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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 ineptitu de? 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 For m science drop-outs. The result is the Biotech Unlimited Dummies' Guide to GM : 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 Aucklan d 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, f or  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

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The following article was kindly provided byUnlimited Magazine.

Unlimited  is published monthly but includes a biotechnologysupplement quarterly.

The GM for dummies series by Rebecca Mcfie is ongoing.

Information about the magazine and other Biotech articles can beaccessed at: http://www.unlimited.net.nz/

GM for  dummiesSick of those dumb-arse questions from scientific illiterates?Journalist Rebecca Macfie isn't! A confessed sciencedummy, 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 doublehelix thingy. But that's about it. And it seems that's sofor   the most of the population. I put the call out tofriends, rellies and colleagues to send me the dumbquestions they'd always wanted to know the answer tobut were afraid to ask, with a promise to hunt downsome answers that are intelligible to Fifth For m sciencedrop-outs.

The result is the Biotech Unlimited Dummies' Guide toGM : 20 questions and 20 answers, which you canphotocopy and circulate to all your non-science friends,colleagues and prying media. The guide continues inthe next issue of Biotech.

The answers are sourced from scientists, lobby groupsand documents from both sides of the Great Rift Valleythat 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 Universityphysicist Peter Wills and Sustainability Councilexecutive director Simon Terry. There's also under my

feet a knee-deep stack of reference materialranging from the Royal Commission on G Mthrough to the latest pontifications of the UK RoyalSociety. I've supplied you with a list of goodwebsites, too.

The answers are far from complete, are notalways straightforward, and will, for   sure,displease one side or other of this most polarisedand at times vindictive of debates. But hey, atleast next time I read about a contaminated cornshipment I'll know what Bt means.

1. What is a gene anyway and how many dowe have?

Thanks to David Dougherty and Jules Mikus weall know about DNA, the molecule in every cellthat contains all our genetic information. DNAitself is a long, thin chain of minute units callednucleotide bases (adenine, guanine, cytosine andthymine — abbreviated to A, G, C and T), whichare described as a four-letter alphabet used towrite biological code. Genes are sections of DNA

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containing particular sequences of nucleotides. Thesesequences are the code for the production of particular proteins, which in turn make up the structure of livingtissues.

Genes themselves make up only a small proportion of our total DNA — perhaps only 10%. It's useful to thinkof DNA as the genetic filing cabinet and the genes as

the individual drop files inside. Each drop file containsthe recipe for one of the proteins needed to carry out aparticular biological function. Humans are thought tohave between 30,000 and 40,000 genes, but scientistsdon't yet know what they all do.

2. Does every species have a unique set of genes?Are rat genes completely different from humangenes?

We humans share around two thirds of our DNA with abanana. Yes, you'll never look at your partner the same

way again. Lots of human genes carry the same or verysimilar information as other species — particularly thosethat dictate basic biological functions like cell divisionand DNA replication. Others are quite different. Usingthe filing cabinet analogy again, 95% of the drop files(genes) in rats and humans might be the same, but theparticular recipes contained in the drop files will bedifferent.

3. How do scientists take genes from one speciesand put them in another?

No, they don't use very tiny tweezers to do it. In plant

GM   the most commonly used method involves usingpathogens called Agrobacteria — naturally occurringorganisms that transfer DNA into the chromosome of aplant and cause a tumour. Scientists hitchhike on thisprocess by removing the gene that causes the tumour and replacing it with the genetic material they want totransfer. They also include a gene for antibioticresistance, which enables them to identify which bits of plant tissue have successfully incorporated the targetgene (see the next question for more on this). Scientistssometimes cite the fact that the pathogens used in thisprocess occur naturally and engage spontaneously inDNA transfer to refute the anti-GM line of argument thatgenetic modification could never occur without human

intervention.

To genetically modify an animal such as a mouse,fertilised eggs are harvested from the female and DNAis injected into the egg nucleus. The egg is thenimplanted into the womb of a female mouse. Thenewborn mouse will carry the new gene, and pass it onto future generations. Marker genes — often for coatcolour — are sometimes added to the mix to indicatewhether the DNA transfer has been successful.

4. What are antibiotic resistance marker genesand why might they be a problem?

When scientists are inserting a target gene intoanother organism, a gene for   resistance to theantibiotic kanamycin is also commonlyincorporated. After a few days the plant tissuebeing genetically modified is dosed with

kanamycin. The samples that survive can then beidentified as having successfully incorporated thenew genetic material. There is concern aboutwhether antibiotic resistance marker genes in GMcrops could lead to antibiotic resistance in thefood chain. Crop and Food plant geneticist TonyConner thinks this is unlikely because the gene isalready widely dispersed through the soil; fo r instance, at Lincoln about one million bacteria per teaspoon of soil are already resistant toantibiotics.

5. What's the difference between G M  and

traditional cross-breeding of plants/animals?

There are key differences. In traditional breedingyou mate things sexually and are limited to thesame species or genus. With GM, scientists takea specific piece of DNA (which they may havesynthesised themselves) and transfer it directlyinto another organism, and are not limited byspecies boundaries. While a traditional fruit-treebreeder might develop two varieties in a lifetime,GM technology could allow the development of anew cultivar in 12 months. But Tony Conner alsoargues GM is part of a continuum from traditional

plant breeding. A hundred years ago scientistsurged great caution with the breakthroughtechnology that we now think of as traditionalbreeding techniques. They warned these newtechniques presented mankind with the ability tomanipulate life in a way never intended by nature.Sound familiar?

6. For  how long have people been eating GMfood, and how much is already on our supermarket shelves?

The Flav'r Sav'r tomato, released to the market inthe US in 1994, was the first GM product to hit the

US market. In New Zealand no G M  crops aregrown commercially, and no G M   fresh fruitvegetables or meat are sold. Some importedprocessed foods sold here may have G Mingredients: Food Standards Australia NewZealand, the regulatory body charged withassessing whether such foods are safe, haspermitted a range of foods containing G Msoybean, canola, potato, sugar beet and cottonseed oil to be sold here. Products like bread,

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yoghurt, biscuits, margarine, confectionery and icecream 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 thisquestion is L-tryptophan, a dietary supplement

manufactured in the 1980s using genetically modifiedbacteria. The L-tryptophan case is a classic example of how difficult it is for  the ordinary mortal to sort fact fromfiction in the G M  debate. The Royal Commission'ssummary of the incident reports that in 1989 37 peopledied, 1500 became disabled and a further 5000 wereaffected after taking L-tryptophan. All were takingproduct manufactured by Japanese firm Showa DenkoKK, which used both a new GM   organism and adifferent filtration system in its manufacturing process.

 According to the commission (and GM advocates), themanufacturing system, not the GM process, was foundto be the cause. Others, including Steven Druker,

executive director of the Alliance for  Bio-Integrity, hasattacked the commission for  its conclusion, saying therewas strong evidence the epidemic was caused byunexpected toxins induced by the genetic changes tothe bacteria.

The UK Royal Society reported early this year that therewas no evidence that eating genetically modified DNAcaused risk to human health. But physicist and anti-GMproponent Peter Wills says there is no way we can besure because there have been no proper epidemiological studies. A recent article in NatureBiotechnology by cell biologist David Schubert also

raises the argument that cells will not respond inpredictable ways to the insertion of a new gene, andthat toxic, allergenic or carcinogenic molecules could beproduced as an unpredictable by-úproduct of GM.

8. When we eat GM  food, are we eating modifiedgenes? What happens to them when we do — dothey alter our DNA?

 According to the Royal Commission, humans consumebetween 0.1 and 1.0g of DNA per day. Most of it isbroken down into fragments too small to be functional,first by cooking and then by digestion. It concludedthere was no evidence to show DNA can be transferred

into and maintained in the cells of mammals. EatingDNA from GM  food is, apparently, just the same aseating DNA from non-GM food.

9. Can New Zealand be "GE-free"? If we were, couldwe corner a global market niche in GE-freeproduce?

GM proponents like Tony Conner say New Zealand cannever 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 were100% "GE-free", sooner or later we'd get foundout.

Others, like Simon Terry of the Sustainability

Council, say trace contamination in isolatedpatches is no barrier to New Zealand being a "GE-free" food producer. He argues overseas buyerswill define our status on the basis of whether wegrow G M  crops commercially and, moreimportantly, whether individual products test "GE-free". With that great big moat around us, NewZealand is perhaps the only nation to be able tolegitimately maintain such a "GE-free" status.

There is certainly considerable consumer resistance to GM food in Europe. A recent surveyshowed 71% of Europeans reject it. In response,

supermarkets such as Sainsbury's and Tescohave reformulated their own-brand products to be"GE-free". A major factor behind this anti-G Msentiment is loss of public confidence in scientificassurances and food safety regulations followingthe BSE and foot-and-mouth-disease crises. USDepartment of Agriculture figures show a major loss of market share for  exporters to Europe; for instance, US corn exports to Europe dropped from2.4 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 CarolineSaunders showing there is more upside for  NewZealand in being "GE-free" than in producing GMfood. Saunders concluded New Zealand would bebetter to delay commercial release of GM  fooduntil the extent of negative consumer attitudes canbe seen, and in the meantime reap a non-GEprice premium in overseas markets.

Tony Conner, however, says the anti-GM stanceof European supermarkets is just a marketinggimmick, and it is gradually changing. He says thebig food companies have GM products ready togo as soon as public opinion changes, and if New

Zealand turns its back on the technology we'll beleft in the dark ages.

10. What is Bt corn?

Bt stands for  Bacillus thuringiensis, a naturallyoccurring soil bacteria that produces a proteintoxic to insects. Genes from the Bt organism havebeen incorporated into corn, making the plantresistant to pests, particularly the corn borer. Btcorn is one of the most widely grown GM crops.

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Organic farmers use a spray derived from the Btorganism to control pests. But Crop and Foodresearcher David Teulon notes there are importantdifferences between genetically modified Bt crops andBt insecticides: pesticides generally contain several Bttoxins, whereas GM plants contain only one, and in GMcrops the toxin is present in the plant at high

concentrations throughout the growing season. Thisraises the spectre of insect resistance to Bt toxins, andTuelon says in a 2002 paper that 17 insect specieshave already shown resistance under lab conditions.

11. What could GM do for the idea of a "greenrevolution" where no pesticides or herbicides areneeded on our crops?

It's tempting here to simply say "lies, damned lies andstatistics" and leave it at that. Both sides of theargument can cite reams of evidence to support their position. But it's a question that provokes strong

responses. Crop and Food Research scientist TonyConner, for instance, says he was drawn to GM scienceprimarily because of the prospect of reduced herbicideand pesticide use and associated benefits to theenvironment. The Life Sciences Network website cites along list of studies showing GM crops have reduced theuse 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 canolaled to a 40% reduction in herbicide cost for Canadianfarmers; and Chinese farmers growing Bt corn reducedpesticide use by 80%. On the other hand, the GM-cautious Sustainability Council reckons the picture is

ambivalent. It cites research based on US Departmentof Agriculture data concluding more herbicides are usedon 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 insecticideuse in several parts of the US. In his 2002 paper, Cropand Food researcher David Tuelon says GM crops havethe potential to increase crop yield and reduceinsecticide use in New Zealand, but much depends onthe species, the range of insect pests, and thealternative 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 weedsand create problems, and there is no reason GM wouldincrease this. Traditional plant breeders have alwaysbred for resistance to pests and diseases, and these are

 just as likely to create superweeds as GM crops. TheRoyal Commission cited a UK study showing there wasno evidence GM plants became more invasive or persistent than non-GM counterparts. However, thecommission 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 self-seeded plants. It said herbicide-resistant GMcrops should not be approved for release hereuntil there is clear evidence about whether theylead 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 non-GM plant (horizontal gene transfer) and createunforeseen results?

GM advocates says horizontal gene transfer (HGT) — the movement of DNA directly from oneorganism by means other than reproduction —happens spontaneously in nature and there is noreason to think GM will increase the incidence.Common maize, for instance, has evolved in partfrom conventional breeding and in part from HGT,

thanks to something called a transposon. This islike a virus that gets into the genome, causing bitsof DNA to migrate into another organism. Thisprocess occurred in a plant called teosinte, whichmutated to create maize, a crop that sustainsmillions of people.

Nevertheless, there is concern about the extent towhich DNA from GM plants might move by HGTto the likes of soil bacteria, creating new biologicalentities capable of causing environmentaldamage. Environmental Science and Research(ESR) scientist Phil Carter has FoRST funding to

study this issue over the next three years. It'shoped the research will provide scientific answersto one area of uncertainty surrounding the releaseof 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 takesaccount of HGT without data applicable to NewZealand conditions.

14. What promise or threat does GM pose tofeeding the third world?

Two fairly predictable streams of argument arise

here, leaving the GM novice struggling to drawhard and fast conclusions. On one hand, anti-GMtypes like Peter Wills argue third world foodshortages are all about ineffective or corruptdistribution and political systems, which GM won'tfix. Pro-GM Tony Conner, who visited China acouple of years ago and was "staggered" by theextent of pest and disease damage to crops,believes GM offers huge promise — which is whythe Chinese have embraced the technology, alongwith other developing economies like the

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Philippines, Indonesia and India. The development of Golden Rice, aimed at alleviating a third world vitamin Adeficiency that causes blindness in 500,000 and thedeath of five million people annually, is the lightning rod.Golden Rice was developed as a joint public-privateresearch partnership, and intellectual property rights tothe seed have been negotiated to allow it to be givenroyalty-free to farmers earning under $10,000 a year.

But don't get too warm and fuzzy about it, as there's abig row about the real potential of Golden Rice. Theantis say the third-world peasant would have to eat 9kgof 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 infertileand therefore third world farmers (and the rest of us) would become dependent on multinational seedcompanies for their seed supply? Could this be anew form of economic colonisation?

The technology to develop so-called terminator or 

suicide genes has been developed, meeting withwidespread concern about the implications for foodsecurity and its potential to be used as a form of marketcapture. Three years ago Gordon Conway, president of the Rockefeller Institute, called on the industry todisavow the technology, saying international patent lawsprovided adequate protection for biotech companiesagainst unlicensed use of patented plant varieties. Inresponse to public outcry some companies, includingMonsanto, have said they won't use terminator genes.Pro-GM scientists say the concern over terminator genes is overdone, arguing that farmers already makewidespread use of F1 hybrid varieties, which revert to

type after the first harvest. They buy new seed eachseason 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'scommercial forestry industry as a mechanism to preventthe spread of pine trees into the wild and reduce allergicreactions to pollen.

16. Why would anyone want to put human genesinto 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 proteinsthat are lacking in people suffering from chronicillnesses, such as lysomal storage diseases whichcause skeletal and muscle tissue deformities and arefatal without treatment. AgResearch was recently givenapproval to develop GM cows in which the humangenes that produce these proteins are inserted into cowembryos. The milk produced by the GM cows wouldcontain the protein, which would then be extracted andpotentially used in new medical treatments. In essence,the GM cow would be used as a protein factory.

 AgResearch says New Zealand's bovine expertiseand BSE- and scrapie-free status gives it anadvantage in this work. In the past, humancadavers have been the source of such proteins.Opponents say it crosses ethical and culturalboundaries to alter the genetic construct of adomestic animal of such importance to humansocieties. 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 discoveryand, if so, why?

Yes, and it already does. It enables scientists totest hypotheses about the role of different proteinsin the development of diseases by geneticallyaltering an animal such as a mouse — either adding or deleting target proteins — and thenseeing what happens. Medical research like thishas been going on in New Zealand for about 25

years. GM is also used in drug production; theRoyal Commission noted that 15,000 diabetics inNew Zealand rely for their survival on insulinderived from GM organisms. Before thistechnology was developed around 20 years ago,insulin was derived from pig and cow pancreases.The commission listed 27 medical therapiesavailable in New Zealand based on GM, includingthe Hepatitis B vaccine, which is produced by GMyeast.

18. What are stem cells, and what's the bigfuss about using them in research?

Strictly speaking, stem cell research isn't GM, butit's just as controversial. Stem cells are the body's"master cells", and have the ability to develop intoany kind of specific cells in the body — heart cells,brain cells and so on. Scientists believe it mayeventually be possible to use stem cells to growreplacement body organs such as livers and toregenerate damaged parts of the body — for instance, brain cells in patients with degenerativediseases like Alzheimer's and to help rehabilitatepatients with spinal cord injury. Very youngembryos are basically a collection of stem cells,and umbilical blood is also rich in them.

Theoretically, embryonic stem cells could begrown into cloned embryos, from which further stem cells would be harvested. The embryo wouldthen be discarded. Not surprisingly, thetechnology is controversial because it raises theprospect of human cloning. Opponents also sayit's immoral to create an embryo for medicalpurposes only to destroy it, but advocates say itpromises potentially huge medical breakthroughs.

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19. If the moratorium comes off next October asplanned, what measures will be in place to ensureany release of GM plants or animals will becompletely safe?

The Environmental Risk Management Authority (ERMA)is the body charged with approving the release of GMorganisms, under the auspices of the Hazardous

Substances and New Organisms Act (HSNO). Applications for release must be publicly notified andanyone can make a submission and demand a hearing.

 An application will fail at the first hurdle if ERMAconcludes it is likely to have any significant health or environmental impact, based on the informationpresented by applicants and submitters as well as anyother research information ERMA chooses to consult. Itdoes not, however, conduct its own scientific research.If the application passes this minimum test, ERMAproceeds to a risk benefit analysis, and will only grantan 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 surewhat the effect of a GM organism might be in 50

years?). Chief executive Bas Walker says ERMAis required to adopt a "precautionary approach",and will make decisions that are "careful, prudentand reasonable".

There is still work to be done to improve theregulatory framework before the moratorium islifted, including how the HSNO Act deals with GM

of human cells and cloning of new organisms fromtissues. It's also likely that a new category called"conditional release" will be enacted. This wouldallow ERMA to dictate the terms of release (for instance, close monitoring of the impact of thenew organism and mandatory reporting of theresults), and would serve as an intermediary stepbetween field trials and full release. The questionof whether the law is adequate to handle issues of liability for harm caused by GM organisms is alsoon 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 financialresponsibility for any harm, that GM content infood is traceable, and that the economic risks of each proposed GM release are assessed.