ALL-PURPOSE CELLS

November 6, 1998
		New cellular research may hold the key to replacing diseased or damaged tissues in humans. This breakthrough, while offering vast medical benefits, has also sparked intense ethical debates. Following an interview with the biotechnology company that funded this research, two medical ethicists debate the concept. *If animation does not play or you do not have Flash 3, please click here.

Nov. 6, 1998: Two medical ethicists debate the use of stem cells. Oct. 30, 1998: Brain cells do indeed multiply. Feb. 24, 1997: The beginning of Dolly, a cloned sheep. More NewsHour Health and Science coverage.     University of Wisconsin features the discovery. Graphics of embryonic stem cells. The full report in Science Magazine	ELIZABETH FARNSWORTH: After more than a decade of work, researchers said today they have isolated and grown basic human stem cells. These are cells that can develop into virtually any tissue in the human body. The stem cells were taken from inner cell mass, the blastocyst, of human eggs that had been frozen or fertilized just days before. The blastocyst is the group of cells from which a human embryo develops. Researchers then coax those stem cells to continue growing in petri dishes. Unlike other adult cells, which die, these stem cells can grow and divide indefinitely. Some scientists believe that in time they will be able to get the cells to differentiate into heart muscle cells, for example, or kidney cells, bone marrow cells, or others. Those cells, in turn, could be directly injected into organs, such as the heart, to replace diseased or damaged tissues throughout the body.
	The "immortal" cells.
	We talk first to Dr. Thomas Okarma, vice president of research and development at Geron Corporation, the biotechnology company that funded this research. Thanks for being with us. DR. THOMAS OKARMA, Geron Corporation: My pleasure, Elizabeth. ELIZABETH FARNSWORTH: Let's go through the University of Wisconsin research step by step. First of all, where did the blastocysts, these basic cells, come from. DR. THOMAS OKARMA: The blastocysts are donated by couples undergoing in vitro fertilization procedures. And, as you know, usually more blastocysts are created than are utilized in order to achieve pregnancy. So after written informed consent was obtained and after the protocols were approved by the institutional review boards, these donors allowed the excess tissue to be donated for the research program. ELIZABETH FARNSWORTH: Tell us - go ahead - sorry to interrupt you. DR. THOMAS OKARMA: Go ahead. ELIZABETH FARNSWORTH: Tell us about the stem cells, more about them. What is so special about them? DR. THOMAS OKARMA: The stem cells are unique amongst all other stem cells isolated to date in that they grow forever because they express the enzyme telomerase, which is the immortalizing enzyme that allows cells to grow forever. In addition - ELIZABETH FARNSWORTH: Let me interrupt you right there. They grow forever, as opposed to once they've differentiated this substance isn't in it and they die? DR. THOMAS OKARMA: That's right. When the embryonic stem cell differentiates into a nerve cell or a blood cell or a muscle cell, the enzyme telomerase is turned off, and the cells that descend from the embryonic stem are mortal. And the point you raise is relevant here for the kinds of transplantation therapies we're trying to develop, because Geron, in addition to having the technology now for the embryonic stem cell, has also reduced to practice cellular immortalization by transferring telomerase gene into differentiated cells. We published that result earlier this year also in science. So the combination of those two discoveries positions us to first derive all cells and tissues of the body from these embryonic stem cells, and then secondly to confer replicative immortality to them by putting in the gene telomerase. The significance of this is that it allows us to genetically engineer these differentiated cells so that they can, for example, not be rejected by the host immune system when they are transplanted into the patient. ELIZABETH FARNSWORTH: Okay. Don't get ahead of me. I'll get to that in a second. But to make this clear. They isolate these stem cells. Then what happened? DR. THOMAS OKARMA: The cells are put through an intensive laboratory process that took years to develop and was first reduced to practice in the monkey. Dr. Thompson isolated primate, monkey embryonic stem cells about three years ago. So after the cells are removed from the blastocyst, they are cultured in a special way on mouse feeder cells, which have been irradiated so they don't divide. These mouse feeder cells provide nutrients that allow the cells to remain alive, yet, growth factors which inhibit their differentiation, so in that process the cells are serially subcultured indefinitely, and they retain their purely potent characteristics and their immortality.
	Opportunities and ethical questions.
	ELIZABETH FARNSWORTH: All right. Can these cells, these stem cells, then be made to differentiate now, or is this in the future, into the kinds of cells that would make say bone marrow or a heart or, you know, some other organ? DR. THOMAS OKARMA: It's a little bit of both. What preceded both the primate and the human isolation is about 15 years of mouse work in the mouse embryonic stem cell system, in which systems we have learned how to develop heart cells and blood cells and neurons. Now, these human cells, of course, were just isolated, so we don't yet know how translatable the lessons from the mouse work will be. But we expect them to be with modification useful so that we can reproduce what has been done in the mouse with these human cells. ELIZABETH FARNSWORTH: Okay. So this takes us back to where you were going in the first place when I interrupted you, the applications of this. Is the idea that you will be able to do what you did in the mouse, that you'll take these stem cells and you can somehow tell the cells to become basically whatever you want it to become? DR. THOMAS OKARMA: That's the idea. Of course, as you say, we will have to isolate specific factors that will allow us to drive the cells down particular differentiation pathways. I would point out, however, that there are already in existence techniques called genetic selection, which allow us to pull from a heterogeneous culture just the cells we're interested in. That technique was, in fact, developed in mice using ES-derived cardiomyocytes. The technique is relatively simple. You have a gene that codes for a drug resistance that is driven by what's called a tissue specific promoter. That means that when that gene is taken up into different cells, the only cell which will be resistant to the drug is the cell that produces that promoter or that actually turns on that gene. So let's say we have a culture that consists of bone marrow cells, cardiomyocytes, and skin cells, and the desired cell is cardiomyocytes. We transfer this gene construct into all the cells, but we only have cardiomyocytes, which are capable of turning on the drug-resistance gene, because the gene construct contains a protein only made by cardiomyocytes, therefore, when we add the drug, the only cells that will survive are cardiomyocytes. ELIZABETH FARNSWORTH: So do you see this as useful mostly for repairing damaged tissue, or even in the future for creating a whole heart? DR. THOMAS OKARMA: In the near-term it will be to repair degenerating tissue. We have the opportunity to repair our mortal bodies with immortalized cells. However, in the mouse work we published in Science Today we have observed when these human cells are injected into mouse that in addition to cells that form from all three germ layers, we're actually seeing tissue and organ organization, which means that the cells have retained their ability to communicate to one another and form the architecture that's required to form an organ. Now, the techniques to control that are, of course, not at hand. So the notion of developing tissues and even organs is further away than the notion of developing cells for transplantation. But we believe it's feasible because of all the containment of that potential within these cells. ELIZABETH FARNSWORTH: And, briefly, Dr. Okarma, we're about to have a discussion about the ethnical aspects of this. How does your company, which holds the patent on some of this, as I understand it, how would you approach the ethnical aspects of this? DR.THOMAS OKARMA: Well, first, we recognize that there are ethnical issues surrounding the derivation and utility of these cells. And in that regard we formed an ethics advisory board many months ago to help us - help advise us about how to deal with these issues, and we created guidelines that tell us we think how to perform this research in an ethnical manner. And those guidelines involve appropriate informed consent, appropriate use of the tissue, and some areas where we will not use the tissue, for example, in human cloning. So while we recognize that these are very special cells with a moral authority, we also see the enormous need medically for patients with all kinds of chronic degenerative diseases also having a moral authority, and so from the helicopter view, what we're doing here is taking tissue that would be frozen indefinitely or discarded, and we're trying to develop tissue from it that will save or prolong human life. ELIZABETH FARNSWORTH: Okay. Dr. Thomas Okarma, thanks for being with us. DR. THOMAS OKARMA: You're welcome.   This report continues: two medical ethicists debate the concept....