Science in Christian Perspective
From: JASA 17 (March 1965): 2-7.
The current theories, particularly the Watson-Crick hypothesis, for the replication of DNA and biosynthesis of RNA and protein are discussed. Possible mechanism for mutations due to alternation in base sequence of the DNA of the gene are reviewed. In view of the extreme complexity and high degree of specificity of the DNA-RNA-protein system and complete inter-dependence of nucleic acid and protein synthesis, difficulties involved in attempting to, construct mechanisms for an evolutionary development for the origin of life are pointed out. The complete dependence of DNA on the living cell for its replication and function emphasizes that DNA is the servant, rather than the master, of the cell.
CURRENT THEORIES CONCERNING DNA, RNA AND PROTEIN BIOSYNTHESIS AND INFORMATION TRANSFER
According to current theories, most if not all genetic information is carried by the DNA of the cell. In higher cells, this DNA is organized into chromosomes contained in the nucleus. The genetic material of a bacterial cell is believed to consist of one long strand of DNA not enclosed within a membrane.
The generally accepted structure for DNA and its mode of replication is that proposed by Watson and Crick
1 Abbreviations: DNA = deoxyribonucleic acid, RNA = ribo nucleic acid, ATP = adenosine triphosphate, AMP = adenosine monophosphate, GTP = guanosine triphosphate, A = adenylic acid, T = thymidylic acid, G = guanylie acid, C= cytidylic acid and U = uridylic acid.
*Dr. Gish is a Research Associate in the Department of Biochemistry in the Research Division, The Upjohn Company, Kalamazoo, Michigan.
(1, 2). Their model consists of a double-stranded helix,
the purine and pyrimidine bases of each strand being
paired with a complementary base in the other strand. Thus, adenine in one strand pairs with thymine in the
other strand, and guanine pairs with cytosine. Watson and Crick's model employs hydrogen bonding as a
sufficient force for template specificity, the 6-amino group of adenine being hydrogen bonded to the 6-keto
group of thymine, and the 6-amino group of cytosine being hydrogen bonded to the 6-keto group of guanine.
They have proposed that during replication of DNA there is a separation of strands and a synthesis of
two new strands, complementary to each of the parent strands. In addition to the presence of the DNA being
replicated, other requirements for this synthesis in clude the four deoxyribonucleoside triphosphates,
Mg++ and the enzyme DNA polymerase. Although the Watson-Crick model has gained wide acceptance, there
are certain difficulties with the model which have yet to be answered (3).
It has since been proposed (5) that DNA serves as a template for the synthesis of m-RNA, there being a
complementary base pairing between the bases of the DNA strand and of the m-RNA as it is synthesized.
Only one strand of DNA is read. In this synthesis, adenine pairs with uracil, thymine with adenine and
guanine with cytosine.
The site of protein synthesis is on the ribosomes, lo cated in the cytoplasm remote from the nucleus and,
in fact, protein synthesis will proceed in the absence of DNA. It was recognized, therefore, that transcrip
tion of the information contained in the genetic ma terial into a specific protein structure must require
some sort of a messenger. Jacob and Monod (4) have proposed that the information contained in the DNA of the gene is carried to the ribosomes by a short-lived messenger, a ribonucleic acid, which they have called
messenger RNA (m-RNA). The information for determining the amino acid sequence of a protein is believed to be encoded in the base sequence of its corresponding messenger RNA. Thus, the base sequence of the DNA of the structural gene determines the base sequence of the messenger RNA, the base sequence of which in turn dictates the amino acid sequence of the protein.
The nature of the amino acid code has been under
nvestigation for some time. Crick and coworkers (6)
have proposed a triplet code, that is, three bases in the m-RNA code for one amino acid. Thus ULTU codes
for phenylalanine, AGA for arginine, GUU for valine, etc. Most evidence so far seems to support a triplet
code. Some important progress has been made in solving this code, and recently at the Sixth International Congress of Biochemistry in New York City, M. W. Nirenberg announced the base sequence code for va line, and predictions for base sequence codes for several other amino acids based upon the sequence for
valine and amino acid exchanges previously known. Prior to this, only the base composition, and not the sequence, of the triplets were predictable.
As previously mentioned, the site, of protein synthesis is on the ribosomes. The ribosomes consist of about 60% RNA and 40% protein. Very little, if anything, is known about their structure or method of synthesis. No doubt the structure of both ribosomal RNA and protein is highly specific. A number of ribosomes are organized into larger units called polyribosomes or polysomes. This is believed to take place under the influence of m-RNA.
Protein biosynthesis is indeed very complex (7). The first step in protein biosynthesis is the activation of the amino acids via an amino acyl-AMP-enzyme complex. Under the influence of an activating enzyme, a reaction between the amino acid and ATP, leading to the formation of an anhydride bond between the carboxyl group of the amino acid and the 5' phosphate group of AMP, takes place. This product is held in a complex with the enzyme. Here specificity in protein synthesis is first exerted, since 1) AA + ATP + E - (AA - AMP) - E + PP 2) (AA - AMP) - E + RNA --2' AA - RNA + E there is a specific enzyme for each individual amino acid. This complex reacts with a cytoplasmic RNA, called soluble RNA (s-RNA), or transfer RNA, to form an activated amino acyl-s-RNA complex. Here again, specificity is exerted, for there is a specific s-RNA for each individual amino acid. I believe we should attach special significance to these activating enzymes, for they represent a true juncture. of protein and nucleic acid chemistry in the living cell. Each is designed to recognize a specific amino acid, the building blocks of proteins, and a specific nucleic acid, s-RNA. Each enzyme must select a specific amino acid from a mixture of 20 or more, cause it to react in a specific manner with ATP, and then each enzyme while in the form of this amino acyl-AMP-enzyme complex must select a specific s-RNA from a mixture of 20 or more, and bring about a reaction between the amino acylAMP and the s-RNA in a specific manner.
Not much is known about the tertiary structure of s-RNA. It is known that the amino acid is combined with the ribose portion of a terminal adenosine, and two cytosines follow in sequence. This A-C-C sequence is common to all s-RNA's, plus a guanine at the other end. Except for these similarities, the sequence for each s-RNA is specific and different from that of each other s-RNA. The A-C-C is enzymatically removed and replaced in a very specific way. The significance of these reactions is, as yet, unknown. The mode or site of synthesis of s-RNA is still unknown. s-RNA is unique among the RNA's by virtue of its content of odd bases, such as thymine (usually found only in DNA), pseudouridine (the sugar is attached to the No. 5 carbon, rather than to the No. 3 nitrogen), 1-methylinosinic acid (a derivative of hypoxanthine) and various methylated bases. The activating enzymes exhibit considerable, although not absolute, species specificity (the rate at which an activating enzyme will activate its amino acid is much faster with its homologous s-]EtNA than the rate with s-RNA from another species).
The amino acyl-s-RNA complexes are transferred to the polyribosomes, the site of protein synthesis, and the amino acids are incorporated into protein. For this, m-RNA is required, of course, to dictate the sequence of the amino acids in the protein. GTP and Mg++ are required. One or more enzymes, called transfer enzymes, not specific for each amino acid, are required. Very little is known about the actual assembling of the amino 'acids into the polypeptide chain, or the requirements for each step in this synthesis which may involve several steps. The transfer enzymes are species specific. For instance, the transfer enzymes from rat liver are not active in the protein synthesizing system from E. coli. The synthesis of the peptide chain is believed to be sequential, beginning at the N-terminus. The steps involved in releasing completed protein from the ribosomes are not known. A releasing enzyme or enzymes may be required.
We should emphasize that, in spite of the great progress that has been made during the past decade or so, the extent of our knowledge concerning the biosynthesis of DNA, RNA and protein is still actually scanty. Most of the material which we have presented must be held as tentative until further evidence is forthcoming. What we have given here has been presented in outline form only. We have said nothing about the systems which synthesize the precursors needed for the synthesis of DNA and RNA. We have said nothing about the complex system in the cell required to generate the energy for this synthesis. Nor have we mentioned the structural integrity of the cell that is required for protein synthesis to proceed at normal rates. We have seen, however, the extremely complex system required to synthesize a protein molecule in the living cell. Furthermore, one of the most striking features of this system is the high degree of specificity exhibited in every detail of the system. Apparently the position of every nucleotide and amino acid is uniquely and purposefully determined. Each of us should stand in awesome wonder as we witness the unfolding of this ingenious plan of the Master Planner.NATURE AND MECHANISM OF MUTATIONS
As we have accumulated some knowledge concerning the replication of DNA and of information transfer, we are now able to postulate mechanisms for certain types of mutations. Nuclear or chromosomal heritable variations may be divided into those variations which involve a change in chromosome number (polyploids, aneuploids) and those variations which involve a change in information content. We will concern ourselves here only with those variations due to changes in information content. Heritable variations due to changes in information content may be subdivided into those occurring by recombination (a reshuffling of the genes by crossing over, transduction, etc.) and those due to mutations. Finally, mutations may be classified as "point" mutations, mutations which may be due to as small a change as a single base pair of the DNA, and larger alterations, such as loss of a piece of a gene.
These base changes may be induced by various means. Inhibitors of the synthesis of nucleic acid precursors, such as 5-amino uracil, which inhibits the synthesis of thymine, may cause chromosomal breaks or mistakes in base pairing. Certain base analogs, such as 5-bromouracil and 2,6=diaminopurine, are incorporated directly into DNA and may cause mistakes in base pairing during replication. Some dyes, such as acridine orange, are believed to be mutagenic by causing deletions and insertions of base pairs. Some chemicals, such as nitrous acid and alkylating agents, bring about these base changes by directly altering the structure of the bases. Nitrous acid, for instance, deaminates cytosine to yield uracil, a normal constituent of RNA. It is highly mutagenic, therefore, towards RNA viruses such as tobacco mosaic virus. Temperature, pH, radiations and ultraviolet light are other causes of mutations. Spontaneous mutations may come about by mistakes in base pairing in the normal replication of DNA or RNA. Under certain conditions, A can pair with C (instead of T) and G with T (instead of C). Certain metabolites of the cell, such as peroxides, may react with the bases of DNA to produce mutations.
Studies that have been carried out during the past
few years have strongly indicated that alteration in a
single base pair is sufficient to cause a mutation. For instance, tobacco mosaic virus (TMV) has been treated
with nitrous acid, resulting mutants have been isolated, and the amino acid composition of the protein compared to that of the wild type. In many cases, it was shown that there had been a single amino acid exchanged in the protein, indicating that a single base pair in the nucleic acid of the virus had been altered. In the studies on abnormal human hemoglobins, it has been shown that a single amino acid has been exchanged in the 0 -chain of the hemoglobin. These result in some cases, such as sickle cell anemia, in severe anemias. Sickle cell anemia is invariably fatal for those homozygous; for this trait. We cannot positively say, however, in these cases cited that only a single base pair has been effected. There may have been another base pair exchanged which did not effect the structure of the protein under study and yet could have exerted a mutant effect. In the case of the hemo-
globins, a mutation may have occurred, in addition to the one which induced the change in amino acid sequence, which affected the mechanism controlling the rate of hemoglobm* synthesis. In the case of TMV,
many mutants were isolated in which there had been no change in amino acid sequence of the protein. Apparently, only a portion of the RNA chain of this virus (6600 nucleotides, M.W. 2,000,000) codes for the protein structure. These mutants were detected by a change in such properties as host specificity or the nature and severity of the disease invoked.
This discussion serves to remind us of the limitations of our present knowledge. We are able to elucidate the amino acid sequence of proteins and thus, as with TMV and the hemoglobins, to indirectly relate certain mutations, which have caused a change in amino acid sequence, to a change in the nucleotide sequence of the genetic material. However, we have no direct knowledge about the sequence of the nucleotides in the genetic material, and we do not have the methods available today that would permit us to undertake a study of, say, the sequence of TMV RNA. It is pos sible that within the next few years, the amino acid code will be solved. That is, we will know the nucleo tide triplet in messenger RNA that codes for each amino acid, and thus indirectly the portion of the nucleotide sequence in the DNA of the genetic ma terial that codes for a certain protein, the amino acid sequence of which is known. As important an achieve ment as this will be, we must be cautioned concerning the exaggerated claims that will be made in the popu lar press and even in some of our scientific journals. Claims will be made that now man in the near future will be able to control inheritance, including his own. This claim has already appeared, even in scientific articles. We might outline some of the stumbling blocks still in our way in this respect, however. Even though we knew the amino acid code, we still would have no idea where the corresponding base change took place in the DNA of the genetic material, because we cannot determine the sequence of the nucleotides in the DNA. If we did know the sequence, even of a single gene, we still would not have the slightest notion of how a change in a particular base pair would be expressed phenotypically, that is, we could not predict how the corresponding amino acid exchange would effect the activity of an enzyme or the integrity of a structural protein, whatever the case may be. Even if we knew this, we would have no way of bringing about a selec tive change in one or two base pairs among several thousand or several million, nor can we imagine how this would ever be possible. Supposing this were possible, we would still have no way of selecting and seg regating a particular gene from among the tens of thousands present in the genetic material. In a bacterium, the genome, which of course consists of many genes, is a single DNA strand of about three million base pairs. The corresponding complexity in a mam malian cell may well be imagined. Finally, no one has yet devised methods by which the genetic material may be removed from the sperm or ovum, manipulated and replaced, with retention of viability. For man to control heredity by a controlled change in the genetic material would thus require his overcoming a whole series of fantastic improbabilities.
PROBLEMS RELATED TO EVOLUTIONARY THEORY
What we have discussed so far, as limited as it has been, should lead us into a consideration of the significance to the origin of life. If, as we believe, the origin of life and therefore the origin of these complex macromolecular systems was by the design and exercise of the creative power of God, then the nature of that origin and the processes leading up to it may well be beyond the power of scientific investigation. I certainly believe this to be the case. These convictions need not affect our scientific ability, our scientific curiosity, nor our willingness or boldness in attacking any problem open to scientific investigation. All of the secrets of the living cell, such as its mode of replication, its ability to vary and adapt, its biosynthetic pathways and its energy systems, are open to study. The scientist who is a creationist leaves the side of his evolutionist colleague only when the boundary between scientific fact and speculation in this area is crossed. And, I may add, that boundary is becoming very diffuse today, especially in evolutionary theory.
Concerning the possibility of the origin of life in a purely mechanistic, materialistic manner, I believe no one has succeeded in stating the problem in a more cogent manner than has A. I. Oparin in his book, "The Origin of Life on the Earth" (8). Many contemporary authors believe that the key to the origin of life may be found in the primary development of those compounds specific to living things, such as proteins with enzymic activities and nucleic acids endowed with genetic properties. Oparin recognizes the futility of such views, stating that the relatively simple laws of thermodynamics and chemical kinetics could not have determined the origin of these complex molecules endowed with highly specific structures and functions.
He states the necessity of there first having arisen a new specific organization, and afterwards, on the basis of it, the substances appeared, not vice versa. Oparin's proposal concerning the nature and origin of this system, I believe, has certain fatal flaws. His proposal will be discussed later. I, personally, cannot imagine either a specific organization or macromolecules endowed with specific structures and functions, arising independently of one another.
Earlier speculations on the origin of life took place during the "golden age of proteins" and proposed that the origin of life was based upon the formation of some catalytically active protein that could be formed autocatalytically. Calvin's proposals followed this line (9, 10). Models have not supported such views (8).
Today we are in the "golden age of nucleic acids;% and speculations are centering around the origin of nueleic acids. It is proposed that all genetic information resides in nucleic acid, that this genetic material is self-replicating, and thus the gap between the inanimate and the living cell may have been bridged by something akin to a virus, which they state is selfreplicating. Such proposals must fail, because among other reasons there is no self-replicating molecule known, virus, gene, chromosome or otherwise. The only self-replicating entity known today is the living cell. It is somewhat dismaying to note how often we find expressed in scientific articles and texts the statement that a virus can replicate itself and that such a self-replicating molecule may have been the precursor to the living cell. In fact, Lindegren has stated (11) that the possibility that something similar to the viruses we now study was a stage in the evolution of more elaborate organisms is "the basic hypothesis which directs the scientific activities of most of the foremost geneticists and biochemists of the present time". If Lindegren is right, then this indicates an appalling ignorance in our scientific community concerning the nature of viruses. A virus, or any other nucleoprotein, possesses no catalytic ability. Outside of its environment in the living cell, it is biologically inert. The synthesis of a virus, a nucleoprotein, calls into play the entire synthetic apparatus of the cell previously discussed in this paper. DNA and RNA precursors are required, the high energy bonds of which are supplied by the energy-producing apparatus of the cell, in itself complex. DNA and RNA polymerases, the entire system of activating enzymes and s-RNXs, transfer enzymes and ribosomes are some of the other requirements. The cell replicates the virus, using information supplied by the virus to produce an exact copy.
Any speculation concerning the primary origin of proteins or nucleic acids must take into account the fact that the specific structure of proteins is dictated by nucleic acid, which itself is synthesized by protein enzymes. Either is helpless without the other, thus neither could have existed independently of one another in a functional system. Since the genetic information of the cell rests largely in its DNA, evolutionists seem to believe today that its primary origin should be assigned first place in an evolutionary scheme. Before synthesis of DNA can take place in the cell, however, DNA precursors must be synthesized froin RNA precursors. Thus, adenylate, guanylate and cytidylate must be converted into deoxyadenylate, deoxyguanylate and deoxycytidylate, respectively, and uridylate serves as the precursor for deoxythy-midylate. All of these syntheses require specific enzymes, of course. On the basis of this fact then, it would seem more logical to assign priority to RNA, since it can be synthesized directly from precursors which must be converted into other precursors for DNA synthesis. How DNA got into the picture would be, then, yet another story.
Alexander Rich, in recent speculations concerning the problems of evolution and information transfer (12), used the same approach that authors were proposing twenty and thirty years ago, namely the primary formation in some primordial sea of an autocatalytic molecule endowed with certain specific functions. His molecule is, of course, a nucleic acid. The same arguments which can be raised against the primary formam tion of a protein molecule from a so-called primordial soup, can be raised with even greater force against the primary formation of a nucleic acid molecule. No nucleic acid molecule has been shown to possess any catalytic ability, let alone any ability to autocatalytically replicate itself. Rich is forced to a liberal use of such terms as "we postulate", "we imagine", "we theorize", "we could imagine", "let us imagine", "we might imagine." Such an exercise, I submit, is not science. As W. R. Thompson would put it, Rich has built those fragile towers of hypothesis based on hypothesis, Surely we must take into account the basic properties of macromolecules that we are discovering today, and these basic properties most certainly would have remained essentially unchanged. Yet Rich and others in their evolutionary schemes, are forced to assign properties to macromolecules observed nowhere in nature today.
Oparin has recognized the futility of such speculations as those of, Calvin and Rich. As stated earlier, he postulates that certain, new biological laws had to be operating before a system of specific, functional molecules could have arisen. He proposes that a new specific organization arose and, based on this, specific molecular systems were formed. Oparin imagines the separation from an organic-rich primordial sea of coacervates, or droplets of colloid-rich material. Such coacervates can form by interaction of certain macromolecules, such as proteins, nucleotides, polysaccharides, etc. We will not detail here the manner in which he proposes such coacervates might have evolved into more complex systems, but will point out certain basic objections to his proposal. First of all, the tendency of any molecule to separate out of solution or to complex with other molecules, compared to its tendency to remain freely dispersed in solution, is proportional to its concentration. This tendency generally is not a function of the concentration of similar molecules.
Thus, the tendency of a protein molecule to form a monomolecular coacervate or a complex coacervate with other molecules would be a function of the concentration of the molecular species involved. The number of protein molecular species that would have arisen by purely chemical means, if this were possible, would have been truly astronomical. The same would be true of the nucleic acids. For instance, a polynucleotide consisting of 10,000 nucleotides (M.W. 3x106) could exist in more than 108000 isomers (13). Taking into account every conceivable sequence and chain length, even ignoring optical isomers, the number would be beyond our imagination. Assuming a total concentration of protein and nucleic acid of even as high as 1 or 2% each, the concentration of any single molecular species would be insignificant. The forces tending to keep these molecules freely dispersed would vastly exceed any forces that might cause them to aggregate and separate. Under these circumstances, I cannot imagine even a fleeting existence of such coacervates.
Another basic objection to Oparin's suggestion is the fact that his coacervates once formed, in order to have ever contributed to higher forms, must have existed indefinitely until they became self-replicating. This would have meant that those coacervate drops which eventually evolved into self-replicating forms would have had to exist for perhaps millions of years without disruption. Such a possibility simply never could have existed. Forces seeking to disrupt such coacervates would have been at work continually. The only way a species survives is for its birth rate to equal or exceed its death rate. It obviously must be selfreplicating. Oparin really never comes to grips with self-replication in his complex coacervate system.
In our discussion on the role of DNA and RNA in protein synthesis we have said nothing about control mechanisms. The existence of control mechanisms is, however, indispensible for the success of any biological system, no matter how primitive. Every metabolic pathway in the living cell is under close control and is coordinated with all other pathways. Cairns has aptly stated (14) that the presence of such control mechanisms converts what might be purposeless or even destructive activity into the ordered systems we find in the living cell today. One type of dontrol mechanism is that proposed by Jacob and Monod (4). They have proposed that the structural genes which code for a series of functibnally-linked enzymes are under control of an operator gene. The operator gene and the structural genes it controls lie adjacent in the chromosome and constitute what they call an operon. The operator gene must function in order for the structural genes to be expressed. The operator gene, in turn, is under the control of a regulator gene which is located on some other chromosome or at some other point in the genetic material remote from the operon. Let us consider, for instance, the induction of the synthesis of the enzyme P -galactosidase in E. coli, in which this enzyme is inducible and not constitutive. They propose that when these cells are growing in the presence of glucose, the regulator gene for galactosidase is elaborating an inhibiter which prevents the function of the operator gene, and thus the synthesis of messenger RNA by the structural gene for galactosidase cannot take place. When glucose is replaced with lactose, the substrate, lactose combines with the repressor, and the operator gene is then able to activate the structural genes in the operon, which include not only that for galactosidase but also that for permease, an enzyme necessary for penetration of lactose into the cell. Messenger RNA!s for galactosidase and permease are formed and the enzymes are synthesized. Removal of the substrate reverses this process. Jacob and Monod have emphasized the importance of such control mechanisms by pointing out that in mutants that have become constitutive for the lactose system, 6-7% of their protein material consists of 0 -galactosidase. In constitutive mutants of the phosphatase system, 5-6% of the total protein consists of phosphatase. It becomes clear then, that the cells could not survive the breakdown of more than two or three of the control mechanisms which regulate the rate of synthesis of enzyme proteins.
One may ask, then, which came first in the alleged evolution of the DNA-RNA-protein synthesis system, the regulator gene, the operator gene or the structural genes? If unregulated expression of the structural gene results in self-destructive activity, it must have been under control from the very start. If the regulator gene was formed before the operon it regulates, what selective advantage would it have conferred upon the system? The same could be said for the operator gene. We see the same situation here on the macromolecular level as on the structural level of, say, the humming bird. In such correlated systems, no individual feature would confer selective advantage until all components were functioning. Thus, in the humming bird, none of its individual unique features, such as its bill, tongue or wing structure, would have conferred selective value until all were present and correlated in a functional system. Neither would regulator, operator or structural gene confer selective advantage until all were present and functioning.
Earlier I have called the present day the "golden age of nucleic acid". At the recent Sixth International Congress of Biochemistry in New York City, the room in which the papers on nucleic acids were being given was crowded to overflowing. Rooms devoted to other sections had as low as 20% occupancy. DNA is being called the "master chemical", the "secret of life". Nucleic acid has replaced protein as the primary molecule in evolutionary schemes. It is claimed that all genetic information resides in DNA of the cell and that DNA is a self-replicating molecule. Furthermore, it is being claimed that the boundary between life and non-life has all but been wiped out. However, there are still some who are willing to come to the defense of biology. Those that are in hot pursuit of the DNA molecule seem to forget that they are chasing only a sub-unit of the living cell. Let us consider for the moment the possibility of synthesizing a biologicallyactive DNA molecule in a test tube, a feat yet to be accomplished (3). Let us forget for the moment that to accomplish this purpose we have extracted DNA and appropriate enzymes from the living cell. We still would have only a miniature factory for producing a particular DNA molecule. In fact, even if we were able to produce all of the DNA in the nucleus of a mammalian cell, we would still be left with nothing but a DNA factory.
Earlier in this discussion we reviewed the complex apparatus that must work with DNA to synthesize a protein molecule. We have noted the many enzymes that must participate, the cooperation of ribosomes and of the energy-producing system which is found in the mitochondria. We might mention the structural integrity of the cell that is so vital to these processes. Roberts has pointed out (15) that almost every part of the cell is suspected of playing some role in protein synthesis, and that disruption of the cell usually decreases the rate of protein synthesis by a factor of a thousand or more.
I believe it is extremely significant that the function built into the DNA molecule has been designed to exert itself solely in the living cell. It is evident then that these DNA molecules did not precede the cell, but both must have existed together from the very beginning. Neither has existence, function or meaning without the other. Hinshelwood has stated (16) that "the building blocks of the cells, wonderful as they may be as structures, are useless by themselves. Cell function depends upon the rhythm and harmony of their reciprocal actions: the mutual dependence of protein and nucleic acid; the spatial and temporal relations of a host of elementary processes which with their sequences and bifurcations make up the reaction pattern of the cell. A system of mutually dependent parts, each of which performs something like enzymatic functions in relation to another will, as can easily be shown, in the steady state appear as a whole to be autosynthetic. No individual part need be credited with a new and mysterious virtue by which to duplicate itself". It is Hinshelwood's view then that nothing less complex than an entire cell is capable of self-duplication.
One of those arising to the defense of biology today is Barry Commoner (17, 18, 19). This heretic has even been bold enough to defy the "central dogma" that information may pass from nuclele acid to protein but never from protein to nucleic acid. He believes that the information content of a DNA molecule is insufficient to dictate the synthesis of an exact copy of itself and that information is derived from some of the protein enzymes that participate as well as from the DNA itself. We can only mention that here in passing, but I would like to quote from one of his papers. He states "the remarkable roles which DNA plays in inheritance are a reflection of certain chemical attributes, particularly its nucleotide sequence and its considerable stability. But these properties lead to replication and determination of inheritance only when DNA is a participating constituent of the living cell. The effects of DNA on inheritance are, rather than simply an aspect of the chemistry of DNA, a manifestation of the living state". He goes on to suggest that, rather than DNA being the secret of life, "life is the secret of DNA" (19).
2. Watson, J. D., and Crick, F. H. C., Nature 171:964 (1953).
3. Cavalierl, L. F., and Rosenberg, B. H., Ann. Rev. Biochem. 31:267 (1962).4. Jacob, F., and Monod, J., J. Mol. Biol. 3:318 (1961).
6. Crick, F. H. C., Barnett, L., Brenner, S., and Watts-Tobin, R. J., Nature 192:1227 (1961).
7. For a recent review see Korner, A., in "Mammalian Protein Metabolism", ed. H. N. Munro and J. B. Allison, Academic Press, New York, 1964, p. 177.
8. Oparin, A. I., "The Origin of Life on the Earth", Academic Press, New York, 19b7.
9. Calvin M., Am. Scientist 44:248 (1956). 10. Calvin, M., Science 130:1170 (1959).11. Lindegren, C. C., Nature 197:566 (1963).
12. Rich, A., "Horizons in Biochemistry", ed. M. Kasha and B. Pullman, Academic Press, New York, 1962, p. 103.
13. Chargaff, E., "Essays on Nucleic Acids", Elsevier Publishing Co., New York, 1963, p. 124.14. Cairns, J., Endeavour 22:141 (1963).
16. Hinshelwood, C., Proc. Roy. Soc. London B146:155 (1956). 17. Commoner, B., Science 133:1745 (1961).
18. Commoner, B., J. Nat. Ed. Assoc., March, 1964, p. 17. 19. Commoner, B., Nature 202:960 (1964).