 The 1958 Nobel Prize in Medicine and Physiology was awarded jointly to Dr. Statham, Beedle, and Letterberg for their work in genetics and heredity. Dr. Statham will lecture this afternoon on the possibility of manipulating genetic change. Dr. Statham. President Carlson, Professor Cush, ladies and gentlemen, after these most laudatory comments, since I am sure that I cannot live up to them, I shall do my best to disillusion you. Who ran away with my manuscript? Professor Cush is initiating the disillusionment. In discussing and evaluating the possibilities of manipulating man's genetic heritage or genetic constitution, the responsibility assigned to me in this symposium, it seems best to lay the foundations by defining what we mean by the terms and what we understand by genetic heritage and by manipulation. As often as true, we can focus on the definition of genetics best by asking further questions. What is a gene? How does a gene act? And how does a gene change or mutate? Before the advent of the new concepts and techniques of molecular biology and genetics, is that better? The answers to these questions were available only in a gross operational sense. For example, a gene is the chromosomal unit of heredity which replicates itself precisely in each cell division and which is characterized, which is inherited by Mendelian laws and which determines a visible distinguishable phenotypic character. And the gene, finally, is subject to random change or mutation, recognizable by a corresponding identifiable change in the resulting phenotype or appearance and behavior of the organism. This change, in turn, is hereditary. Today, we are able to enlarge upon these definitions and terms of molecules, as Professor Cush implied, with specific chemical structures and biological functions. May I have the first slide, please? For example, we can now speak of a gene as a molecule of DNA, deoxyribonucleic acid, of which you see the classical progenitor molecule as described first by Watson and Crick in their now famous formulation. This molecule is composed of a double helix. You can see the two helices intertwined, each of which is made up of two backbones of alternating sugar and phosphate units to which are attached four different pyrimidine and purine bases. The individuality of each gene depends on the exact sequential order of the bases along each single strand. The bases are arranged on the two intertwined strands of the double helix in a complementary order, such that adenine on one strand is held to thine on the other and guanine to cytosine by hydrogen bonds, thus maintaining the double helix. The rungs in the helical ladder are the hydrogen bonds attached to the bases on the opposing helical strands. May we have the next slide, please? If you can see this, this is an actual atomic model of the same molecule, showing in greater detail and greater accuracy the actual spatial arrangement of the atoms making up this complicated molecule. It should also be pointed out that this is only a small segment, maybe one hundredth or a thousandth of the total length of the DNA molecule. And finally, the third slide, please, to show you that this has some reality aside from models and diagrams. If you can see that you see the long thread extending throughout the background granular material, this is a thread of DNA, in this case isolated from mitochondria of Norospera in our laboratory. This is a typical appearance of a DNA thread as isolated from most antimaterial bacteria, bacteriophage, or other DNA containing genetic entities. We can visualize the essential genetic function of replication of each gene. May I have the next slide, please? As an enzymatic process of assembly of two new daughter strands on the parental strands, each of which, through the same specific pairing of bases, serves as a template or pattern in the assembly process. This is the upper portion of the diagram. The G is the gene. This is replicating to form a duplicate of itself, upwards. We also have a clearer picture of gene action with one strand of the same DNA model, the gene, serving as a template for the enzymatic assembly of a complementary single-stranded molecule of another type of nucleic acid, RNA, ribonucleic acid, which serves as a messenger, M, to carry the information coded in the base sequence of the DNA from the nucleus of the cell to the cytoplasm. This is the lower portion, the transcription process. Here in the cytoplasm, this information is read by the protein factories of the cells, the ribosomes, and transcribed by the assembly of activated amino acids into enzymes and other proteins. These enzymes are protein catalysts which have very specific jobs to do in the cell, and the total complex of enzymes of each cell determines all the potential complex properties and characteristics of that cell, that is, its metabolism, its function, and ultimately, in a more complex relationship, its appearance and behavior. Thus, the entire sequence of events involved in the translation of the genotype into phenotype is interpretable as a translation of DNA into protein by steps which we are coming to understand in greater and greater detail. One of these is illustrated in the next slide, please. At the top of this slide, you see the messenger RNA molecule, which is a direct replica, if you like, or complement of one of the DNA strands. You see each triplet code of bases represented by the GCA, for example, on the messenger RNA, attracts by complementation to it a molecule of another type, small molecular type of RNA called adapter RNA or transfer RNA, as shown on the right, that CGU is specifically bound to, attracted to the three coding bases on the messenger RNA. Each adapter RNA molecule is specific for a particular amino acid, which you see down at the other tail end. If these are each then bound in correct sequence, as determined by the particular type of triplet in the messenger RNA, this brings the amino acids in correct sequence and configuration to form by loss of water, to form a polypeptide chain, which is a protein and because of its sequential array of amino acids, it has the specific functions in the cell, which are gene determined. You can see from this figure also that at the molecular basis, mutation can be thought of and at the simplest level is indeed thought of as an exchange of one base for another, such that, for example, GCA might become GUA in the messenger RNA. And you can see how this would determine the, eventually, the synthesis of or the incorporation into the protein molecule of a new amino acid replacing the one originally called for by the original code. May I have the lights, please, or slide off. Depending on the particular amino acid involved in the replacement and the importance of its position in the enzyme molecule, the enzyme activity of the product may be qualitatively altered or may vary quantitatively from complete in activity, even if it is indeed synthesized, to normal activity or even to enhanced activity of the, quote, mutant enzyme. The development of these general concepts of molecular genetics has been due to several factors. One has been the extensive use of microorganisms referred to by Professor Cush, such as fungi, bacteria, and even viruses in attacking and clarifying the problems of the nature of the gene, of mechanism of gene replication, mechanisms of gene function, and the mechanism of mutation. Another factor has been the rapid increase in knowledge of the intimate structure of the complex macromolecules, such as the nucleic acids and the proteins, which make up the enzymes and structural constituents of the cells. One of the important recent advances conceptually has been the consequence of what we have just been going through, and that is that there is indeed a one-to-one relationship between the detailed molecular structure of the gene and the detailed molecular structure of the enzyme. The third important factor has been the development of techniques for isolating these molecules and for studying their interrelationships and their activities, as in in vitro systems prepared free of cells, operated and studied in a test tube in the laboratory. As examples of this, we may mention the x-ray diffraction analysis of DNA, which led to the recognition of its helical structure. The chromatographic techniques, which have been developed for the separation of minute quantities of materials, such as amino acids or peptides, and these are making possible the determination of the precise amino acid sequence, which make up an enzyme, as shown in the next slide, which we give an example of the first end, the detailed amino acid sequence in the first enzyme, which was so completely analyzed, ribonuclease. Slide off, please. Finally, techniques for the separating and reforming nucleic acid double helices, which are now available, are making it possible to detect base sequence similarities or homologies between two samples of DNA in a single-stranded form, or between DNA and RNA and study these, and use these as methods for isolating and studying messenger RNA and comparing its structure with DNA, for example. Finally, the development of cell-free systems capable of protein synthesis in a test tube is making possible detailed study of the role of RNA in this process, that is, the messenger RNA, with a consequence of approaching solution of the amino acid code, as it was called. For the purposes of this symposium, however, more pertinent than the details of these accomplishments is the emerging view that the principles of gene, nature, and action we have been outlining are, in essence, the same for all forms of life, from viruses to man, apparently including this triplet amino acid code. Hence, we may fairly confidently predict that to the extent to which we learn how to manipulate genetic change in microorganisms, we may in time and should in time be able to do so with higher multicellular organisms, including man. Let us therefore examine what might be meant by manipulation of genetic change. I would like to define manipulation in a broad practical or operational sense in terms of the experimental control or modification of the phenotypic expression of the genetic makeup of a cell or organism. As Dr. Glass pointed out so eloquently this morning, and the previous talk this afternoon, survival, selection, and evolution of a species must operate primarily at the level of interaction of its phenotype with its environment. However, in exceptional circumstances, the participation of an individual in the survival and evolution of his species may be decreased or prevented solely at the genetic level, as in cases of genetic sterility. Since, as we have seen, the long chain of reactions from genotype to phenotype runs from DNA to RNA to enzyme. And from the complex of enzymatic activities to ultimate phenotype, there are obviously many points of attack for control of operation of the overall sequence. This is illustrated in a crude sort of way by the next slide. The next one, please, which shows the action of a gene at the bottom of the slide determining the abilities, potentials of a cell, on up through tissues, organs to the ultimate organism, and finally these in turn interacting in a complex, as yet ill-defined way to determine the higher, some of the higher qualities of living organisms. And I slide off, please, to the extent to which we can indeed control gene expression, either by changing the genome or the gene itself, the genetic complex of an organism, or by regulating its functioning, we will be manipulating genetic heritage and change. Let us clarify these possibilities by categorizing them as different classes of biological engineering. We might call them eugenic engineering, or eugenics, genetic engineering, and eugenic engineering. Eugenic engineering or simply eugenics would involve the selection and recombination of genes already existing in the gene pool of a population. The effective application of eugenic engineering would require the identification of desirable and undesirable forms or alleles of genes, and the bringing of them together in combinations advantageous or desirable, both for the individual and for his species. Genetic engineering I would define as the change of undesirable to desirable genes by a process of directed or controlled mutation. And lastly, eugenic engineering, as the name implies, would be a designed modification or control of the expression of existing genes in an organism so as to lead to a correct more desirable phenotype. It should be noted in regard to all three categories that their effective application would require not only the technical know-how of a very high degree, but also that the manipulator be able to recognize or design a desirable gene or combination of genes in terms of their effects on an organism in relation to its environment. And as Dr. Glass pointed out, we cannot even predict what the environment of man will be in another century. Say nothing of ten years from now. As of now, we have only a limited technical know-how, and we are perhaps even further from the state of wisdom and insight needed to apply it advantageously, even if it were available. Let us now examine each of these three classes of biological engineering a little more closely with respect to the state of the art in microorganisms and the possibilities of their application to man. Eugenics, as you know, is to be discussed by Dr. Shockley, so I will not infringe too much, I hope, on his discussion this evening. But I want to make a few points. One of these is to emphasize that recombination of desirable existing genes and the elimination of harmful ones by selective breeding in any organism requires the ability to identify the presence of an undesired gene even when it is not obvious from the phenotype as for a recessive gene in a diploid organism. In haploid microorganisms, in contrast, all genes show their effects in each individual. In certain of the heritable, heritable metabolic disorders in man, however, as Dr. Reed pointed out one instance this morning, quantitative chemical tests are now available sensitive enough to distinguish an individual with two normal genes, so-called homozygous normal, from an individual with one normal and one mutant gene, the heterozygous individual. In such a case, eugenic counseling can be applied wisely and effectively. Examples of this type are PKU, phenylketonuria, and galactosemia. These are both hereditary metabolic diseases in man which have untreated result in mental retardation. They are characterized by the inability of the individual to metabolize the amino acid phenylalanine and the sugar galactose respectively. Sensitive tests for detection of other hidden mutant genes will undoubtedly be developed as biochemical knowledge of the basic effects of these genes in the organism becomes available. Microorganisms, in contrast to man, have another important attribute, which applies not only to selective breeding and other techniques of gene recombination, but equally to the applicability of induced mutation or gene change. This attribute is a function of their size and simplicity so that an astronomically large population of individual cells can be grown and examined easily and rapidly. Hence, the microbial geneticist can afford to be satisfied if one bacterium out of a million is recovered with the sought-for genetic attributes, whether these result from a rare recombination of existing genes or from an equally rare mutation. Obviously, the situation is different with man. In microorganisms, because of their unique attributes already mentioned, several exceptional mechanisms of gene recombination have been discovered. Now I have the next slide, please. One takes place, as shown at the bottom, through cell-to-cell contact and passage of the, in this case, red bacterial chromosome from one cell, the F-plus or male cell, to the F-minus or female cell. Subsequently, gene reassortment takes place with daughter cell progeny receiving different combinations of the parental genes. This phenomenon was first observed at a recombination frequency of one in 10 to the eighth cells in the mixture. But now, with improved techniques and more fertile strains, the frequency can be as high as one in 10. Another type of gene transfer and recombination, also shown in this slide at the top, is the phenomenon of transformation. This involves the transfer of genes, the red material, in the form of DNA molecules in solution from one bacterial cell to another. It is then incorporated and recombined into the genome of the receptor cell. Thirdly, genic DNA, as shown in the middle, in the central line, genic DNA can be transferred from one bacterial cell to another via its incorporation into a bacterial virus, the little tail-like materials around the hexagonal head and the tail showing coming out of a burst bacterium looks like an Easter egg breaking. This process of transfer is called transduction and may be crudely compared to the transfer of the malaria parasite from one animal to another by a mosquito. Slide off, please. It seems rather unlikely that any of these processes can be applied directly to higher organisms and to man. Several considerations are involved in this conclusion. First is the relative infrequency of gene transfer by these methods, even in bacteria. Even if the efficiency could be raised to 100%, which is questionable in view of the multicellular structure of an organism such as man, unless it could be applied to germ cells, there would still remain the problem that human somatic cells are diploid, having two representatives of each gene instead of one as do the haploid cells of most microorganisms or the germ cells of man. Gene transfer applied to somatic cell, therefore, would have to be, in order to be completely effective, would have to involve the two genes in each cell. A saving consideration here, however, is that most gene mutations, as was pointed out by Professor Glass, most gene mutations are recessive and harmful. And one normal or active cell per gene is enough to correct most mutant phenotypes. So one might have to transfer only one gene and get it incorporated into a cell in order to counterbalance or repair a genetically determined malfunction of metabolism. This is true for the simple mutant metabolic disorders of man of which we've already mentioned, such as PKU and galactosemia. In spite of these limitations to the applicability of microbial type gene transfer to man, they conceivably could be used indirectly, even with man. It is now possible, and this is pure speculation, it is now possible to grow some types of human cells and animal cells and culture in the laboratory and even to clone them. By this term is meant the isolation of a single cell and the growth of its progeny daughter cells to extremely large numbers. Thus, in essence, human cells can now be grown and experimented with just as can bacterial cells. Studies of such human cell strains have indeed shown that in some cases the cells retain the phenotypic, this enzymatic, characteristics shown by the individual from whom they were derived. Thus, it seems feasible to attempt recombination and mutation studies with suitably marked or identifiable strains, just as was done successfully with bacteria. Already encouraging results have been obtained. The formation of hybrid mammalian cells, I use hybrid in a certain limited sense, of hybrid mammalian cells has been reported in mixed cultures, as detected by morphologically distinctive chromosomes used as identifying markers. May I have the next slide, please? Probably most of you are familiar with the appearance of human chromosomes. Just to refresh your memory, by using this slide, you can see that there are various sizes and shapes, and some of these, in the case of particular aberrations or changes in the chromosomes, can be even more distinctive and characteristic than these that you see here, which are relatively or completely normal. Also, the second encouraging type of result, which is only a beginning to date, is the transfer of drug resistance characters of one mouse cell line to another cell line by DNA, as in bacterial transformation. And this has been reported by two laboratories. Transduction, the third method of bacterial recombination or transfer via a virus vector, is currently receiving considerable attention as of possible significance in the production of tumors in animals by tumor viruses. And just to bring this to you with a little concrete illustration, the next slide will show the transformation of human, normal human cells on the left in culture. Transformation to a changed morphology and an increased malignancy as determined in animals. Similarity to tumor cells by exposure to a tumor virus. This is taken from the work of Anders. Slide off, please. It thus seems not too fanciful to foresee the possibility of applying some or several of these bacterial techniques of gene transfer and recombination to human cells in culture. Even a rare recombinant cell in tissue culture could, in theory, be selected and grown to very large numbers. Similar considerations as to selectivity and culture apply to the second class of biological engineering. Genetic engineering or directed mutation. In microorganisms we are already learning techniques of producing mutations in a somewhat nonrandom manner by the use of chemical mutagens such as nitrous acid or formaldehyde which attack certain groupings on the nucleic acid molecule specifically and by the use of synthetic molecules related to the nucleic acid bases, the analogues of these bases. These latter molecules or analogues are incorporated into DNA during its replication and in the next phase of replication apparently upset the pairing process such that the wrong natural base gets in place of the right natural base when it is matched up with the strand containing the analog or slightly altered base. This produces a mutation. With these beginnings I think there is indeed ground for hope that with further knowledge and with better and more specifically tailored mutagens perhaps we can reasonably hope to increase the selectivity of mutation considerably. Another potential future approach to directed mutation is via the synthesis in the laboratory of a desired molecule of DNA with all of the correct configuration and base sequence down the strands. This tailored molecule or any desired DNA molecule if it can be isolated in pure state from an organism or a cell can probably be amplified by already known enzymatic replication processes to any needed quantity. They cannot today but I think we can anticipate this. This new or isolated gene can then hopefully be introduced into mammalian cells and culture as in bacterial transformation. Then as the final step in this procedure if the rare desired transformed cell can be selected and cultured the new cells so derived could conceivably be transplanted back into a living organism there to correct a defective function of the original host cells. The problem of transplant rejection and immunological process as you know which would be involved in such a scheme may be obviated by future progress and understanding and controlling the host immunological processes responsible for the rejection or conceivably by using the prospective host's own cells and culture for as receptors for the transformation process. I think that the applicability of this general approach to human cells derived through any technique of gene transfer or recombination is obvious and need not here be elaborated further. Thus in an indirect but theoretically feasible way we may foresee the future possibility of a purposeful manipulation of genetic change even in man. Finally I want briefly to consider the third class of biological engineering as I have defined it euthanic engineering. You may remember that I have defined this as the control or regulation of gene expression so as to alter the phenotype without necessarily altering the genes themselves. It should perhaps be pointed out that genetic change in somatic or non-germinal cells of an organism may be considered as a type of euthanic engineering in contrast to genetic change in germ cells since it would not be such a change would not be perpetuated in the germ line therefore not perpetuated in the species but would be of value to the individual. It should further be pointed out that development and differentiation from one cell to a complex organism most reasonably is now viewed as involving the regulation and control of gene expression by selective processes of gene activation and repression. Hence normal development may itself be considered as the prototype of euthanic engineering with the developing organism itself as the engineer at the throttle. From this point of view and considering that a great deal is already known about the regulation of gene activity and expression in microorganisms the prospects of euthanic engineering in man seem perhaps the most immediate and promising of the three classes we have mentioned. We now speak learnedly and impressively about end product feedback metabolic control mechanisms shown in the next slide please. With an end product feeding back and interrupting a sequence of biochemical changes either at the conversion of gene to enzyme is in the lower arc repression or as actual interference in the action of a gene once it has been synthesized has been converted to an enzyme and we speak equally learnedly about operons and operator genes. Next slide please. Structures deduced from a bacteria studies and bacterial genetics in which various portions of the bacterial chromosome the DNA molecule the double helix which you see up there the O at the far left is an operator locus which can be turned on or off by a complex repression or induction stimulation mechanism and if it is turned on it turns all on all the genes down the line or if it's turned off it turns off all the genes down the line and this may indeed also be a process of regulation which is involved in as we mentioned in differentiation and development. Slide off please. All of these processes and structures are concerned in turning these microbial genes on and off. We are indeed beginning to recognize and study analogous processes of control in mammalian organisms and cells. Obviously the more we know about these the more able we will be to superimpose from outside a control on these same processes which are controlled inside the cell. In a practical sense even it is gratifying and striking to realize that the simplest form of euthanic engineering is already standard human therapy. This is the limitation of the production of an undesirable or harmful metabolite or in-product metabolism, intermediate metabolism, by dietary limitation of its source, its precursor as of the amino acid limitation of the amino acid phenylalanine in PKU or phenylketonuria or of galactose in galactosemia and such limitation of the source of these harmful materials is actually proving quite effective in these two instances at least in preventing the mental problems and mental retardation. Thank you. Which is consequent to untreated cases of these genes. It should also be pointed out that replacement of a missing or defective gene product also constitutes euthanic engineering and we already know about these although we don't recognize them immediately without consideration as such. Effectively used examples include substances readily carried in the blood or missing normal blood constituents such as gamma globulin which is absent in the presence of certain mutant genes in agamoglobulinemia or hormones such as insulin in diabetes or perhaps in the future needed enzymes. I have tried to present at least a bird's-eye view of some of the possibilities for the experimental control and manipulation of genetic materials which I have termed biological engineering. I think it is obvious that this sequence of development of this in the future can be expected to take a course in early occurrence or fruition. One would first would be the one we are already in as I mentioned the correction of genetic metabolic defects by some kind of therapy which I have indicated some possibilities. Secondly would be the extension of this to the of these procedures to the germline with the elimination of a defective or mutant gene by its replacement by a better gene. And thirdly and even further away would be the engineering related to multiple gene characters involved in intelligence, lower learning, and other higher orders of complex interaction in an organism. But I think we can be optimistic perhaps in expecting some time and I would hesitate to put a date on this that with increased understanding of the molecular basis of learning and of intelligence we can at least hope to do something in this area as well. I would hesitate to predict precisely when and to what degree these various principles and techniques of the newer molecular biology and genetics will be successfully applied to man. However you will perhaps have gathered that I'm optimistic that this will come in time perhaps sooner than we anticipate with the breaking of a few major technical barriers. It behooves us then as we are doing in this symposium while biological engineering and the controlled manipulation of genetic change are still possibilities in the future to devote some time and deliberate thought to the even more difficult question of how this knowledge is to be used wisely for the welfare mankind. Thank you. May I again ask that any questions you have with reference to this lecture be sent to the front? Because Professor Reid didn't get around to answering your questions this morning. There were too many. Don't give Professor Reid's questions to Dr. Tatum. This happened with Professor Glass. A whole lot of Dr. Reid's questions turned up for you. If I bring a few up we can start in. The question has come before me is does it make any difference which DNA strand is duplicated in the messenger RNA. I think if you consider the coding as we understand it you realize that it does and that one is the complement of the other so that if one strand is duplicated it might well make nonsense and if the other strand is replicated or transformed into messenger RNA it would make sense and apparently this is what happens and this is our picture at the moment. That's a very good question. I've been asked to rename the three classes of biological engineering with a brief definition of each. I would just request that whoever would like to find out about this come up and look at the manuscript. Have specific human traits been traced to specific genes and chromosomes? If so how has this been done? Many one has a question here of definition what is a specific human trait if one is concerned with metabolic defects which are unitary characters or with eye color or something of this kind yes these have been traced certainly to specific genes because of the pattern of inheritance. In some cases they in rather rare cases as yet in man and Dr. Reed and Dr. Glass can correct me if I pull a boner on this they have been traced to identifiable chromosomes particularly when a characteristic or trait is sex-linked behaving in a certain way in heredity such that it is inherited from mother to mother to son and so on as and when it this trait is distinguished by a gene on the X chromosome which can be identified just because it does it has a certain pattern of inheritance. There is a beginning now which is proceeding very rapidly and effectively to identifying various other genes on particular chromosomes by virtue of linkage whether the two characters go along together in more than a random predictable proportion of the time these are then located together on the same chromosome and we are slowly starting to build up a gene map of man as has been done previously with Drosophila with corn with Neurospora with bacteria and so on so forth. We'd only point out that the more genes are so located the faster the process goes as it rolls it gets more effective more efficient all the time so we can anticipate this precise identification. Question can DNA be synthetically created? DNA can indeed be synthesized enzomatically but not as yet in a test tube. This means you have to have a template or something. You have to have a template before you can do it yes but once you have the template once you inject a piece of DNA presumably you can do it odd-lib. Is that correct? Yes. Quite a nice trick as a matter of fact if you don't do it from scratch. It is indeed. How does ionizing radiation actually affect the DNA molecule on its bases? I'm sure Dr. Glass could answer this much better than I can and I think as a matter of fact he did answer this to some extent. Depending on the strength of radiation of the ionization and the number of active ionizing particles involved over what an area in the chromosome they extend one may expect smaller rearrangements even point mutations replacement of one base by another or grosser aberrations or distorted breaks and recombinations of chromosomes or even deletions pieces taken out of the chromosomes and the broken ends reforming. Ionizing radiation then can operate in a great quantitatively different sense and by several different types of mechanisms all of which presumably involve the breaking of the bonds holding the backbone together. Will popular moral attitudes prevent or permit the conception of a human organism in the laboratory assuming the limitations of perception? I think this is moral attitudes is not my concern at this lecture. We'll pass this to one of the next speakers. Is it definitely decided now that DNA cannot produce proteins but only produces RNA which then produces proteins? I would say one can never definitely decide in absolute hundred percent assurance that something does not take place. All we can say is that according to present experimental evidence the best that is currently available the only model we know for gene expression is via transfer of the specificity to transcription to RNA and then to protein. What is your opinion on the idea that a certain amount of memory or instinct is contained in the RNA molecules as shown by experiments on the planarian worm? I don't know what my opinion has to do with the facts of science. This is sort of a hunch. I would only comment that first place that memory or instinct are two different aspects of biology. We have good reason to believe from the study of other organisms, the homing instincts and the vocabulary of birds and the vocabulary of the bees and ants and translating information from one individual to another. The breeding habits and the nesting habits in the care of young animals that these are instinctive reactions they cannot be learned and that these must in some way be determined by the genetic RNA perhaps mediated by genetic DNA perhaps mediated by RNA but certainly it would be difficult to see how they could be passed from one generation to another and stored in RNA in these organisms. I think there is currently some skepticism and some disagreement as to the planarian experiments but I would finally point out that there is increased interest in the molecular basis of learning and memory in a number of different laboratories and again there is some evidence that proteins might be involved and there is equally good evidence that RNA might indeed be involved. All I can say is that the problem is being attacked and there seem to be some methods of approaching the problem at an experimental level. We don't know as yet. Might manipulation be affected? Manipulation of genetic material or the genome presumably might it be affected through deletion of deleterious genes without their replacement? This assumes the deleterious gene can be identified a big if. A gene even though deleterious presumably in many cases is still doing something and it would if this something is indeed essential for the viability or the life of the organism it could not obviously be deleted without lethality. If the gene is doing absolutely nothing then I see no reason why it could not be so deleted but if it's doing absolutely nothing it's equally apparent I think that it doesn't do any harm while it's there. No, those are the ones I've answered. I've got some lulus for instance. Will the healthier Chinese gene pool finally overwhelm the world? How would you like to try that? I'll leave that for you sir. Thank you. That would be within the prerogative of the moderator I believe between the DNA of the body cells and that of the reproductive or germ cells. So far as I am aware there is no difference known between these two DNAs with the exception of the fact that the DNA that in the body somatic cells the DNA is double in a diploid organism. Yeah, worth extension of that. As a matter of fact what about the DNA in plants that's compared to animals? It's remarkably similar as it is in bacterial viruses or in bacteria. Presumably at the present time you couldn't tell the difference just by the analysis of the DNA between a salmon and a number of these components. How about how about the difference between the DNA of a tree and a member of the symposium? I think equally a little bit. Now between a bacterial virus with some bacterial viruses members of this symposium or of this panel one could tell one could indeed distinguish because certain bacterial viruses have odd bases which are not characteristic, not characteristically present in these other organisms. Would not euthanics add to the genetic load that had brought to childbearing age more individuals without ordering the phenotype that would indeed be passed on. I think that this would indeed be true. I would only point out that as we improve the euthanic treatment or correction of defects if we complete the job of proving it we alter the environment such that there would point it out there would be no selective advantages for having one versus the other really as long as we're in an environment where the euthanic treatment were available under this type of environment to be a detrimental gene. All the folks who said the answer I'll tell you it's a fine collection of questions. I want to make a highly personal remark. There was a question how did Dr. Kush get his first name? I have already answered that question and I need to wear a clothes season on that. Thank you.