Genetics with a conscience

Making Genes, Making Waves
January 31, 2003

Ian Wilmut admires the crusading spirit of a social activist biologist

Jon Beckwith is a distinguished biologist who is also a social activist.

This autobiography charts his journey through both aspects of his life in the second half of the 20th century: the research of his professional career, and his personal crusade to inform society of biological developments and involve us all in deciding how the new knowledge should be applied. Since he has made a significant contribution in both areas, the book is a fascinating read. He provides a frank but kindly description of his collaborators and other researchers, and an insightful account of science as practised in several very different laboratories.

Beckwith was one of the first scientists to combine genetic and molecular techniques in order to understand the way genes function. In particular, he pioneered the development of methods that are now routine for the isolation of specific genes from their normal site into viruses. This explains the first part of his book's title. The process, known as gene cloning, made it possible to begin to assess the role of specific genes and to study the mechanisms that determine the tissue and stage of development when genes are active. In Beckwith's laboratory there were now opportunities to study the DNA sequences that initiate activity (expression) of a gene, and to analyse mechanisms that regulate processing and secretion of the proteins whose synthesis is directed by the genes. Many of the findings of this pioneering research with bacteria were seminal: they informed and guided later research in other species, including mammals.

Each of these steps is described in plain language, not jargon, making the book readable for non-specialists. By recording the development of experimental approaches, Beckwith shows that science does not often progress in a simple, direct manner, unlike the description given by James Watson in The Double Helix of how he and Francis Crick found the structure of DNA. Progress often depends on reaching forward to test an ambitious hypothesis and discovering that it is wrong. Sometimes, more can be learnt from being wrong than from being right. This was true of the research leading to the recognition of the cytoplasmic proteins required for the export of proteins from cells, as described by Beckwith.

One procedure now in common use in molecular biology involves combining segments of different genes in order to analyse the role of the different regions of the DNA in a cell. This grew out of a series of experiments aiming to combine elements of two genes, one of which was always retained in the bacterium while the other was exported. Beckwith and colleagues predicted that with different combinations the novel protein would be either retained or exported, thereby revealing regions critical for export.

Segments of the fused protein were, however, found to be retained within the cell wall. In this unusual location the protein was unable to metabolise the sugar lactose to sustain the bacteria.

At first, Beckwith and his colleagues were frustrated and disappointed, until they appreciated that bacteria modified in this way provided entirely new opportunities to study mechanisms that export proteins. The bacteria lost the ability to metabolise lactose because the cells moved the hybrid protein into the membrane. However, it was to be expected that in a population of millions of bacteria there would be cells with mutations that spontaneously prevented the synthesis of the proteins that transported the enzyme to the membrane. Only such a mutant cell would be able to metabolise lactose and so survive in medium in which lactose was the sole energy source. Use of such a "selection medium" enabled the group to identify genes and proteins with that function.

Beckwith has collaborated with a range of strong personalities. He has immense respect for, among others, Sydney Brenner, a recent Nobel laureate, and the French Nobel laureate Jacques Monod, both of whom he worked with after completing his PhD.

Those whose research creates important social opportunities face many dilemmas. But when considering them one must always remember that neither scientific progress nor its likely applications can be predicted. Research often advances through chance events, as Beckwith documents; and our inability to predict its applications is equally important. Modern molecular biology, for instance, depends heavily on the ability to use enzymes to cut out specific pieces of DNA. Yet these enzymes, mostly isolated from fungi, were first studied purely for their academic interest with no anticipation of their practical value.

How then is scientific research to be managed? In my view, it is important that a research programme explores a wide range of subjects, some of which may have no obvious potential application. It is unwise to think of limiting the areas of active research solely on the basis of expected outcome. In the longer term, the greatest benefit from research will come from wide-ranging projects to ensure rapid progress - with regulation of any applications, if necessary. During the period covered by Beckwith, he - and many of us working in the area - felt that the regulation of the use of new knowledge in human genetics was lacking to prevent potential misuse.

It is often forgotten, as described by Anne Kerr and Tom Shakespeare in their book Genetic Politics: From Eugenics to Genome , that during much of the 20th century many countries had eugenic breeding programmes, some of which continued until recently. These often had the support of prominent geneticists. Beckwith has been concerned to ensure the accurate collection and interpretation of genetic information in humans to ensure that the revolutionary new knowledge provided by the human genome project is used to everyone's advantage. As soon as he established his methods for gene isolation, he was concerned about their potential misuse with humans and argued that such research should not take place.

A later concern arose from rather inadequate studies suggesting a link between a specific chromosomal abnormality and male criminal behaviour.

More recently still, Beckwith served on a working group to study the "ethical, legal and social implications of the Human Genome Project".

Despite the comparative lack of concern in the national media, the knowledge from this project has always struck me as potentially far more dangerous than that arising from my own research in cloning (nuclear transfer), partly because it will affect everyone.

Scientific developments are often said to be transforming and destroying society at an ever-increasing rate, but I am not sure this is the case. It certainly appears that we quickly take for granted those advances made in our own lifetimes. This is true of both the physical sciences and biology.

We expect aeroplanes to land automatically in fog. Most households in wealthy countries have a range of electronic equipment that depends on the transistor and other late 20th-century inventions. It is less than 50 years since antibiotic treatments became routine, and since then there have been many other medical advances, including microsurgery, use of hormones for contraception and therapy, IVF and organ transplantation. But if we look back to the 19th century, can one imagine a more fundamental challenge to the way in which we think and behave than Darwin's theory of evolution?

For Beckwith, a major dilemma has been the difficulty of combining active scientific research with social activism, particularly in relation to his own research. Both activities can be all-consuming, not only of time but also of nervous energy. Also, some in the research community look askance at those who spend time improving the "public understanding of science".

There is no doubt that Beckwith's career was, at times, threatened by his political stance, such as his resistance to the Vietnam war. And, less immediately, promotion depends on publication of research papers. A researcher who spends time on public information and debate publishes fewer research papers - though this concern may be less important now that the scientific community generally recognises its obligation to describe its research; both its potential benefits and its risks. Society is very much the better for the efforts of those such as Beckwith who clearly enjoy the challenge of describing complex issues to non-specialists and participating in debates as to how new knowledge should be used.

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

Making Genes, Making Waves: A Social Activist in Science

Author - Jon Beckwith
ISBN - 0 674 00928 2
Publisher - Harvard University Press
Price - £18.50
Pages - 242

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