Genes, Cells and Brains

The Promethean Promises of the New Biology

Hilary Rose, Steven Rose

• Publisher: Verso
• Year: 2013
• Print ISBN:
  9781781683149
• eBook ISBN:
  9781781684498
• Topic: Philosophy
• Subtopic: Cell Biology

Our fates lie in our genes and not in the stars, said James Watson, co-discoverer of the structure of DNA. But Watson could not have predicted the scale of the industry now dedicated to this new frontier. Since the launch of the multibillion-dollar Human Genome Project, the biosciences have promised miraculous cures and radical new ways of understanding who we are. But where is the new world we were promised?

Now updated with a new afterword, Genes, Cells and Brains asks why the promised cornucopia of health benefits has failed to emerge and reveals the questionable enterprise that has grown out of bioethics. The authors, feminist sociologist Hilary Rose and neuroscientist Steven Rose, examine the establishment of biobanks, the rivalries between public and private gene sequencers, and the rise of stem cell research. The human body is becoming a commodity, and the unfulfilled promises of the science behind this revolution suggest profound failings in genomics itself.

1

From Little Genetics to Big Genomics

In 1992, at the start of the surprisingly short decade-long march towards the sequencing of the human genome, one of its key initiators, geneticist Walter Gilbert, pulled a glittering CD out of his pocket and held it up to his audience announcing: ‘soon I will be able to say “here is a human being; it’s me”.’¹ Gilbert’s brilliant piece of theatre was echoed by other leading molecular biologists in their campaign to win public support and enthusiasm for the Human Genome Project (HGP), the ambitious international effort to sequence the three billion nucleotides that constitute the human genome, at a cost then estimated at $3 billion – a dollar a nucleotide. It seemed not to matter how often molecular biologists employed the same theatrical device, whether in California or at London’s Institute for Contemporary Arts; holding up a CD to their spellbound audiences and saying this is human life itself was a brilliantly chosen trope. The CD, so familiar to the audience of a 1990s high-tech society, was recruited to symbolise the merger of molecularisation and digitalisation of biomedical research heralded by the HGP. Human genomics simultaneously offered a new definition of human nature, and new Promethean powers to repair and even re-engineer that nature.

THE DOUBLE HELIX: ACHIEVEMENT AND ERASURE

It had been a long march since 1953, when the Cambridge-based biologists Francis Crick and Jim Watson described the now famous double helix structure of DNA, composed of vast linked chains of four small molecules, the nucleotides – or bases – adenine, cytosine, guanine and thymidine (A, C, G and T). At King’s College London, the biophysicist Maurice Wilkins and the X-ray crystallographer Rosalind Franklin were also working on the structure of DNA. Thanks to their head of department’s bad management they had each separately been given the same problem to work on. Wilkins assumed he was in charge, and passed on Franklin’s critical data to the Cambridge pair. She was unaware that her images of DNA crystals had been ‘shared’ – or more bluntly, stolen – without her knowledge or consent.

With the last sentence of Crick and Watson’s path-breaking Nature paper, ‘It has not escaped our notice that the [specific] structure we have postulated immediately suggests a possible copying mechanism for the genetic material’,² DNA’s career was launched. While the significance for the life sciences was immediately recognised by the international scientific community, there was little public interest. The media did not pick up on its significance, and it was decades before the life scientists learned to practice megaphone science, piling hyperbole on hyperbole, heralding the birth of the HGP.

It was Watson’s The Double Helix, published fifteen years later, after both Franklin’s death and the three men’s shared Nobel Prize in 1962, which put DNA into the public arena. When the three gave their acceptance speeches at the Nobel Ceremony none spoke of their late colleague’s contribution. Watson’s book unblushingly revealed the arrogance and ambition of the Cambridge pair, the rivalries, personal jockeying for position, unauthorised acquisition of data and his own total inability to behave appropriately towards Franklin as a senior scientist whose crucial X-ray skills had made the model possible. Many scientists saw the book as bringing science into disrepute, thereby revealing more about their longing for a lost golden age than their knowledge of the history of science. They had erased the memory of so many savage disputes in the past – notably Newton’s battle with Leibniz to secure the prior claim to having invented calculus. As President of the Royal Society, Newton appointed a committee to adjudicate on the matter and drafted its predictable conclusions himself. The charge that Watson had smirched the good name of science was unconvincing, as conference gossip among researchers enjoyably recounts such conflicts, why the results from X’s lab should be taken with a pinch of salt or why scientist Y has reason to believe that an old enemy Z was the referee who had delayed their paper to secure priority over Y. From this perspective Watson let the side down by informing the public of what only scientists were supposed to know. In his autobiography Wilkins notes that, at the time, he and Crick had talked of suing Watson,³ who became known, not entirely to his comfort, as Honest Jim. Meanwhile, his account of the inner workings of science – as slightly less than ‘pure’ – sold like hot cakes.

While the injury to Franklin is now publicly recognised and has been symbolically corrected – one of the new King’s buildings in London is named the Franklin Wilkins Building – what is less well known is how the injustice was exposed. The writer Anne Sayre, married to X-ray crystallographer Donald Sayre, was a close friend of Franklin. Both she and her husband and indeed many crystallographer colleagues were profoundly angered by Watson’s unjust and insulting treatment of Franklin. Drawing on this network, Sayre published a biography of Franklin in 1975.⁴ The story was seized upon by the nascent feminist movement as providing unambiguous evidence that Franklin’s male colleagues had systematically diminished her contribution, and that Wilkins had de facto stolen her X-ray photographs. Wilkins was sufficiently disturbed by this claim that he asked one of the London Women and Science group, whether she thought he had in fact done so. Watson characterised Franklin as not only difficult, but also incapable of recognising the theoretical significance of her own images. Only the theoretically minded (i.e. men like himself and Crick) were up to the job. To this Watson added an unpleasant sexist commentary on her appearance. It was left to a second biographer, Brenda Maddox, to point out that Franklin in fact dressed very elegantly, having developed an interest in fashion after working in a laboratory in Paris.⁵ But her dress aesthetic was manifestly outside Watson’s capacity to recognise, let alone appreciate. Watson himself poured petrol onto the flames by observing that ‘the best place for a feminist is someone else’s lab’, although ironically his unwitting exposure of the institutionalised sexism within science nourished the growing feminist criticism of science.

LITTLE SCIENCE, BIG SCIENCE

In the 1950s Watson’s declared ambition was a Nobel Prize, not yet patents and profits. His research was university-based, relied on one powerful technology – X-ray diffraction – and cardboard or tin cut-out models of the four bases, A, C, G and T. Genetics was then, to use Derek de Solla Price’s term, a Little Science.⁶ Little Science had a low ratio of capital to labour. Laboratory work was hands-on, craftwork, from synthesising reagents to building equipment, from pipetting solutions to washing the glassware at the end of the experiment. Papers were frequently single-authored, or at most bore two or three names.

Over the subsequent decades, genetics and molecular biology have been irreversibly transformed into Big Science. For genomics – the analysis of entire genomes – to arrive required the fusion of human genetics and molecular biology, a fusion only made possible by the new informatics. With this new configuration the capital– labour ratio was reversed. The manufacture of equipment and the production of reagents has been outsourced to specialist firms, and laboratory practice has become automated. Today’s sequencing laboratory consists of a huge bleak space with identical machines about the size of a domestic microwave spaced out along the benches. A gowned technician silently tends the machines, while the researchers sit in their offices reading the printouts. Nothing could be further from the bustle of both scientists and technicians competing for space in the busy labs of the 1950s.

The papers coming out of the big sequencing labs can have several hundred authors – even entire institutes. Knowledge has become intellectual property and must be patented. The research investment is too great for it to be left to chance whether the media will or will not cover the story. Press releases are now carefully crafted by the lead researchers together with the university press office. Meanwhile the journal publishing a paper also works to amplify its impact and thereby reinforce its own status as a prestige journal, first by online prepublication of the paper and then by providing a summary written by a science journalist to explain the paper’s importance in its field and its possible contribution to health care and wealth creation. These new practices of science communication position the research most favourably in a market where knowledge has become intellectual property. Although the major newspapers all have science correspondents, ‘churning’ – reproducing a press release – has become a common media practice. When this happens the science writers of the fourth estate fail in their critical role and become part of megaphone science.

Meanwhile research is on the move both physically and financially, away from the universities towards spin-off companies and beyond. Big Pharma has got bigger as mergers first hyphenate and then delete once famous names. Burroughs Wellcome became Wellcome became Glaxo-Wellcome became the conglomerate GlaxoSmithKline, leaving the name Wellcome only to the giant London-based charitable trust. This revolution has been fuelled by the hopes of many that biotechnoscience will generate genetic diagnoses that will lead smoothly into clinical interventions, from gene therapy to new drugs. All the known problems of translation, of getting biomedical research innovation from bench to bedside, have been smothered in a sea of hype. In the process, leading biologists and geneticists have become entrepreneurs, interested as much in the value of their stocks and shares as in the smooth and successful running of their laboratories.

This shift in the entire production system of the life sciences with the entry of entirely new stakeholders with different cultural values is exemplified by Watson’s own career path. In the 1990s, as the Director of one of the powerhouses of US molecular biology, Cold Spring Harbor, he was told by one the researchers in the lab, Tim Tully, of a promising new discovery about a molecule that might enhance memory. His scientific excitement, Tully reported, was equalled only by his delight at the prospect of patents and ‘shed-loads’ of money. (Watson’s often quoted and typically caustic interventions in the genomics narrative serve as both benchmarks and catalysts.) Tully, very much one of the new bio-entrepreneurs, responded by spinning out a private company and then leaving Cold Spring to work for it. Fuelled by high-profile praise in the media, Tully became – briefly – a celebrity scientist. But as the hopes for his molecule faded, the firm, like so many start-ups begun with high hopes and readily available venture capital, crashed. The fact that his project later re-emerged phoenix-like from its ashes, refinanced and relocated to California, is indicative of the extraordinary ups and downs of biotechnoscience within globalisation.

The HGP would have been inconceivable without this transformation, as the painstaking stepwise analyses that had characterised the early days were swept aside by robotic instrumentation and giant computers requiring major financial support. Routine work – of the sort that Watson once derided as capable of being done by a team of monkeys, and that would have taken thousands of skilled technicians decades to finish – could now be completed by machines in weeks or days. Even the superfast technology of the 1990s and the early years of this century now seems a remote memory.

A crucial step in this transformation of science was a decision made in 1980 by the US Supreme Court. Ananda Chakrabarty, a microbiologist working for General Electric, had genetically engineered bacteria able to break down oil – thus with the potential to clean up oil spills – and had sought to patent it. The US patent office (in the name of its officer, Diamond) had earlier rejected the claim on the grounds that a living organism could not be patented, but was overruled by the Supreme Court. (Two decades later a legal judgment in a lower court in the US effectively reversed the Diamond v. Chakrabarty ruling, but it is unlikely that this will conclude the patenting fight, as too much money is at stake.)

In the same year, the US Congress passed the Bayh–Dole Act granting universities intellectual property rights over inventions and products arising from federally funded research. These two decisions opened the floodgates. Now it seemed anything could be patented – bugs, constructed animals such as the Oncomouse (engineered at Harvard, designed for cancer research), and even strands of DNA. The first patent for a gene, that for insulin from genetically engineered yeast, was granted to the biotech company Genentech in the same year. In the context of a near pandemic of obesity and its consequence, diabetes, the importance of this patent is evident. Bayh–Dole and Diamond–Chakrabarty are the twin markers of the transformation of a once disinterested science into one that is very much interested. Today, for the leading sequencers of the HGP and their successors, prestige, with the Nobel Prize still the ultimate symbolic achievement, remains. But money has joined prestige and become entangled with the control of intellectual property, patents, and access to hugely profitable stakes in instrumentation, biotech and pharmaceutical companies. This new hybrid production system of science is radically different from that of the past.

TO MAP OR TO SEQUENCE?

DNA has two distinct functions in the life of the individual and of the species. As Watson and Crick had immediately realised, its double helical structure means that, when unwound, each strand of the helix serves as a template on which the other can be built – resulting in two identical molecules of DNA. This makes possible the transfer of genetic information, coded for in the strands of DNA, from one generation to the next during reproduction. The second function is its central role in the cellular economy. The code written in unique sequences of As, Cs, Gs and Ts is read by the cell via an intermediate, RNA (a molecule similar to DNA), to direct the synthesis of proteins. At the time of the Watson–Crick paper it was assumed that one gene coded for one specific protein. Crick called this the Central Dogma of molecular genetics: ‘DNA makes RNA makes protein makes us’. He described DNA as an informational macromolecule, and saw the flow from DNA to protein as a one-way transfer of information. Again, it was Crick who put it most succinctly: ‘Once information has got into the protein it can’t get out again.’ Knowing the DNA sequences, the molecular biologists believed, would provide the key not merely to understanding genetic mechanisms but also to intervening in them, manipulating both cell metabolism and heredity. But sequencing at the time, in the 1970s, presented a formidable technical problem. There was, however, a more promising approach: mapping.

In humans the DNA that comprises the genes is located within twenty-three pairs of chromosomes, present in the nucleus of every cell in the body. One of each pair is inherited from each parent. The chromosomes are individually recognisable under the microscope by their characteristic shape. One pair of chromosomes differs between males and females; females have two X chromosomes, males one X and one Y; the other pairs are numbered one to twenty-two. Long before they were known to be made of DNA, techniques for mapping where the genes lie along the chromosomes had been pioneered in what was for many years the geneticists’ favourite organism, the fruit fly. Mapping and identifying the genes in human chromosomes was technically much harder, but the clinical interest in identifying disease-associated genes made it the research priority of the 1970s, and a substantial number of disease-related genes had been mapped to particular chromosomal regions.

In the decades following his formulation of the Central Dogma, the elegant clarity of Crick’s slogans became distinctly fuzzy. Not merely were the information flows less unidirectional than he had imagined, but it had become clear that genes coding for proteins only constitute a tiny proportion – less than 2 per cent – of the DNA in the human genome. The remaining 98 per cent of the DNA in the genome was disparagingly referred to by molecular biologists as ‘junk’, as it was thought to have little or no biological function. So why sequence the entire genome, as the HGP proposed, if much of the sequence would be ‘junk’? The term, however, proved to be seriously misleading, with painful consequences for the hope...

Table of contents

• Cover
• Title Page
• Copyright
• Dedication
• Contents
• Introduction: Prometheus Unbound?
• 1. From Little Genetics to Big Genomics
• 2. Evolutionary Theory in the Post-Genomic Age
• 3. Animals First: Ethics Enters the Laboratory
• 4. From State to Consumer Eugenics
• 5. The North Atlantic Bubble
• 6. The Global Commodification of Bioinformation
• 7. The Growing Pains of Regenerative Medicine
• 8. The Irresistible Rise of the Neurotechnosciences
• 9. Promethean Promises: Who Benefits?
• Afterword
• Acknowledgements
• Notes
• Index