National Regulations Should Reflect Risks of GE Crops

By Arpad Pusztai - Scientific Consultant to GenOk, Tromso, Norway
BioSpectrum
January 06, 2006

Engineered artificial gene constructs may undergo mutation and evolution to an end, therefore making the safety assessment of GE crops an exercise without a firm predictive scientific basis.

Acceptance of products and associated agricultural practices of the biotechnology industry is running into problems, probably due to the perception held by many scientists that the technical ability of biotechnology industry to produce safe genetically engineered (GE) crops has developed faster than the understanding of the underlying scientific principles of gene splicing. Consumers and scientists alike feel that the possible consequences for health and environment of the spread of GE crops are not properly understood and that without sufficient research funding and having generally agreed methodologies for assessing the unique risks of GE crops, we shall never be able to properly address them. It should not be surprising that societal concerns about genetic engineering of something as basic as our food and how they are produced are high and no matter of patronizing platitudes by the scientific, political and industrial establishments will make these concerns to go away.

Bizzare approach

The approach of the biotechnology industry to the safety of its products or the understanding how society perceives risk is bizarre. The harsh treatment of sceptics and dissident scientists does not demonstrate the establishment's great willingness to listen to views not in tune with their pre-set ideas. Openness is not much helped either that due to the high cost of biological testing, biotechnology companies only do minimal and superficial environmental and health risk assessments. Cost will also be a major factor in their reluctance to finance research to develop scientifically sound methodologies but rather they prefer to declare the present agricultural practices to grow GE crops as safe and that foods prepared from them present no risks for the consumer. The fact that in the decade since the introduction of GE crops only one human feeding study has been conducted and basic academic animal nutritional/toxicology studies published in peer-reviewed journals are also few and far between gives plenty of ammunition to those who oppose GE crops.

Presently there is an intensive scientific and legislative debate in many countries, including India, about the possibility of the large-scale growing of GE crops without jeopardizing the GE-free status of organically or conventionally grown crops. Pro-industry scientists advocate that even with cross-pollinating crop species only a few metres of separation distance between GE and non-GE crops will be adequate to prevent genetic pollution. However, in the laboratory to prevent the escape and proliferation of untested experimental GE organisms, all developmental work is strictly contained. Moreover, to guarantee the purity of certified seeds even the industry specifies considerably larger separation distances. Thus, for contract growers of certified hybrid seeds, such as hybrid corn, distances of 400 m or more are demanded. In contrast, the biotechnology industry proposes to release GE crops into the environment without adequate biological controls to prevent their dispersal or the artificial transgenes they express. According to their proposals, the strict safety guidelines that apply to GE organisms in the laboratory are not deemed to be necessary when these are grown in open fields, but without scientifically justifying this double standard in safety conduct. One might consider that even more stringent safety controls should be enforced in the natural environment than in the laboratory, particularly as we do not have a backup with products of this irreversible technology. Moreover, there is already sufficient evidence to show that engineered artificial gene constructs may undergo mutation and evolution to an end that we are not aware of, and therefore making the safety assessment of GE crops an exercise without a firm predictive scientific basis. Indeed, one cannot safety assess something that has not yet evolved.

Genetic contamination

In the absence of adequate methods to remove inserted transgenes, once the seeds are genetically contaminated, it will be nearly impossible to recover the original uncontaminated seed stock. Under the regulatory systems of most countries, testing of seeds for genetic contamination is done after the event and not before. In the USA and Canada the whole seed system has become contaminated after ten years of large-scale commercialisation of GE crops. Thus, even though only about one percent of the corn seeds sown in Iowa (USA) was StarLink, in the absence of adequate separation between the GE and non-GE cornfields and segregation of the seeds after harvest, about 50 percent of the corn produced contained the StarLink transgene, demonstrating that coexistence of GE and non-GE crops is impossible. The proposal by the MS Swaminathan Task Force that regions in India representing either primary or secondary centres of genetic diversity for major crops such as rice should be conserved for posterity as "agro-biodiversity sanctuaries" and "organic farming zones", is manifestly impractical and will not stop the genetic contamination of rice crops in other areas. In a democracy once the floodgates are opened it is impossible to control who grows what. It also means that other parts of the country will be opened up for GE crops. This therefore is nothing but a back door entry to introduce them by a slight of hand which, on the face of it, appears to give false assurances to people that there is no threat at all that genetic contamination will spread in the country.

Risks of GEOs

In order to satisfy the legitimate demands of the scientific community and society any large-scale growing of GE crops and their coexistence with crops grown using traditional and organic agricultural practices must be based on or at least take into account the scientific guidelines as laid out very recently in the authoritative ESA (Ecological Society of America) Report on the possible risks of GEOs (genetically engineered organisms) because these may create new, and more vigorous pests and pathogens; exacerbate the effects of existing pests through hybridisation with related transgenic organisms; harm non-target species of organisms; disrupt biotic communities, including agro- ecosystems; cause irreparable loss or changes in species diversity or genetic diversity. Therefore GEOs require greater scrutiny than crops produced by traditional breeding

We shall also have to consider that GEOs may pose risks to the environment because we have little or no prior experience with the trait and host combination; GEOs may proliferate and persist without human intervention; genetic exchange is possible between a transformed organism and non-domesticated organisms; trait confers an advantage to the GEO over native species in a given environment.

If these principles are not taken into account in proposed legislations, the large-scale growing of GE crops can irreversibly harm our environment by genetic contamination of our traditional crops and weeds by cross-fertilization and by horizontal gene transfer respectively. Moreover, in the absence of science-based regulation of the cultivation of pesticide-producing (i.e. Bt-toxin) GE crops, the development of resistance in pests to biopesticides which are also used in organic or traditional agriculture will be speeded up. The uncontrolled large-scale cultivation of herbicide-resistant GE crops will not only contaminate our environment but also lead to the creation of herbicide-resistent superweeds and thus increase rather than reduce the chemical-load of the land and endanger our clean water supply.

Transparency

It is therefore not unreasonable to suggest that the environmental and health risks or safety assessments of GE crops/foods should not be carried out only by biotechnology companies but it must also be verified by independent scientists through a transparent funding system. Any controlling legislation must also be based on these assessments and debated by all stakeholders in the society. The basic rule must be that, since we all want to live in a healthy and natural environment and eat foods which will not endanger our health, we are all entitled to scrutinise the evidence relating to the safety of GE crops. Secrecy is therefore against the public interest and unjustified. GE technology is irreversible and therefore we have to seriously weigh up the pros and cons of its introduction. In democracies it is the people's inalienable right that they should be able to decide whether society can afford to take on the very real risks and the possibly dangerous consequences of genetic engineering for the possibly vain hope of some future benefits for society.

Source: http://www.biospectrumindia.com/content/columns/10601061.asp

Hawaii Serves As World's Biotech Lab

By Paul Elias
Associated Press
January 13, 2006

LAIE, Hawaii -- Genetic engineering saved Ken Kamiya's papaya farm on Oahu's north shore, and it may yet rescue the orchid from the grips of a nasty flower-killing virus.

But in Kona, Una Greenaway lives in dread that biotechnology will ruin her organic coffee plantation. Pineapple industry officials have made it clear they want nothing to do with genetic engineering.

So it goes in the Aloha State, where genetic engineering has riven a state just now awakening to the fact that balmy and remote Hawaii has _ for better and worse _ long served as the world's largest outdoor biotechnology lab.

Since scientists first planted the spectacular commercial flop that was the Flavr Savr tomato on a small plot here in 1988, federal regulators have approved more than 10,600 applications to grow experimental biotech crops on 49,300 separate fields throughout the United States. More of these are in Hawaii than any other state.

Through the powers of biotechnology, low-nicotine tobacco, disease-resistant cotton and soy immune to weed killer are grown here. Hawaii's genetically engineered corn projects outnumber even those grown in Iowa and Illinois.

Biotechnology companies say the weather affords them a year-round growing season, while anti-industry activists say the five-hour plane ride from California gives the "gene jockeys" remoteness from prying eyes.

Whatever the reason, farmers such as Kamiya are satisfied with genetic engineering's effects on Hawaii.

Kamiya has grown papayas, Hawaii's best selling fruit behind pineapple, since he got back from serving in the Vietnam War in 1969. He lived through three crop-killing epidemics and the vagaries of farming, but by the early 1990s his farm, along with the entire Hawaiian papaya industry, was finally on the brink of destruction. They were at the mercy of a cureless virus.

Scientist Dennis Gonsalves, a native Hawaiian then at Cornell University, developed the clever idea to genetically splice a harmless piece of the virus into papaya trees _ essentially vaccinating them in much the same way people fight the flu.

The gambit worked, and today, the virus is a mere nuisance for the $16 million industry _ even for the 50 percent of papayas grown conventionally and without virus protection in Hawaii. That's because the virus has fewer places to roost now.

"Gonsalves saved our butts," Kamiya said as he wandered among the mini-palm trees bearing ripe yellow fruit on the 15-acre farm he leases from Brigham Young University, which maintains a campus in Laie some 40 miles north of Honolulu.

The day before, Kamiya spent five hours in Honolulu at a meeting helping to defeat a proposed measure from qualifying for the ballot that would have banned genetic engineering on Oahu island and effectively put him out of business.

But that's precisely what Hawaiian organic coffee growers like Greenaway and others want. They're shocked Hawaii has become biotechnology's chief laboratory and are concerned about their economic future.

Greenaway worries that the creeping march of biotechnology in Hawaii will soon spell her financial ruin if consumers fear famed Kona coffee was somehow tainted by biotechnology.

Researchers in the state are attempting to genetically engineer coffee plants to grow decaffeinated beans, which don't occur naturally. The researchers haven't yet grown their experimental coffee plants outdoors, even though federal regulators gave permission in 1999.

Still, Greenaway is haunted by the prospect that the work will move outdoors, then mix with her crop and dilute her coffee's punch. She worries no caffeine junkie paying $20 a pound for Kona coffee wants that.

"Genetic engineered coffee would be an economic disaster in Kona," Greenaway said.

In many ways, the biotechnology debate in Hawaii is a microcosm of the global debate over biotechnology.

There hasn't been a single allergic reaction or other health problem credibly connected to consuming biotech food. Still, many scientists do worry about the threats biotechnology poses to the environment, mainly through inadvertent cross-pollination with conventionally grown crops. That poses a particular problem for organic farmers who charge a premium to guarantee customers their groceries are free of genetic engineering.

The industry and its supporters proudly point out that biotechnology is actually helping small farmers by reducing pesticide use. Close to 8 million subsistence farmers throughout the developing world are growing genetically engineered soy and corn that require less toxic weed killer and bug spray, making farming better for the environment and for those toiling in the fields.

Yet, growing numbers of consumers and activists fret that the major biotechnology companies _ specifically the titan Monsanto Inc. of St. Louis _ are asserting a Microsoft-like grip on the world's food supply that will ultimately kill organic and family farms.

In Hawaii alone, several anti-biotech measures have been introduced recently in the Legislature mimicking laws in four California counties banning biotech, though none have passed here so far. A federal lawsuit filed last year effectively halted all experiments in Hawaii that involve splicing human genes into plants to produce medicine.

That kind of skittishness resonates with large food producers, which in the past have succumbed to consumers' skepticism about biotech food.

In 2000, McDonald's Corp. successfully cowed potato farmers to reject genetically engineered potatoes. Two years ago, bread makers forced Monsanto to abandon its plans to market genetically engineered wheat. And recently, pineapple industry representatives wrote the University of Hawaii that the industry doesn't want or need biotechnology.

But Steve Ferreira, a University of Hawaii researcher working on genetically engineered papaya, thinks those growers' sentiments would change if they were facing the decimation of their crops.

"Their need is not as urgent as it was with the papaya farmers," Ferreira said.

Custom-Made Microbes, at Your Service

By Andrew Pollack
NY Times
January 17, 2006

There are bacteria that blink on and off like Christmas tree lights and bacteria that form multicolored patterns of concentric circles resembling an archery target. Yet others can reproduce photographic images.

These are not strange-but-true specimens from nature, but rather the early tinkering of synthetic biologists, scientists who seek to create living machines and biological devices that can perform novel tasks.

"We want to do for biology what Intel does for electronics," said George Church, a professor of genetics at Harvard and a leader in the field. "We want to design and manufacture complicated biological circuitry."

While much of the early work has consisted of eye-catching, if useless, stunts like the blinking bacteria, the emerging field could one day have a major impact on medicine and industry.

For instance, Christina D. Smolke, an assistant professor at the California Institute of Technology, is trying to develop circuits of biological parts to sit in the body's cells and guard against cancer. If they detected a cancer-causing mechanism had been activated, they would switch on a gene to have the cell self-destruct.

Jay D. Keasling at the University of California, Berkeley, with part of $42.6 million from the Bill and Melinda Gates Foundation, is trying to take up to 12 genes from the wormwood tree and yeast and get them to work together in E. coli bacteria to produce artemisinin, a malaria drug now extracted from the wormwood tree.

J. Craig Venter, the maverick scientist who sequenced the human genome, wants to create microbes that produce hydrogen for use as fuel.

To be sure, scientists have been putting genes into bacteria and other cells for three decades. The term "synthetic biology" seems to include various activities, some of which are not altogether new.

"This has a catchy new name, but anybody over 40 will recognize it as good old genetic engineering applied to more complex problems," said Frances H. Arnold, a professor of chemical engineering at Caltech.

Some synthetic biologists say they will go beyond genetic engineering, which often involves putting a single foreign gene into a cell. The human insulin gene, for instance, is put into bacteria, which then make insulin for use as a drug. But there have been genetic engineering projects involving multiple genes, so the number of genes alone is not enough to define synthetic biology.

Rather, the difference seems more about mind-set. "We're talking about taking biology and building it for a specific purpose, rather than taking existing biology and adapting it," Professor Keasling of Berkeley said. "We don't have to rely on what nature's necessarily created."

Also new is an engineering approach - the desire to make the design of life forms more predictable, like the design of a bridge. That could be because many leaders of the field are not biologists by training.

Ron Weiss of Princeton is a computer scientist. Michael Elowitz of Caltech trained as a physicist, and Drew Endy of the Massachusetts Institute of Technology as a structural engineer. Mr. Endy and colleagues at M.I.T. have started a "Registry of Standard Biological Parts." The parts, called BioBricks, are strings of DNA that can perform certain functions like turning on a gene or causing a cell to light up.

In theory at least, these components can be strung together to build more complex devices, just as an electronic engineer might put together transistors, resistors and oscillators to build a circuit. Scientists at the University of California, San Francisco, and the University of Texas used some BioBricks to engineer bacteria so that a sheet of them could capture an image as photographic film does. The microbes were altered so that those kept in the dark produced a black pigment while those exposed to light did not.

Some scientists envision that biological engineers will one day sit at computers writing programs for cells, like software developers. But the code would be written in sequences of DNA, rather than computer language. When finished, the programmer would press the "print" button, as it were, and the DNA would be made to order.

The field is also starting to attract some investment. In June, venture capitalists put $13 million into Codon Devices, a startup company in Cambridge, Mass., that is developing a way to synthesize long stretches of DNA far less expensively than existing methods. The founders include Professors Church, Endy and Keasling.

Professor Keasling is also a co-founder of Amyris Biotechnologies, which is helping make the malaria drug. And Mr. Venter has started Synthetic Genomics to work on his energy-producing microbes.

What make the engineering approach possible are the inner workings of a living cell. Genes, made of DNA, contain the instructions for producing proteins, which carry out most functions in cells. Some proteins can bind to DNA, turning particular genes on or off. This interplay, which is one way that cells regulate themselves, is not too different from how electronic circuits function, with one transistor turning another on or off.

To make the blinking bacteria, for instance, Mr. Elowitz designed the biological equivalent of an electronic oscillator. It uses three genes that trump one another like the rock, scissors and paper in the children's game. Gene X makes a protein that turns off Gene Y. Gene Y makes a protein that turns off Gene Z. And Gene Z makes a protein that turns off Gene X.

So if Gene X is on, it will turn off Gene Y. But the absence of Protein Y allows Gene Z to turn on. Protein Z then turns off Gene X, allowing Gene Y to turn on, turning Gene Z off, and so on. So the three genes turn on and off in an endless cycle.

To make the bacteria blink, Mr. Elowitz programmed a gene for the production of a fluorescent protein to be turned on whenever Gene Z was off.

Some newer efforts involve trying to manipulate entire colonies of microbes to cooperate with one another. They take advantage of something called quorum sensing, a natural communications system that bacteria use to determine whether there are enough of them present to mount an attack.

The bacteria secrete a particular chemical into their environment that they and their brethren can detect. When many bacteria are present, the level of this chemical in the environment increases. The concentric circle bull's-eye pattern was made by engineering E. coli to respond to a quorum-sensing chemical from a different microbe.

Some bacteria were programmed to produce a green fluorescent protein at high concentrations of the chemical. Others were programmed to produce a red protein if exposed to a somewhat lower concentration.

The bacteria of both types were mixed together and spread on a surface. In the center were placed some microbes that emitted the chemical, which diffused away from the center. The bacteria closest to the center were exposed to a high concentration. Those programmed to respond to high concentrations turned green. Some of the bacteria further away turned red.

The work, published in Nature in April, was led by Mr. Weiss of Princeton and Professor Arnold at Caltech. Mr. Weiss, an assistant professor of electrical engineering and molecular biology, is now trying to use similar principles to help control the differentiation of stem cells into different types of tissues in different locations.

"That's how the body develops its organs," he said, "by relying on cell-to-cell communication."

The two scientists also published a paper in Nature the same month in which they used quorum sensing to control bacterial populations artificially, by engineering the microbes to turn on a suicide gene if the concentration of the quorum-sensing chemical grew too high. As soon as the first cells started killing themselves, the concentration of the chemical would drop, so the remaining cells could recover.

The demonstrations, however clever, also illustrate problems inherent in designing biological circuits, as opposed to silicon ones. One is that living things are always dividing and evolving.

Indeed, the population-control system breaks down within days because some of the bacteria mutate so that the suicide gene is not switched on.

Those bacteria, having a selective advantage, quickly take over the colony, said Lingchong You, lead researcher on the project at Caltech and now an assistant professor of biomedical engineering at Duke.

Another challenge is that the genes of the circuit can interact with the native bacterial genes in unexpected ways.

There is also great variability among living creatures. The blinking bacteria, for instance, do not light up in unison, but at greatly varying rates. Even a newly formed daughter cell will not blink in sync with its mother cell, despite being almost identical genetically.

"You write the same software and put it into different computers, and their behavior is quite different," Mr. You said. "If we think of a cell as a computer, it's much more complex than the computers we're used to."

For that reason, some scientists say, it might be difficult ever to make biological engineering as predictable as bridge construction.

"There is no such thing as a standard component, because even a standard component works differently depending on the environment," Professor Arnold of Caltech said. "The expectation that you can type in a sequence and can predict what a circuit will do is far from reality and always will be."

The unpredictability could lead to safety risks. What if the novel organisms were somehow to run amok? In addition, the same technology could be used to synthesize known pathogens based on their published DNA sequences.

Scientists have already created a poliovirus from scratch and more recently recreated the 1918 pandemic flu virus.

"It's quite clear this technology could be dangerous" if misapplied, Mr. Endy of M.I.T. said.

The field is starting to grapple with whether it should be regulated and, if so, how. Scientists set up a safety framework for research when genetic engineering was invented in the 1970's.

Much of the concern centers on efforts to make entire microbes. Some scientists call this synthetic genomics as opposed to synthetic biology, though there is considerable overlap. A big concern is making pathogens by synthesizing their DNA based on published DNA sequences.

The Alfred P. Sloan Foundation has given $570,000 to M.I.T., the Venter Institute and the Center for Strategic and International Studies, an independent policy research organization, to study the societal implications of synthetic genomes. The group hopes to have a report by midyear, said Gerald L. Epstein, senior fellow for science and security at the strategic studies center.

In March, the Health and Human Services Department set up the National Science Advisory Board for Biosecurity to give advice about research with potentially nefarious uses. That board in turn established a working group on synthetic genomics and synthetic biology that met for the first time in November.

David A. Relman, chairman of the working group, said the challenge was to weigh the promise of the field against the perils.

"We fully recognize the inherent beneficial and very positive attributes of all of this work," said Dr. Relman, an associate professor of medicine at Stanford, "and don't want to stifle it or curtail it or constrain it for no substantive reason."

Source: http://www.nytimes.com/2006/01/17/science/17synt.html

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