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You want to Clone? Go Ahead! New Scientist 9 May 98 6

MANY laws being introduced to ban human cloning, and some already on the statute books, have loopholes that might allow cloners to evade them. Human cloning by nuclear transfer, the technique used to create Dolly, isn't even explicitly prohibited by Britain's 1990 Human Fertilisation and Embryology Act, one of the world's most thorough attempts at regulating human reproduction. "The law bans all kinds of cloning except for the Dolly technique," says Barney Wyld, a spokesman for the Human Fertilisabon and Embryology Authority in London. However, he adds that anyone wanting to clone a person would have to apply to the authority for permission-which would be refused. 6 In the US, legislators have tried to ban cloning at the state and federal levels. California has already passed an anti-cloning law and 21 other states are considering bans. Seven federal bills have been pmposed In Congress. Lori Andrews, an expert in the lepi aspects of repmduction at the Chicago-Kent College of Law, says that recent technological advances may make much of that legislation obsolete. For example, at least I 1 state bills and Cali- fornia's cloning ban pmhibit cloning involving the replacement of a human egg's nucleus with that of another human cell. But researchers in Neal First's laboratory at the University of Wis- consin at Madison have already put the DNA of primates into cows' eggs that have gone on to develop into early embryos (This Week, 24 January, p 5). If the same technique can pro- duce normal human embryos, then these laws could be circumvented. Otker loopholes are created by poor word. lng. At least eight state bills would prohibit the cloning of a genetically identical person, but Andrews notes that eggs carry mitochondrial DNA In their cytoplasm--.so a clone created by nuclear transfer would not have identical DNA. But even an airtight law could be challenged by Americans who might claim it Infringes their constitutional right to repro- duce. "There already is an infertile man who is thinking of challenging the Califomia law," says Andrews. Hell Boyce,

The Price of Profit
Is the race for Patenting of genes and organisms hampering Medical Research?
New Scientist 16 May 1998

US Biotech Patents 1986-96: US corporations (18 346) Foreign corporations (10 507) Individuals in US (2293) Individuals abroad 0.219) US government (718) Foreign governments (262)

CARPENTERS take the tools of their trade for granted. Having bought wood and a hammer, they can use them to make whatever they choose. Nobody from the timber yard or the tool store will come along years later and claim a share of the profits. For scientists crafting tomorrow's drugs, such independence is a rare luxury. The companies that develop or discover the tools and raw materials of the biotechnology trade keep strict control over what other people do with them. These tools include the DNA sequences of key genes, fragments of genes from humans, animals, plants and killer organisms such as HIV, cloned cells, enzymes, animals with deleted genes, and silicon chips coated with DNA for rapid screening of DNA samples. To get their hands on these key resources, medical researchers often have to sign agreements that may inhibit how they are used, or guarantee the company that developed them a share of any resulting profits. Many say this is hampering progress towards understanding and treating disease. Alarmed by such suggestions, Harold Varmus, head of the US National Institutes of Health (NIH) near Washington DC, set up a working group earlier this year to investigate. It is due to issue its preliminary report early next month. The working group has already heard a large number of complaints from researchers, says its chairwoman Rebecca Eisenberg, a law professor at the University of Michigan in Ann Arbor. Among them is a weighty dossier submitted by the US Association of University Technology Managers. To help gather evidence, the NIH has set up a website where researchers can anonvmouslv report cases where thev believe their work has been hindered bv restrictive licences. Among the most frequent causes for complaint are confidentiality clauses and agreements that oblige researchers to show their manuscripts to a company before 'Some companies insist on the right to licences on discoveries arising from use of their materialy publication. Another problem is that some companies insist on the right to automatic licences on any future discoveries arising from use of their material, and "reach through" provisions that entitle them to a royalty on any profits earned by any product developed with their tools. "It's a really big problem if you have to sign lots of these agreements," says Eisenberg. "They might have inconsistent provisions." In addition, she says, "licences and material transfer agreements with companies are taking longer to negotiate, so it may take weeks or months to get a reagent or material, which would hold up the research". Biotechnology companies defend such restrictions on the use of their technologies, claiming that they are expensive to develop and so should attract reasonable rewards. But the industry is split on how secretive companies should be about their hard-won data, and on the terms on which others should be allowed to use them. The most controversial issue is access to important DNA sequences. Publicly funded bodies and institutes around the world have agreed to publish immediately anv gene sequences-partial or complete they discover. This policy, which they reaffirmed in March at a conference in Bermuda organised bv Britain's Wellcome Trust, is essential for making progress in research, they say. Besides the trust itself, organisations that uphold this principle include the NIH's National Center for Human Genome Research, the European Commission, the Human Genome Organisation and Britain's Medical Research Council. Some private organisations are equally open about their gene sequences. The US- based pharmaceuticals company Merck has published the DNA sequences of fragments, known as expressed sequence tags (ESTs), of thousands of genes in a database called the Merck Gene Index. "We took the view that this was a research tool," says Tom Caskey, senior vice-president for research at Merck. The company believes that giving an army of academics access to its gene data is a more economical way of getting further useful results than doing all the work itself. "We are allowing more discoveries to be made by our policy," savs Caskey- Other companies take a different view. Human Genome Sciences, based ill Rockville, Maryland, and Incyte Pharmaceuticals of Palo Alto, California, impose strict conditions on access to their privately generated treasure chests of genetic data. HGS has been particularly criticised for applying for patents on fragments of genes that appear to have no knownn function-a key requirement of patented inventions- other than for detecting that same gene in a biological sample. The company also angered medical : searchers recently bv applying for a patent on one of the bacteria that causes meningitis. HGS insists its policy is justified. "We've filed for a very large number-300,000 individual EST sequences, [including] a fragment for each human gene," says William Haseltine, the chairman of HGS. "But it doesn't mean people should stop working on the whole gene." He says that more than 150 public scientific institutions have agreed to "material transfer agreements", which give them access-mostly free of charge-to genes and clones owned and patented bv HGS. "There's plenty of room to do research," he says. Subscribers to Incyte's database can inspect six bacterial genomes that are not available in the public sector, including those of Staphylococcus aureus species notorious for developing resistance to antibiotics. Some owners of genoniic data are less restrictive. Robert Blackburn, senior Pattent attorney at Chiron in Emeryville, California which sequenced the hepatitis C virus, savs the company has published all its data on the virus. "You can't patent information," he points out. The conipany will take legal action only if it believes someone is selling products that infringe its patents on diagnostic tests for the virus, he says. But Chiron does not permit free access to some features of the vrus. For example, it licenses out use of the protease protein, an enzyme vital for the virus's survival and a key target of drug makers. Highlighting the divisions in the industry, Blackburn agrees with Caskev at Merck that ESTs should not be patentable, and is unhippy that the US Patent and Trademark Office has granted patents on them. The worry for critics of this policy is that such patents could be used to claim royalties on drugs that happen to include a patented DNA sequence within them.

All the profits

While access to DNA sequence data has dominated the row over research tools until now, the availability of other essentials, including genetically altered animals and DNA-coated silicon chips, is also becoming controversial. It was complaints about access to strains of mice with certain genes deleted in specific organs and tissues that prompted Varmus to set up the NIH working group. The animals, called Cre-loxP mice, were developed by the chemicals giant Du Pont, and researchers were complaining about the terms of the licensing agreements for access to the mice. These included an open-ended royalties arrangement that they feared could have allowed Du Pont to take all the profits from any product they developed. Du Pont has since amended the terms, reducing expected royalties to 25 per cent or less. But like Chiron, the company insists that the licences are necessary and reasonable. Royalties would be paid only if a licensee produced a profitable product, says Bob Greutzmacher of Du Pont's technology transfer office. "There's no charge provided it's for research purposes only. We have 150 academic licensees, and most of the feedback from them is good," he says. Answers to these problems may come from the NIH working group's report. The evidence it is collecting should certainly help establish whether the licences are impeding the development of vital medicines. It might even put biotechnology researchers back on level terms with the humble carpenter. Andy Coghlan

Health officials are standing by a transtasman deal on genetically altered food despite problems found in rats which ate modified potatoes. British researchers found that rats fed on potatoes modified with genes from snowdrops and jackbeans, to resist pests, ended up with damaged immune systems and stunted growth. This has been seized on by opponents of a deal the Govem- ment signed with Australia last month to allow in unlabelled food as long as it had not been "substantially modified." Alliance MP Phillida Bunkle said the discovery that modified potatoes had apparently damaged the growth of rats showed it was impossible to tell how far up the food chain the effects of genetic clmges would travel. But the Minister of Agriculture, Lockwood Smith, and the Australia New Zealand Food Authority have given assurances that genetically modified foods will not reach shop shelves if there is any doubt about their safety. Dr Smith said last night that such foods would not be allowed on sale without passing rigorous safety assessments by the authority on a case-by-case basis. He added that since agriculture and horticulture began, farmers and growers had tried to improve their herds and crops genetically through breeding. Australian and New Zealand health ministers, including Tuariki Delamere, agreed last month to adopt a two-step safety check by a genetic manipulation advisory committee and the food authority. But Phillida Bunkle, who is calling for all modified foods to be labelled, said it was unworkable for the food authority to promise that foods over which there was any doubt would not make it to shops. She said the authority did not do tests of its own, but relied on those of the owners of the crops, which were not disclosed because of "commercially sensitivity." And because modified foods contained completely new genes, they could produce novel proteins with unpredictable results, hence, no safety tests could be devised.

NZ Herald 12 Aug 98 LONDON -
THE TIMES, London, August 13, 1998

Scientist's potato alert was false, laboratory admits

BY NIGEL HAWKES, SCIENCE EDITOR

WARNINGS about genetically modified food issued by a scientist earlier this week were improper and misleading, a top British nutrition laboratory admitted yesterday. The scientist involved, Dr Arpad Pusztai, 68, has been suspended by the Rowett Research Institute in Aberdeen and will retire. He had claimed that experiments with genetically modified potatoes had shown immune-system damage in rats that ate them for more than 100 days. The Rowett said yesterday that this was not true. The data to which Dr Pusztai had referred, first in an interview with World in Action and then with The Times and other media, did not involve genetically modified potatoes. Rather, it involved feeding trials in which a protein from the jack bean, a lectin, was added to a potato-based feed. Since this lectin is known to harm the immune system, the damage was not surprising. The institute does intend to carry out feeding trials with a potato modified by inserting the gene for this lectin, called Con A, but has yet to start. It said it "regrets the release of misleading information about issues of such importance to the public and the scientific community". Professor Philip James, the director, had suspended Dr Pusztai from all responsibility for the studies, and put Dr Andrew Chesson, head of research, in charge. Dr Colin Merritt of Monsanto, the leading company involved in gene-modified crops, said: "It seems the researcher leading this programme was out of the country ... Meanwhile, Dr Pusztai had gone to the media. Basically he has picked up non-genetically modified potato data, in which the naturally occurring poison Con A has been added, and read that as the effect of transgenic modified potatoes. It is an awful mistake and these revelations are absolute dynamite." Last night Dr Pusztai said that his main concern was to ensure colleagues were not dismissed. From his Aberdeen home, he said: "I do not want to speak right now because I have effectively been sacked." Dr Pusztai is thought to have arrived in Britain from his native Hungary in 1956. He is a leading world expert in lectins and, according to institute sources, has an "enormous international reputation". He has worked at the institute for 20 years.

Genetically modified potatoes can damage the immune systems of rats, according to British research that calls into question the safety of the new technology. Professor Arpad Puztai of Aberdeens Rowatt Institute said he fed five rats modified potatoes that carried genes from the snowdrop for 110 days equivalent to 10 years in human terms research:showed that the rats suffered form slightly stunted growth and were more likely to be vulnerable to disease. The Australian Consumers Association said the findings only added to its concerns about the genetic modification of foods.

"We've really argued all along for a precautionary principle - that is these products are presumend guilty before they are proved innocent".

Environment groups say that it took decades before the full dangers of pesticides like DDT were known or the ability of BSE (mad cow disease) to also infect humans.However the ANZFA says no genetically modified foods would be allowed into Australia until they had passed rigorous safety standards. . "We'll take a cautious approach," said - authority spokes-woman Lydia Buchanann- "If there's any doubt it won't be on the shelves." Australian and New Zealand health ministers agreed only last month to allow genetically modified food to be produced and sold in Australia and New Zealand after a two-step-safety check from a genetic manipulation advisory committee and the food authority. The first applications are expected soon, although it's likely to be nine months before the first foods are approved. -However, it's unclear whether all genetically modified foods will be identified, the ministers only agreeing that foods substantially modified by genetic manipulation should be labelled. 'This is in line with United States practice, although in the European Urhon all such foods have to be labelled. 'The Australian Consumers' Association said the new research strengthened its demand for all genetically modified foods to be labelled. "It definitely strengthens the need for labelling, that's simply a matter of consumers' rights to know and choose," Carole Renouf said.

In Britain, Professor Puztai said his results meant that genetically modified crops should be tested more rigorously before being cleared for human consumption. "We are assured that this is absolutely safe and that no harm can come to us from eating it. But if you gave me the choice now, I wouldn't eat it" he said. 'We need to be far more careful in devising testing programmes it is expensive, it is long, but nevertheless it is the only way that you will be able to pick up differences. 'We are for less haste and more testing" Professor Puztai said. Britain's agriculture ministry said the genetically-modified potaoes had not been, approved for human consumption -in Britain, although soya and some other genetically modified products have been on sale for about two years.

The particular strain tested was not thought to be sold commercially anywhere in the world. Monsanto Co, the multinational agro-chemical group that is among the pioneers of the new food technology, said that all genetically modified food was safe and had undergone rigorous trials. "There have been more than 25,000 field trials conducted on 60 crops in 45 countries around the world ... and not one of the regulatory agencies in those countries has said that there is a safety issue," a Monsanto spokesman said. But many Britons are anxious about meddling with nature to pro. duce food. More than 40 of the 300 experimental sites growing genetically modified trial crops have been damaged in the past six months by environmental campaigners. Prince Charles, himself an organic farmer, fuelled the debate in June with a warning that genetic engineering of food "takes mankind into realms that belong to God and God alone."