Cooper Union forum; 6; Fall 1970

From the Great Hall of the Cooper Union in New York City. National Educational radio presents a lecture entitled reproduction the mystery of life. This lecture was recorded for broadcast by station WNYC. Now to introduce the speaker. Here is the chairman of the Cooper Union forum series. Dr. Johnson a Fairchild speaker it is the gentleman who was here last year it is very very wonderful to talk to coax him back in the Great Hall. Back to get him down a native New Yorker if you want to hold out against him. His medical degree is from The New York Medical School. The neurology at the Metropolitan Hospital has a list of credits online along with like I could go on rating credits about drugs again Dell for a very long time but if.

You served in the United States Army and there's a neuro psychiatrist. He's currently associate clinical professor of medicine in the neurology and pathology at the New York Medical College flower for you know hospital director of the psycho genetic laboratory at Metropolitan Hospital and a very nice area. And I'm delighted that he was able to get here this evening. Doctor again Del. Thank you Professor Fairchild after such a glowing introduction I'm sure every one is in for something of a let down. I repeat that. The scope of the title of my talk is so vast that a full year of lectures every day in the week

would scarcely do justice to the subject. Some of the important aspects of reproduction. I shall have to forego discussing such factors as the psychological the environmental the endocrine to logic and even the media or logic. However even though I am limiting myself I can't resist bringing in a few tidbits that I uncovered in the course of researching this particular topic. For example did you know that the sea horse has some kind of strange maternal instinct. The male that is apparently he carries the young in a brute power outage and ultimately when they're ready to emerge he gives birth to the young sea horses. Then a rather romantic animal is a worm known as the

pillow. Its name suggests the South Seas and that's where this worm hails from. Apparently this creature is moved by cycles and rhythms which are rather unique. We're all pretty familiar with the menstrual cycle and there seems to be a certain reasonableness about tying something in with the phases of the moon every month. In the case of the Palermo worm However there are apparently two or three nights only in which sexual activity takes place during the course of a year. In some fashion the worm is driven by the need to shed sperm and eggs a couple nights after the full moon and the highest tides in the South Pacific. So this happened seven or eight days after high tide in

November and another time in October. Apart from that the animal is rarely seen. There's a similar creature on the west coast known as the Grunion. The type of fish which behaves pretty much the same way and I suppose for any ambitious awhile Aji students here tonight as might be and I study to determine what is the common factor. Back of this particular cycle in both the Grunion and the polow. Now. The granules behavior is quite colorful. On the highest tide. She moves up towards the beach closely followed by her husband male partner. And. With the highest wave gets real high up on the beach. And with her tail actually digs a hole in the sand and lays her eggs. And as the male sprays of sperm onto the eggs

both of them proceed back into the ocean never coming back to see their children Atar and the kids emerge about 10 or 12 days later again at high tide. So they hit the first big wave and go back into the sea. These are very colorful kinds of stories and the forces which drive them are indeed intriguing. As I said that's not the subject of our discourse tonight. Let me add a few other oddities from the animal world in regard to diversity of reproductive habits that exist. There is a very suspicious male spider I think has good reason to be suspicious because if he moves into quite a lady he's likely to get eaten up. He circumvents this by sneaking up on her wrapping or open a silk shroud

and then proceeds to work as well. And succeeds in carrying on the species by having intercourse under those circumstances. Another rather curious animal is a fishing frog also lives in the sea. The male has a rather tiny creature and his partner is fairly large. What he perceives to do is to sink his teeth into a spot on our. Back. And he remains there practically for the rest of his life. He just stays put till ultimately the circulation of the female becomes pretty much the circulation of the male and this is excellent timing because just at the time that she is ready to produce eggs he gets the signal through this common bloodstream and produces sperm while up for it was Asian.

Briefly most of you are probably familiar with the queen bee who takes off on a flight from the hive and has a number of swains pursuing her. Most of them drop by the wayside. One sturdy character finally catches up mates with her and then promptly dies. Because he leaves in her. What is the equivalent of a penis. Along with testicles. And now she has both egg and sperm to manipulate as she will. And in effect she can control whether the actually produces are fertilized or not. Sort of anticlimactic is the behavior of the federal. Too late the follow up was a play which I never got to see but I don't know I can imagine. Perhaps what the subject matter is the Faroes is another one of these natural situations or should I say situations in nature in

which there was a kind of reversal of roles. And here the female is the one with the plumage. And humans of course this is not unfamiliar. But in the animal world it's generally the male is kind of Granny. But this is reversed and so the male is kind of dull and he's consigned to sitting on the nest and hatching the eggs while his lady goes sporting. And then one final tidbit out of the animal world. A certain type of fish picks up the fertilized eggs. After this has been accomplished and preserves them in his mouth and at the appropriate time simply regurgitate the young fish. And that's their mode of marriage and childrearing. What with that diversion I think I'll proceed to some of the matter that I really

focused on. I mentioned. Oh I'm sorry. As I said the prospect of covering such a large field sort of scared me when I first glimpsed some of the possible attacks on the problem. But I was helped finally to a solution to the problem. Of what to cover in this one hour by two articles I read recently in two separate popular medical journals. The first story is headed. Three Americans share the Nobel Prize for work on the replication of viruses. The other account is succinctly labeled artificial placenta sustains the fetal lamb. And is dramatically illustrated by a

photo of a lamb. Reclining in what looks like a fish tank full of fluid. Those people up front may be able to see this I'm sorry I don't have a slide to me Jack but there is a picture of a nice lamb I squalled reclining in a fish tank full of fluid with some pipes attached to it. I thought as I read the two articles. Here in a way they are the opposite poles in the research efforts of our scientific investigators. The one an attempt to recreate the environment of the war from a mammal like ourselves and the other a search for the key to the mystery of reproduction and life itself in organisms so tiny only the electron microscope renders them visible. What I shall attempt to do now is share

with you some of the knowledge. About reproduction obtained through clinical observations and laboratory determinations in humans and other organisms. I shall also try to give you some idea of the microscopic and molecular data underlying modern day concepts of reproduction and related problems. Related problems if we have time may well include some ideas in regard to the causation of cancer and also the relationship of some of the genetic chemicals to the process of memory. Present day children are unlikely to be misinformed about their origins. I grew up in an era when parents still told their kids that stocks brought them from heaven or that they came from some unknown place. Through the agency of the doctor's little black bag.

There were a peace of course were deliberate mistruth rationalized as necessary for reasons of modesty or morality. Primitive societies were not inhibited by such considerations. Give the children every opportunity to learn at first hand the facts of life. However they too fall into error and many primitive peoples fail to connect the cointel sexual act with conception. Pregnancy is variously ascribed to some direct influence by the sea or the moon or even lizards. Only three hundred years ago all educated men believed that the egg contained an embryo. Just like that. Whose growth depended upon activation by the sperm. An alternative hypothesis was that the sperm contained the embryo which had

to be deposited in the ovum for further growth to take place. Luhan hawk the Grand Old Man of the microscope living in about that time turned his lenses on sperm and thought he could make out the embryo there in. So you see prevailing ideas can certainly influence them. Most quotes objective investigator. Many believed or selves that some forms of life came into being through a spontaneous generation. Insects arose from garbage and rodents from rags in the middle of the 19th century. Louis passed term laid to rest the idea that organisms could arise by spontaneous generation. Modern bacteriology now are more often called microbiology rests on the foundation Louis Pastore built in his work on fermentation and his demonstration that the

decomposition of organic matter is due to the action of microorganisms. I think it was balance Sanny as quoted by Paul the proof some years ago who said microbes must have parents. The human egg or ovum is present in great numbers in the ovaries at birth. One think I read something in the neighborhood of 300000000 another author already stated something like 100000 to 200000. These are all Ogoni of which are the predecessors of eggs that are likely to become fertilized. Now puberty that number has reduced to about 40000. The others deteriorate. Assuming that active production of eggs goes on for about 30 years in the human female and that there are about 12 menstrual cycles per year about 300 to 400 over actually become available for

fertilization during the lifespan of women. Roughly that means that about 1 ovum for every hundred present in the ovaries is released for possible conjunction with sperm. The nail is certainly prolix. As primitives or produced as you know in the testicles in enormous numbers as high as 200 million have been estimated in a single ejaculation. Now the factual basis for the understanding of reproduction was established in 1875 when her twig was able to observe and recognize the events for it was Asian. The cell theory had been established by slight Nish one about that time who demonstrated that Sal was with a unit of structure of most organisms tissues organs and the whole

creature really aggregates of individual cells both sperm and ovum were now shown to be cells. The human organism composed of billions of billions of cells destructed a skin bone muscle blood nerves and so on is derived from a single cell contributed by the father and a single cell from the mother. The fusion of these elements into the zygote a single cell again with the nuclear elements of sperm and ovum begins the complicated development culminating at birth and the appearance of a new human. A remarkable series of events occurs following a sexual intercourse destined to accomplish conception. Sperm deposited in the vagina progresses upward through the cervix of the

uterus into the body of that organ and out again into the organ duct saw fallopian tubes which connect the uterus with the ovaries. The egg meets numerous Burma's high up in the fallopian tube and is penetrated by one of them though several may enter the outer arm of the ovum. However only one sperm nucleus fuses with the egg because. The zygote or fertilized egg now divides into two cells then four then eight and so on. As cell division and growth takes place in the early stages of the embryo. The blastula as the spherical aggregate of cells is called goes back the way the sperm came from the fallopian tube into the uterus. This ball of cells burrows into the uterine

wall and continues dividing. For nine months cellular division will go on with gradual differentiation from the blastula stage into more and more complex arrangements. Now embryos at different ages obtain either through a spontaneous abortions or those induced was a therapeutic reasons have been intensively studied. The beginnings of the various organs and their final differentiation. Have been plotted on a fairly accurate timetable. In general we know when eye formation begins and when the eye is finally finished as a seeing Type organ. Similarly for the heart and nervous system muscles bones and so forth. In many instances when a child is born with a specific defect we can tell at what point in the intrauterine development things went wrong.

Now in this connection the United Nations scientific committee on the effects of atomic radiation reported recently that many of the children born in Hiroshima and Nagasaki who had been in the womb when the bombs exploded there are now mentally retarded. And I say numerous and beans in contrast with control groups of the same age who are not exposed to. Gamma rays at that time. Now the greatest number of such individuals is mentally defective kids with those who are in the uterus at about the 13th and 14th week of just Asian. When the bomb fell. This suggests that it was at that period that brain vulnerability to radiation is greatest. Remarkable additions to our knowledge of the little living embryo have been

accumulating in the past several years. In part. This is a consequence of studies done on the amniotic fluid. The one element surrounding the embryo popularly called the Bag of waters the amniotic sac and its contents provide a protective and probably a nutrient the nutritive ambience for the fetus. This sack can be quite readily pierced by a needle inserted through the abdominal wall. And fluid removed without much risk to the fetus. Interestingly a blunt object like a needle that has a shield on it striking the fetus elicits an avoidance movement. The fetus seems to swim away from the intruding instrument. Many such punctures of the amniotic sac have been done for a variety of reasons. For example to determine the state of the fetus in cases of our age in

compatibility to determine the presence or absence of certain important chemical substances like enzymes and eye bodies. And finally to study the chromosome pattern. Of the child in utero. What is the object of such intrusions into the fetal world. Perhaps not too far in the future we shall be able to diagnose abnormal conditions in the developing embryo and institute treatment to correct the defect or deficiency. As a matter of fact. Transfusions have and have indeed been given to the fetus in some instances and the correction of serious anemia accomplished. Surgical procedures have even been done not animal fetuses without interfering with the progress progress of the pregnancy. The land that I mentioned at the beginning of this talk was

removed before term Bice's Aryan section and placed in an artificial womb and provided with a mechanical placenta. This man was carried along for 20 hours in this artificial uterus and then allowed to begin life as a newborn outside the tank with its man made any out of fluid. The animal survives and thrives and apparently I'm normal young sheep. The experiment is not just a clever trick it offers the prospect of really treatment of individuals with under developed lungs due to prematurity. I quote doctors say Paul one of the inventors of the operators who says. Many fetuses delivered at 20 to 28 weeks could be saved by giving them aspire a Tory supporter why their lungs finish developing. Another big dream of the future is the possibility of correcting chemical

defects like cystic fibrosis Fino getting urea and diabetes before birth so that a new born child will not be at a disadvantage in his growth and development to adult. Up to this point in our discussion I've given you a rather generalized account of events from conception to birth of a human child. We have described the success of the visions of the zygote a fertilized egg into two cells and four eight and so on. The mechanism which causes cells to arrange themselves in certain forms so that a blood vessel will result or a leg or an ear. This is unknown. The cells which originate from those I go in the earliest divisions have the potentiality of developing into complete individuals. Each cell In the two cell stage can separate from its companion cells and originate a new cluster of cells which ultimately can

become a whole individual. In this you will recognize the way in which identical twins are formed. Now if this separate roll of each cell were to take place in the four cell stage identical quadruplets would result. Cells with such capabilities are called Toti potent. Each cell must have received from the zygote identical substances capable of directing cell divisions and the systematic development needed to produce a complete individual from animal studies. We know that the material that is present in the nucleus of the zygote and which is distributed equally to each daughter cell that was ours and the division of the fertilized ovum is chroma to Comet in that form must be the bearer of heredity. The stuff which in the zygote of the cat dictates the development of kittens in the dog puppies and in the human human

babies. Commenting can be seen under the microscope in dividing cells and for each species there is a constant number of characteristically shaped bodies of chromosomes. Every cell in the human being with one important exception has 46 chromosomes which can be identified as 23 pairs. In the fruit fly the chromosome number is 8 and in the chimpanzee the number is 48 to extra chromosome don't necessarily mean any superiority. The one exception I mentioned is the sex sell or get meet the right bag and that your sperm each has one have the chromosome number of the rest of the body cells. When fertilization occurs the chromosome number of the zygote is then the same as for all the other cells in the human this parent has 23 chromosomes. As does the egg. The

zygote thus has 23 pairs each pair having both a paternal and maternal chromosome. Chromosomes. Arrangements of genes which in turn are the factors determining individual traits like eye color height hair color shape of years possibly intelligence amount of insulin in the pancreas types of hemoglobin and so on. In the early divisions of the zygote the genes in any one cell must be doing the same work going on in every other totally potent cell. However at some time in the course of development certain cells start to differ from their neighbors. Some go on to become bone cells others become skin or blood or muscle or brain. The genes must not all be acting in the same way. Those which influence the cell to manufacture

hemoglobin will not be signaling for skin or bone. Those directing the manufacture of insulin will not be concerned with producing the rocks. And ingenious and dramatic experiment which illuminates to a degree the enigma of cell the pre and differentiation and its relationship to the gene complement in the soundless is the following. With micro surgical techniques it is possible to take the nucleus of an intestinal cell of an adult frog and free it of the cytoplasm. At the same time the nucleus of a fertilized egg of a fertilized frog egg was similarly distracted out. The intestinal cell nucleus was then implanted into the egg that had lost its nucleus the egg was permitted to resume its development in a tank with the required from stuff in oxygen. It began to divide

form a ball of cells of last July and eventually grew into a respectable looking temple. Had the intestinal salad not been the subject of this experiment. It would have gone on doing what intestinal cells do. It's accreting enzymes for digestion of food producing move and functioning as part of the lining of the gut all under the direction of the genes of the chromosomes in its nucleus. The fertilized egg with the intestinal nucleus behaves as if it still retained its original putting it in other terms. That combination of genes necessary for the proper activation of an intestinal cell or inactive when the organism is a zygote a single cell. Once differentiation as proceeded to the point. Where is a God which must function the necessary genes switch on all other switch off when the differentiated nucleus is

placed in an environment of non differentiation. The genes having to do with intestinal function stop acting those needed for early embryonic development resume activity. Now this leads to the feeling among scientists that all the genes for all functions. A president can follow in the nucleus of every cell in the body. We can now redefine our discourse reproduction the mystery of life remains mysterious but less so. We're quite knowledgeable about the anatomy and physiology of reproduction in ourselves as well as in most creatures. Simply stated to reproduce a human being. What is required is the nuclear contents of a spare wrist Sepideh egg with its nucleus and the proper environment for the fertilized egg or zygote to divide and continue to divide to grow and continue to grow

until the full term fetus is formed ready for delivery. Brilliant brilliantly achieved in the current generation is the knowledge of the nature of the nuclear contents the chromosomes and their constituent genes. Through advances in molecular chemistry and genetic theory we have reached the point where we can say that the crux of the problem the individual's reproduction is the problem of chromosome reproduction or replication which in turn is dependent upon molecular reproduction. The growth of the cell. Ultimately its division into two cells requires a manufacture or synthesis of a variety of substances. And among the most complex materials the proteins. These have been studied for many years. There's only been since World War Two that methods of analyzing protein have been available. The invention of such

things as the high speed sought refuge chromatography and X-ray crystallography only in the past 20 years or so gave the organic chemist the means to analyze the components of protein enzymes which have become a household word as competitors of the detergents are also proteins. In cell and body metabolism they are extremely important. Being involved in a great variety of metabolic tasks. The key to protein formation in the cell lives in the nucleus and specifically in the chromosomes and their component genes. But before we can determine how the gene directs the production of protein we have to know what protein is. Protein of humans and most other organisms consists of the elements carbon oxygen hydrogen nitrogen arranged in a characteristic way in sub units called amino acids.

Other elements also enter into protein structure but our focus will not be on them in this discussion. Amino acids are the building blocks of protein. 20 of them are identifiable in the protein molecule which is made up of the springs or sequences of amino acids. These amino acid sequences are also referred to as poly peptide. The structure of many proteins have been worked out in recent years and some of in some of the size in the laboratory. So the way in which they are put together is pretty clear. Normal adult human hemoglobin the red pigment of our red blood cells is a protein consisting of two pairs of amino acid chains designated alpha and beta respectively. Each Alpha chain has one hundred forty one amino acids each made a chain as a hundred forty six amino acid that only the number of the amino acids has been determined but also the sequence in which their hits together.

Linus Pauling an outstanding champion of civil rights and an eminent investigator in many areas of science made a great contribution to molecular research when he suggested that the abnormal behavior of the hemoglobin of sufferers from sickle cell disease was due to a chemical difference from normal adult human hemoglobin sickle cell anemia or disease. It has to do with certain activities of red blood cells which under state conditions are likely to turn into crescent shaped things which stick together and result in from both cities. They then clog up blood vessels and you get all kinds of symptoms from leg ulcers to paralysis of one side to coma and that and mortality rate among people suffering from this pretty high. Well colleagues of Linus Pauling firing up his suggestions were

able to demonstrate that the molecular structure of sickle cell disease that is of hemoglobin wizen D different from normal hemoglobin. It was known that the condition was in the heritage in the Indian fashion and that Im a globe and gene for sickle cell is a mutant from the normal gene which produces adult human hemoglobin called a 1. The exact difference between sickle cell hemoglobin and the normal is finally determined to be just one amino acid in the hundred and forty six of the beta chain. It was logical to conclude then that the gene giving rise to the BETA team of amino acids in sickle cell disease was different than the gene for normal in the bone and the beta chain containing questions then arose. How do genes determine the protein structure. What

differences are there in mutated genes for these answers we must turn to the chemistry of the chromosomes chromosomes have been analyzed and found to consist of proteins and substances called nucleic acids. For a long time it was thought that must be the chromosome of the protein that results in the reproduction of more protein. Two significant experiments establish the fact that it was a protein. In the experiments the subject of study was in the one instance bacteria and in the second case viruses. I should add that both kinds of organisms are extremely important in molecular biology and much of what we know today stands from studies done on these organisms. Experiment number one involve two strains of pneumococcus a bacterium which can cause pneumonia and one strain has a capsule

and is designated to be a strain or smooth strain because its colleagues have a smooth configuration. The R strain or rough strain is without a capsule and it's called these are as you can guess rough an outline whereas both of these are strain and the ass usually give rise only to bacteria like themselves. Occasionally an arced brain will mutate spontaneously and as such mutated bacteria then go on to produce smoove type colonies. In this sense viruses are like humans. Mutations occur once in a while but in the micro organism The occur more frequently and are more easily detected. One researcher found that the added killed S type a small bacteria to colonies of the or rough type he was able to produce a new mutation to the S-type practically at will. The reason then that the

smooth pneumococcus must have a gene for capsule production. But the rock does not. The dead as bacteria then must contribute something of the nature of Gene material so that it could act like the archetype. On further analysis it was found that an extract of the smoove type organisms produced the mutation just as well as the whole kill bacteria. When this X extract was analyzed it was found to be nuclear capacity and not protein. The experiment with viruses led to the same conclusion. Nuclear gas it is a substance in the chromosomes which is responsible for protein synthesis by the cell. Viruses are not visible except with the electron microscope. With this instrument one can see that most viruses consist of two major parts and then a core and an outer coat refined chemical techniques

led to the conclusion that the code is protein in nature and that the inner core is nuclear as it was also observed that one can get the core without the code into a bacterium. And this kind of virus feeds on bacteria and then this core inserted alone into the body of the bacterium would reproduce not only another core but also would reproduce the protein coat. So a pretty good case was made out for nuclear asset as being the determining factor in the production of protein and bacteria and viruses. And the conclusion is that in humans too. The nuclear gasses are responsible for the synthesis of proteins in cells. Now an important aspect of nuclear capacity is the fact that it can we

constitute itself and in terms of cell division this will be extremely important because as we've mentioned the chromosomes are handed on from generation to generation after appropriately dividing. And it would be necessary for some kind of chemical substance which could do this to perform that kind of stuff. The next step in elucidating the mechanisms of cellular inheritance was a correlation of the structure of nuclear gases and its signals to the cell to produce specific kinds of protein. The concept of a genetic code reflects the theory that nuclear arsenal act as a blueprint or template for the production of proteins and Symes in by the cell for its metabolism growth and reproduction. At this point. I'll list the essential conclusions regarding the genetic code without going further into the evidence leading to these principles.

If my words are not easily grasped don't be upset. I will try to clarify them later when we present some slides. The major component of human chromosomes is the nuclear acid de oxy rubber nuclear gases. It can. It consists of a sugar a phosphor of acid and substances which we shall call simply bases. That the four bases or rather significant aspects of D and E as the oxy vitamin D gases from your link on. The order in which these bases occur appears to determine the kind of amino acids that will be manufactured. To spell out a single amino acid a sequence of three bases is required if we designate the four bases by the initial letter in each of them namely G and C. Then they can be 64

combinations of 3 letters to arrive. These are called Triplets. Illustrate with a hypothetical situation. So pause and give them protein which will call protein anything has a string of amino acids in the sequence and all avenues to see an entire city in fennel alanine is the determinant determined by the triplet 18 and those seen by the triplet TTC and tyrosine by TTC. And that is the order in which the bases would be arranged. And in this fashion would convey the message to the cell to make protein. This also suggests the chemical basis for mutation. If the order of basis is disturbed if

in the process a chromosome we duplications. If the DNA molecule fails to copy itself exactly. And let's say he introduces the wrong letter. Then a different amino acid will be called for and in turn a different protein will emerge and in consequence the behavior of the individual will be affected much as in the instance of sickle cell hemoglobin in sickle cell disease. Will the further comments on the the acid and genetic theory for later. I should like to mention briefly another suspected world of nuclear gases in a sense when a cell produces protein when it divides and produces two replicas of itself. It exhibits a kind of memory. A pattern of reaction is stored in the nucleus to be put into action when required.

This analogy to memory or perhaps to data processing that some investigators do wonder whether what we call memory in ourselves might not be needed by nuclear gas in the brain cells. Some experiments with my seem to show that animals trained to do certain tasks develop what we asked in the gang in cells involved in those particular acts. Of a clinical investigators have been attacked and been attempting to improve the memory of individuals sometimes as well along in age whose memory begins to fail and they have enriched their diet with stores of DNA or RNA. To date there has been no confirmed result. Nothing that we get this positive. When our discussion of reproduction began with the consideration of the cellular aspects a friend

was Asian and we had Gen.. We then focused on nuclear events and cell division. The distribution of chromosomes to the descendants of the fertilized ovum. Next we inquired into the nature of protein including enzymes and looked for answers to the problem of that since synthesis by the cells that put its nuclear protein the basic ingredient of the genes a kind of computer plant for the cell and the blueprint for everything from itself to the completed organism. The living things under discussion with the human bacteria and viruses the mysteries of reproduction and heredity partly clarified. Through molecular chemistry and exist in similar form in single cell microorganisms as well as in the billion fold complexity of man. Answers to the one provide answers to the other. You've heard Dr. Edward Kendall speaking on the topic reproduction the mystery of

life. This was one of the 969 series of lectures recorded at the great hall of the Cooper Union in New York City by station WNYC. The chairman for the Cooper Union was Johnson a Fairchild. This program was distributed by the national educational radio network.