ngin - Norfolk Genetic Information Network

2 August 2002

HUMAN NATURE ON COLLISION COURSE WITH GENETIC ENGINEERING/DISILLUSION WITH GENETIC ADVANCES DEPRESSES BIOTECHS

It's not only the WorldComs and Enrons who've betrayed investors with a vacuous charade. According to the first article below:

"Human Genome Sciences chief executive William Haseltine predicted in March 2000 that, within two or three years, his company would be selling drugs derived from a new understanding of human genes. The world is still waiting.

The company, which raised nearly $2 billion on its promise to develop drugs by analyzing the function of genes, is still years away from bringing a product to the market. Its shares, which were trading at $103 in early 2000, are now priced at less than $15.

Human Genome Sciences (HGSI) is one of dozens of drug developers whose shares have plummeted in the last year amid a series of disappointing results from clinical trials and, recently, from the possible effects of an insider trading probe at ImClone Systems Inc. (IMCL)"

According to Adrian Hobden, president of Myriad Pharmaceuticals, part of Myriad Genetics, "The financial community believed there would be these tremendous breakthroughs in a short period of time, but that belief was not based on any reality."

Paul Herrling, head of research at Novartis AG, spins it thus, "At this point, there is an element of belief, and an element of vision."

But that vision is not just misleading investors but distorting our health care. 'Single gene diseases' account for less than 2% of all diseases and so the focus on genes in tackling disease diverts attention and vast resources away from the real causes of ill health which are overwhelmingly environmental and social.

And there are other dangers, both biological and political, that stem from the hyping of genetics and genetically based 'solutions' to human problems. (see item 2)

1. Disillusion with genetic advances depresses biotechs
2. Human Nature on Collision Course with Genetic Engineering

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1. Disillusion with genetic advances depresses biotechs

Toni Clarke, Reuters

Human Genome Sciences chief executive William Haseltine predicted in March 2000 that, within two or three years, his company would be selling drugs derived from a new understanding of human genes. The world is still waiting.

The company, which raised nearly $2 billion on its promise to develop drugs by analyzing the function of genes, is still years away from bringing a product to the market. Its shares, which were trading at $103 in early 2000, are now priced at less than $15.

Human Genome Sciences (HGSI) is one of dozens of drug developers whose shares have plummeted in the last year amid a series of disappointing results from clinical trials and, recently, from the possible effects of an insider trading probe at ImClone Systems Inc. (IMCL)

The disillusion follows what many now describe as overly optimistic expectations of the speed at which medical advances would emerge from advances in molecular biology that culminated in 2000 with the mapping of the human genome.

"The financial community believed there would be these tremendous breakthroughs in a short period of time, but that belief was not based on any reality," said Adrian Hobden, president of Myriad Pharmaceuticals, the drug discovery unit of Myriad Genetics.

Drugs from gene analysis probably won't reach the market for another 10 or more years, scientists now say. Yet many pharmaceuticals companies are relying on genomics, or the analysis of gene function, to help spawn a new generation of blockbusters able to fight complex diseases such as cancer.

NO BLOCKBUSTERS ON THE HORIZON

A study by research company Datamonitor found that at least five of the world's biggest drug companies do not have any such blockbusters in their pipelines, even though in 2001 they spent record amounts on research and development.

"Drug companies are in a transitional period where they are moving from traditional chemistry to biotechnology, and they are on a learning curve," said Jeffrey Trewhitt, a spokesman for the Pharmaceutical Research and Manufacturers of America, a drug industry group.

"It is literally a matter of learning to use this technology," he said.

Last year, the number of new drug applications filed with the U.S. Food and Drug Administration fell 20 percent to 111 compared with the previous year's 138, while the number of new drugs approved fell 30 percent to 66 from 94.

It is far from a given, however, that genomics is the panacea for the drug industry's doldrums that many had hoped it would be.

Millennium Pharmaceuticals Inc. (MLNM), which like Human Genome Sciences was founded on the belief drugs could be developed from genes, has yet to produce a drug of its own. It conceded earlier this year that the process is taking longer than it expected.

"Whether genomics can provide new targets quickly and cost-effectively enough remains a major question," Joseph Dooley, Accenture consulting firm analyst, said in a report.

Genomics companies believe that if they can discover the function of a particular gene, they can use mass screening techniques to find a chemical compound that might interfere with the gene and perhaps halt progress of a disease.

The problem, skeptics say, is that it is difficult to pinpoint whether a gene or protein that appears to have interesting biological characteristics is in fact the cause of a disease.

"Biological function or significance of a drug target does absolutely not equal medical or clinical significance," said Toni Schuh, chief executive of Sequenom Inc., a company that claims it is able to help scientists isolate clinically relevant genes.

"The finding that a protein is involved in the control of blood pressure does not mean that manipulating this target with a drug enables you to control blood pressure in a human being," Schuh said.

Most drugs over the last 50 years have been developed against a limited number of molecular targets that were already known to be clinically relevant.

"Penicillin was developed by the observation that fungi inhibited bacterial growth," said Steven Delco, an analyst at Fortis Securities Inc. "Many drugs were discovered that way; somebody noticed something in nature that had an effect in humans."

These targets, however, seem to have been mined to exhaustion. Finding new ones is the challenge.

"Genomics can solve the problem," said Jonathan Rothberg, chief executive of CuraGen Corp., a company that's betting gene analysis will help lead to drugs for hitherto intractable diseases.

"Just as Ford industrialized cars, I'm industrializing molecular biology," he added.

But an increasing number of companies now feel that throwing compounds at targets is only useful in combination with techniques and technologies that can identify which of the discovered targets definitely lead to disease.

"High throughput screening is useful but does not absolve you from using your brain," said Paul Herrling, head of research at Novartis AG, which is pouring millions of dollars into genomics and other genetic research.

Some big drug companies are beginning to recognize the limitations of functional genomics, a process that has been likened to reading 50,000 books in order to discover information contained in just five books. The question now is, how to figure out which five books are the relevant ones.

The answer may be in genetics, but genetics with a new twist. The mapping of the human genome has made it possible for the first time for companies to compare the genes of healthy populations with those of populations in generally poor health, then flag those points in the genome where risk factors for a particular diseases are more prevalent.

One of the first big drug companies to invest substantially in genetics is GlaxoSmithKline Plc (GSK), which over the last five years has accumulated 80,000 samples of human DNA. The company now can go into this database and begin to compare the genetic makeup of, say, asthma patients, with those of healthy individuals and, using information gleaned from the genome, pinpoint the variations that may be associated with the disease.

"Genetics and genomics will play a major role in the future of the healthcare industry," said Alen Roses, head of genetics research at GlaxoSmithKline.

Over the next two to five years, the biggest use of genetic information will likely be to create genetic profiles to establish who is most likely to benefit from existing drugs and who is most liable to suffer a potentially serious side effect, he said.

"Creating safer products is becoming even more necessary if they are to compete in this highly regulated market," Roses said.

With all genetic research, however, the promise of new drugs is still just a promise.

"At this point," said Herrling, "there is an element of belief, and an element of vision."

***

2. Human Nature on Collision Course with Genetic Engineering

Worldwatch Institute

Human genetic engineering could be the next major battleground for the global conservation movement, according to a series of reports in the latest issue of World Watch magazine, published by the Worldwatch Institute, a Washington, D.C.-based research organization. While previous struggles have involved protecting ecosystems and human societies from the unpredicted consequences of new technologies, this fight over high-risk applications of human genetic engineering is a struggle over who will decide what it means to be human.

"Many countries have already banned reproductive cloning, and the U.N. is working on a global treaty to ban it, but even more powerful and much more dangerous are the related technologies to modify the genes we pass on to our children," says Ed Ayres, Editor of World Watch magazine. The contributors to this special issue call on the U.N. and national governments to ban the technology known as inheritable genetic modification.

Many uses of human genetic technology could be beneficial to society, but as political scientist Francis Fukuyama writes in the magazine, our understanding of the relationship between our genes and whatever improvements we might seek for our children (and their descendants) is dangerously deficient. Fukuyama warns that "the victim of a failed experiment will not be an ecosystem, but a human child whose parents, seeking to give her greater intelligence, will saddle her with a greater propensity for cancer, or prolonged debility in old age, or some other completely unanticipated side effect that may emerge only after the experimenters have passed from the scene."

Human genetic engineering has ramifications that reach far beyond the life of a single child. Several contributors highlight the disastrous results of the last serious effort to engineer genetic perfection. In the early part of the 20th century, scientists and politicians in the United States relied on the alleged science of eugenics to justify the forced sterilization of tens of thousands of people who were judged to be "feebleminded,", "mentally defective" or "epileptics". Hitler passed his own sterilization law soon after taking office in 1933, heading down the path toward the Holocaust.

The U.S. biotechnology industry-which dominates the global industry-has become an increasingly powerful economic and political force, with revenues growing fivefold between 1989 ($5 billion) and 2000 ($25 billion). Aided by the equally rapid revolution in computing, laboratories that once took two months to sequence 150 nucleotides can now process over 30 million in a day, and at a small fraction of the earlier cost. The number of patents pending for human DNA sequences has gone from 4,000 in 1991, to 500,000 in 1998, to several million today.

"We are publishing this special issue because we donét want to lose the opportunity to decide openly and democratically how this rapidly developing technology is used," says Ayres. "This isn't a fight about saving whales, or the last rain forests, or even the health of people living today. The question is whether we can save ourselves from ourselves, to know and respect what we do not know, and to put the breaks on potentially dangerous forms of human genetic engineering."

Excerpts from the authors of the "Beyond Cloning" issue of World Watch

Invigorating Racism: "There are precedents for breeding that are politically manipulated. You only have to think of the Nazi German ideal, the blond blue-eyed German." -Nadine Gordimer, Nobel Prize recipient in literature for 1991.

Heightening Discrimination: "What is called a deficiency - mental, physical, or other - is socially defined. For example, the perverse world order of globalization dictated by commerce, greed, and profits regularly treats women, children, and poor people as inferiors. Without strong democracy and true transparency, this kind of discrimination can be used to justify human genetic manipulation, manifested in eugenics programs." -Vandana Shiva, director of the Research Foundation for Science, Technology, and Ecology, and author of Stolen Harvest: The Hijacking of the Global Food Supply.

Oh Brave New World: "Our new understanding of genomics and the neurosciences is almost making possible a generation of HyPE [human performance enhancement drugs] that could be used in more sinister ways, e.g., to control dissent." - Pat Mooney, author of Shattering: Food, Politics, and the Loss of Genetic Diversity, and executive director of ETC Group.

Turning Babies into Commodities: "The story of an 'enhanced' humanity panders to some of the least attractive tendencies of our time: techno-scientific curiosity unbounded by care for social consequence, economic culture in which we cannot draw lines of any kind, hopes for our children wrought into consumerism, and deep denial of our own mortality."-Tom Anthanasiou, author of Divided Planet: The Ecology of Rich and Poor and Marcy Darnovsky, Associate Executive Director of the Center for Genetics and Society.

Widening Economic and other Inequalities: "Genetic engineering will artificially confer heritable advantages only on those who can afford to buy them." -Judith Levine, author of My Enemy, My Love: Women, Men, and the Dilemma of Gender.

The Law of Unintended Consequences: "the attempt to master human nature through biotechnology will be even more dangerous and consequential than the efforts of industrial societies to master non-human nature through earlier generations of technologies." -Francis Fukuyama, Bernard Schwartz Professor of International Political Economy at The John Hopkins University School of Advanced International Studies, author of The End of History and Our Posthuman Future: Consequences of the Biotechnology Revolution.

Destroying the Basis of Democracy: "The new eugenic technologies are being actively promoted by influential scientists, writers, and others who see themselves ushering in a new epoch for human life on earth. They speak with enthusiasm of a 'post-human' future in which the health, appearance, personality, cognitive ability, sensory capacity, and lifespan of our children have all been genetically modified. They anticipate, with scant concern, the inevitable segregation of humanity into genetic sub-species, the 'GenRich' and the 'Naturals'." -Richard Hayes, executive director of the Center for Genetics and Society.

Creating a New Terror Weapon: "It is this potential for genocide based on genetic differences, which I have termed 'genetic genocide'é that makes species-altering genetic engineering a potential weapon of mass destruction, and makes the unaccountable genetic engineer a potential bioterrorist." -George J. Annas, Chair, Department of Health, Law, Bioethics and Human Rights, Boston University School of Public Health.

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