One of the most thrilling and beautiful events in biology is the development of a fertilized egg into a living breathing individual. This takes place in full view if the individual happens to be a frog but, if a mammal, is hidden away in the dark folds of the uterus. In either case, however, the processes are neatly parallel – starting with the totipotent fertilized ovum, the first few cell divisions give rise to the 8–16-cell morula, each cell of which is still totipotent. A few more cell divisions produce a defined structure, the blastocyst, containing 150–250 cells in the form of a hollow shell, the placenta-forming trophoblast, which contains an inner cell mass consisting of 20 or 30 pluripotent cells, the embryonic stem (ES) cells. These are able to multiply indefinitely and to differentiate into any tissue or organ, but are no longer able to generate an entire individual. During the embryonic stages succeeding the blastocyst, developmental potency gradually diminishes until, at the end, most of the cells in mature tissues and organs are irreversibly committed to their biological roles and unable to multiply or develop further. However, a few proliferative cells, adult stem cells, can be found in most tissues. And adult cell nuclei can be reprogrammed by insertion into an enucleated egg cell, generating totipotent clones that can undergo full-scale embryonic development (which has led to the cloning of animals – frogs many years ago, more recently sheep, cows and dogs). Most recently, it has been reported that skin cells could be converted to stem-cell-like pluripotency by the introduction of functioning copies of just four growth-controlling genes. Although this has been celebrated in the media as defusing the politics of human stem cells, the celebration is premature, as there is a long way to go before it can be determined whether these cells are really equivalent to embryonic stem cells and are medically safe.

Though long known from mouse studies, human embryonic stem (hES) cells were not isolated, for technical reasons, until 1998, an event that has engendered a true scientific revolution with untold medical and scientific potential. In Cell of Cells, Cynthia Fox has some very interesting stories to tell about the science and where it is headed, and she also addresses in depth the political storm that it has stirred up. On the scientific side, we learn about the exciting discovery that hES cells can develop into haemopoietic (blood-forming) stem cells that can be used to repopulate the bone marrow, enabling the individual to accept an organ or an engineered cell from the same donor – an organ transplant or a therapeutic gene that bypasses immune rejection. And there are adult bone-marrow stem cells that can morph into cardiac tissue and repair damaged hearts. Great progress has been made in the development of neural stem cells for the treatment of Parkinson’s, multiple sclerosis, amyotrophic lateral sclerosis and other brain diseases, and it may not be long before stem cells will enable the repair of spinal-cord injuries. Fox reports the surprising discovery of ovarian stem cells, overthrowing the standard view that the human ovary at birth contains all the ova that a woman will ever have. She goes on to note the disparity, unique to humans, between menopause and death. While the activation of ovarian stem cells could postpone menopause – unquestionably a good thing for overall health – it could also interfere with population control and could enable very aged people to become parents.

The medical promise of stem-cell research, not surprisingly, has generated enormous pressure on scientists and their organizations. Intense international competition is probably responsible for the fraudulent research at the University of Seoul whose exposure in 2006 has ruined South Korea’s scientific reputation and has seriously damaged that country’s science as a whole; not everyone realizes that research progresses in fits and starts, and, despite its tremendous promise, the stem-cell enterprise has yet to provide any of the widely expected quick fixes. Fox shows how this has presented an opportunity for charlatans and pseudoscientists to launch the not only worthless but criminally dangerous enterprise of “treating” human diseases with untested or frankly phoney stem-cell preparations.

On the political side, the current state of the art involves growing blastocysts from extra fertilized ova (concepta) obtained by in vitro fertilization and destined to be discarded, or from an ovum “fertilized” by nuclear transplantation. This has ignited a major political conflagration, especially in the United States, largely fuelled by the Christian Right, which equates the extraction of hES cells from a blastocyst with abortion. After all, does not every fertilized ovum represent an unborn child, endowed by God with an immortal soul and therefore with an incontrovertible right to be born? But, one may ask, what happens to the soul when hES cells are extracted? Does not every hES cell and its progeny have its own soul? Or perhaps the soul is trypsin-sensitive and is destroyed by the trypsin (enzyme) used for the extraction of stem cells from the ensouled blastocyst. And if an hES cell is produced by nuclear transplantation, does the nucleus come with the soul of its donor, and is this transmitted to all its progeny? And if the soul is immortal, whether the conceptus is flushed down the toilet or used for the production of stem cells, would it not go on to eternal salvation? So what’s the problem?

It is interesting that religions are far from unified on “ensoulment”. According to Thomas Aquinas (following Aristotle and St Augustine), ensoulment of males occurs at forty days and of females at ninety days. Many modern Catholic moral theologians would allow research before the development of the “primitive streak” (the brain primordium) at fourteen days. Jewish views hold that hES cell research entails no moral issue since genetic (ie, embryonic) materials are not even part of a human being until implanted in a womb. Islamic views generally place ensoulment at the 120th day and hold that a very early embryo has no moral status. And some US Protestant denominations have expressed support for embryonic stem-cell research, including the General Assembly of the Presbyterian Church and the United Church of Christ.

Nevertheless, according to the Christian Far Right, the twin modern heresies, the science of evolution and the biology of the stem cell, are anathema because they deny the immutability of the (human) species and mock the sanctity of the soul. Although radical theology has failed to interdict the former, a spirited defence of the immortal soul, embodied in the 2001 US Presidential ban on funding for hES-cell research, has all but wrecked hES-cell research in the US. Whereas the attempt to ban the teaching of evolution is an assault on our intellectual integrity and has been successfully fought in the courts, the Presidential stem-cell ban is an edict that cannot be fought and is a declaration of war on the scientific enterprise, adding one more nail to the coffin of science in the US. Ironically, as pointed out by Irving Weissman (quoted in Cell of Cells), this aspect of Bushism is not unlike Stalin’s embrace of Lysenkoism. Representing a profound misinterpretation of Marxism, it was supposed to support the USSR’s political philosophy that everything, including genetic evolution, could be fitted into a “socialist” fabric, and it set back biology in the then USSR by at least fifty years.

Fox devotes a great deal of attention to these political issues. In addition to the above, she emphasizes the exodus of scientists from the US to more permissive countries, such as Singapore, which has been enabled to develop and lavishly fund a world-class stem-cell programme, and Israel, which already had one. Fox notes that the US (and a few obsequious followers) have not taken this lightly and have been pressuring the UN, thus far, fortunately, unsuccessfully, to enact a worldwide ban on all forms of cloning – a particularly offensive form of Christian proselytizing. This is at least partly responsible for an ongoing controversy, between advocates of hES-cell and adult stem-cell research, motivated by nationalism and scientific egotism as well as by moralization.

Cell of Cells is a wonderful book for the biologist, containing hundreds of interviews, thoroughly referenced citations, and careful notes. It is a very entertaining and readable presentation, replete with charming and highly personal stories about the researchers in the world of stem cells and their venues, addressing these issues and many more with scholarship and thoroughness. Unfortunately, it is not such easy going for the non-scientist. Cynthia Fox seems to lose sight of her intended lay audience by frequently failing to define terms, by drifting in and out of scientific jargon, and by mixing a peculiar form of lay vernacular with scientific terminology – for example, the agents that dissociate the cells of a blastocyst are sometimes, oddly, referred to as “chemicals”, and at other times, correctly, as “enzymes”. More importantly, the lay reader is never properly introduced to the biology of embryonic stem cells. All of this could have been easily remedied by the inclusion of a good glossary, a few diagrams, and the opening paragraphs of this review.

Cynthia Fox
CELL OF CELLS
The global race to capture and control the stem cell
546pp. Norton. £17.99.
9780393058772

Richard P. Novick is Professor of Microbiology and Medicine at NYU School of Medicine in New York. He has authored some 220 original research articles and is editor or a co-editor of several books, most recently, Gram-Positive Pathogens, published in 2006.

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