Anders Persson has PhD in sociology from the University of Gothenburg, Sweden. He has a background in sociology of science and science ethics.

Stellan Welin is a professor of biotechnology, culture, and society at the University of Linköping, Sweden. He has a PhD in philosophy and has participated in several projects on the ethical issues in emerging biomedical technologies.

Contested Technologies

Xenotransplantation and Human Embryonic Stem Cells

By Anders Persson, Stellan Welin

Nordic Academic Press

Copyright © 2008 Nordic Academic Press and the authors
All rights reserved.
ISBN: 978-91-85509-05-8

Contents

Preface,
1. Background, positions, controversies,
2. Xenotransplantation: development and controversies,
3. The ethics of early clinical trials,
4. Human embryonic stem cells: developments and debates,
5. The commercialisation of biomedical science,
6. Summing up: risk, therapies, values, and vested interests,
References,

CHAPTER 1

Background, positions, controversies

In this book, we will discuss two contested technologies, xenotransplantation and stem cell technologies, paying particular attention to human embryonic stem cell technologies. Both technologies are deeply embedded in the molecular medicine of our time. We will use this first chapter to provide a general background on molecular methods and to position ourselves in the interdisciplinary field of science studies.

1.1 The rise of molecular medicine

The book of life

In February 2001, two prestigious scientific journals, Nature and Science, devoted thick special editions to the revelation of the gene sequences of the human genome (International Human Genome Sequencing Consortium, 2001, Venter et al., 2001). Apart from highlighting a scientific breakthrough, the two publications illustrated that it was a negotiated publication. The two competing consortia, one private and one public, had agreed on the forms and time of publication. The race ended with two winners who could both claim priority.

The publication of the human genome was also a significant media event at the highest political level. The American president at the time, Bill Clinton, appeared at a media event to celebrate the publication, and proclaimed that the sequencing of the human genome was like looking into the ‘book of life’. It supposedly overshadowed all previous human discoveries, including the wheel, the steam engine, electricity, and the atomic bomb. It was as though humanity was able to gain true knowledge of itself for the first time.

Such awe of the human genome, and the hyperbole it inspired in the likes of Clinton, is by no means a new phenomenon. It is deeply embedded in popular culture. In a study of how genes and modern genetics are viewed in American popular culture, the sociologists Dorothy Nelkin and M. Susan Lindee claim in their book, The DNA Mystique: The Gene as a Cultural Icon, that the concept of the gene has become essential in defining human (individual) identity, and is seen as an almost a magical entity that may replace the religious concept of the soul (Nelkin & Lindee, 1995). They also demonstrate how interpretations of the gene have influenced both our definitions of social problems and practices to treat these problems.

The papers in Nature and Science not only marked a historical breakthrough in biology. They also represented the merging of biological knowledge and technology with another powerful technology of our time, information technology. Each copy of the journals included a CD-ROM with the full inscription of the human genome.

However, there were also important differences between the public and the private actors in the field of human genome research. While the public consortium opened up all its databases to the scientific community, the private consortium, Celera, did not, which led to a protracted debate around this exception to the publication rules of Science (Duncan, 2001). According to Celera, their intention was to be able to make money from selling access to their superior databases. Economic logic eventually won out over profit, since no one is interested in paying for something they can get for free. Celera is no longer in business in the genomic area.

This type of interplay between public and private spheres is something we will meet many times in the history of the development of xenotransplantation and human embryonic stem cells. In particular, it is one of the most divisive issues in the fierce debate over the commercialisation of these technologies. Much of the development dealt with in this book was dependent to some extent on private firms and private money, especially in the case of xenotransplantation.

The DNA code and recombinant DNA

The developments leading up to the joint publication of the human genome had begun nearly fifty years earlier. In 1953, Francis Crick and James Watson published their discovery of the structure of the DNA molecule (Watson & Crick, 1953). In the decades following, more details of the so-called genetic code were revealed. It was learnt that there are specific combinations of three nucleic acids (of which there are four in the DNA molecule: adenine, cytosine, guanine, and thymine), coding for specific amino acids (of which there are twenty), and that these combinations of nucleic acid triplets make up genes and can, through the mediation of RNA, combine amino acids to make proteins, the basic building blocks of all living terrestrial organisms. The molecular basis for many hereditary diseases was also discovered.

In 1973, an American research group led by Stanley Cohen and Herbert Boyer published an article on a technology, which proved to be highly important for the application of the new molecular knowledge (Cohen et al., 1973). They had developed a technique to isolate and amplify individual genes and insert them into other cells, a technique that later became known as recombinant DNA technology. Cohen, Boyer, and their co-workers used so-called restriction enzymes that had been discovered a couple of years earlier to cut DNA sequences and splice them into bacterial plasmids. These plasmids are extrachromosomal DNA that can be found in certain bacteria. The plasmids are then used to carry the desired gene into other bacteria, where the gene will be able to express itself by making the same protein it was coded for, producing it in the other organism. By culturing such transgenic bacteria in bioreactors, it is possible to produce huge amounts of recombinant proteins that otherwise would be difficult and expensive to produce. The most common bacteria used for this purpose is E-Coli (Escherichia coli). The recombinant products can be used for various medical purposes. Production of human growth hormone is one example of a recombinant product that has been used in clinical treatment for a long time now. It used to be very expensive to produce large amounts of human growth hormone. It had to be derived from the brains of deceased humans, while collection was a dangerous procedure as the brain substance and the eventual medical product could be infected with various diseases. Today, not only are bacteria used in this kind of manufacture, but transgenic animals such as cows can be used to produce medicines in their milk.

The technologies resulting from the ability to splice genes and put them into new places, where they (with luck) fulfil the same function, are a cornerstone of biotechnology. The number of genetically modified plants used in agriculture for food production and for industrial purposes is expanding. The use of transgenic mice, which can carry a gene (or lack a specific gene) that produces a human disease, is very important in medical research and crucial to the early phases of testing new drugs against human diseases.

It can be argued that biotechnology carries great promise for a nation’s economic development. At a time when traditional industries, such as the manufacturing industry on which Sweden built much of its welfare state, are struggling with severe problems, new technologies like biotechnology and information technology are seen as the new basis for maintaining and expanding that welfare.

Early worries: the Asilomar conference

In the 1970s, when recombinant DNA technology was still very new, a debate began about the products of this technology. Could the manipulation of DNA, intentionally or unintentionally, result in new dangerous micro-organisms? Were the safety measures used in laboratories sufficient to cope with the new technology? Recombinant DNA was seen as something completely new. Using this technology, man could for the first time produce strains of organisms that had never existed in nature before. (Berg et al., 1974) A committee of the National Academy of Sciences headed by Paul Berg, a leading scientist in the area who had published a paper on the matter, proposed a voluntary moratorium on certain kinds of recombinant DNA research until the risks could be evaluated. These questions were discussed and debated at a conference that one commentator described as:

… The Woodstock of molecular biology: a defining moment for a generation, an unforgettable experience, a milestone in the history of science and society. (Barinaga, 2000: 1584)

The conference, where about 140 scientists, lawyers, and journalists gathered to discuss the possible dangers associated with the newly developed recombinant DNA technology was held at the Asilomar Conference Center in California in February 1975. The Asilomar conference, heavily dominated by scientists, concluded that the scientific community on its own was able to develop effective safety guidelines, and should persuade Congress not to restrict this kind of research by legislative means (Barinaga, 2000).

While the risks discussed at the Asilomar Conference may be regarded as technical, the developments in biotechnology, especially medical biotechnology, have also raised a range of wider ethical questions. Reflecting on the Asilomar conference many years later, participants such as Paul Berg noted that in many ways the success of the conference was due to the decision to restrict the discussions to the possible biological hazards associated with the technology, and not discuss wider ethical matters. Berg and others noted that if such matters had been brought up, the Conference probably would not have reached the same conclusion (Barinaga, 2000).

The Asilomar Conference highlighted a theme that is also found in our material, which is that technological development is claimed to have created risks to the public. Arguments are made that it is time to institute a moratorium, to think, and to investigate the risks, and proceed only after careful deliberation. However, in the case of xenotransplantation, where such a moratorium has been proposed to evaluate the risks of retrovirus infections to the public, it was far from clear whether there had been sufficient deliberations on what the risks actually were. This will be discussed in greater detail in next chapter.

1.2 Aims and limitations of the book

In this book we will discuss two particular research fields or technologies associated with molecular medicine, namely xenotransplantation (transplantation of cells, tissues, and organs between species) and human embryonic stem cell research (hereafter hESC research). Due to the rapid development of knowledge and techniques in cellular and molecular biology, these two fields evolved quickly during the 1990s. Xenotransplantation was the first to emerge, while hESC research began in 1998, when the first human embryonic stem cell line was derived. Both fields are still very much with us, and although general interest in xenotransplantation has declined somewhat of late, it is still considered promising in the development of therapies for severe and wide-spread medical conditions.

At the same time, both fields are controversial, however. As regards xenotransplantation, the animal rights movement has vigorously challenged the view that it is ethically acceptable for humans to use animals as research subjects and as organ sources. Another controversial topic in this field is the risk of the spread of pathogens from animal transplants to human recipients, and in the worst-case scenario, to the rest of the population. This controversy has divided both laymen and scientists engaged in the debate over the development of xenotransplantation. In the field of hESC research the controversial issue from the very beginning has been the use and destruction of human embryos for the derivation of stem cells. From some religious and philosophical standpoints, the destruction of a human embryo to derive stem cells is considered morally wrong. The Catholic Church and various anti-abortion groups and organisations have taken this position. We will discuss these issues later.

Sociology and ethics

One of our aims with this book is to outline and analyse the controversies surrounding xenotransplantation and hESC research. We will do this by using theories and concepts developed in the field of ‘Science and Technology Studies’ (STS), as well as apply more traditional ‘philosophical’ analytical tools. STS is devoted to the social study of scientific and technology developments, and their dependence and impact on society. In particular, we will use analytical tools from controversy studies, where the aim is to understand how controversies over technologies develop and are resolved. A series of important questions will be addressed. Which arguments and actors can be identified in the debate? What strategies are used by the different actors? What kind of alliances and power-relationships can be traced?

It is important to note that this book is not an attempt to give a fully-fledged history of the scientific and technical development of the two fields. Even though we will outline the historical and technological background, we have concentrated our analyses and discussions on certain themes that are crucial not only for xenotransplantation and hESC, but also for the development of medical biotechnology in general. In varying degrees, we have touched on these themes or problems in published articles on our work in the two fields. The book may therefore be seen as a summing up of this work.

Some themes to be discussed

In xenotransplantation, a disagreement emerged on how and when to start early clinical trials. This was to some extent related to the risk of infections from the animals used (namely pigs), but also from the fact that alternative technologies already existed, in the shape of human organ transplantation. These problems will be discussed in the context of the Helsinki Declaration and other ethical guidelines that are intended to govern medical research on humans. There is also the issue of using transgenic pigs and, in particular, the ethical issues involved in using baboons for research.

In hESC, we will discuss the status of the human embryo and various ways to argue for the acceptability of using and destroying embryos. We will also take a closer look at some of the politically motivated ethical discussions, and focus on reconstructing the reasons behind the stem cell decision made by President Bush in 2001. We will comment on the recently discovered possibility of avoiding the embryo problem by creating stem cells with ’embryonic properties’ from other sources.

Another theme that will be dealt with is the issue of the commercialisation of biomedical research. Developments in technologies, such as xenotransplantation and stem cell therapies, have been increasingly dependent on commercial funding. One might even say that their development would be impossible without such funding. Even if critical voices have been raised against what is perceived as the commercialisation of academic science, most actors seem to have accepted the situation. The critical question remains, however, of whether and how dependence on commercial funding has had negative side effects; in other words, what happens when the commercial market system with its norms and expectations meets science, and its norms and ways of functioning? Does commercialisation pose problems when it comes to patient safety and research ethics? These questions will be addressed in this book with special regard for small biotechnological companies that have engaged in xenotransplantation and hESC research. We will apply both sociological and philosophical tools to understanding and discussing the development of each of these themes.

1.3 Theoretical perspectives and central concepts

The driving forces of scientific and technological developments

A common view when it comes to scientific and technological developments today is that they are inevitable. These developments seem to be driven by a kind of unassailable logic that humans can neither stop nor deflect. There is something inherently alluring in the possibility of scientists pursuing new knowledge, even if they know it is potentially dangerous. Robert Oppenheimer, the scientific leader of the Manhattan project that developed the first atomic bombs at the end of World War II, exemplified this point by saying,

When you see something that is technically sweet, you go ahead and do it and you argue about what to do about it only after you have had your technical success. That is the way it was with the atomic bomb. (Oppenheimer, quoted in Wheeler & Ford 1998, p. 222)

Some scientific and technological problems are so inherently interesting and exciting that scientists cannot abstain. Thus, in one view, development is driven by human curiosity. Other views emphasise the role of business and economic factors in scientific and cultural development.

Science and technology are part of the modern project that dates back to at least as early as the Enlightenment. In the modernist view, science and technology are seen as success stories. After the atomic bomb and World War II, it is perhaps no longer quite so self-evident that the progress of science and technology is for the good of mankind. There are many concerns for the future. It also seems that science and technology have produced some of the risks we are living with today, such as global warming. Yet as paradoxical as it may sound, to solve such problems we need science and technology.

(Continues…)Excerpted from Contested Technologies by Anders Persson, Stellan Welin. Copyright © 2008 Nordic Academic Press and the authors. Excerpted by permission of Nordic Academic Press.
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