How a frog gave legs to human fertility research

Almost every week seems to bring television or newspaper reports describing an advance in biomedical knowledge in a manner that raises anxiety about ethical choices. The introduction to Whose View of Life? suggests that it "offers an argument for studies of biology and society that bring together the diverse types of expertise and perspectives informed by science, history, philosophy, bioethics and policy. The challenges are too important to be left to only one perspective or another; all points of view are essential to informing decisions about the biosciences that both help to define and are defined by who we are."

In making that case, the book gives a broad historical account of biological advances, including contemporary reactions to these advances, in chronological order, beginning with Aristotle and ending with present-day biology. Reference is made to biologists, philosophers, popes and parliamentarians in Europe and, later on, North America. While Islamic attitudes are briefly mentioned, there is nothing on any other religious traditions besides Judeo-Christian thought and belief. The author is an academic at the University of Arizona and in the sections concerned with the 20th century and the present day there is an emphasis on the US.

Certain key questions have been common to all ages and societies. In particular, "when does human life begin?" Clearly, to some people the moment of fertilisation is decisive, whereas to others there are critical moments at various stages of pregnancy. This has apparently been true throughout the ages.

There are two very different proposals for mechanisms that might account for the production of offspring that resemble their parents. In "pre-formation", a small version of the adult was thought to lie within the sperm ready to grow and develop to full size in the appropriate environment. In Aristotle's alternative view, reproduction depended upon bringing together fluids from male and female but also upon the action of the telos or individual identity. This concept was different from the Christian soul, as all living things were held to have a telos .

Early Christian, Jewish and Muslim teachings all judged that abortion was not homicide if it was induced early in pregnancy. All three taught that the ill-formed early conceptus lacked humanity, which did not appear until after about 40 days "ensoulment" changed the status of the embryo. The first papal decree against contraception and abortion as sins was issued in 1588, but a new pope rejected this ruling three years later.

As the 19th century drew to a close, experiments were carried out with the embryos of sea urchins, chickens and frogs, which laid the foundations for modern research on stem cells and nuclear transfer. Fundamental differences in the mechanisms that regulate development were revealed by the response to the separation of cells from two-cell frog and sea-urchin embryos.

Whereas two smaller sea urchins formed, only an imperfect tadpole developed, reflecting the localisation of specific factors in the cytoplasm of the frog's egg.

Similar experiments were carried out in mammals almost 100 years later when it became technically possible to manipulate much smaller embryos. The ability to obtain two identical young by embryo splitting has recently been used in research and in livestock breeding programmes. This research led to cloning and the derivation of pluripotent stem cells. Many thousands of children have now been born to previously infertile couples by production of embryos in vitro. This opportunity also arose from basic research to understand the maturation of gametes and fertilisation.

The plan to map the human genome has raised other ethical issues that are at least as difficult as those concerned with reproduction. Furthermore, the new genetic knowledge will affect a greater proportion of the population than assisted reproduction. When genes were first identified, different attitudes to the use of research were soon apparent. Some hold that new knowledge, particularly that gained with public funding, should be for the common good. Others point out that companies will not invest the huge sums necessary to exploit the new observations unless they have patent protection. Thus, in the US there was a direct clash between the biotechnology company Celera and the government's National Institutes of Health.The author discusses this but does not mention the key role of John Sulston and of the Sanger Centre in Cambridge in maintaining the high-quality public programme that continues to this day.

The ethical issues most in the public eye concern embryo-derived stem cells and cloning; and here there is a marked difference between the US and the UK. In Britain, the expectation is that such techniques will be regulated and supervised, but this is not the case in the US. The Bush administration is blocking attempts in the United Nations to ban reproductive cloning unless there is a similar prohibition of cloning to produce stem cells. As things stand, it is legal in many parts of the US to attempt to produce a cloned child.

Errors and omissions in such a wide-ranging book are inevitable. In the discussion of human embryonic stem cells, no mention is made of the fact that two laboratories derived such cells from mouse embryos in 1981. They were used extensively in research and their existence stimulated research to derive such cells from human embryos. But it took another 15 years to derive human embryonic stem cells because of differences between species even at this very early stage of development.

The issue of stem-cell research illustrates the case made by the author that citizens and legislators alike should have a greater understanding of biology and its present and imminent ethical challenges. In this book, more emphasis could have been placed on the ethical and social implications. But it will be very valuable to students of ethics and social sciences for having provided a full historical record of the relevant advances in biology.

Ian Wilmut is head of the department of gene expression and development, Roslin Institute.