Sunday, January 5, 2014

The History of Genetically Modified Orgamisms (GMOs)

Given the interest and activism around the question of labeling genetically modified organisms (GMOs), we thought it would be a good time to go into more depth about this important topic.

In our previous articles, we have discussed the many concerns about genetically modified organisms (GMOs). Unfortunately, we have reached a point where GMOs make up a majority of certain crops (e.g. corn, soy, sugar beets, canola, etc.) that are grown in the United States. We feel this might be a good time to expand on the history of GMOs, how we got to this point, and try to understand how GMOs made their way into widespread use in agriculture.

In this post, let's take a brief look at the history of how GMOs came into existence.

In 1925 Sinclair Lewis published ARROWSMITH, the first modern novel to focus on science and its practitioners. It tells the tale of Martin Arrowsmith, a young precocious Midwesterner whose winding medical career takes him from small town private practice to the gilded halls of a great metropolitan research facility in the Big Apple. Along the way he discovers a bacteriophage (a virus that infects bacteria), and wades into a plague epidemic in the jungles of an exotic Caribbean isle. The book won its famous playwright a Pulitzer prize in 1926, which he famously refused on the grounds that the committee’s rules for consideration were disingenuous.

But his swashbuckling character of the pioneering Dr. Arrowsmith captured the imagination of a bright young kid in a small Brooklyn coastal neighborhood called Sea Gate. Though Paul Berg was born the same year Lewis walked away from his Pulitzer, the book was still a popular read a decade later when young Paul found it in the local library. It changed his life. He wanted to be that doctor. As it turned out, he was ...

Following his naval service on a sub chaser in the Second World War, Berg studied chemistry and microbiology in Cleveland at Case Reserve University, and later at Washington University in St. Louis. Years later, he accepted an invitation from Stanford University’s Medical Center, where he established a new department of biochemistry with his mentor Arthur Kornberg. And it was there in 1972 that he became the first scientist to insert DNA from one species into a molecule of another, producing recombinant DNA (rDNA) ... and in so doing, created a new DNA sequence never before found in nature. It was a truly revolutionary process which won him the Nobel Prize.

A year later, Herbert Boyer and Stanley Cohen managed to introduce a gene for tetracycline resistance into E.coli bacteria, and the race to develop transgenic organisms was on. By 1976, Boyer had joined 29 year-old venture capitalist Robert Swanson in founding Genentech, the corporate forerunner of the biotechnology industry. Their company became the first to express human genes in bacteria, leading to the development of synthetic insulin and human growth hormone.

Experiments involving the genetical modification of bacteria led the way for a good reason - their relatively simple genome. Even so, what researchers began discovering was astonishing. New recombinant DNA sequences could be created between any two species, no matter how distant their respective origin. In essence, there was no barrier to mixing genetic material from a virus to a bacterium, or from an orchid to a human being. The Greek’s mythological chimera, an animal with the head of a lion, body of a goat, and tail of a serpent, while not a practical application of the new science, is a perfectly feasible mash-up of gene sequences.

The list of animal/human chimera is growing. Implantation of human stem cells in animal embryos is yielding cybrids for specific research protocols ... human blood and heart valves in pigs, human livers in sheep, and human brain cells in mice. The latter is the nucleus of a long term study by Dr. Irving Weissman at Stanford University’s Institute of Stem Cell Biology. He and his colleagues are searching for new treatment options for diseases like Parkinson’s, Alzheimer's, and intractable brain cancers such as glioblastoma. Thusfar Weissman’s team has successfully created mice with about 25% human neurons ... the ultimate goal being 100%. Each step towards that objective is fraught with ethical and philosophical quandaries.

Yet another arena of genetic engineering has been characterized as pharming, the linguistic amalgam of ‘farming’ and ‘pharmaceuticals’. Which is precisely what it connotes. Human serum albumin, a necessary protein component of blood plasma was first produced in transgenic (genetically modified) potato and tobacco plants by a Dutch and German team in 1990. Since then, a raft of other therapeutic proteins followed, including antibodies, hormones, enzymes, and veterinary vaccines. But the industry faced a dramatic setback in 2002 when ProdiGene, one of the more prominent commercial startups in the sector, was involved in two separate incidents of contamination. In Iowa, their GM corn cross-pollinated a neighboring field. And in the other event, ‘volunteers’ from a previous soy harvest adulterated the succeeding crop, causing all 500,000 bushels of soybeans to be destroyed. The USDA fined the company over $3 million, though a watchdog group later discovered the Agriculture Department had made a $3.75 million, no-interest loan to the company, effectively requiring taxpayers to subsidize the clean-up costs.

Despite the governments gentle reproof, a number of pharming startups went belly-up. The concern over the possibility that genetically modified genes could ‘escape’ was not just a case of eco-paranoia - these are plants were specifically engineered to produce drugs. Many scientists who otherwise support GMOs in general, are considerably more wary of the chance that living pharmaceutical factories could wind up sharing their modified genes with crops destined for our dinner tables. Human plasma in your soup, anyone?

Which brings us to perhaps the most closely watched segment of GM biotech - FOOD. The animal side of the equation is still very much under scrutiny. The most visible aspirant is beleaguered AquaBounty Technologies, developers of a genetically modified salmon. Insertion of a single gene from a Pacific Chinook into its Atlantic cousin has produced a fish with double the growth rate of the original. Years after perfecting the technology, AquaBounty is still seeking regulatory approval to sell what their opponents call ‘frankenfish’ to the public.

The approval process for transgenic plants has been a very different story. Not a single acre of US land was planted with GM seeds in 1980. Today that number is 75 million acres, on which 88% of corn (the number one crop in the US), 93% of soybeans, 94% of cotton, 90% of canola, 75% of the Hawaiian papaya crop, 90% of sugarbeets (which comprises 54% of all the sugar sold in this country), and a large and growing percentage of alfalfa, the 4th largest crop after corn, soy, and wheat are grown from GM seed. At present, there is no transgenic wheat on the market, but that’s not to say it doesn’t exist.

It is estimated that between 70% and 80% of all the processed foods offered by American supermarkets contain genetically engineered ingredients. That number is only an educated guess since no labels informing consumers of the presence of GM ingredients is required by either federal or state governments at this time. Worldwide, biotech crops are now planted on over 470 million acres and counting according to CropLife International, an industry trade group.

Why should we be concerned about this transformational development in our food supply? After all, the companies who design and manufacture genetically engineered plants point to a series of scientific studies that found no harmful effects on humans or animals consuming their products. They go on to cite approvals granted by regulatory agencies of the US government, ranging from the Food and Drug Administration (FDA) to the EPA and the Department of Agriculture (USDA).

But are the research studies proffered by these companies accurate and complete? The answer is no. Let’s go back to the world’s biggest crop. Corn. At this point in its evolutionary history, corn is among the most significantly altered of all the plant genomes. The first step was the addition of a gene from a naturally occurring soil bacterium, Bacillus thuringiensis (Bt). This bug produces a protein toxin deadly to a wide variety of insects - among them the European corn borer and Western corn rootworm. Dating back to the late 1930’s in France, Bt was sprayed directly on a crop like any other insecticide.26 In fact it became a favorite of organic gardeners. But the compound breaks down quickly in sunlight, or washes away in a hard rain. Those shortcomings were overcome by inserting the bacteria’s genes in the plant’s genome.

A Belgian company was the first to encode Bt genes in tobacco plants. But it was Monsanto’s Bt NewLeaf potatoes in 1996 that became the first GM crop approved by the EPA to be grown commercially in the US. They repeated their potato success with corn. As with the tuber, the resulting genetically modified corn expressed the toxin in its tissues throughout its life cycle, from germination to harvest. Not only the corn itself, but its pollen contains the insecticide, which is toxic to a wide range of non-target insects. Among them, bees who feed on the pollen (and carry it back to the hive), and monarch caterpillars feeding on milkweed dusted with pollen. The end result is often the same - Bt is lethal to both species and many more besides.

Some unexpected traits have predictably appeared in the gene encoded Bt proteins, which were not present in the natural bacteria’s. When dispersed in pollen or mulched into the soil, the proteins don’t readily degrade like their natural antecedents. Studies have shown Bt transgenes not only remain in the soil for months, but their levels build over successive plantings. That’s not all. The National Institutes of Health published results of a 2006 Canadian study citing the presence of cry1Ab (the Bt transgene coding the protein toxin) in the St. Lawrence River, 50 miles downstream from their test cultivation plot, demonstrating the ability of the GM Bt to travel from place to place in the water column.

The bigger issue is resistance to the toxin, building in the very insects it aims to control. This comes as no surprise to the scientific community. Resistance from insects to pesticides and weeds to herbicides is an expected outcome. In the case of the Bt toxin, the anticipated immunity has taken somewhat longer to appear because many countries mandated that each field of Bt corn (and other crops like cotton) have a smaller, adjacent crop of non-Bt corn alongside. The idea was that the non-GM crop would act as a “refuge” for targeted insects to escape the holocaust next door. Thereby delaying the inheritance of the recessive genes responsible for evolving resistance to the pesticide. It seemed to work ... for a while. In 2005 only one of the pests, the corn ear borer, had acquired resistance.

Let us be clear - this is the road map for a long, protracted war. The kind of struggle in which all the victories are pyrrhic and the conflict drags on indefinitely. But it is not a regional conflagration being waged in a few isolated pockets. This is a World War.

Dr. Rebecca Malamed, M.D. and Mr. Ben Young Mason

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