The following article was kindly provided by Unlimited Magazine.

Unlimited is published monthly but includes a biotechnology supplement quarterly. The GM for dummies series by Rebecca Mcfie is ongoing. Information about the magazine and other Biotech articles can be accessed at: http://www.unlimited.net.nz/

GM for dummies
Sick of those dumb-arse questions from scientific illiterates? Journalist Rebecca Macfie isn't! A confessed science dummy, Macfie finds the answers to the 20 things about GM most folk want to know (and you can simply photocopy and pass on)
Rebecca Macfie 30 November, 2002 &Sunday, 2 March, 2003

Am I alone in my scientific ineptitude? I suspect not. From school I recall something about genes being the "packets of inheritance" and DNA consisting of a double helix thingy. But that's about it. And it seems that's so for the most of the population. I put the call out to friends, rellies and colleagues to send me the dumb questions they'd always wanted to know the answer to but were afraid to ask, with a promise to hunt down some answers that are intelligible to Fifth Form science drop-outs. The result is the Biotech Unlimited Dummies' Guide to G M : 20 questions and 20 answers, which you can photocopy and circulate to all your non-science friends, colleagues and prying media. The guide continues in the next issue of Biotech. The answers are sourced from scientists, lobby groups and documents from both sides of the Great Rift Valley that is the GM divide. On the pro side are two scientists, Crop and Food's Tony Conner and Genesis Research's Andy Shenk. On the cons side are Auckland University physicist Peter Wills and Sustainability Council executive director Simon Terry. There's also under my

feet a knee-deep stack of reference material ranging from the Royal Commission on G M through to the latest pontifications of the UK Royal Society. I've supplied you with a list of good websites, too. The answers are far from complete, are not always straightforward, and will, for sure, displease one side or other of this most polarised and at times vindictive of debates. But hey, at least next time I read about a contaminated corn shipment I'll know what Bt means. 1. What is a gene anyway and how many do we have? Thanks to David Dougherty and Jules Mikus we all know about DNA, the molecule in every cell that contains all our genetic information. DNA itself is a long, thin chain of minute units called nucleotide bases (adenine, guanine, cytosine and thymine abbreviated to A, G, C and T), which are described as a four-letter alphabet used to write biological code. Genes are sections of DNA

containing particular sequences of nucleotides. These sequences are the code for the production of particular proteins, which in turn make up the structure of living tissues. Genes themselves make up only a small proportion of our total DNA perhaps only 10%. It's useful to think of DNA as the genetic filing cabinet and the genes as the individual drop files inside. Each drop file contains the recipe for one of the proteins needed to carry out a particular biological function. Humans are thought to have between 30,000 and 40,000 genes, but scientists don't yet know what they all do. 2. Does every species have a unique set of genes? Are rat genes completely different from human genes? We humans share around two thirds of our DNA with a banana. Yes, you'll never look at your partner the same way again. Lots of human genes carry the same or very similar information as other species particularly those that dictate basic biological functions like cell division and DNA replication. Others are quite different. Using the filing cabinet analogy again, 95% of the drop files (genes) in rats and humans might be the same, but the particular recipes contained in the drop files will be different. 3. How do scientists take genes from one species and put them in another? No, they don't use very tiny tweezers to do it. In plant GM the most commonly used method involves using pathogens called Agrobacteria naturally occurring organisms that transfer DNA into the chromosome of a plant and cause a tumour. Scientists hitchhike on this process by removing the gene that causes the tumour and replacing it with the genetic material they want to transfer. They also include a gene for antibiotic resistance, which enables them to identify which bits of plant tissue have successfully incorporated the target gene (see the next question for more on this). Scientists sometimes cite the fact that the pathogens used in this process occur naturally and engage spontaneously in DNA transfer to refute the anti-GM line of argument that genetic modification could never occur without human intervention. To genetically modify an animal such as a mouse, fertilised eggs are harvested from the female and DNA is injected into the egg nucleus. The egg is then implanted into the womb of a female mouse. The newborn mouse will carry the new gene, and pass it on to future generations. Marker genes often for coat colour are sometimes added to the mix to indicate whether the DNA transfer has been successful.

4. What are antibiotic resistance marker genes and why might they be a problem? When scientists are inserting a target gene into another organism, a gene for resistance to the antibiotic kanamycin is also commonly incorporated. After a few days the plant tissue being genetically modified is dosed with kanamycin. The samples that survive can then be identified as having successfully incorporated the new genetic material. There is concern about whether antibiotic resistance marker genes in GM crops could lead to antibiotic resistance in the food chain. Crop and Food plant geneticist Tony Conner thinks this is unlikely because the gene is already widely dispersed through the soil; for instance, at Lincoln about one million bacteria per teaspoon of soil are already resistant to antibiotics. 5. What's the difference between G M and traditional cross-breeding of plants/animals? There are key differences. In traditional breeding you mate things sexually and are limited to the same species or genus. With GM, scientists take a specific piece of DNA (which they may have synthesised themselves) and transfer it directly into another organism, and are not limited by species boundaries. While a traditional fruit-tree breeder might develop two varieties in a lifetime, GM technology could allow the development of a new cultivar in 12 months. But Tony Conner also argues GM is part of a continuum from traditional plant breeding. A hundred years ago scientists urged great caution with the breakthrough technology that we now think of as traditional breeding techniques. They warned these new techniques presented mankind with the ability to manipulate life in a way never intended by nature. Sound familiar? 6. For how long have people been eating GM food, and how much is already on our supermarket shelves? The Flav'r Sav'r tomato, released to the market in the US in 1994, was the first GM product to hit the US market. In New Zealand no G M crops are grown commercially, and no G M fresh fruit vegetables or meat are sold. Some imported processed foods sold here may have G M ingredients: Food Standards Australia New Zealand, the regulatory body charged with assessing whether such foods are safe, has permitted a range of foods containing G M soybean, canola, potato, sugar beet and cotton seed oil to be sold here. Products like bread,

yoghurt, biscuits, margarine, confectionery and ice cream could contain GM ingredients. 7. Has anyone died or got sick from eating GM food, and how do we know? The incident that most often comes up in answer to this question is L-tryptophan, a dietary supplement manufactured in the 1980s using genetically modified bacteria. The L-tryptophan case is a classic example of how difficult it is for the ordinary mortal to sort fact from fiction in the G M debate. The Royal Commission's summary of the incident reports that in 1989 37 people died, 1500 became disabled and a further 5000 were affected after taking L-tryptophan. All were taking product manufactured by Japanese firm Showa Denko KK, which used both a new G M organism and a different filtration system in its manufacturing process. According to the commission (and GM advocates), the manufacturing system, not the GM process, was found to be the cause. Others, including Steven Druker, executive director of the Alliance for Bio-Integrity, has attacked the commission for its conclusion, saying there was strong evidence the epidemic was caused by unexpected toxins induced by the genetic changes to the bacteria. The UK Royal Society reported early this year that there was no evidence that eating genetically modified DNA caused risk to human health. But physicist and anti-GM proponent Peter Wills says there is no way we can be sure because there have been no proper epidemiological studies. A recent article in Nature Biotechnology by cell biologist David Schubert also raises the argument that cells will not respond in predictable ways to the insertion of a new gene, and that toxic, allergenic or carcinogenic molecules could be produced as an unpredictable by-product of GM. 8. When we eat GM food, are we eating modified genes? What happens to them when we do do they alter our DNA? According to the Royal Commission, humans consume between 0.1 and 1.0g of DNA per day. Most of it is broken down into fragments too small to be functional, first by cooking and then by digestion. It concluded there was no evidence to show DNA can be transferred into and maintained in the cells of mammals. Eating DNA from GM food is, apparently, just the same as eating DNA from non-GM food. 9. Can New Zealand be "GE-free"? If we were, could we corner a global market niche in GE-free produce? GM proponents like Tony Conner say New Zealand can never be completely "GE-free", if only for the fact that, as recent experience has shown, low-level G M

contamination in our seed imports is inevitable. Even tourists arriving here having recently eaten, say, a GM tomato, will pass the seed into our environment. Therefore if we claimed we were 100% "GE-free", sooner or later we'd get found out. Others, like Simon Terry of the Sustainability Council, say trace contamination in isolated patches is no barrier to New Zealand being a "GEfree" food producer. He argues overseas buyers will define our status on the basis of whether we grow G M crops commercially and, more importantly, whether individual products test "GEfree". With that great big moat around us, New Zealand is perhaps the only nation to be able to legitimately maintain such a "GE-free" status. There is certainly considerable consumer resistance to GM food in Europe. A recent survey showed 71% of Europeans reject it. In response, supermarkets such as Sainsbury's and Tesco have reformulated their own-brand products to be "GE-free". A major factor behind this anti-G M sentiment is loss of public confidence in scientific assurances and food safety regulations following the BSE and foot-and-mouth-disease crises. US Department of Agriculture figures show a major loss of market share for exporters to Europe; for instance, US corn exports to Europe dropped from 2.4 million metric tonnes to close to zero by 2000, as a result of GM cropping. The Sustainability Council cites 2001 research by Lincoln University Commerce Professor Caroline Saunders showing there is more upside for New Zealand in being "GE-free" than in producing GM food. Saunders concluded New Zealand would be better to delay commercial release of G M food until the extent of negative consumer attitudes can be seen, and in the meantime reap a non-GE price premium in overseas markets. Tony Conner, however, says the anti-GM stance of European supermarkets is just a marketing gimmick, and it is gradually changing. He says the big food companies have GM products ready to go as soon as public opinion changes, and if New Zealand turns its back on the technology we'll be left in the dark ages. 10. What is Bt corn? Bt stands for Bacillus thuringiensis, a naturally occurring soil bacteria that produces a protein toxic to insects. Genes from the Bt organism have been incorporated into corn, making the plant resistant to pests, particularly the corn borer. Bt corn is one of the most widely grown GM crops.

Organic farmers use a spray derived from the Bt organism to control pests. But Crop and Food researcher David Teulon notes there are important differences between genetically modified Bt crops and Bt insecticides: pesticides generally contain several Bt toxins, whereas GM plants contain only one, and in GM crops the toxin is present in the plant at high concentrations throughout the growing season. This raises the spectre of insect resistance to Bt toxins, and Tuelon says in a 2002 paper that 17 insect species have already shown resistance under lab conditions. 11. What could GM do for the idea of a "green revolution" where no pesticides or herbicides are needed on our crops? It's tempting here to simply say "lies, damned lies and statistics" and leave it at that. Both sides of the argument can cite reams of evidence to support their position. But it's a question that provokes strong responses. Crop and Food Research scientist Tony Conner, for instance, says he was drawn to GM science primarily because of the prospect of reduced herbicide and pesticide use and associated benefits to the environment. The Life Sciences Network website cites a long list of studies showing GM crops have reduced the use of agricultural sprays. Bt cotton (see "GM for dummies, part one") is said to have led to a 38% reduction in pesticide use in South Africa; GM canola led to a 40% reduction in herbicide cost for Canadian farmers; and Chinese farmers growing Bt corn reduced pesticide use by 80%. On the other hand, the GMcautious Sustainability Council reckons the picture is ambivalent. It cites research based on US Department of Agriculture data concluding more herbicides are used on GM Round-up Ready soybeans and little, if any, impact has been made on insecticide use as a result of Bt corn although Bt cotton has reduced insecticide use in several parts of the US. In his 2002 paper, Crop and Food researcher David Tuelon says GM crops have the potential to increase crop yield and reduce insecticide use in New Zealand, but much depends on the species, the range of insect pests, and the alternative pest control systems available. 12. By engineering plants to be more pest or disease resistant, isn't there a risk they might spread into the wild and become superweeds? Conner says non-GM plants already cross with weeds and create problems, and there is no reason GM would increase this. Traditional plant breeders have always bred for resistance to pests and diseases, and these are just as likely to create superweeds as GM crops. The Royal Commission cited a UK study showing there was no evidence GM plants became more invasive or persistent than non-GM counterparts. However, the commission also expressed concern at evidence some

GM herbicide-resistant crops survived two or three types of herbicide, resulting in the need for potentially more toxic sprays to control selfseeded plants. It said herbicide-resistant GM crops should not be approved for release here until there is clear evidence about whether they lead to the use of more toxic sprays and whether there is an increase in herbicide-resistant weeds caused by cross-pollination from GM crops. 13. Can genes cross from a GM plant to a nonGM plant (horizontal gene transfer) and create unforeseen results? GM advocates says horizontal gene transfer (HGT) the movement of DNA directly from one organism by means other than reproduction happens spontaneously in nature and there is no reason to think GM will increase the incidence. Common maize, for instance, has evolved in part from conventional breeding and in part from HGT, thanks to something called a transposon. This is like a virus that gets into the genome, causing bits of DNA to migrate into another organism. This process occurred in a plant called teosinte, which mutated to create maize, a crop that sustains millions of people. Nevertheless, there is concern about the extent to which DNA from GM plants might move by HGT to the likes of soil bacteria, creating new biological entities capable of causing environmental damage. Environmental Science and Research (ESR) scientist Phil Carter has FoRST funding to study this issue over the next three years. It's hoped the research will provide scientific answers to one area of uncertainty surrounding the release of GM crops in New Zealand. In the meantime, the ESR researchers say it will be "very difficult" for the Environmental Risk Management Authority (see #19) to develop a risk framework that takes account of HGT without data applicable to New Zealand conditions. 14. What promise or threat does GM pose to feeding the third world? Two fairly predictable streams of argument arise here, leaving the GM novice struggling to draw hard and fast conclusions. On one hand, anti-GM types like Peter Wills argue third world food shortages are all about ineffective or corrupt distribution and political systems, which GM won't fix. Pro-GM Tony Conner, who visited China a couple of years ago and was "staggered" by the extent of pest and disease damage to crops, believes GM offers huge promise which is why the Chinese have embraced the technology, along with other developing economies like the

Philippines, Indonesia and India. The development of Golden Rice, aimed at alleviating a third world vitamin A deficiency that causes blindness in 500,000 and the death of five million people annually, is the lightning rod. Golden Rice was developed as a joint public-private research partnership, and intellectual property rights to the seed have been negotiated to allow it to be given royalty-free to farmers earning under $10,000 a year. But don't get too warm and fuzzy about it, as there's a big row about the real potential of Golden Rice. The antis say the third-world peasant would have to eat 9kg of the rice a day for it to remedy a vitamin A deficiency; the pros say they'd only need 200g. 15. Is it true that seeds from GM plants are infertile and therefore third world farmers (and the rest of us) would become dependent on multinational seed companies for their seed supply? Could this be a new form of economic colonisation? The technology to develop so-called terminator or suicide genes has been developed, meeting with widespread concern about the implications for food security and its potential to be used as a form of market capture. Three years ago Gordon Conway, president of the Rockefeller Institute, called on the industry to disavow the technology, saying international patent laws provided adequate protection for biotech companies against unlicensed use of patented plant varieties. In response to public outcry some companies, including Monsanto, have said they won't use terminator genes. Pro-GM scientists say the concern over terminator genes is overdone, arguing that farmers already make widespread use of F1 hybrid varieties, which revert to type after the first harvest. They buy new seed each season in order to continue reaping the benefits of their superior yields and qualities. The Royal Commission commented that terminator technology should be investigated for New Zealand's commercial forestry industry as a mechanism to prevent the spread of pine trees into the wild and reduce allergic reactions to pollen. 16. Why would anyone want to put human genes into cows? Isn't milk perfect enough as it is? It's not so much a matter of making milk better, but rather using it as a vehicle to deliver certain proteins that are lacking in people suffering from chronic illnesses, such as lysomal storage diseases which cause skeletal and muscle tissue deformities and are fatal without treatment. AgResearch was recently given approval to develop GM cows in which the human genes that produce these proteins are inserted into cow embryos. The milk produced by the GM cows would contain the protein, which would then be extracted and potentially used in new medical treatments. In essence, the GM cow would be used as a protein factory.

AgResearch says New Zealand's bovine expertise and BSE- and scrapie-free status gives it an advantage in this work. In the past, human cadavers have been the source of such proteins. Opponents say it crosses ethical and cultural boundaries to alter the genetic construct of a domestic animal of such importance to human societies. AgResearch and Crop and Food are also experimenting with GM plants to find out if they can also be used to produce human proteins. 17. Could GM speed up new drug discovery and, if so, why? Yes, and it already does. It enables scientists to test hypotheses about the role of different proteins in the development of diseases by genetically altering an animal such as a mouse either adding or deleting target proteins and then seeing what happens. Medical research like this has been going on in New Zealand for about 25 years. GM is also used in drug production; the Royal Commission noted that 15,000 diabetics in New Zealand rely for their survival on insulin derived from GM organisms. Before this technology was developed around 20 years ago, insulin was derived from pig and cow pancreases. The commission listed 27 medical therapies available in New Zealand based on GM, including the Hepatitis B vaccine, which is produced by GM yeast. 18. What are stem cells, and what's the big fuss about using them in research? Strictly speaking, stem cell research isn't GM, but it's just as controversial. Stem cells are the body's "master cells", and have the ability to develop into any kind of specific cells in the body heart cells, brain cells and so on. Scientists believe it may eventually be possible to use stem cells to grow replacement body organs such as livers and to regenerate damaged parts of the body for instance, brain cells in patients with degenerative diseases like Alzheimer's and to help rehabilitate patients with spinal cord injury. Very young embryos are basically a collection of stem cells, and umbilical blood is also rich in them. Theoretically, embryonic stem cells could be grown into cloned embryos, from which further stem cells would be harvested. The embryo would then be discarded. Not surprisingly, the technology is controversial because it raises the prospect of human cloning. Opponents also say it's immoral to create an embryo for medical purposes only to destroy it, but advocates say it promises potentially huge medical breakthroughs.

19. If the moratorium comes off next October as planned, what measures will be in place to ensure any release of GM plants or animals will be completely safe? The Environmental Risk Management Authority (ERMA) is the body charged with approving the release of GM organisms, under the auspices of the Hazardous Substances and New Organisms Act (HSNO). Applications for release must be publicly notified and anyone can make a submission and demand a hearing. An application will fail at the first hurdle if ERMA concludes it is likely to have any significant health or environmental impact, based on the information presented by applicants and submitters as well as any other research information ERMA chooses to consult. It does not, however, conduct its own scientific research. If the application passes this minimum test, ERMA proceeds to a risk benefit analysis, and will only grant an approval if the benefits of release outweigh the risks. 20. Will this regime ensure complete safety? Probably not. There will always be some element of uncertainty (for instance, how can it be known for sure what the effect of a GM organism might be in 50

years?). Chief executive Bas Walker says ERMA is required to adopt a "precautionary approach", and will make decisions that are "careful, prudent and reasonable". There is still work to be done to improve the regulatory framework before the moratorium is lifted, including how the HSNO Act deals with GM of human cells and cloning of new organisms from tissues. It's also likely that a new category called "conditional release" will be enacted. This would allow ERMA to dictate the terms of release (for instance, close monitoring of the impact of the new organism and mandatory reporting of the results), and would serve as an intermediary step between field trials and full release. The question of whether the law is adequate to handle issues of liability for harm caused by GM organisms is also on the agenda for public debate. The Sustainability Council argues the law needs to be changed to ensure that those using or developing GM organisms carry full financial responsibility for any harm, that GM content in food is traceable, and that the economic risks of each proposed GM release are assessed.