Send in the Clones

It turns out that I'm going to do a bit more Bio 101 before getting deeper into the ethical issues surrounding HESCs and other cutting edge biotechnology. This is partly to address the issues around cloning which the commenters raise, partly because I think the ethical issues come into crisper focus when we have more detailed biological background, and partly just as a bit of self-indulgence.

It's hard to get used to thinking of ourselves as colonies of trillions of individual organisms, but in a sense we are. Actually if you want to adopt the most liberal view of matter, the number is in the quadrillions. We are examples of metazoans -- the multicellular animals. Metazoans are composed of eukaryotic cells, as are plants, which are in some ways even more fascinating, but I'll leave them aside for now.

Here's the Just So story, which is probably actually true. Sometime over a billion years ago, somewhere in the ocean, one particularly large cell swallowed a smaller cell of a type called archaea. Or maybe the archaea parasitized the larger cell, or just moved in. Anyway, the smaller cell was not digested and instead, it happily took up residence and started to replicate inside the larger cell. When the larger cell divided, each daughter cell took some of the intruders with it, and so it went. These cohabiting cells evolved together and, in the end, turned out to be more than the sum of their parts. The smaller cells were particularly good at an essential metabolic process which produces the cellular energy supply, a molecule called ATP, from breakdown products of sugar and fat. They came to specialize entirely in doing this, and gave up most of their DNA and the ability to live independently, but in exchange, they got fed and protected by the big cell in which they lived.

Something else happened, perhaps even more marvelous. The eukaryotic cells began to reproduce sexually. It's possible that another symbiosis is involved, and that the nucleus of the eukaryotic cell is, like the mitochondria, an endosymbiont which eventually captured most of the cell's DNA, except for that remaining in the mitochodnria, but that's fairly speculative. In any event, prokaryotes -- like the bacteria and archaea -- can exchange genetic material, but they don't do it in a systematic way and they routinely reproduce without bothering. Their DNA floats around aimlessly and is fairly simply organized. Eukaryotes, as I'm sure you know, have their DNA organized into packages called chromosomes, which come in pairs, one set donated by progenitor A and the other by progenitor B. Most of the details of which one we consider male or female can vary depending on the species but in my view, there is one determining factor: the female progenitor contributes all of the mitochondria, and the male contributes only nuclear DNA.

There would seem to be several disadvantages to this system, most notably, you can't reproduce unless you can find a partner. Actually, some metazoans, even among the highly complex tetrapods (i.e., certain lizards and fish), regularly reproduce asexually and they save sexual reproduction for special occasions, but still, why bother at all? And an organism with a terrific, kickass genome is going to find it's wonderfulness diluted in its offspring, by its inevitably inferior mate.

It turns out that the reason sexual reproduction is such an advantage that evolution has preserved it throughout the long history of the metazoans has to do with the dynamic nature of evolutionary fitness. Sexual reproduction remixes the genes with every generation, producing all sorts of variation on which natural selection can work. It also allows favorable mutations to spread systematically throughout a population. The two-chromosome system allows recessive genes, which may code for characteristics that are not favorable this year, to continue to lurk within a population so they are available when times change. Sexually reproducing species are better at evolving, and in the long run, that's even more important than being better at living in the here and now. Hence it is the eukaryotes, with their fabulous gift of sex, who developed the complex colonies of cells we call animals, whereas the prokaryotes never got past elaborate forms of slime.

There are trillions of cells in your body, of more than 200 different kinds. Together they maintain an internal ecosystem, which also happens to be inhabited by something like 100 trillion bacteria. On a good day, 100% of those bacteria are harmless, if not beneficial. They are an essential part of the ecosystem which is you. If you want to count your cellular endosymbionts, the mitochondria, that's where we get into the quadrillions.

I know, I know, you already knew all of this. But it's good to review it and get it all straight once in a while. Now, what is a clone?

A clone, most broadly, is simply a line of cells derived from a single cell and therefore all having the same DNA. In that sense, your whole body is a clone, specifically it is a clone of the zygote, the fertilized ovum, from which you arose. But, if you took a cell out of your cheek and managed to culture it in a petri dish, the resulting mass of skin cells would be a clone as well. So when biologists speak of "cloning," they don't necessarily, in fact they don't normally, refer to creating whole metazoans.

But they could. One result of cloning could be a second (or third or fourth) complete organism with the same DNA as an original organism. In order to get that to happen, however, you would have to get the clone not only to continue to reproduce asexually to produce larger numbers of cells, you'd have to get the cells to follow the developmental program that produces the whole animal. All of those 200+ cell types in your body are ultimately descended from the zygote, so they must have gone through various changes to get to their present state. They all have the same DNA. They way they become specialized is to have particular stretches of DNA turned on or off. Cells that still have the potential to become any kind of specialized ("somatic") cell are HESCs. There are other stages of stem cells that can become various subcategories of cell types, but not any cell type.

So, although that mass of skin cells in a dish is indeed a clone of your cells, it's not much use, because those cells cannot give rise to anything but skin cells, which you probably don't need because your body can heal skin wounds naturally. But suppose you need neurons -- nerve cells -- which don't normally replicate in the adult? You would need a supply of stem cells which can give rise to neurons. Or suppose you wanted to grow a whole organ, consisting of various cell types, organized into a complex structure? Ditto, you'd need stem cells that could begin to follow the developmental program for your kidney or heart.

So here's where so-called therapeutic cloning comes in. Although you can clone many kinds of somatic cells, you need stem cells. What do you do? Get a zygote that has exactly your own DNA. And that's where Somatic Cell Nuclear Transfer comes in, a special kind of cloning intended to create HESCs. Just because the result is called a clone does not mean that anybody has either the intention, or for that matter the ability, to grow a person from it.

In fact, regardless of what people may think are the ethics of it on other grounds, there is no ethical way to attempt it because there is no guarantee that the resulting person would be healthy. Right now, if we could make a person the same way Ian Wilmut made Dolly the sheep, we would expect that person to be unhealthy, specifically, to age prematurely. This is because, if you take the nucleus from a somatic cell, that cell is the product of many cellular divisions since the zygote first formed. In natural conception, the zygote gains a new genetic endowment provided by specialized cells in the body called germ cells, in the testes or ovaries. These DNA molecules are fresh, as it were, destined to replicate many times. But each time they do, terminal structures on the ends of the DNA molecules called telomeres shorten. Eventually, the DNA can replicate no more, and the cell line is extinguished. This is why death is inevitable.

The zygote produced by SCNT has old DNA. It is abnormal. Can that ever be fixed? Maybe, but meanwhile, when we talk about cloning people to produce HESCs, we are not, repeat not, talking about making genetically identical copies of existing people. Well, almost identical - remember that the mitochondria have their own DNA, which comes from the donor of the ovum, and unless that happens to be your mother, they won't be identical.

So we aren't talking about anything that will ever become a human being, although we are talking about something which is otherwise just like a human embryo, at a very early stage, except that it's sitting in a petri dish rather than a woman's fallopian tube.

So, with all that out of the way, what's wrong with that? Even if the mitochondria is bovine?