Genetic Modifications You May Not Know About

by | 1.13.2014 at 1:37pm | 1 Comment
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T cells have been genetically modified to fight cancer

Human T cells have been genetically modified to fight cancer

While much attention is focused on genetically modified foods and the debate over their safety, fewer people are aware that many other genetically modified organisms (GMOs) and cells are in development. These genetic modifications include new crops and food products, but also trees that have been wiped out by disease, animals altered to produce useful products and microorganisms engineered to combat cancer. Shahid Naeem, director of the Earth Institute Center for Environmental Sustainability, and Matt Palmer, senior lecturer at Columbia University’s Department of Ecology, Evolution and Environmental Biology, offer their perspective on these new developments.

Trees

Chestnut tree forests once extended from Maine to Florida, but the American chestnut was decimated by chestnut blight in the first half of the 1900s. The Forest Health Initiative is attempting to restore the chestnut through genetic modification. The symptoms of chestnut blight are caused by oxalic acid released by a fungus that attacks the tree.

A chestnut forest

A chestnut forest

Scientists at the State University of New York in Syracuse transferred a wheat gene that encodes an enzyme that neutralizes oxalic acid, as well as disease resistant genes from Chinese chestnut trees, to the American chestnut to give it blight resistance. The strategy could provide a model for restoring other trees that have been wiped out or are struggling to survive, such as the American elm, ash and eastern hemlock.

“I’m very much in support of saving trees that are on their way out and bringing them back,” says Palmer, “because I feel we have a certain moral obligation to the species, especially when the causes of its decline are linked to us. … And I have a little more comfort doing genetic modification for restoration or conservation purposes, because it’s basically done by academic and government scientists. I think the peer review system through which these things are going to be operating, as opposed to the profit-driven system, would more easily reveal the risks and address them.”

ArborGen, a commercial forestry company, has used genetic modification to produce a eucalyptus tree that is more advantageous to the paper and wood pellet industries. Lignin, a component of plants that provides structure, must be removed during the manufacturing process to improve the quality of paper. ArborGen has altered the balance of the two types of lignin in eucalyptus trees to make it easier to remove and yet still available for energy production. It has also developed a freeze-tolerant eucalyptus tree so that the tropical tree can be grown in the southeastern U.S., expanding its potential growing area four-fold.

Cellulosic ethanol, considered the next generation of biofuel, can be made from sugar in the cell walls of plants, but cellulose, the main component of plant cell walls, is tightly bound up with lignin in trees. Scientists at Purdue University genetically modified the lignin composition of poplar trees so that the cellulose can be more easily separated from the lignin. In addition, the amount of plant growth hormone has been reduced so that trees can be planted closer together to enhance productivity.

A recent report by the Center for Food Safety cites concerns that GM trees consume double the amount of water as normal trees, spread seeds and pollen over long distances, and require large amounts of fertilizer and pesticide. If wild trees interbreed with GM trees, they could become more vulnerable to pests and diseases.

Palmer is also concerned that if a GMO escapes into the wild and has some competitive advantage, it will increase over time, producing potentially unmanageable, unintended consequences. “Once the genie is out of the bottle, you can’t put it back in,” says Palmer, “But I don’t draw a bright line that says you shouldn’t be messing with nature because we’ve been doing it all along, and in some ways, we have an obligation to do better with what we have. We’ve already converted these lands, so isn’t it better to get more productivity out of the lands we’ve already converted than to continue to convert more lands? “

Animals

Scientists at Utah State University inserted the gene for spider silk from golden orb spiders into goat DNA, producing an animal whose milk contains the protein for spider silk.

A golden orb spider. Photo: Josoroma

A golden orb spider. Photo: Josoroma

Spider silk is lightweight, stronger and more elastic than any manmade material, and its thermal conductivity is comparable to copper. The silk proteins in the goats’ milk are dried, dissolved and then spun into microfibers which have the potential to be used medically for artificial ligaments, tendons and eye sutures, as well as for bullet-proof vests, high fashion clothing, car airbags, electronics and applications in space. Scientists are also researching engineering the spider silk gene into alfalfa plants, silk worms and even bacteria.

“There are legitimate concerns about genetic modification,” says Naeem. “But we often don’t know what the actual risk is…what is actually the risk if the gene for silk production jumps from the goat to the cow? …Is it going to be far more cost effective and valuable to the silk industry to have silk genes put into goats? There’s a lot of excitement in being able to do that, but really is the actual benefit worth it?”

At the Roslin Institute near Edinburgh, Scotland, the gene in hens responsible for ovalbumin, a protein in egg white, was modified with human genes that encode for the production of complex human proteins. The hens then lay eggs containing medicinal proteins with the potential to treat malignant melanoma, arthritis and multiple sclerosis. Theoretically, hens could be genetically modified to produce medicines for diseases such as Parkinson’s, diabetes and cancer as well.

The last known passenger pigeon, shot in 1900.

The last known passenger pigeon, shot in 1900.

Passenger pigeons were once widespread in the U.S., but by 1914, they had become extinct due to over-hunting. The Long Now Foundation aims to restore the species by inserting DNA from museum specimens into the band-tailed pigeon.

The strategy is to gradually modify a related species through genetic modification, though scientists are unsure how much passenger pigeon DNA, for example, would be necessary to do it. This is just one of several animal “de-extinction” projects going on around the world.

Insects

Olive flies, the main pest of olive crops, have become increasingly resistant to pesticides. To reduce the olive fly population, Oxitec, a British biotech company, genetically modified male olive flies so that when they mate, they pass along a gene that causes female offspring to die in the larval stage. The male offspring do not die, and can pass the gene along to the next generation. Oxitec applied for permission to test the GM olive flies in Spain, but in December, withdrew its application in order to conduct more research on the effects of the GM flies on its predators and parasites.

In assessing this form of pest control, “You have to compare the alternative,” says Palmer. “Is the alternative that you lose the olive industry? Is it that you spray a lot of chemical pesticides that we know are breeding resistance, affect our water quality and are having impacts on non-target organisms? The nice thing about using GM pests to fight pests is that the olive flies are only going to breed with other olive flies.”

To combat dengue fever, a disease affecting over 100 million people worldwide that has no known vaccine, researchers at the University of Oxford genetically modified the male mosquito that spreads the disease to stall the insect’s development at the larval stage. To develop further, the offspring of the GM mosquitoes require the antibiotic tetracycline, which they cannot get naturally from their habitat. In the wild, the GM mosquitoes mate with females, but their offspring never develop beyond larvae, which eventually reduces the population. Oxitec has conducted successful field trials in Brazil ,Malaysia and the Cayman Islands; Florida, which had 22 local cases of dengue fever this year, is considering releasing the GM mosquitoes at a test site if FDA approval is granted.

Microorganisms

California-based Amyris is genetically modifying yeast and other microorganisms to produce spices, flavorings and fragrances that have traditionally only been obtainable from exotic plants. The process is similar to brewing beer, but instead of producing alcohol, the yeast produces Biofene, a customized hydrocarbon that provides the basis for cosmetics, flavors, fragrances, and even drugs, jet fuel and rubber. Amyris’s robotic systems rejigger yeast DNA, by design as well as randomly, producing over 1,500 new GMOs a day. The company has already manufactured artemisinin, a malaria remedy traditionally harvested from the sweet wormwood plant; pills are being distributed globally.

In another attempt to combat malaria, scientists at the Johns Hopkins Malaria Research Institute in Maryland genetically modified a bacterium found in mosquitoes so that it secretes proteins lethal to the malaria parasite. In a study, the number of mosquitoes with the malaria parasite decreased by 84 percent.

A tsetse fly. Photo: David Bygott

A tsetse fly. Photo: David Bygott

Researchers at the Yale School of Public Health genetically modified two bacteria in tsetse flies to be resistant to the parasite that causes sleeping sickness. When both are transmitted to the next generation, the GM tsetse flies infiltrate the fly population, and provided that the GM flies comprise 85 percent of the tsetse fly population in the area, the incidence of sleeping sickness declines.

PaxVax, a U.S. vaccine company, has developed a cholera vaccine containing a GM cholera bacterium that doesn’t produce the toxins or reproduce the cholera bacteria; people don’t get sick, but do develop immunity. One trial of the GM cholera vaccine found that a single dose resulted in an immune response in 90 percent of the recipients. The company recently applied to Australia’s government to test the vaccine there.

Biofilms, which occur when bacteria stick to each other in a sheet, are found in hospitals and are often resistant to antibiotics. Scientists at Singapore’s Nanyang Technological University genetically modified the bacterium E. coli (most strains of it are not harmful) to secrete anti-bacterial chains of amino acid molecules when it comes into contact with P. aeruginosa, the bacterium that often causes biofilms and sepsis in hospitals.

Staphylococcus biofilm. Photo: Penn State

Staphylococcus biofilm. Photo: Penn State

The E. coli is also armed with an enzyme that breaks up biofilms and is programmed to go after P. aeruginosa when they are linking up. Most antibiotics destroy both good and bad microbes, but the GM E. coli can target specific harmful microbes. Other scientists are working on GM E.coli to seek out and attack cancer cells.

Cells

A team from the Perelman School of Medicine at the University of Pennsylvania has genetically modified T cells (a type of white blood cell involved in immunity) into super T cells to combat cancer. The T cells are removed from a patient’s blood, given a receptor that recognizes a protein found on the surface of most leukemia cells and a mechanism that prompts the T cell to proliferate once it finds its target. The super T cells are then injected back into the patient to fight the cancer. In trials of 59 patients with lymphocytic leukemia who had exhausted other treatment options, 26, including 19 children, became cancer-free.

According to the New Yorker Magazine, it took over a decade and $3 billion to sequence the first human genome, but in the years since, the price has been dropping dramatically. This rapid development of the technology has enabled scientists around the world to experiment with many applications of genetic modification.

The human genome, printed. Photo: Adam Nieman

The human genome, printed. Photo: Adam Nieman

The public needs to be aware of these developments, but need we be afraid of them? Palmer believes that GMOs offer benefits such as productivity and disease resistance, and may have advantages that promote conservation, public health and adaptation to climate change. The facts are that the evidence is strong for many of the advantages they offer, he says, while the disadvantages and risks are still more hypothetical than realized.

“Life is full of risks and concerns,” says Naeem, “yet we don’t do anything about them. … For example, we know that some of the many food additives we put into food are carcinogens. Climate change is an enormous problem, but we don’t seem to be rising to the challenge. The risks in GMOs can be very real, but they’re so unknown. … Especially at a time of upheaval when climate is changing, habitat is fragmenting, the world is changing yearly in ways that are hard to know, it makes it even more difficult to figure out what the risks will be.”

On the other hand, “You’re never going to prove that something is absolutely safe,” says Palmer. “Science never gets you there. You use evidence to evaluate risk. If we were only going to do things that were 100 percent safe, we would have no medicine, we would have no transportation infrastructure, we wouldn’t be living life as we know it. … The most important plea I’d make for genetic modification is for there to be an honest discussion about its risks.”

 

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One Response to “Genetic Modifications You May Not Know About”

  1. Lon Levin says:

    A well researched balanced presentation of the issues. Thanks

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