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The human genome map, the death of genetic determinism and beyond

The rationale for the public funding of the Human Genome Project - a project to uncover the exact molecular composition of the genes that make up Homo sapiens - was that, apart from explaining many aspects of human behaviour and development, it would revolutionise healthcare by making possible exact predictive medicine, and unfailingly accurate diagnosis and perfect treatment of diseases. However, when the results of this attempt to map ‘the book of life’ were finally announced in February this year, they proved to be something of an anti-climax. Mae-Wan Ho explains why there was little in these results to justify the extravagant claims made about this costly project.


THE complete human genome map was announced just before Valentine’s Day [1]. But it was an anticlimax for the proponents, despite much effort to keep up the hype. The scientists declared themselves ‘surprised’. The ‘book of life’ turns out to have as few as 30,000 genes. Craig Venter, whose company Celera raced the publicly funded sequencing consortium to the finishing line, was the only one to read the implications correctly. The number of genes is far less than needed to support the extravagant claims throughout the past decade that individual genes determine not only how our bodies are constructed and what diseases we suffer from, but also our patterns of behaviour, our intellectual ability, sexual preference and criminality.

Facts of life [2]

*The human genome has about 30,000 genes, twice as many as a fruitfly and 10,000 more than the simple roundworm.

·        There are only 300 unique genes in the human (genome), which are not in the mouse.

*    Forty percent of the genes were previously unknown.

·        One hundred and thirteen genes have been transferred into the human genome from bacteria.

·        There is no genetic basis for race; humans all over the world share 99.9% of their DNA.

·        The ‘complete’sequence is still riddled with gaps.

·        The fugu fish has the most concise genome, it has no ‘junk’ DNA.

·        More than 95% of the human genome is ‘junk’ DNA.

·        The coding regions for proteins occupy only 1.1% of the human genome.

·        About 50% of the human genome are proviral sequences and transposable elements, many with reverse transcriptase.

·        One of the most common transposable elements, Alu, tends to cluster where there are genes.

·        Chromosomes vary widely in the number of genes they contain.

·        Most mutations occur in males.

·        There are 250,000 proteins made by the 30,000 genes.

·        The dog is 85% identical to a human in terms of genetic sequence and many of the 380 inherited diseases in dogs are similar to those in humans.

·        There are more than four million genetic differences between humans found so far.

·        One thousand seven hundred and seventy eight genes have been identified with diseases so far, from asthma to Alzheimer’s.

‘We simply do not have enough genes for this idea of biological determinism to be right,’ said Venter. ‘The wonderful diversity of the human species is not hard-wired in our genetic code. Our environments are critical.’ Many of us have been saying the same decades before the idea for the human genome project had ever been conceived of.

Genetic determinism is dead

John Sulston, Head of the Sanger Centre in Cambridge in the public consortium, attempted to save face by appealing to ‘executive’genes that do very sophisticated ‘management’ work. ‘What we are doing is to increase the variety and subtlety of genes that control other genes.’ But that only leads us into the infinite regress of having to postulate genes that control genes that control yet other genes. What Sulston should have added, at the end of his sentence, is the phrase ‘that respond to the environment’. Genetic determinism is dead, and has been dead at least for close to 20 years [3].

Worse yet, ‘Mapping the genome could be route to disaster’, headlines a newspaper [4]. Excitement in the drug industry could be short-lived, according to a report compiled by investment companies Lehman Brothers and McKinsey. The human genome project could be too big for the biotech and pharmaceutical companies to handle, and could bankrupt the industry. The ‘information overload’ will cost much more than previously thought. The report draws on interviews with experts throughout the industry, and concludes, ‘Perhaps the most surprising and compelling discovery is that, in fact, genomics threatens to increase not only the associated research and development costs, but also the average cost per new drug.’

I have referred to human genomics as ‘a scientific and financial black hole that swallows up all public and private resources without any return either to investors or to improving the health of nations’[5]. Now that the bubble has burst, it is time to take stock and seriously rethink healthcare.

The project to sequence the entire human genome has cost the public $3 billion in the US and hundreds of millions of pounds in the UK. Now, scientists are telling us this is just the end of the beginning, and much more money is needed before the goods can be delivered in terms of miracle cancer cures, eradication of disease, genetic enhancement, gene therapy, personalised medicine and a prescription of lifestyle based on our genetic makeup. Indeed, the UK government is investing at least £2.5 billion over the next five years on ‘human genomics’ in a misguided attempt to identify all the genes that predispose the UK population to disease (see box). This, at a time when the national health system is in financial crisis and research and development of other aspects of healthcare has been sorely neglected.

But even if the goods can be delivered against all odds, they will be beyond the means of the average taxpayer because private companies are aggressively staking out their claims on our genome. The pace of gene patenting has accelerated to a frenzy. Applications for patents in the US have gone from an annual 150,000 in the late 1980s to 275,000 today. In October last year, there were patent applications on 126,672 human gene sequences. By February 2001, there were 175,624, a 38% jump [6]. The US had granted patents for millions of SNPs (single nucleotide polymorphisms) and gene fragments for which functions are unknown before it tightened the patent laws in December 1999. The human genome is already covered with dozens of times more patents than there are genes, because multiple patents are being granted over the same stretch of DNA. Such patents are seriously distorting healthcare and stifling scientific research and innovation [7].

Of patenting and gene testing

Among the human genes and cell lines patented and sold by corporations are those stolen from indigenous peoples under the pretext of providing medical care, and even coercion is used. DNA databases of entire populations such as those of Iceland and Tonga have been sold to private companies. The Swedish government is in negotiation with another company for the ‘ethical’ takeover of its population database, and the UK government is planning to establish one of its own.

Some 740 patented gene tests are already in the market, and hundreds more are in the pipeline. For cases where such tests can help to diagnose and treat patients, exorbitant licence fees have prevented them from being used. On the other hand, healthy people testing positive are denied employment and health insurance. Insurance companies in the UK can now require individuals to reveal the results of genetic tests. At the same time, prenatal and pre-implantation diagnoses are eliminating human foetuses and embryos carrying genes said to predispose them to cancer as adults.

Governments are diverting large amounts of tax money into human genomics research which benefit the corporations. This is the real disaster for public health for it has narrowed the options for healthcare and foreclosed other promising approaches. It is also a major distraction from the real causes of ill health - which are overwhelmingly environmental and social - which will end up marginalising and victimising those most in need of care and treatment.

Long before we were told there aren’t enough genes to support the genetic determinist view, many scientists had concluded that there are no simplistic explanations for diseases in terms of single genes, because the action of each gene is modified and affected by many other genes. The connection between genes and disease becomes all the more tenuous when it comes to conditions such as cancer, heart disease, diabetes, schizophrenia, intelligence, alcohol abuse and criminal behaviour, where environmental and social factors increasingly predominate.

There are hundreds of variants in each of the 30,000 genes in the genome. Craig Venter’s Celera has identified over 4 million SNPs - variants of genes that differ by a single base. Each person is genetically unique, except for identical twins at the beginning of development, before they can accumulate genetic mutations independently. It is impossible, in principle, to give the prognosis for any disease for an individual, let alone predict his or her lifestyle based on the person’s genetic makeup [5].

More than a decade of somatic ‘gene therapy’ has met with no success. On the contrary, there have been deaths and numerous adverse events, the causes of which remain largely unknown. Many hazards are already evident from existing scientific findings. These include immune reactions to genetically modified constructs and creation of new viruses due to recombination between artificial gene therapy vectors and dormant viruses in the genome.

Nevertheless, arch genetic determinists and other prominent scientists as well as ‘bioethicists’ are advocating human germline gene therapy and human cloning. They see the creation of a gene-rich class of human beings to be inevitable due to the free reign of the global marketplace. The rich will pay to genetically enhance their offspring, in the same way that they will pay for expensive private education. Consequently, there will be a genetic underclass - children of the poor - that will eventually become a separate, inferior species. Social inequity can thereby be translated into genetic inequity and vice versa. Fortunately, this genetic determinist fantasy will never come to pass. Unfortunately, it is fuelling the resurgence of eugenics and genetic discrimination, giving rein to the worst prejudices of our society.

Send in the clones

The cloning of Dolly the sheep first raised the possibility that the same procedure could be used to create a human being. This met with universal opposition from citizens and governments all over the world. However, human cloning came back on the agenda as companies and their scientists pushed for approval of ‘therapeutic’ human cloning, the creation of human embryos for the purpose of providing cells and tissues for transplant. In January 2001, the UK became the first government in the world to pass a law that makes this legal, even though the available scientific evidence indicates that such human cloning is totally unnecessary and immoral (see the article ‘The unnecessary evil of ‘therapeutic’ human cloning’ in this issue.) ‘human’ clones have even been created, by transferring the genetic material of a human cell into the egg of the cow and the pig. Apart from the moral objections, such interspecific hybrids are well-known to result in gross abnormalities. Against this background, the international trafficking of human organs is already rife, and eggs and embryos will be added to the list. At least 50 women are needed to provide enough ‘empty’ eggs to clone a single human embryo. Advertisements for egg donors have appeared on the Internet.

Another development is xenotransplantation, the creation of ‘humanised’ pigs by genetic engineering to supply spare organs and cells for transplant into human beings. This is so clearly a case of bad science and big business putting the world at risk from pandemics of viruses that cross from pigs to human beings that it should be banned immediately (see the article ‘Xenotransplantation: How bad science and big business put the world at risk from viral pandemics’ in this issue).

All the developments in and around human genomics stem from the mechanistic paradigm that still dominates western science and global society at large.

Mary Shelley’s brilliant novel, Frankenstein, was not just a parable of the arrogant scientist playing God, it is also about  mechanistic science out of control today, in pursuit of corporate profit.

The irony is that contemporary Western science across the disciplines is rediscovering how nature is organic, dynamic and interconnected. There are no linear causal chains linking genes and the characteristics of organisms, let alone the human condition. The discredited paradigm is perpetrated by a scientific establishment consciously or unconsciously serving the corporate agenda, and making even the most unethical applications seem compelling.

It is high time scientists across the world free themselves from the corporate agenda, to work in partnership with the organic uprising from the grassroots, to recover and revitalise the holistic perspectives of traditional knowledge systems, and to secure food and health for all.

Endnotes

1.   See ‘Men and women behaving badly? Don’t blame DNA’, Robin McKie, Observer, 11 February 2001; ‘Gene code opens new fields of medicine’, Tim Radford, The Guardian, 12 February 2001.

2.   See ‘Genome project’, The Guardian, 12 February 2001; ‘Unexpected bits and pieces’, Henry Gee, The Guardian, 12 February 2001; ‘Genome discovery shocks scientists: Genetic blueprint contains far fewer genes than thought - DNA’s importance downplayed’, Tom Abate, San Francisco Chronicle, 11 February 2001; ‘Analysis of human genome discovers far fewer genes’, Nicholas Wade, New York Times, 12 February 2001.

3.   Ho, M.W. (1998, 1999). Genetic Engineering Dream or Nightmare? Turning the Tide on the Brave New World of Bad Science and Big Business, Gateway, Gill & Macmillan, Dublin.

4.   ‘Mapping the genome could be route to disaster’, Leo Lewis, The Independent on Sunday, Business, 11 February 2001.

5.   Ho, M.W. (2000). ‘The human genome sellout’. Third World Resurgence #123-124, 4-9; also ISIS News#6, September 2000, www.i-sis.org/humangenome.shtml <http://www.i-sis.org/humangenome.shtml>.

6.   ‘The profits that kill’ Madeleine Bunting, The Guardian, 12 February 2001.

7.   Regalado, A. (2000). ‘The great gene grab’. Technology Review, September/October, 49-55.

Dr Mae-Wan Ho, Director of the Institute of Science in Society (ISIS), is a Visiting Reader in Biology at the Open University, UK, and a Fellow of the US National Genetics Foundation.

Box story:

The establishment of population DNA databases - for whose benefit?

THE UK Government is investing more than £2.5 billion in human genomics research, part of which is to establish a UK population database to examine links between genes and health and disease. Dr Mae-Wan Ho raises concerns about such a project, particularly with respect to invasion of privacy and genetic discrimination. She points to increasing collusion between governments and biotech corporations in such projects and warns that the focus on genes is a major distraction from the overwhelming causes of ill health, which are environmental and social. It will also marginalise and victimise those who need healthcare most of all.

The UK Medical Research Council (MRC) is to commit at least £1.9 billion to ‘health genomics;’ research over the next five years - in addition to the UK Government’s £675 million already earmarked for constructing tech facilities to study genes and proteins [1]. This will coincide with the establishment of a UK Population Biomedical Collection by the Wellcome Trust in collaboration with the Departments of Health. The MRC’s contribution to that project will be approximately £20 million. Sir George Rada, speaking for the MRC, said: ; ‘The recent publication of the first draft of the human genetic code is just the first step in understanding more about the human body. Scientists are now looking for possible links between particular genes and health and diseases. Working out the functions of these genes is key to designing new approaches to detecting illness early and to preventing and treating diseases. The Collection promises to be one of the most exciting scientific initiatives of recent times. It could deliver benefits for the health of many generations to come.’

The study will, in the first instance, involve half a million volunteers donating blood samples from which their DNA would be extracted. The same volunteers will provide lifestyle information to the researchers. Over a period of years, this information would be tracked against their medical records. A small number of regional centres across the UK will be set up to recruit volunteers, with the overall study centrally managed and co-ordinated.

Such studies have already raised concerns over the invasion of privacy and the erosion of civil rights. The genetic data will also result in individuals being discriminated against in employment and health insurance [2]. The database can fall into the hands of a private company and be further sold to subscribers. The Icelandic population database was indeed sold by the government to Decode Genetics, a California-based company. The Swedish government, similarly, is in negotiation with another company over that country’s population DNA database. This collusion between governments and the biotech industry is an extremely worrying trend.

The MRC has given an assurance that ‘The information and samples collected will be held in public ownership for public benefit and there will not be exclusive access to it by any one organisation or commercial company.’ But there is no guarantee that the policy of successive governments, or of the same government, will remain unchanged. We were told that public financing of the human genome project would keep the human genome in the public domain. That has not been the case. Patenting of human genes and cell lines continues, and private companies have benefited enormously by ‘mining’ the public database [3].

Governments are increasingly diverting public finance into mega-projects that benefit biotech companies rather than the public. The undue focus on human genomics has narrowed the options for healthcare and foreclosed other promising approaches. It is also a major distraction from the real causes of ill health, which are overwhelmingly environmental and social, and will end up marginalising and victimising those most in need of care and treatment.

·        Most diseases are complex, and correlation between genes and disease is weak.

·        Genetic differences are, much more often than not, swamped by environmental influences.

·        So-called ‘single gene diseases’ such as cystic fibrosis and sickle-cell anaemia make up less than 2% of all diseases. And even those are subject to influence by many other genes and by the environment, so that prognoses based on single genes are notoriously unreliable.

·        Practically all populations are genetically diverse, with hundreds of variants in every gene. Thus each individual is genetically unique in their ‘predisposition’ to different diseases.

·        Recent research with gene-chip technology confirms that gene regulation is global: the expression of many, many genes is changed in response to a single chemical signal [4]. There is simply no reductionist, magic-bullet approach to health [3].

The health of nations will be infinitely better served by devoting resources to disease prevention, to phasing out the hundreds of known carcinogens among industrial and agricultural chemicals, rather than by identifying the genes that ‘predispose’ people to ill health.

1.         ‘MRC science budget allocation enables further development of health genomics research’, MRC Press Release MRC/69/000, 22 November, www.mrc.ac.uk <http://www.mrc.ac.uk>.

2.   See ‘Genetic civil rights alert’, ISIS News#6, September 2000, www.i-sis.org <http://www.i-sis.org>.

3.   See ‘Human Genome. The biggest sellout in human history’ by Mae-Wan Ho, ISIS Report, September 2000, www.i-sis.org <http://www.i-sis.org>.

4.   Magasnik, B. (2000). ‘Global regulation of gene expression.’ PNAS 97, 14044-5.

 

 


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