Professor Robert McKinnell, of the Department of Genetics and Cell Biology at the University of Minnesota, talks with MPR’s science reporter Rich Dietman about the controversy and research concerning cloning.
Read the Text Transcription of the Audio.
Cloning is a word that is rich in biological meeting. And since it is so rich. I think we had better for the purposes of this discussion narrow it down two nuclear transplantation cloning can be used as a word that describes reproduction in a certain type of reproduction in plants. It is used in molecular biology. It's used in microbiology for our purposes today. I think we can talk about cloning and terms of nuclear transplantation because to the layperson, this is the procedure that that is being referred to in the newspapers in the magazines and so far. So what is nuclear transplantation nuclear transplantation is a means by which animals most notably frogs can be produced.With the genetic material of a body spell inserted into an egg that has been deprived of its genetic material and what is genetic material was so we can rephrase that by saying is putting the DNA component of a body cell into an egg that's been deprived of its nuclear DNA. What you do is take cell when you say a body cell a skin cell or a muscle cell and you remove the nucleus of that sell and you take the nucleus from the sale of another animal and you take that nucleus and you put it into the cell that has been deprived of its nucleus that would be nuclear transplantation. But we put the nucleus of a body cell into a special kind of cell and egg cell and the reason we use an egg cell instead of a skin cell or a liver cell or brain cell.Is that the egg cell has all of the nutrients and support mechanisms to get an organism going or so then say Martha Salas Kinsale. So we take the Excel and Riri remove its DNA do we remove is its genetic instructions? So it's sitting there with all the support mechanisms, but without a set of blueprints of sort of like a Akon contractor who has a steel and the bricks and a sand and cement sitting on a vacant lot waiting for the architect to bring the blueprints when the blueprints arrived in this case the nucleus of another cell.The DNA of another cell then the two of us put together and if circumstances are right and that means if there is a some Harmony and the developmental system that is constructed then a patent a tadpole May develop a young organism May develop for an adult organism made $2, depending upon circumstances which are not at all thoroughly understood even a 1979. Well, there is a long history of frogs. I think you can imagine that it would be extremely difficult to take eggs from a soil or from a a an elephant or from a mouse and manipulate those for experiments in nuclear transplantation. As a matter of fact, you can do that now, but when this one this business was started when the cloning procedure was I was started the experimental organism of choice was a frog because of fog Hanford.2018 you can I watch the development of these eggs in a simple laboratory dish that's easy to work with imagine trying to get 2000 South eggs for instance. It can be done but it is not at all easy and I think biologists like business people like anybody else want to do it in a in a reasonable system. That's that's technically feasible to manage. And so we use frogs and besides that there's a long history of experimental embryology with frogs the experiments that preceded what we might do today call cloning. For some reason we have a feeling that cloning is right on the frontiers of Science and it's just brand new as a matter of fact, the ideas have been with us for many many years. I suppose that concern for what the nucleus of a cell can do probably.Is back to the late 19th century? Early embryologist when they have good microscopes could see you that I sell was constructed of a nucleus and cytoplasm. They knew that the nucleus underwent gyrations wearing chromosomes were formed in the chromosomes pull apart and this followed a very beautiful pattern and I think my heart just simply asked a question. You know, what what is the significance of these chromosomes and this nuclear material one notable person who was from the University of Freiburg by the name of Hans spemann on spam and said there is a way of testing this and I won't go into the details of that unless you're particularly interested in the details, but Hans payment I put a noose that is a lasso riaa Loop of hair and having a baby here, which was a very fine monofilament of the day. They didn't have nine. I'm back in the late 19th century and early twentieth-century. So you was baby hair you put a baby hair noose around a freshly fertilized and fibia neg. This was the frog with a salamander, but the principle is the same and he constricted the news until the egg was dumbbell shaped and if the egg was freshly fertilized, which it was then it could only have a nucleus in one portion of the dumbbell the other portion of the dumbbell with nucleus less. It was deprived of DNA only he didn't use the word DNA in those days. He then said what will happen if I keep this news around the egg for a while. But what happened was that the nucleated portion that is a portion that contain the genetic material divided and it divided again and a divided again until there was a small cluster of cells Then he said if I loosen the news and allow one of the descendants of that original nucleus and course now there were many nuclei if I allow one of the descendants of that original nucleus to Traverse the little bit of egg and go over to the other portion of the dumbbell that the non-nucleated portion is that I can ask a question. I can ask Will a descendant of a nucleus still contain all of the genetic determinants. He didn't even use the word Gene. So you talked about determinants. Well the that nucleus contain all the genetic determinants to farm a full embryo or simply a partial embryo. So you did Extremely Loud one of these nuclei to Traverse over to the other part to Traverse the cytoplasm over to the other part of the egg. Then he separated the two fragments the original portion of the egg developed into a whole and complete embryo and so did the second portion. So he said that as a nucleus divides, it does not divide the determinants rather. It replicates did the determinants and I caused any person who takes General biology today knows that any person who takes high school biology notes after that was a remarkable observations of the day and I would like to point out that that second embryo was a cloned embryo it was it an embryo produced by nuclear transplantation without a sex act therefore. It was a asexually reproducing. So, it's January cloning and Percy's experiments were taking place right at the turn of the century. So they're quite old there are some animals that reproduce at least occasionally. Asexually aren't they and that in natural conditions? So in effect while they they it's not referred to as cloning at least I don't think it is. It is similar. It's closer to what what we might get from a clone the botanist refer to a sexual reproduction is cloning and there is absolutely no reason why you couldn't refer to the asexual reproduction in animals as cloning. They said they saw those are certainly phones in the sand in the original meaning of the word the word template means a butt or a snap part wig and her friend since in the case of hydro, which is a freshwater animal person or a Minnesota Street and she's take off freshwater Hydra and look at it under the microscope is very tiny. You can see that the Simpsons off Buds and taste buds form full. Hydro complete Hydra asexual reproduction is cloning. As you well know there is a great deal of work on your way at least some centers in this country and around the world dealing with cloning and the as far as I know and understand it's being done mostly with very small organisms bacteria different kinds and these bacteria are being cloned in such a way so that they will produce certain things that are helpful to humans notably insulin and some other hormones which have recently been produced by cloned bacteria. What about cloning and higher animals? Let's say in mammals. Why is it that you intend at least that it's gets more and more difficult to produce clones as you get into more complex organisms. I think the best thing that a scientist can do in 1979 is to answer a question like that by saying I don't know. I really don't know and I don't say that facetiously I said just as simply as a as a a statement of fact and then neither does anybody else know there are no cloned mice. There are no clone cows and there are no clone people. Now I make this statement because I am a Scientist and I follow the scientific literature there on Oaklawn mice and Oaklawn people. Now you might say well aren't there newspaper accounts of this and the answer is there are some newspaper accounts which are generally considered by the scientific community community. Probably not be true. So at least in the scientific literature there is No, such thing as a clone mammoths and your question is why and my answer is I don't know a Nobel laureates add recently. We haven't cloned mice are mammals are the mammals because the mammalian egg is too small to manipulate with the instruments that we have. That's a simply is not true. I can make mistakes open a Nobel Laureate make mistakes and this particular Nobel Laureate and medicine as a matter of fact, I made a ghastly mistake because the mammalian egg has been micromanipulator has been punctured. It's been operated on and it has survived these operations for literally for years. And this is in the scientific literature so we know we can take a I'm a million a week and punctured we can add material. You can remove material then we can take that mammalian egg if it's been fertilized and place it into the womb of a surrogate mother. And with proper genetic tags, that is dark hair color in a white mouse for instance of white hair color in a dark Mouse with appropriate genetic tags. We could show that the little mouse Barn sounds three weeks later was a mouse that develop from that operated egg, but the egg has not developed as a result of the cloning procedure. The cloning procedure has not been successful and any mammalian species despite the fact it's been studied in European lab Laboratories and the legs have been studied in American Laboratories literally for years. So we don't know I suspect and simply him is only a matter of time that we know more about mammalian eggs and I suspect that in sometime in the future that we will be successful in some of these experiments What is why isn't that cloning? What's the difference between cloning? And as you said taking of the egg from a mouse and implanting it with the genetic material from another mouse and then putting it back in but what I was referring to to marking the egg so that we know that it's the operated egg that is survived Shakespeare. But actually it's not a matter of inserting a nucleus that has been obtained from a body cell that was these experiments that I'm referring to that have taken place in California that have taken place in Poland have taken place in several Laboratories in England these experiments involve taking a mouse egg and puncturing it as I said adding cytoplasmic material or adding some other kind of chemical but not adding a nucleus. Drew nuclear transplantation has not occurred with mammalian eggs. With a viable cloned organism resulting now. Let me repeat that or let me paraphrase it. Cloning with a viable mouse or rabbit hat as a result of the experiment has never taken place now certainly investigators have taken mammalian eggs rapid eggs and mice eggs and happy nucleated the eggs much as we do in frogs and have inserted into these enucleated egg nucleus. So yes nuclear transplantation has taken place. This is the first step in cloning. Has a mouse a rabbit or a human being ensued from these experiments. The answer is no and some cases it will start to divide some cases of egg with former small cluster of cells, but thus far these eggs have died. So now and why did they died which was your question a little while ago? I don't know why they died and neither do the investigators. Who do these experiments know why they died. We simply have to plead ignorance. There have been some very Sensational stories in the media and also at least one book which was written that I believe last year or the year before that claimed that human being had been cloned and it's my sense from your book that you wrote it at least in part to put some things in perspective particularly with regard to some of those more Sensational reports. Is that true. Did you feel when you set out to write this book that you were going to try and put this ship put this whole matter of cloning the whole process of cloning in some perspective and if so, what is that perspective that book you alert allude to is probably David Roberts book and David Robert did as a matter of fact stimulate a lot of interest in this area to the extent that the House of Representatives with a subcommittee on healthy environment held hearings and you testified and I testified at those hair. And I really looked forward to those hearings because David Robert had been invited. Let me tell you a little bit about that. He was invited to testify at these hearings and he said he wasn't well and was unable to appear. So the hearings were delayed until he would be well and a new date was set and he was invited again and the second time he said he would appear but at the second time that he said he would appear he failed to appear. He said he was off selling his book that was more important. So none of us scientists who were looking forward to meeting David dobrik. He was going to tell us all all about the things that we didn't know about David Roberts refuse to appear so we never got to hear him speak, but we did have our hearings and there are newspaper accounts. Some of them were elegantly written. It is appropriate to mention a local newspaper. I'll Luc hope and the Minneapolis Tribune wrote a superb review of nuclear transplantation. And the story is literally can dance to about a half a page of newsprint and it the story is told with great Precision. It's not an error has to my knowledge in that entire story. But that's sort of an exception a many of the stories that originated from those herrings work were inaccurate. And so I thought well a year has elapsed since those hearing perhaps the the dust has settled and perhaps the time to tell the story again and they say why we do our experiments and they say what kind of results we get. So yes, this this relates to to the publicity that was That occurred about a year ago and hopefully now after yard now the dust has settled raps are not quite so excited perhaps now we can look at it again and instead of of clouding the issue with whether or not a human being has been cloned. Let's say what the biologists are interested in when they do these experiments. It's my sense that person would have to have some knowledge of basic biology in order to get much out of your book. Is that is that you're feeling to not I think that Telling any story requires a little bit of effort upon the on the part of the reader. I will acknowledge that if I look at A Treatise on economics if I look at a discourse on molecular cloning, if I look at a report on the future economic productivity of that of the Twin Cities or whatever it takes it takes some effort and I think probably takes a little effort effort to read this book, but I I think that any person is willing to put a little effort into it to think about what the sentences mean and read it slowly and carefully I think that most people most thoughtful people will find that the story will come through and the story that I want to tell in that particular book is a story that biologists don't simply Do experiments for the for the fun of it. There is a rationale for our experiments in the first place it cost money to do biological research and dollars are scared and dollars are hard to come by so we don't waste those precious resources asking for velous questions. And so I go to some lengths in the chapters and that book just say what are the not frivolous questions that we relate to that we work with when we do cloning experiments and none of these. None of these relate to the reproduction of a human being and I got all the way through. I think it's in the FB log. I say that money spent in biomedical research search should address health problems of the American people after all they pay taxes and the Good Ole American people want something for their tax dollars. They spend the tax dollars with the anticipation that problem such as aging problem such as cancer and some of the others that I dress in this book will be solved. If not solved that will learn something about these problems so that other people will work in these areas and eventually will we will control these these problems we spend money in this area for the benefit of human beings. We don't spend money to reproduce other people. Asexually reproduction is not the problem. We've got plenty of people in America and plenty of people in the world. We don't need to reproduce some asexual. What we need to do is solve existing problems. How are what are some of the ways in which cloning can be used as a tool to help solve some of medical problems like cancer and a drink that you mention cancer first. And this is a story has been told over and over again, but it's not solved the others cancer solved, you know, some people say wanted to put cloning you haven't cured cancer with cloning. Well neither. Does anybody else cured cancer accepting a very limited sense? Of course, some cancer patients are cured by surgery radiation chemotherapy, but nevertheless it's an awful problem and there are many biologists and biomedical scientist who are concerned about this awful problem. And just to make a long story relatively short some of us who have done cloning research on nuclear transplantation research think that we would like to First characterize at least some kinds of cancer with respect to their capability of giving rise to other kinds of cells and if we can characterize cancer cells by their capability of giving each other kind of cells then perhaps we can gain insight into the controls that allow us to produce other kinds of self. So what we have done is the following this is a real quick simplified version bluebirds earthworms people and frogs all have cancer since we work with Roswell talk about frog cancer. Frogs have cancer in Saint Chris nuclear transplantation was first developed that is a cloning procedure was first developed in frogs. What we can do is take a frog egg and remove its nucleus just as we have done and other conventional cloning experiments, but instead of taking a a a nucleus from a lung cell or a nucleus from a skin cell or nucleus from a gut cell we can go to one of those Cancers and take the nucleus from a cancer cell but my malignant tumor and put that nucleus and to the previously enucleated a now. I suppose you could say three things may happen. When is it can just sit there with us introduced malignant nucleus and do nothing. The transplanted egg with a cancer nucleus in it might divide and form of all of cancer cells know this is those are two possibilities. And neither of those occurs are finally that transplanted egg can develop into some kind of an organism and it does it develops into a tadpole and the tadpole is muscle has got it has scam that has eyes and has a brain and I can swim now every single cell and every nucleus of every cell is a descendant from a previously enucleated egg, but they're no longer giving rise to cancer cells. They're giving rise to normal cells are near normal self. They're not really no more than your normal to the point that we have a tadpole and we feel that if we can characterize what it is about the egg cytoplasm that tells that cancer cell nucleus don't produce more cancer nuclei produced normal nuclei are near nominal. If we can understand those controls, we feel that we can go a long way to providing useful information that perhaps clinicians can exploit. As I say distressingly down the pipe 5 years or 10 years, but hopefully someday it may be useful. One of the one of the focuses then he isn't so much the finished product. Is that what goes on between that the very very fine layer between the nucleus and the cytoplasm and that you're trying to understand more about what goes on in terms of the transmission of messages that transmission of messages the interactions. It's hard to say this about moving one's hands. There is an interaction between the nucleus and the cytoplasm that those are those incident like that. Those words are classic words and an experimental embryology. We talked about nucleocytoplasmic interaction. We know that material flows from the cytoplasm in the nucleus, and we also know that information flows from the grease out of the cytoplasm and we know there are controls that I use the word earlier constrain with that can with respect to human beings. Now we're talkin about nuclei that are constrained. We know that there are messages or That constrains that inserted nucleus to do something that is harmonious with the cytoplasm and we want to know more about that. So we know what the controls are with respect to genetic information specifically with respect abnormal genetic information. We want to be able to control malignant cells biologically rather than with guns. So to speak if you think about it the marvelous surgeon that removes a malignant tumor doesn't cure the tumor. He removes it the tumor still a tumor is not been it has been removed from the patient and that's a marvelous thing. The radiologist who x-rays that tumor isn't curing a tumor you make sure the patient but he's not curing the tumor the radiation kills tumor cells and the chemo therapist who gives the the cancer patient a drug is not curing a a cancer cell. He's killing a cancer cell. And we and I can tell you I will make it personal it personal I would be happy to have surgery and radiation and chemotherapy if necessary If I Had a Million it too much because that's all it's available. But there are biologists and Physicians who looking ahead to the next generation of how one manages cancer and if it wouldn't it be nice if we knew enough about cell biology wouldn't it be nice if we know enough about cell biology that we can manipulate those cells and make them do what they're supposed to do without having to kill those cells because it hurts us. You know, I don't particularly want to be operated on I will happily submit myself to the surgeon and his scalpel scalpel if that is necessary, but wouldn't it be nice to have a cocktail that will constrain those malignant cells to behave themselves? Now that is not an unreasonable request that biologists can talk about because we have these model systems such as cloning and many many others. This is just one model system. I think Unfortunately they receive too much publicity. It calls attention to cloning. When is it matter fact, there are all sorts of things that all sorts of of operational procedures to the sell-by. I'll just have to gain new insight into controls.