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Is patching human genes any more immoral than patenting nerve gasses?
New Scientist Editorial 12 July 1997 19

NO legislation is framed to edify or entertain, but the European Biotechnology Patent Directive - 4000 words that have been nine tortuous years in the making - has a decidedly serious feel to it. Next week in Strasbourg, MEPs will bravely consider its fate, while Greens and others opposed to virtually anything with the word genetic in it will be working overtime. For if the directive is passed, it will give companies across Europe free rein to patent human genes and cells. Two years ago, an earlier draft was comfortably defeated, prompting the opponents of gene patenting to claim a victory of "conscience over commerce". But then the wording was so fudged it was impossible to tell whether it was ruling patenting in or out for human genes, and doubtful whether anybody's conscience was ever in danger of being compromised. This time the directive is clearer: the patenting of human genes is definitely "in" provided you actually do some science on it-that is, isolate, manipulate or copy the DNA. And this time the vote will be closer: socialists who make up the largest group in the European Parliament have promised broad support. But ideologically speaking, the debate will be dominated by the same old rhetoric. Industry lobbyists will argue that a "no" vote means no patents, fewer new drugs and an exodus of companies quitting Europe in favour of more favourable climes. None of which will wash because the European Patent Office has been allowing companies to patent human genes and transgenic crops and animals on an ad hoc basis for several years. All the new directive will do is limit the grounds on which Greens and their allies can fight each new application. Opponents of gene patenting, on the other hand, will claim that it is a nonsense to allow patenting of human genes because they already exist in nature and so cannot be invented. And besides, granting a patent on a gene to one company stops others from using that knowledge. These arguments sound more convincing, but they also fall apart on closer inspection. Human genes do exist in nature but not in a form that doctors could use to combat disease. And yes, patenting a gene does exclude others from commercially exploiting the same piece of DNA-but it also means that details of the research become public knowledge. Without patents, companies would simply keep their research into human genetics secret. Does anyone want that? But for most opponents of the directive, none of this matters much.What they really object to is not the technicalities of patenting but the much wider business of genetic engineering and the commercialisation of research into human DNA - something they regard as scary and immoral per se. It is easy to see why people are swayed by emotive arguments that equate human DNA with life itself. But DNA is not life: it cannot replicate unaided. We should not fall into the trap of giving it abstract powers it doesn't possess. This is not to deny that there are risks attached to human genetics research or that there are difficult ethical and moral problems here. The real question is whether patents have a big part to play in dealing with these problems. Many protagonists seem to take it for granted that they do. They seem to believe that it makes perfect sense to try to turn patent laws into a barometer of what is right and wrong. History tells a different story. Key aspects of the technologies that brought us nuclear bombs, nerve gases, electric chairs and land mines have all been patented this century. Nobody ever understood this to signal that the moral issues had been resolved. Indeed, it would be absurd to debate the rights and wrongs of capital punishment and land mines with reference to patenting policy. That is because we have other laws and conventions that deal with these things. Yet when it comes to patenting genes and anything else biological, people seem to lose sight of this-and not just the Greens and the anti-genetics lobby. The European directive falls into precisely this trap by explicitly forbidding the patenting of whole human beings, cloned or otherwise. There was no need for such an exclusion because once again we have other laws that prohibit moves in this direction. And such statements only help to turn those who grant patents into something they should never be-arbiters of what is right and wrong.


Spliced rice: crops that produce human proteins are already being grown

Human Harvest Festival New Scientist 12 July 1997 17 Kurt Kleiner

HUMAN proteins could soon be grown and harvested just like any other crop, thanks to genetically engineered rice developed by Applied Phytologics, a company based in Davis, California. The technique could make it cheaper to produce many bioengineered proteins such as those found in detergents. The most common way of manufacturing bioengineered proteins is by brewing them with the genetically engineered microorganism in a bioreactor. Some researchers have begun experimenting with plants, often leafy crops such as tobacco (Technology, 16 July 1994, p 20). But Applied Phytologics is the first company to try using a cereal, says Roger Beachy, head of plant biology at the Scripps Research Institute in La Jolla, California, and a sqentific adviser to the company. "I think it's going to dawn on the industry shortly that in plant biotechnology cereal grains are going to be the crop to work with," says Raymond Rodriquez, chairman of Applied Phytologics. In March the company planted 4200 rice plants engineered to manufacture alpha-lantitrypsin, a human protein that could be used to treat liver disease and haemorrhages. The rice will be harvested in September and the protein extracted by malting, in which the grain is allowed to germinate. The idea, says Rodriquez, is to use existing agricultural techniques on a mass scale to make products at low cost. In normal malting, the seed produces an enzyme that begins to turn the starch in the seed into a sugar. Applied Phytologics engineers the seed so that, instead of expressing the normal enzyme, it expresses the protein the company wants to produce. Later the protein can be extracted from the malted grain. Rodriquez says his company will concentrate on products for which there is great demand, such as enzymes for washing powder, or proteins used to stop blood products clotting. The demand for these products will make it economical to produce hundreds of tonnes at a time. Rodriquez expects to be producing commercial quantities of nonmedical products within four years, and to have regulatory approval for some of the medical products within seven years. Kurt Kleiner.

Antipodes clampdown: New Scientist Wilson da Silva Sydney 5 April 1997

AUSTRALIA and New Zealand are poised to introduce what may be the world's toughest regulations governing the sale of food made from genetically modified plants or animals. The regulations were prepared by the Australia and New Zealand Food Authority (ANZFA) and are likely to come into effect before the end of the year. Companies who want to market modified foods will have to apply to the ANZFA for approval, which will subject each application to scientific scrutiny in a process that could take as long as a year. if approved, foods containing more than 5 per cent genetically modified material will have to be labelled as such. Manufacturers who want to sell food to which genes have been added must provide data on the sources of the new genes and full sequences of the DNA they have manipulated, the vectors used to ferry the genes into place and the marker sequences that indicate whether they have been successfully introduced. They must also provide information on the potential of the genes to cause disease or produce toxins, and on any previous uses of the genes in food. Similarly stringent requirements will apply if no genes have been added, but if some of a plant or animal's natural genes have been deleted. The ANZFA believes this regime is the strictest so far proposed anywhere. "They are saying that everything is guilty until proven innocent," says Rosemary Robins, a specialist in ethics and genetics at the University of Melbourne, who supports the plan. Industry groups are less happy, however. "It's overkill," says Pam Saunders of the Australian Food Council. The regulations will be reviewed by Australian and New Zealand health ministers in April or May, and could be implemented within a few months. They will not require approval by the two countries' parliaments. Under existing laws, there is nothing to prevent most genetically engineered foodstuffs from reaching grocery shelves in Australia and New Zealand. However, a voluntary moratorium agreed by the food industry and the countries' governments has been in place since 1993. Wilson da Silva, Sydney


Phillida Bunkle ...protesting. Winsome McCaughey ... opposes mandatory labelling
Sue Kedgley ...'open slather'

Should you know whether the food you eat is genetically modified? Not usually, say the authorities. Others, however, are angry.

NZ Herald Feb 98

Alliance MP Phillida Bunkle is considering making another bid to force the labelling of genetically modified foods. She is supported by campaigners for natural food. After trying unsuccessfully last year to introduce legislation on such labelling, Phillida Bunkle said yesterday that opposition MPs might make a second bid for a law change following a recommendation from the Government's food watchdog to allow the sale of many genetically modified foods without warning labels. Initially, New Zealanders had been told all genetically altered food would be rigorously evaluated and labelled, except where the modified content was under 5 per cent, or the altered food was substantially equivalent."

But Australia-New Zealand Food Authority chairwoman Winsome McCaughey said yesterday the authority would not be seeking mandatory labelling on foods produced using genetic technology that were substantially equivalent to their conventional counterparts. It would only require case-by-case analysis of foods that had been significantly modified. However, Phillida Bunkle maintains it is a fundamental right that people be told what they are eating, particularly as the long-term effects of genetically 'modified food are unknown. "People should at least haye the right to know when they are eating genetically modified food, so they can judge for themselves whether to accept the risk." She warns there will be a groundswell of protest from New Zealanders against Health Minister Bill English signing the ANZFA recommendation into law. It is, she says, far weaker than the original draft standard proposed last year. That draft proposed banning the sale of modified foods unless they had been speciflcally authorised. It said that foods containing more than 5 per cent of genetically modified ingredients should be labelled, even if the modified ingredient were not significantly different from its conventional counterpart. But foods with lower levels of modification would not need to be labelled. These included foods with new genetic material, such as tomatoes engineered to be insect- resistant and potatoes modified to reduce bruising. The authority would allow negative labelling" of a third category. Where it could be proven foods had been produced without using gene technology, they could be labelled as containing no genetic modifications. Winsome McCaughey says there are many practical difficulties with widespread compulsory labelling - tracking individual food components, enforcing such requirements, limited evidence that such labelling was useful for consumers and possible inconsistencies with world trade agreements. Phillida Bunkle responds that "huge" numbers of New Zealanders made submissions asking for strong standards but appear to have been ignored. The decision is extremely contemptuous" of consumers and the consultation process, she says, and politicians had misused it to cave in to powerful industry lobby groups. Last October Consumer Affairs Minister Robyn McDonald said products that contained modified food should say so on the label. "There is not a heck of a lot we can do about mad cow disease after the event. We don't want to be in that position with genetically modified food so we are pro- ceeding cau- tiously," she told a Guild of Food Writers conference. But other ministers did not agree. Agriculture Minister Lockwood Smith said then the labelling would only arise if there was a question of safety. However, Guy Hatchard, director of the Natural Food Commission (a lobby run by the Natural Law Party), says the latest recommendation fails to take account of the latest research. He says that shows the risks of genetically altered food are greater than previously thought. And Safe Food Campaign spokeswoman Sue Kedgley criticises the standard as "far worse" than what had initially been proposed. "It's basically open slather on genetically engineered foods in New Zealand - we'll have genetically modified food turning up as ingredients across the board," she says. "This just follows the American line that says you don't have to separate modified and conventional foods, such as soybeans." She says the Australian food industry has obviously overwhelmed the authority, probably because consumers tended to prefer the natural product when given a choice of labelled foods. "They've just capitulated to industry pressure. The Government is buying a fight if it accepts the recommendation, because there is huge consumer concern about the issue," she says. - NZPA

Australia and New Zealand Food Authority Fax:+64-4-473 9855 Tel: 9942 E-mail: [email protected]

The outcome: New Zealand signed on to a toothless policy

By CATHERINE MASTERS NZ Herald Aug 98

The Government yesterday signed a transtasman deal allowing genetically modifled foods into the country without labelling. The decision has angered campaigners who say we have a right to know what we are eating. They are angry despite the Government's leaving the door open for change by saying further international information on the matter would be considered. The Alliance health spokeswoman, Phillida Bunkle, said last night that she would sue the Government for increasing her and other women's risk of getting breast cancer. "I've already spoken to a barrister." She said she had a possibly precancerous condition of the breast and wanted to avoid excessive oestrogen, which she said was found in genetically modified soya. Soya is in 60 per cent of all processed foods but Phillida Bunkle said the Government's refusal to insist on labelling meant she would not know which products contained the genetically modified variety. "I want to avoid excess oestrogen because it increases my risk of developing invasive breast cancer and I won't have the option under this regime ... Genetically modified soya was found in staple foods such as baked goods, cakes, biscuits, breads, some flours, pastries and anything protein enhanced, she said. The Associate Minister of Health, Tuariki Delamere, said 'hardline purist calls" for all such modified foods to be labelled were impracticable. 'The compliance costs of meeting such a demand would be huge and would inevitably impact on the price of food to ordinary New Zealanders." The standard adopted by the Australia New Zealand Food Standards Council struck a sensible middle course, he said. It meant the foods must be assessed for their safety for human consumption and listed in a table before they could be sold. The fight for labelling, however, has the bacldng of various environmental groups and the Royal New Zealand College of General Practitioners. A letter to the Prime Minister, Jenny Shipley, from the college's environmental working party said the council was not the body to decide what should be introduced into the food chain of patients. The technology should be rigorously tested for at least 25 years before it could be declared free from risk of causing diseases.

US Envoy "aggressive" in genetic food row NZ Herald 30 Nov 98

WELLINGTON - Former associate healer minister Neil Kirton backs claims -the United States bullied New Zealand over the testing and labelling of genetically modified food. Mr Kirton said yesterday that he was visited on the issue twice by an 'aggressive" US Ambassador Josiah Beeman. Mr Kirton said Mr Beeman visited him twice in about February or March of last year after he made statements calling for compulsory labelling of genetically modified food.

"On the first occasion it was the first time I had had a visit from a diplomat to see me. I was struck dumb by the aggression showed by Beeman to my stance, and the bullying tactics he used.' Mr Kirton said the comments made by Mr Beeman were along the lines of how his stance would affect US-New Zealand trade, relations. He understood Mr Beeman was in contact with other ministers on the issue, including the Minister for International Trade, Lockwood Smith. Mr Kirton said that after he was sacked as minister, his replacement and then New Zealand First colleague Tuariki Delamere had decided to support the stance on non-labeling promoted by the Australian-New Zealand Food Authority, despite the strong opposition of the NZ First caucus. 'There was a very, very vigorous and acrimonious debate in the NZ First caucus because' he [Mr Delamerel had made the decision without getung approval from the caucus]. Mr Kirton sWd he supported because he believed consumers had a right to know what was in food they were buying. Mr Delamere said yesterday, through a spokesman, that he had "never had any contact from anyone in the US Government" about the issue. He Was responding to the claim by AIliance team spokeswoman Phillida Bunkle and Greens co-leader Jeanette Fltzsimons that the government had been pressured. They cited cabinet papers which said: "The United States and Canada to a lesser extent are concerned in principle about the kind of approach advocated by The Austrlalian-New Zealand Food Authority and the demonstration effect this may have on others, including the European Union. The United States have told us that such an approach could impact negatively on the bilateral trade relationship and potenially end any chance of a New Zealand-US Free Trade Agreement." Phillida Buncle said her bill to make labelling of genetically modified food compulsory was defeated because of the US pressure. NZPA

More than a dozen field trials on genetically altered crops in New Zealand.
NZ Herald 2 Dec

The Environmental Risk Management Authority has just granted a biotechnology firms permission to genetically alter sugar beet under the Hazardous Substances and New Organisms Act. This is the authority's first such approval, but it says more than a dozen experiments have already taken place with the permission of its predecessor. However, it says those trials would not have resulted in genetically modified products ending up on people's dinner plates. The trials - in contained fields - included experiments on potatoes, pine trees, tainarillos, apples, broccoli, barley and even genetically altered sheep. Approval was granted by the Interim Assessment Group, which,advised the Ministry for the Environment. The Environmental Risk Management Authority replaced that group in July. Last night, the pressure group Revolt Against Genetic Engineering (Rage) said it was taking legal action against the authority over its decision to approve the latest application, by the Kimihere Rearch Centre in Canterbury, for a second trial of sugar beet that is resistant to a herbicide. The Rage coordinator Mary-Anne Howard-Clark said despite the authority's assurances, too many variables existed in the field trial for the public to be assured it was safe. Wrightsons were interviewed on Kim Hill concerning their involvement in beet.

Hypothetical situations and Bias in Consumer Sampling June 98 NZ Herald

June 98 Wendy Johnson of Friends of the Earth accused an Environmental Risk Management Conference of being under the control of scientists on the side of the genetic engineering industry. Dr. Oliver Sutherland claimed public consultation had been as inclusive as possible. However Kathleen Scott of Friends of the Earth complained that a survey asking customers if they would object to an apple being genetically-engineered so as to increase its size, improve its flavour or reduce the need for pesticides as biased.complaining that the questioning ignored whether they would be as happy to eat pork with human genes, or soys beans with viral genes. Sue Muggleston tried to defend this by saying "We didn't feel it appropriate to ask about hypothetical situations.

GE Companies Support Labelling Bowditch Group Newsletter #136 March 20, 1998 http://www.bowditchgroup.com.

Novartis chairman Alex Krauer told analysts at the company's annual financial results meeting that "We are in favor of labeling. We want to be open and transparent. That means we acknowledge the wish of the European consumer to know what he or she buys." As to whether foods should be labeled based on the presence of novel proteins, or the presence of modified DNA, or on some other basis Novartis has taken no position. Wolfgang Samo, head of Novartis's Agribusiness Division, has said that he would be in favor of a label that "says whether a food could contain genetically modified material." He believes that a "non-GMO" market segment could develop, as The Bowditch Group has suggested.

News reports (St. Louis Post Dispatch) suggest that Monsanto may be ready to change its position on food labeling in Europe. Tom McDermott, Monsanto spokesman in Europe, indicates that the company remains opposed to labeling in the U.S., but may be willing to accept labeling of GMO-containing foods in Europe, as public sentiment seems to demand it.

Artificial Human Chromosomes New Scientist Andy Coghlan 5 April 1997

ARTIFICIAL human chromosomes have been created for the first time - an achievement hailed as a milestone in genetics. The researchers, Huntington Willard and his colleagues at Case Westem Reserve University in Cleveland, Ohio, dismiss the idea that their chromosomes are a prelude to the construction of synthetic life forms. But they hope that artificial chromosomes will help to explain how chromosomes work, and provide safe vehicles for shuttling DNA into patients undergoing gene therapy. Chromosomes are made up of linear bundles of DNA. They form the inheritable genetic blueprints of higher organisms, ranging from yeast to human beings. Because yeast chromosomes are among nature's simplest, they have been thoroughly studied and the first artificial versions made a decade ago. But no one has ever built human chromosomes, which are much larger and more sophisticated. "Chromosomes have always been considered a black box since the early 1900s, when it was first established that they carry inheritable genes," says Willard. "Our research establishes the pieces you need to make them." Willard's team has proved what geneticists have long suspected-that human chromosomes must have three basic types of DNA.

The first requirement is for DNA that encodes inherited genetic information. To build their chromosome, Willard's team used DNA taken from the white blood cells of laboratory staff. The second vital ingredient is telomeres, long strands of repeating DNA sequences that appear at the tips of chromosomes. "The telomeres are the caps at the ends that keep the DNA from being eaten away, and which stop individual chromosomes from binding together, which would jumble the information," says Willard. The team made telomeres by linking together thousands of short synthetic DNA units. The third requirement is centromeres, which provide the physical scaffolding that enables a duplicate chromosome to split from the original when cells divide. Like telomeres, centromeres consist of many repeats of the same short DNA sequence. Centromeres usually form the distinctive kinks near the middle of chromosomes. Willard and his colleagues report in the current issue of Nature Genetics (vol 15, p 345) that they made artificial centromeres for the first time by linking together units of bases called alpha satellite DNA. Next, Willard introduced the three components into human cancer cells that had been grown in culture. He did this by wrapping them in fatty globules called lipids, which can pass through cell membranes. The researchers found that the cells automatically assembled the foreign material into chromosomes. In one cloned cell line, Willard detected a totally artificial chromosome, made purely from the foreign components. This chromosome was passed on to all daughter cells along with all the pre-existing human chromosomes. This, says Willard, proves that the chromosome is fully functional and inheritable. Now that the bare essentials of a human chromosome have been established, geneticists can tinker with the components to learn more about how they work. "This will open the door to understanding chromosome rules," says Willard. He adds that such chromosomes might provide a way of smuggling beneficial genes into patients undergoing gene therapy. The gene shuttles are usually viruses, genetically engineered to be harmless. But these can trigger immune reactions in patients, or disrupt genes that protect against cancer. "This result is an important landmark in terms of constructing artificial human chromosomes," says Melissa Rosenfeld of the National Human Genome Institute in Bethesda, Maryland.

Genetically Engineering Plant Flowering from New Scientist
Stephen Day is a freelance science writer based in York

Geneticists have identified four main groups of flowering genes in Arabidopsis. The first pushes the plant towards blooming during the long summer days. The second delays flowering when the days are short. Another relays information about the temperature and tips the balance towards producing blooms when the weather warms up in spring. A final group responds to the plant's internal state and presses the flowering button more insistently as plants grow older and bigger. This allows factors such as rainfall, soil quality and disease, which affect a plant's growth rate, to influence flowering. "Intuitively, I would feel that there are several different routes to flowering," says Coupland, "and I would imagine that they could well counteract each other." Whatever the conditions, though, Arabidopsis will always flower eventually. Under natural conditions, it may bloom any time from around three weeks to nearly a year after germination. But as Coupland's research shows, a sufficiently strong push on a single pathway can hotwire the decision-making circuits, creating plants that flower on demand.

Coupland's group used a gene that promotes flowering when the days are long, encouraging Arabidopsis to flower in summertime. Up to a point, the more daylight hours there are when the plant is growing, the quicker it will come into bloom. Plants carrying only mutant copies of the gene, however, lose this response. Length of day has no effect on how quickly they flower, hence the gene's name-CONSTANS or CO. In normal plants, long days stimulate the CO gene to produce more of a protein called CO, which in turn stimulates other flowering genes. Coupland's genetically engineered weed produces a hybrid protein, which consists of CO attached to a steroid receptor. The receptor prevents CO from doing its work by keeping it in the body of the cell, away from the nucleus where it would normally activate other genes. Dousing the plants with the right steroid, however, turns the receptor into a taxi. "When the steroid binds to the receptor, the receptor moves to the nucleus," says Coupland. It's not quite sunshine in a bottle, but it has the same effect. A similar principle could be used to make crops flower in response to the weather forecast, rather than the weather itself. "You can unlink flowering from environmental signals," says Coupland. "There are cases where it would be advantageous to have plants flowering slightly earlier than normal." In Canada, for example, where the short summer means that the oil seed rape crop does not always have time to ripen, forcing plants to flower a couple of weeks early might make all the difference. This assumes that other plants can be engineered in the same way as Arabidopsis, which is by no means certain. "It is not yet possible to tell how far you can extend the research to other species," says Coupland. His team is now testing whether the CO gene can induce tobacco plants to flower. But if the work on plant flowering is to progress, researchers need to study genes that are common to many flowering plants. And herein lies a problem. The DNA sequences of the genes involved largely remain a mystery. This is the case even in the much-studied Arabidopsis. The weed's entire genome is currently being sequenced but, as yet, there is no way that geneticists can be sure that the genes they are studying in Arabidopsis are also found in other plant species. However, one group of genes has emerged that several plants share. When activated by CO or by one of the other flowering control pathways these act like a "floral switch" making a shoot grow into a flower. At the Salk Institute for Biological Studies in La jolla, California, Detief Weigel has been studying one of these genes, called LEAFY. Arabidopsis plants that lack a working copy of the gene make abnormal flowers containing leaf-like organs. And the familiar snapdragon, Antirrhinum-which is only distantly related to Arabidopsis-has a sin-dlar gene that switches the plant from making a shoot to producing a flower. Working with Ove Nilsson from the Swedish University of Agricultural Sciences in UmeAl Weigel's team introduced extra copies of LEAFY into Arabidopsis. At least four other genes are needed in the floral switch, but the researchers wanted to see whether they could push the whole mechanism into the "on" position by artificially activating LEAFY alone. Sure enough, the genetically engineered plants did flower earlier than normal.

Next, the team added extra copies of LEAFY into aspen trees. The result varied from plant to plant probably depending, say the researchers, on how much protein the new genes were producing. "We have examples were the plants just get a few inches tall and then make flowers and die," says Weigel. "We also have ones that make it into the greenhouse and grow as bushes." The fact that the LEAFY gene has the same effect in plants as diverse as Arabidopsis and aspen suggests that it could be used as a universal "on" button to induce early flowering in all plants. Weigel and Nilsson's instant bonsai could bring tree breeders out of the woods-literally "What we have so far certainly wouldn't be useful in the field," says Weigel. "But where it would be useful would be in a breeding programme. If you can make plants flower earlier, then you can make breeding quicker." Of course, tiny trees growing in the laboratory could not tell you much about their ability to thrive in a real forest. But molecular biologists can now pinpoint individual plants with particular characteristics such as disease resistance, by looking at their DNA. So breeding with pint-sized trees is feasible. "You breed in the characteristic you want using the tiny plants," says Weigel. "Then you simply remove the introduced gene by standard genetic crosses and you have normal trees again." There may be ways to shift flowers in space as well as time. Not only do Weigel and Nilsson's aspens flower very early, they also make isolated flowers rather than many blooms clustered into catkins. Research with Arabidopsis and Antirrhinum may explain what is going on. Both plants normally produce flowers on tall flowering stems which keep on growing until the plant dies. Blooms appear on all sides of this spike, but something keeps the floral switch in the "off" position at the growing tip.

In January, Desmond Bradley and his colleagues, also at the John Innes Centre, reported that at least one of the genes involved in this process is the same in both Arabidopsis and Antirrhinum. In Arabidopsis, the gene is called TERMINAL FLOWER 1, or TFLI, because mutations in the gene produce short flowering spikes that end in a bloom. TFLI is normally very active in cells near the tip of the flowering stem, where it inhibits LEAFY and other floral switch genes. The equivalent gene plays a similar role in Antirrhinum. However, by introducing extra copies of the LEAFY gene into Arabidopsis, Weigel and Nilsson showed that they could override TFLI's protection of the shoot tip. Arabidopsis with extra LEAFY genes produce a bloom at the tip of the flowering stem. In the genetically engineered aspen trees, this process may have reached its limit. Catkins are just squashed up flowering stems, and in the miniature aspens the tip of the catkin appears to turn into a flower before any side-blooms have formed. Following this work, genetic flower arranging could be just around the corner. "One slightly frivolous example would be to make novelty ornamental plants," says Weigel. "If you could turn all the lateral shoots into lateral flowers, for example, you could have a rose which not only had a flower at the apex of each branch, but also flowers in all of the leaf axils." A less colourful but more practical application would be crops tailored to produce more fruits or seeds, or to make these more accessible for harvesting. Genetic flower arranging could also be used to change the shape of a plant. Normally, growth occurs only at the shoot tip and at the bud at the base of each leaf. Each growing point can form either a flower or a shoot, but not both, so manipulating the position of flowers can alter a plant's shape. "You might want to change the architecture of a plant for growing in a particular environment, making it more bushy or more elongated," suggests Bradley. Aspen plants carrying extra copies of LEAFY, for example, do not grow into trees because at some stage in their development the shoot tip turns into a flower. When this happens early, the plant cannot make enough leaves so it dies. In plants where this occurs later, shoot tips tum into flowers, encouraging side branches to grow from buds lower down the plant, creating a bush rather than a tree. Controlling flowering may not be just about "switching on" flowers though. Turn off vegetative growth, and flower production may occur by default. At the University of California at Berkeley, Renee Sung has found two genes responsible for early shoot growth. Arabidopsis plants that lack working copies of these develop a "live fast, die young" attitude that would make a rock star look like a shrinking violet. "In mutants," says Sung, "the shoot apex begins some kind of activity in the embryo." Exactly what is happening becomes clear shortly after sowing. The seedlings open their two seed leaves (the cotyledons) and then, instead of making a normal shoot, they bolt and produce a tiny flowering stem. A month or so later, consumed by flowers, the mutants die. Such leaps in our understanding of the genetics of flowering are set to change farming and horticulture. But Coupland, Weigel and their colleagues are not the first to goad plants into flowering. Traditionally, apple growers shook recalcitrant trees awake by beating their trunks with sticks. Plants often bloom when things seem to be going badly wrong, in a lastditch attempt at reproduction.

Genetic Engineering for a Cooler Planet

GENETICALLY engineered cyanobacteria may soon be used to soak up carbon dioxide from the atmosphere and turn it into a raw material for biodegrad- able plastic, say Japanese researchers. Scientists at Japan's National Institute of Bio- science and Human Technology in Tsukuba Science City and the Research Institute of Innovative Tech- nology for the Earth in Kyoto say that they can make the cyanobacterium (Synechococcus sp.) produce up to 10 per cent of its dry weight as polyhydroxy- butric acid (PHB). Joining PHB in a copolymer with hydroxyvalerate produces a biodegradable plastic. The only raw materials that the altered bacteria require to produce the PHB are water and carbon dioxide. The Japanese scientists want to use the engineered organism to extract C02 from exhaust gases in factories-simultaneously reducing emissions of a greenhouse gas while making a useful product. The cyanobacteria are usually found on beaches and use light and C02 to produce glycogen. The researchers have inserted a gene from the bacterium Alcaiigenes eutrophus, which itself usually produces PHB from hydrogen gas, sugars and water. Inside its new host, the gene uses the cyanobacterium's light and C02 pathway, but produces PHB rather than glycogen. Under normal conditions, the altered cyano- bacterium produces very small quantities of PHB. But by artificially varying the environment between light aerobic and dark anaerobic conditions, the Japanese researchers have increased PHB yields. The researchers are also looking at a naturally occurring species of cyanobacterium that produces 27 per cent of its dry weight in PHB, says Yasuo Asada, head of molec- ular bioenergetics at the Tsukuba bioscience institute. "It's very difficult to commerciallse at the moment because production costs [of genet- ically engineered cyanobacteriuml are not cheap," he says. "I want to increase the yield up to around 50 per cent." Peter Hadfield, Tokyo


New Genetic material shows blue amongst red intestine cells in lactose intolerant rats, given gene therapy.
This effect remained stable for several months, unlike the results of some other gene therapy experiments (NZ Herald).

NZ team lead world research NZ Herald 3 Sep 1998

By KEITH PERRY

Scientists at the Auckland School Of Medicine have found a way to treat genetic disorders that promises a pili to cure diseases such as stomach cancer and diabetes. The team, headed by molecular biologist Professor Matthew During, have used a gene-therapy treatment taken orally to cure the world's conunonest genetic disorder, lactose intolerance, in rats. It is hoped that within a decade a 'dose" of the same gene therapy will be used to combat inherited conditions m humans, such as haemophflia, intestinal cancer, cystic fibrosis attd obesity. Professor During cured lactoseintolerant rats by delivering a eating gene into the tissue that needed it. He found that the rats could digest lactose after only one oral dose of the missing genetic material. Professor During said the breakthrough cleared the way for a whole generation of new gene-therapy drugs. Gene therapy is a method of treating diseases caused by genetic abnormalities by replacing the defective gene with a corrected one. Problems have always existed with targeting the specific tissue containing the faulty gene and keeping the corrected gene functioning long term. Professor During is liaising with the Dunedin medical team that made world headlines when they identified a stomach-cancer gene that has afflicted generations of a Maori whanau. Professor Tony R6eve, of Otago University's cancer genetics laboratory, said his researchers would be very interested in exploring Professor During's findings.

"The results sound extremely interesting." The Auckland University researchers inserted the missing gene b-galactosidase, which produces the lactose-digesting enzyme, into rats' intestines. The gene was incorporated into cells lining the rats' gastrointestinal tract, allowing them to metabolize lactose. Six months later the rats remain tolerant to lactose, suggesting that a one-dose pill could be used to treat human genetic diseases. New Zealand's dairy industry could reap huge benefits in terms of exports as the disorder is prevalent in Asia and Africa and means victims cannot digest dairy products. Sufferers are advised to avoid dairy products altogether and are consequently at risk from calcium deficiency and osteoporosis. "This research brings gene therapy pne step closer to the clinic," Professor During said yesterday. 'Delivery of the missing gene has always been tke problem, but this research makes it feasible to give gene therapy orally in the form of a pill. "The experiment is important proof of principle for the treatment of other genetic disorders." He said that while there were safety issues to be addressed before clinical trials on humans could begin, the team believed the technology would lead to the development of a singl"hot oral vaccine that could be much cheaper than repeated treatments. It also meant babies could be treated in the womb and be cured of genetic disorders such as haemophilia before they were born. Professor During said it was important to realise that the scientists were not advocating genetic engineering. They were simply replacing a defective non-functioning gene with a working one. A Dairy Board spokesman, Robin Fenwick, said last night that the research was of tremendous significance. 'It represents a major break through and we would welcome any research that helps overcome lactose intolerance.

Comment: This particular technique is relatively innocuous in application because it can be applied to cells in the lining of the gut, but a previous attempt by the same team to perform gene therapy on two little girls suffering a severe terminal brain deficiency were much less so involving direct injections of material into the brain, which gave only temporary respite thus effectively proplonging their suffering.

Subject: Time to think about gene therapy in womb - US experts Reuters

Maggie Fox, Health and Science Correspondent

WASHINGTON, Sept 25 (Reuters) - Leading U.S. researchers in gene therapy say it is finally time to think about trying the still-experimental technique in the womb. While they are not asking permission to try the technique -- yet -- they asked advisers to the National Institutes of Health (NIH) on Thursday and Friday to think about the implications of such an experiment. The idea would be to "fix" babies with genetic defects before they are born. But there is a long list of safety and ethical considerations.

"This meeting was not designed to ask for approval, but the sense of the committee is that the technology has advanced enough that this is an appropriate time to discuss this in a public forum," said Dr. W. French Anderson, one of the pioneers of gene therapy, who was speaking to the committee. Anderson said he thinks his lab is only about two to three years away from being able to do this. His lab did the first-ever gene therapy experiments on a human in 1990, when it tried to use the technique to treat children with ADA deficiency, a genetic defect that leaves them with no immune system. Such babies often become "bubble children," forced to live in a plastic bubble to protect them from infection. Anderson has tried injecting genes that control production of ADA into the children, in the hope their bodies will take up the genes and start producing their own. He has had mixed results and no outright cure.

To do any of this work, he has to get permission from the NIH and its DNA advisory committee, which consists of scientists, lawyers and other experts. Anderson said he believes that gene therapy might work better before a baby is born, because its body is still forming and might absorb the new genes better. One of the biggest risks is that the new gene would be absorbed not only by somatic cells -- the cells that make up most of the body -- but by germ cells -- eggs and sperm. If that happened, the new gene could be passed down from generation to generation.

"The level of inadvertent germline transmission should be extremely low but, how low?" asked Anderson. He said the committee had asked him to come back with information from animal tests that would indicate how often this might happen.

And that leads to an even stickier question - could and should scientists do it on purpose? "Does that by itself open up the potential for great harm by opening the door for intentional germ line gene transfer when most of us believe we are at least 10 or 15 years away from technically being able to do it," Anderson asked.

The book is still open on whether regular gene therapy is safe. It is still only allowed on the very sickest and most desperate patients. "We need 10 to 15 years experience with somatic cell (gene therapy) to see if there are no problems," Anderson said. "The clock has just started ticking. Most of the gene therapy patients have been terminal cancer patients and they have died." It is possible that gene therapy itself could cause cancer, Anderson says. "If every patient who gets gene therapy develops leukaemia after 10 years, you clearly don't want to do germ-line therapy," he said.

The retroviruses used to deliver genes into the body insert their gene loads randomly. "If they happen to go into next to a cancer gene, it might turn on the oncogene, or if it goes in next to a tumour suppressor gene it might knock down the defence of the immune system," Anderson said.

Many groups oppose Anderson's proposed experiments. The Council for Responsible Genetics issued a statement calling the the idea ominous and a step toward the creation of "designer babies." "If this first proposal is accepted how much longer will it be before ... any child who doesn't measure up to some arbitrary standard of health, behaviour or physique is seen as flawed?" it asked.