Liberation Biology

Scientist Lee M. Silver on cloning wars, bioethical battles, and new and improved genes

From the May 1999 issue

(Page 2 of 5)

Silver: Somatic cell gene therapy is very difficult to do. A living person has millions of cells, and you are trying to get a new gene into a reasonable percentage of those cells to fix a disease like cystic fibrosis. Cystic fibrosis patients have a defective gene that keeps them from making a certain protein. So in theory, if you put the good gene into those cells, they could make the protein. This would prevent the buildup of fluid in the lungs of cystic fibrosis patients, the most deadly symptom of the disease. In practice, though, it is very, very difficult to get those genes into a large number of cells. This has always been the case.

However, I should say that whenever I have said that something was hard or impossible, I have been shot down by the advance of science. There are a lot of people working with somatic cell gene therapy who are very smart, and maybe they will figure out the magic bullet that will get the DNA into the right cells and make it work. And if it works, it will work overnight. In other words, if you can figure out how to get DNA into a large number of cells in a target tissue, that's it. If you can get over that barrier, then somatic cell therapy will be possible for lots of folks. I don't see it happening right away, but I could be surprised.

Bone marrow gene therapy is the first one that will work. Because you take out the bone marrow from somebody, you add the gene, you find the one cell in a thousand that has picked up the gene. Then you multiply that cell and then put the modified bone marrow cells back in.

Reason: What about germ line therapy? Germ line therapy means introducing a gene into an embryo or egg at an early stage of development so that the gene appears in every cell in an animal or person's body. Is germ line gene therapy more feasible than somatic cell therapy?

Silver: Absolutely. Germ line therapy is easy. We have already gotten it to work on lots of different animals. Mice were the first animals in which it was perfected. It has been working on mice now since the 1980s, when the genes for human hemoglobin were put into embryos. Since that time, it has become commonplace and easy to do. My graduate students learn how to do it in their first year. There are tens of thousands of people who can do germ line genetic engineering on animal embryos. And the important thing is that, under the microscope, you can't distinguish a mouse embryo from the human ones. So if you can do it with mice, you can, in principle, do it with humans.

Reason: Looking over the horizon, what is the next big thing in biotech?

Silver: The DNA chip. The reason the DNA chip is so powerful is that up until now, if you wanted to figure out whether you have the breast cancer gene, or the cystic fibrosis gene, or the gene for sickle cell anemia, we would have to do an assay for each gene. Somebody would take your blood--take your DNA--and look at the relevant gene to see if you had the normal version or the version which predisposed you to a disease. That is what people do now in clinics, assaying one gene at a time. You get a result back 24 hours later. But once all 70,000 human genes are catalogued, a DNA chip will be able to look at all 70,000 of your genes at the same time. And you will get your results back in three hours. You need almost no DNA to do it, just a scraping from your mouth. A DNA chip genetic assay could also be done on an early embryo, giving you a complete profile.

This is going to revolutionize medicine. It is also going to revolutionize our understanding of the connection between genes and who people are. For example, say you are born with a predisposition to a hot temper. This temperament is not the result of a single gene. There is no such thing as a hot-tempered gene. There are probably a multitude of combinations of 30 or 40 different genes that together in certain combinations predispose people to have a hot temper. Using the DNA chip, you can assay 10,000 people to find out the constellation of genes that predisposes you to a hot temper, or predisposes you to being depressed, or predisposes you to any kind of trait. That is phenomenal. Most people right now don't understand the power of this yet. The incredible thing is that this technology already exists. What we need now are the 70,000 genes to put on the chip. We are waiting for the Human Genome Project [which is being coordinated through the National Institutes of Health and the U.S. Department of Energy] to finish; then we can take those 70,000 genes and put them on a DNA chip.

The original version of that project was simply going to catalog all the genes present in human beings--the genome. There are, according to the latest estimates, somewhere between 60,000 and 90,000 genes comprising the human genome. The catalog by itself doesn't do very much--which is where the DNA chips come in. The 70,000 human genes come in different forms. For example, say gene A comes in forms 1, 2, and 3. Using the DNA chip, we can look at people that have form 1; look at people that have form 2; and look at people that have form 3. By looking at the various forms of gene A, we will be able to determine what effects the different forms have on people--how they affect their health and their behavior, etc. That will be the next step of the Human Genome Project.

Reason: What do you think about artificial chromosomes? Are we going to have those soon?

Silver: Yes. An artificial chromosome will again give you unprecedented power to alter cells. Because right now when we put genes into cells, we are putting in one gene at a time. The artificial chromosome means that you can create what I call "gene packs." You can hook 40 genes on this chromosome. The function of some of the genes will be to shut down natural genes, while others [will] replace natural functions. In the next two or three decades, we are going to be able to build modules of 30, 40, 50, or 100 genes on an artificial chromosome and insert it in the genomes of human embryos and other creatures.

Reason: In Remaking Eden, you basically come out in favor of human cloning. Would you consider cloning yourself?

Silver: I am not interested. I already have my children. Obviously, I have been asked this question many times. I felt the need, probably instinctive, to have children with my wife. And I didn't want to have children that were just for me. I wanted to have children that consummated my relationship with my wife to the greatest extent, and that is why I have my children.

Reason: Why do you think there was such a negative reaction when Ian Wilmut of the Roslin Institute in Scotland announced that he had cloned a sheep? Why do most people oppose human cloning?

Silver: Let me answer you this way. In the spring of 1998, I gave a lecture to a group of well-educated residents from Princeton, New Jersey, who were not scientists. I began by telling them about the bewildering number of high-tech treatments now available to infertile people. I told them that there were a number of reproductive protocols under consideration, including cloning. But before I discussed cloning in detail, I wanted to get their opinion on another fertility protocol. The protocol under consideration is for cases of severe male infertility, when only the precursors of sperm were present. The proposed treatment entailed the injection of one of the man's testicular nuclei containing all of its DNA into an egg cell from his wife that had previously had its nucleus removed. Anyway, I go through this whole long thing and I say, you come out with a baby and the baby kind of looks like the father. The baby might even kind of behave like him, but unless you told anybody, nobody would know that it wasn't just a son produced in the normal way between him and his wife. Is his son a clone? And two-thirds of the people said, no, the son is not a clone.