The Science of Cowboys

I have come to accept ants as a part of my life. I meet them in my kitchen, my living room, my bathroom. At work, I wonder why my cursor is moving by itself across the computer screen, until I note that it has six legs. And when I go to the hot water dispenser, a battalion of them is waiting to walk away with my coffee cup. The bright side to this forced sharing of living and working spaces is the opportunity to contemplate the extraordinary organization of ant societies: multiple individuals with defined roles toiling together for the good of the whole.

Like ants, my body is a community (and not just for germs). It comprises trillions of microscopic living entities called cells, which work together in a hierarchical, coordinated, and interdependent fashion for my wellbeing. It is this same cellular nature that underlies the promise of stem cell therapy.

The cells of the embryo have an ability to divide and grow to produce all the organs and tissues of the body, a capacity that cells lose long before adulthood. (An exception is the liver whose marvelous regenerative ability has kept our bars and pubs a little fuller than they might be otherwise.) When in need of new organs, therefore, we must turn to transplants and the attendant miseries of finding suitable donors, surgery, and tissue rejection.

But a change is in the works. Last year’s Nobel Prize for Medicine was awarded, in part, for the discovery of embryonic stem (ES) cells, which, like the cells of the early embryo, have the ability to produce all of the body’s tissues and organs. Until recently, ES cells could only be obtained from embryos. Now, however, methods are in place to obtain ES cells from an adult.

One such procedure involves nuclear transplantation. Let me illustrate using the humble but honourable bao zi (Chinese steamed bun). For the uninitiated, bao zi are white roundish buns stuffed with one of various fillings. Imagine inserting a syringe into the centre of one bao zi, extracting its red-bean filling, and then injecting it with green-bean filling.

The bao zi structure roughly resembles the cell, whose outer cushion of cytoplasm occupies the same peripheral position as the white bready portion of the bao zi, and whose inner nucleus is like the bao zi filling.

The production of ES cells by nuclear transplantation is similar, using fine needles to remove the nucleus of a one-celled embryo (the fertilized egg) and replace it with the nucleus of an adult cell. Remarkably, the environment provided by the embryonic cytoplasm reprograms the genes within the adult nucleus to an embryonic state. The result is an ES cell whose nucleus and cytoplasm are from different sources. My illustration breaks down, since the ES cell multiplies, while the bao zi gets eaten. Well, every model has its limitations.

Still, at the end of the day you have adult-derived ES cells and a full belly, so everyone’s happy, right? Not so fast. There is strong resistance from some quarters to “destroying” a human embryo by removal of its nucleus. In addition, the very early one-celled human embryos required for this technique are in drastically short supply.

So how can we get around these ethical and practical concerns? British scientists reported last week that they had successfully combined the cytoplasm of an early cow embryo -- a fertilized cow egg, to be precise -- and an adult human nucleus to generate “almost human” ES cells called cytoplasmic hybrids. While this process does not destroy any human embryos, it raises ethical problems of its own, since this human-cow ES cell may be capable of developing into a person. And if forming an entire individual is not likely for the moment, the ultimate goal is to use such cells to regenerate tissues for human recipients.

So what’s the big deal? While everything else in these cow-human hybrids may have a human identity, there is one component that will always retain its “cowness” - the mitochondria. These structures, which bear a passing resemblance to the Indian sweet jalebi (my mind is never far from food), serve a variety of important functions, not least of which is to provide energy from respiration. Mitochondria inevitably come along with the cytoplasm, like your mother- and father-in-law come along with your spouse. Thus, these recently created hybrid ES cells have cow mitochondria.

It could be argued that we have already used baboon hearts in transplant operations, and anyone who could gain 10 extra years of good living at the cost of carrying around a few cow mitochondria in their heart or pancreas might be happy to stick a finger in the eye of some arm-chair ethicist who would deny her or him the added days to walk the Earth.

But do we know whether such cytoplasmic hybrids will behave fully like human cells? The mitochondria are now known to control many more functions than previously appreciated. Perhaps most interestingly, mitochondria seem to influence longevity. Now, the natural life-span of a cow is around 20 years, and there is evidence that this limit is partly determined by the mitochondria. This then raises the possibility that cow mitochondria could affect the life-span of an organ, tissue or recipient.

Human-cow cytoplasmic hybrids will not enter the clinic any day soon, and further experimentation will address these concerns. In the interim, we can give some thought to a catchier name for these cells. Hu-Moo deserves some consideration, as does Cow-Boy. And what about turtles? They live for hundreds of years. I think I’ll take some of their mitochondria, thank you very much! But I’ll have to defer further, uh, ruminations. About two million ants are ferrying my bao zi to the windowsill.