrived at the structure of DNA reads more like a spy thriller than a journal article.12 In one of the great ironies of scientific research, the principal contributors of the data-Rosalind Franklin and Maurice Wilkins, the crystallographers whose data revealed the double helix, and Erwin Chargaff, the organic chemist who discovered the equality of A and T and of G and C-were bypassed, essentially by their own choice. They simply did not take the biochemist James Watson and his physicist friend Francis Crick-a kind of scientific "odd coupie"-seriously. Indeed, Cbargaff has become an outspoken critic of the entire genetic enterprise, pointing to the way in which its practitioners have sought to explain away the mystery of nature. He writes in his autobiography, Heraclitean Fire,

If it is the real purpose of science to teach us true things about nature, to reveal to us the reality of the world, the consequences of such teaching ought to be increased wisdom, a greater love of nature, and, in a few, a heightened admiration of divine power. By confronting us directly with something incommensurably greater than ourselves, science should serve to push back the confines of the misery of human existence. These are the effects it may have had on men like Kepler or Pascal. But science, owing to the operation of forces that nobody, I believe, can disentangle, has not persisted in this direction. From an undertaking designed to understand nature, it has changed into one attempting to explain, and then to improve on, nature.13

Chargaff's conclusion, while somewhat embittered (he says of himself that be was born with a stone in his shoe), is a sobering one. It would seem that molecular genetics fits the mold of that unregenerate science which C.S. Lewis has described. Wondrous discovery seems always tainted by a certain arrogance.

But once DNA's role in heredity had been established, another question loomed large. If DNA is the genetic material, then its role must be to direct the synthesis of all the cell's proteins. Yet protein synthesis was known to occur in the cell's cytoplasm, while DNA was restricted to the cell nucleus. How then did DNA transmit its instructions?

The answer to this question was first formulated by Francois Jacob and Jacques Monod, two French biochemists working at the Pasteur Institute. They were studying a fascinating bacterial phenomenon called induction, in which a new degradative enzyme was produced by growing cells when a substance was introduced into the culture medium which could be broken down and utilized for growth tinder the agency of that degradative enzyme. Furthermore, the process was reversible. On removal of the substance serving as a food source, the degradative enzyme quickly disappeared from the bacterial cells. Perhaps the most interesting aspect was that the induction process was under genetic control. The gene which produced the degradative enzyme was regulated by a second, closely linked gene. The French biochemists hypothesized that the gene producing the degradative enzyme was copied to form an intermediate template which was unstable, being constantly broken down and resynthesized. This molecule was proposed to be made up of ribonucleic acid (RNA), a close relative of DNA, which had been found in high concentration at the site of protein synthesis in growing bacteria.

Subsequently it was shown in several laboratories that DNA was actually copied into a polymer called messenger RNA (mRNA), again by complimentary base-pairing to ensure a faithful copy, by an enzyme system called RNA polymerase. Enzymes called DNA polymerases had previously been described which were responsible for copying DNA, and they used so-called deoxynucleoside triphosphates, activated forms of the A, T, G, and C bases attached to the sugar unique to DNA, 2-deoxyribose. The RNA polymerase used a similar set of precursor molecules, A, U (uracil), G, and C, but this time the sugar was ribose instead of deoxyribose. Verification that this mRNA molecule was the 11 transcript" of the genetic material was obtained by demonstrating its movement from the site of synthesis in the nucleus to the protein-synthetic machinery in the cytoplasm. This machinery consisted of a complex structure called a polysome, made up of a series of so-called ribosomes attached to the long mRNA molecule, rather like pearls on a necklace.

The future of genetic research, its application in medicine, agriculture and industry, for the benefit of mankind, is tremendously promising.

  It had also been shown that there was a direct linear relationship between the DNA sequence of a given gene and the amino acid sequence of the protein for which that gene coded. How, then, was the mRNA sequence in the cytoplasm translated into the sequence of its protein product? The answer was that there needed to be adapter molecules which could "read" the sequence of bases in the mRNA and then introduce the correct amino acid into the protein chain at each point. It was found that this function was performed by another type of RNA molecule called transfer RNA (tRNA). This molecule was essentially two-headed, as might be expected for an adapter; one end carried the specific amino acid and the other a series of bases which served as a recognition point for a particular three-base sequence in the mRNA. Each tRNA had its unique 11 anticodon" recognition site, unique to the amino acid it carried. So, for example, the mRNA sequence CCC dictates the binding of a tRNA with the anticodon GGG which carries at its other end the amino acid proline. Every time CCC appears in the mRNA sequence, a proline-tRNA will bind by base-pairing of its GGG anticodon to the mRNA codon CCC and its proline will be introduced into the protein chain. In the total code word dictionary there are sixty-one combinations of three bases which code for a specific amino acid and three others which signal the termination of protein chains. Almost all the amino acids have more than one code word, hence more than one tRNA carrying that amino acid. This "degeneracy", as it is called, presumably allows for some mutations to occur without leading to errors in the sequence of amino acids in the protein. The code has been shown to be universal. All species of organisms use the same code word dictionary.

The Future of Molecular Genetics

Here, then, in outline, is the state of our knowledge of molecular genetics. The future of genetic research, its application in medicine, agriculture and -industry, for the benefit of mankind, is tremendously promising, Already our knowledge of the hereditary mechanism has opened up new avenues of investigation in understanding cellular differentiation, and the de-differentiation which goes on when tissues become cancerous. New insights into the production of the antibodies which protect us from invasive agents and tumorforming cells are forthcoming.

One of the most powerful "tools of the trade" is gene splicing, a process whereby genes from different sources can be joined in new combinations for study of their interaction or for amplification of a given gene sequence. The key step in the process is the application of a unique group of enzymes called restriction endonucleases which cut the DNA double helix in a special way to yield what are called "sticky ends". Two different DNA molecules so treated can then be mixed and joined in new combinations never before possible. One such new possibility, which is really foundational for the whole process, is the subsequent joining of the DNA molecule(s) of interest with a special DNA structure called a plasmid. Plasmids are circular DNA molecules found in certain bacterial strains as a separate replicating element, like a miniature chromosome. When opened by treatment with restriction enzymes, they, too, form "sticky ends", and, after joining with the new DNA combination under study, can be reintroduced into the bacterium and allowed to reproduce. In this way, the new DNA sequence introduced into the plasmid may be replicated thousands of times, thereby providing large amounts of that particular gene for study. Genetic engineering applications include the treatment of genetic disease, the production of new plants for increased world food production and the design of new bacteria to break down industrial pollutants.One of the most exciting opportunities provided by the new genetic techniques is the study of the numerous cellular proteins for which no known function exists. The enormous resolving power of the gene splicing approach is brought to bear on these unknown substances by making use of the fundamental molecular relationship between the synthesis of DNA, RNA, and proteins which we have just reviewed. The process begins with the isolation of a new protein molecule which it is desired to study as to structure and cellular function. As in most cases, the amount of material available for study is miniscule, but there are, because of molecular genetics, some new tricks to play.

One approach is to determine a short part of the protein sequence of the new protein, perhaps a length of six amino acids at one end. This can be done with a few micrograms of the protein. Then a "gene" is synthesized in a DNA synthesizer with the proper sequence to code for the six amino acids-eighteen nucleotides in the sequence, each triplet the complementary sequence to the mRNA codon for that amino acid in the code word dictionary. This eighteen unit DNA sequence, radioactively labeled to allow for its subsequent identification, is then introduced into an extract of the total cellular RNA of the species from which the unknown protein had been obtained. In this extract are all the mRNAs of the cell, and the eighteen nucleotide long DNA fragment selects from the entire mixture the only completely complementary sequence, that of the mRNA coding for the unknown protein, and forms a stable DNA-RNA "hybrid" of the kind which forms transiently during the process of transcription. Since this is the only DNA-RNA hybrid in the extract, nuclear DNA having been excluded, the unique binding characteristic of double-stranded nucleic acids allows for a separation of this molecule from the rest of the cellular RNA.

Actually, the molecule as it emerges from the separation process is still mostly single-stranded mRNA, but with an eighteen nucleotide section at one end bound to the synthesized DNA fragment. This structure can now be converted to a completely double-stranded hybrid DNA-RNA molecule by means of another enzyme, found in certain viruses, called reverse transcriptase. This enzyme, as its name indicates, can take an RNA template and make a DNA-RNA hybrid, given the appropriate activated building blocks, the deoxynucleoside triphosphates. In this way the entire mRNA molecule is converted to a hybrid structure-in essence the mRNA has been re-converted to the form of one strand of its original gene! Now we can separate the two chains, and treat the DNA single strand with DNA polymerase to generate the double-stranded DNA, its form as a gene.

In the double-stranded form, DNA can now be spliced into a bacterial plasmid, as outlined earlier, and the plasmid placed in a bacterium and multiplied,

After large-scale growth of the bacterium, the plasmid can be re-isolated, and the DNA, coding for the unknown protein, introduced into a protein synthetic system for the large-scale synthesis of the still unknown protein.

The tremendous resolving power of the molecular genetic system is now apparent. All that is needed in this case is a tiny fragment of information-a six amino acid sequence of a huge protein molecule-and we can synthesize the entire protein in large quantities for detailed studies of its structure and function.

A Genetic Pilgrimage into the Center of a Pea Plant

This, then, is the present state of our understanding of the molecular biology of the gene. It is amusing to speculate on the kind of reaction Gregor Mendel might have displayed if he were suddenly thrust into our era and given a molecular biological explanation for his genetic experiments. When he first observed the results of his pioneer experiments with smooth and wrinkled peas, be could never have dreamed of the drama that was acted out within the intricate structures of his little garden plants. The pollen grains which he took with a fine camel's hair brush from the stamens of one smooth-pea plant, when dusted on the stigma of a second wrinkled pea plant, actually introduced into the plant's reproductive apparatus a molecule of DNA. This molecule, it turns out, was totally responsible for Mendel's observation of invariable formation of hybrid plants which produced only smooth pea seeds.

The mechanism of this kind of inherited change constitutes one of the most fascinating processes ever elucidated in the natural sciences. As we follow the DNA molecule from its source in the pollen grain into the recipient plant's reproductive apparatus, the first step in the process involves an interaction with the tissues of the stigma and the swelling and germination of the pollen grain. A pollen tube then forms and penetrates the ovary at the base of the stigma. The sperm cell, carrying its DNA molecule, enters the embryo sac and fertilization occurs. Complex mechanisms ensure that only one pollen tube enters the ovule, regardless of the number of pollen grains which germinate.

Fertilization brings the sperm cell into close association with an egg cell in the embryo sac. The DNA molecule of the sperm cell and the corresponding DNA molecule of the egg cell are then brought together, and the result is a new cell with two copies of each gene of the pea plant, one gene copy from each of the two DNA molecules. Included in this genetic repertoire would, of course, be the gene sequence encoding the instructions for smooth pea seed coats from the sperm and of wrinkled pea seed coats from the egg. How, then, do the results of this combination, the hybrid plants, finally yield only offspring with smooth seed coats? Mendel had talked about dominant and recessive factors in the expression of seed coat shape, but what was happening at the molecular level? The answer, stated simply, was that the gene sequence dictating smooth pea seed coat carried information for the conversion of all seed coat components into the variety producing smooth peas. But to do this, a vast panorama of events were first necessary. To begin with, the single fertilized egg must undergo a series of cell divisions, each time first duplicating its two DNA molecules and then segregating them into the daughter cells in such a way that a perfect copy of each of the original DNA molecules appears in each. The process of duplication of the DNA molecules, mediated by a DNA polymerase, is enormously complicated in higher organisms. The DNA of the pea plant, as in all higher organisms, is present in all its cells in the form of a complex DNA-protein structure called chromatin. The fundamental unit of the chromatin is a bead-like structure called a nucleosome which is composed of several kinds of histone proteins surrounded by several coils of the double-helical DNA. In its extended form, as, for example, during replication, the chromatin looks very much like a string of beads, the individual nucleosomes linked to each other by connecting segments of the continuous DNA double helix. At other times, the chromatin structure is more tightly folded into helical structures in which the subunit is made up of six tightly associated nucleosomes. In this form there are approximately 1000 lengths of DNA per unit length of chromatin.

Because the protein components provide stability and assistance in folding during formation of the chromosomal structures essential to cell division, it is equally essential that the integrity of chromatin be maintained during DNA duplication. The mechanical requirements of this process are staggering. To begin with, the DNA molecule in higher plants carries about 2 billion base pairs and has an overall length of about 60 cm. Given the fact that the average plant cell is microscopic in size, it is evident that the DNA molecule must be very highly folded and compacted. Yet, for copying to occur, this structure must be unfolded at least transiently, and also unwound, since the DNA is still in a double-helical form. The copying by DNA polymerase occurs at a rate of 1000 base pairs per minute, with as many as 10,000 polymerase molecules functioning at different points along the incredibly long DNA-protein structure. The complexity of this unfolding-untwisting process is awesome, given the highly compacted state of chromatin, the simultaneous copying at 10,000 points, and the high rate of movement of the polymerase molecules. One turn of the double-helical structure is duplicated each second, and the process is complete in three and one-half hours. A carnival night in midsummer is dull by comparison with this spectacle!

Then, in order for cell division to occur, the two newly formed duplex DNA molecules must be completely separated and then divided into the 14 chromosomal segments characteristic of the pea plant at cell division. This part of the process, because of its visibility in the light microscope, is more familiar to us. Yet, even here, the molecular events, involving the enormous compacting of the chromatin and the formation and movement of the mitotic spindle, which aligns and then separates the pairs of chromosomes, are staggering in their complexity. The chromosomes of the pea plant are formed from chromatin by a supercooling process 

The analogy here might be to a giant steel fabrication plant in which massive wheels and conveyer belts cooperate to twist and turn, unwind and rewind, bend and stretch, open and close mile long sections of a fifty mile-long flexible steel bar to produce the half-mile long finished product!

which the already tightly wound nucleosomal arrays are wrapped back and forth in a process which may somewhat resemble the way you might make a narrow compress out of a roll of bandage. At this level, there are 10,000 lengths of DNA per unit length of chromosome! As for the other components involved in cell division, we are only now elucidating the structure of the contractile proteins of the spindle fibers and we have only the barest understanding of the microfilaments in the cell cytoplasm which they presumably work against to effect the movement of chromosomes and the formation of the new cell membranes of the daughter cells.

Thus far we have followed our DNA molecule through one stage of division of the fertilized egg, and this processes of transcription of the DNA into messenger RNA and then translation into protein must occur. The latter process has been well characterized over the past decade but the process of transcription is only now beginning to be described for higher organisms. It begins in the cell nucleus with the synthesis of an RNA transcript of the DNA. This molecule is a precursor of mRNA, and contains, in addition to the sequence of codons which will be used for protein assembly, a series of internal sequences which must be removed beforei the molecule leaves the nucleus. At present we have no hint as to the function of these internal sequences, or "introns", but they are present in most genes of the DNA of higher organisms. Our gene for the synthesis of the smooth seed coat will therefore f irst need to have its intron sequences removed and the coding sections spliced together in the precise order for the sequence of protein to be produced. The picture is one of a long RNA molecule being generated from the DNA template-with transient unwinding and separation of component nucleosomes in the chromatin matrix as with replication-and the sequential excision of intron sequences and re-splicing of adjacent coding sequences as the RNA bends and folds to bring each succeeding intron into the proper form for action. The analogy here might be to a giant steel fabrication plant in which massive wheels and conveyer belts cooperate to twist and turn, unwind and rewind, bend and stretch, open and close mile long sections of a fifty mile-long flexible steel bar to produce the half-mile long finished product!

But our pea seed coat mRNA is not ready yet! After transcription, a special enzyme introduces a long sequence of adenine nucleotides to form what is called a "polyA tail". We are not certain as to the function of this structure, though mRNA molecules with the polyA are somewhat more stable. At the same time, an s conenzyme system works on the head-end of the mRNA molecule to add a short sequence called a "cap". The 11 cap" generally involves a G nucleotide and sometimes added methyl groups. In our pea seed coat mRNA molecule there would be a methyl group on the G nucleotide and another on the next base in the sequence.

At this point the completed mRNA is transported to the site of protein synthesis in the cytoplasm. Special proteins then combine with the mRNA, perhaps to enhance ribosome binding. Ribosomes then attach at appropriate points and tRNAs with their attached amino acids come into play as dictated by the mRNA sequence. The growing protein chain, as it elongates and extends from the polyribosomal structure, is channeled through the cell membrane surface so that modification of the seed coat components can occur "on location". And so ends the journey of our gene for smooth pea seed coat; reproduced, transcribed and the transcript modified, translated and the protein product delivered to the seed. The total number of steps in all these processes exceeds many hundreds, and almost all have their origin in a specific gene as well. We have touched on only a few of the most important steps. We have not touched on the myriad of events involved in the process of embryogenesis, whereby that single fertilized egg differentiates into all the tissues of the plant. But there is little known of this process from a molecular standpoint at present.

Science in Historical Perspective

If and when we have completed our exploration of this vast complexity, will we be tempted to say that we have explained it? Does our mechanistic explanation really suffice? Certainly it did not suffice in the minds of many of the early scientists, who found in their work the opportunity to explore God's creation and that "larger framework" in which to grasp their role and destiny. Malcolm Dixon, world-renowned biochemist of King's College, Cambridge, spoke of the religious faith of some of these in an address at the meetings of the British Association.

Robert Boyle, who ... might as much as any man be called the founder of chemistry ... also played an important part in the foundation of the Royal Society. He stated that he found few atheists among men of science. He wrote much on the relations between Christianity and science and learned Hebrew and Greek in order to study the Scriptures. He gave away a large part of his income for Church and missionary work, spent large sums on translations of the Bible, and by his will founded the Boyle lectures for the defence of Christianity against attacks.

... Kepler, the great astronomer, - . . worked out the laws of motion of the planets which were employed by Sir Isaac Newton in his great work on gravitation. He believed that in discovering natural laws he was, as he put it, 'thinking God's thoughts after Him.'

Newton himself was perhaps not quite orthodox, but he was a firm believer in God and in the Bible, and wrote a great deal on theology and on biblical interpretation. I need not remind you of the tremendous importance of his contributions to science: gravitation, the laws of motion, astronomy (especially of the solar system), the tides, optics, the telescope, spectroscopy, the nature of light, the differential calculus-tbese are only some of the subjects on which his work makes him the greatest British scientist of all time. One of his letters throws some light on the motives behind his work. Writing about his great work, the Principia, he says, 'When I wrote my Treatise about our system, I had an Eye upon such principles as might work with considering men for the Belief of a Deity and nothing can rejoice me more than to f ind it usef ul f or that Purpose. "14

Dixon then goes on to extend the list of eminent physicists-Michael Faraday, Lord Kelvin, Sir George Stokes, Clerk Maxwell, Lord Rayleigh and J.J. Thomson, each of whom was a devout believer.

As to the faith of other groups of scientists, he goes on level of detail behind every process we have examined,so that the aggregate may be another thousand-fold level of complexity yet to be explored!

At Cambridge in the first half of the 19th century there was little or no science; the credit for creating an interest in science there is due to two deeply religious men, Adam Sedgwick, Professor of Geology, and J.S. Henslow, Professor of Botany. Professor Coulson mentioned last year how Sedgwick preached to the miners at Newcastle. It was Henslow who got Darwin interested in science, and Darwin spoke of his deep religious sense. It seems that Darwin himself was a believer at the time when he did his great work on the origin of species. In that book he speaks of the laws impressed on matter by the Creator and of life having been originally breathed into a few forms or into one, and he prefixed to the book a quotation from Bacon, 'Let no man think ... that a man can ... be too well studied in the book of God's word, or in the book of God's works'. Later, however, he tells us rather sadly that he gave up his faith and subsequently even lost all appreciation of beauty in poetry, music and art. Alfred Russel Wallace, who independently arrived at the same conclusions as Darwin, and at the same time, was certainly an orthodox believer.

The list of religious men in the fields of biology and medicine also includes Lord Lister, Sir James Simpson, Edward Jenner, Louis Pasteur and Gregor Mendel. Dixon concludes:

... These men largely made the scientific method and As St. Paul also reminds us, "For since the creation of
yet were firm believers in Christianity, and they were the world God's invisible qualities-his eternal power
not aware of any inconsistency. and divine nature-have been clearly seen, being understood from what has been made

The stock explanation advanced by those who believe that religion and science are irreconcilable is that they must have kept their religion and their science in watertight compartments in their minds. But there is not the slightest evidence for this, and as we have seen in many cases there is evidence that this was not so. It would be much truer to say that they approached their research in the spirit of the 'research worker's text', that text which Lord Rayleigh prefixed to his collected scientific papers and which is carved on the great door of the Cavendish Laboratory, 'The works of the Lord are great, sought out of all them that have pleasure therein."15

Perhaps we will be tempted to say that our scientific forebears knew so much less than we. And, clearly, our
knowledge of the gene has grown a thousand-fold beyond what Mendel could have even dreamed of! Yet,
in all their magnificent complexity, present scientific descriptions seem to be only partial and tentative
pictures of what we are studying. There is, in fact, a strong feeling that there may be another whole layer or level of detail behind every process we have examined so that the aggregate may be another thousand-fold level of complexity yet to be explored!

As Lincoln Barnett says in The Universe and Dr. Einstein,

In the evolution of scientific thought, one fact has become impressively clear: there is no mystery of the physical world which does not point to a mystery beyond itself .... Man's inescapable impasse is that he himself is part of the world he seeks to explore; his body and proud brain are mosaics of the same elemental particles that compose the dark drifting clouds of interstellar space; be is, in the final analysis, merely an ephemeral conformation of the primordial space-time field. Standing midway between macrocosm and microcosm, he finds barriers on every side and can perhaps but marvel, as St. Paul did nineteen hundred years ago, that the world was created by the word of God so that what is seen was made out of things which do not appear.16

What, then, of the Author of this magnificent work? How do we view our Creator in light of all the ever-multiplying complexity and diversity which confronts us. Can we not see Him as grander and mightier than we ever dreamed?

As St. Paul also reminds us, "For since the creation of yet were firm believers in Christianity, and they were the world God's invisible qualities-his eternal power not aware of any inconsistency. and divine nature-have been clearly seen, being understood from what has been made...17


Shallis, "The Point of Cosmology," Irish Astronomical journal, Vol. 1, P. 266. 

2Weinberg, The First Three Minutes, Fountane, London, 1977, p. 149. 

3Lewis, C.S., The Abolition of Man, Oxford Univ. Press, Oxford, 1943, p. 47. 

4Lightman, A., "To The Dizzy Edge" Science 82, October, 1982, pp. 25-26. 

5Ferris, Timothy, "The Other Einstein" Science 83, October, 1983, p. 39.

6Cole, K.C. "The Scientific Aesthetic," Discover, December, 1983, pp. 62-M. 

7Ibid. p. 62. 

8Herrmann, R.L., "On Taking Vows in Two Priesthoods, Christianity and Science," Yale Journal of Biology and Medicine, Vol. 49, p. 455-459, 1976. 

9Mendel, G., de Vines, H., CorTeus, C. and Tschermak, E., "The Birth of Genetics" Papers in English Translation. Genetics, Vol. 35, Supp., 1-47, 1950. 

10Avery, OT., MacLeod, C.M. and McCarty, J., "Studies on the chemical Nature of the Substance Inducing Transformation in Pneumococcal Types," Journal of Experimental Medicine, Vol. 79,137-158,1944. :


12Watson, J.D., The Double Helix, Atheneum, New York, 1968. 

13Chargaff, E., Heraclitean Fire, Rockefeller Univ. Press, 1978, p. 120. 

14 Dixon, M., Science and Irreligion, Falcon Booklets, London, 1953, pp.5-6. 

15Ibid., pp. 6-7. 

16Barnett, L., The Universe and Dr. Einstein, Signet, 1957. 

17Romans 1:20, Holy Bible, New International Version.