Most people probably don’t think about insects when they hear about genetically modified (GM) animals. But in fact, scientists are actively working on genetically altering some of these tiniest animals in the hopes of enhancing public health, crop production, and animal health.

Some scientists are trying to engineer insects so that they can no longer transmit human or animal diseases. Other scientists are using biotechnology to fight agricultural pests, either by altering “biological control” insects to better control agricultural pests or modifying pest insects themselves to reduce their populations. Other research is focused on beneficial uses of insects, such as developing honeybees resistant to disease or engineering the silkworm to produce pharmaceutical proteins.

"You have to try to understand the ramifications. It's the responsible thing to do when you are doing any form of intervention that is manipulating and changing the environment." Ravi Durvasula. At the same time, the development of GM insects raises significant concerns as well as challenges to the regulatory system. One of the unique aspects of GM insects compared to other biotech products is that some of them will be deliberately released into the environment with the intention that they survive, reproduce, and/or pass their genes to the wild population. Because ecosystems are ever-adapting biological systems, the consequences of releasing such insects can be very difficult to predict. GM insects might disrupt ecosystems by, among other things, displacing other insects, altering predation patterns, or passing their modified traits to wild relatives in ways that were not intended by scientists.

"The environmental risks with insects, as with fish, are very significant. We're talking about an uncontrolled situation. They cannot be controlled once they are let out." says Peter Jenkins, an attorney and policy analyst at the Center for Food Safety, a Washington, DC-based public interest advocacy group.

However, the potential benefits of the technology have appeal to both developed and developing countries because insects have enormous impacts on human health and crop production worldwide. Thomas Miller, professor of entomology at the University of California, Riverside, believes California’s agricultural richness could be protected by using GM insects.

"The number of problems we have from exotic pests is enormous. It's estimated that California gets a new pest every 60 days," Miller says. "That's a new threat to the state, and it's increasing because transportation is increasing. We are being asked to perform miracles, but to do that we have to use the best technology we've got and that is biotechnology."

The bollworm damages cotton plants by eating through the cotton flower or tunneling through the cotton boll to devour the seed. Miller is trying to create a GM bollworm that carries a gene lethal to its own offspring. If it works as expected, this GM bollworm will reduce the bollworm population and the damage caused by it. The cost of the pink bollworm is easy to calculate because there are figures for cotton production before and after it [the bollworm] arrived," Miller says. "The cost is very high."

"Supporters, mostly growers, eventually want [the GM bollworm] to be a major tool in getting rid of the pink bollworm." Thomas Miller. Before they can test these GM bollworms in the field, Miller and his colleagues need to understand how GM insects spread through wild systems. To achieve this, they inserted a gene from jellyfish into bollworms not containing the lethal gene, in order to monitor bollworm dispersal and mating. Because the inserted jellyfish gene produces a fluorescent protein, the researchers can track the spread of the genes from GM insects to wild ones.

Two years ago, they released the GM fluorescent bollworm moths into cages at a secure U.S. Department of Agriculture facility in Phoenix. Next year, the researchers plan to release these GM moths in an open field in eastern Arizona. With this test, the researchers hope to answer questions regarding how well this gene will move through the wild population. It's the next step toward getting a permit to do a full field release of the bollworms containing the lethal genes – a development that is eagerly anticipated by some. "Supporters, mostly growers, eventually want this to be a major tool in getting rid of the pink bollworm,” says Miller.

GM insects may also be engineered to produce pharmaceutical compounds. Much in the same way that GM bacteria produce human insulin, the silkworm has been turned into a protein factory by inserting genes for human proteins. The Japanese-engineered silkworms still produce silk, but they also produce proteins such as collagen, used for wound healing, and albumin, used to treat severe blood loss. Currently, these products are derived from pooled human blood donations.

"Making these pharmaceuticals into active compounds by classical methods means you have to isolate these proteins from the blood or tissue. It's very tedious and it costs money," says Florian Wurm, professor of biotechnology at the Swiss Federal Institute of Technology in Lausanne, Switzerland. Also, protein extracts from human sources may transmit diseases.

The silkworm is a natural “factory” to produce medical proteins, Wurm says, because they have the ability to make large quantities, and there is little risk to humans by using this technology.

"There's very little outside review happening. It's all happening in the dark in a lot of ways and we are trying to shed some light on it." Peter Jenkins

"If I were to have a choice...between a product that comes from the donation of blood from 1,000 people or a product made from silkworms, guess which one I would take," Wurm says. "It's a purified product from an organism that is far away from the human species. It can't transmit viruses or parasites to me. We have a tremendous benefit from using such organisms for our purposes."

While silkworm-produced proteins may enter clinical trials in the next year or two, widespread use of products is probably 10 to 20 years away.  In addition to making protein pharmaceuticals, GM insects may help curb the spread of human and animal diseases. Mosquitoes, tsetse flies, kissing bugs, ticks, fleas, lice and other insects are well known carriers of human and animal illnesses. Much of the research into GM insects is aimed at disease prevention.

Ravi Durvasula, MD, assistant professor of medicine at Yale University School of Medicine, is working on one such project to stop Chagas’ disease, a parasitic illness carried by the kissing bug that kills 50,000 xpeople annually in Central and South America. Kissing bugs acquire the Chagas’ parasite by feeding on infected people and animals, and pass the parasite on when they feed on other non-infected humans and animals.

Durvasula’s group has engineered bacteria that makes the kissing bug’s gut inhospitable to the Chagas parasite and prevents transmission of the disease. Durvasula is optimistic about this technique, but many environmental studies still need to be completed.

"It's one thing to work in a lab or in a greenhouse. But going into the natural environment and releasing genetically modified bacteria is quite a challenge," he says. Studies Durvasula’s lab are doing include looking at how these genes migrate. "If we release these bacteria that are targeted toward the kissing bug population, what if the [GM] bacteria make their way into houseflies, ants or other insects that live in houses?"

"It's the responsible thing to do when you are doing any form of intervention that is manipulating and changing the environment," Durvasula says. "You have to try to understand the ramifications."

Thomas Scott, professor of entomology at the University of California, Davis, agrees. Scott studies dengue fever and malaria transmission. Intuitively, it makes sense to genetically modify a mosquito so it can no longer transmit malaria or dengue fever, Scott says, but it's a difficult proposition that could have unintended consequences. For example, the genes meant to make a mosquito unable to carry the malaria parasite could jump into other kinds of bugs with unpredictable results. Or, it may be unsustainable, meaning the genetic modification may cut down on disease transmission for a while, but then the pathogen somehow gets around the genetic barrier, causing malaria transmission to come back with a bang.

"We have to define exactly what we are going to be releasing. We need to understand the epidemiology of the disease, what kind of measurable impact the modified mosquito will have and what the parasite's response will be to whatever we throw at it," he says. "These malaria parasites have developed resistance to a whole slew of antimalaria drugs, so the potential is there for the pathogen to circumvent the barrier we put in front of it; that would be an undesirable outcome. We could conceivably end up with something worse than what we started with."

The World Health Organization estimates that between 300 and 500 million clinical cases of malaria occur each year, and over one million people - mostly children under the age of five - die from malaria, a disease closely tied to poverty. Malaria is most rampant in sub-Saharan Africa, where children can suffer between 300 and 1,000 infected bites during a season, Scott says. Conventional methods of control, such as spraying bed nets and the insides of houses with insecticides, can help control malaria. But the bugs have developed resistance to insecticides and many people in third world countries and their governments can't afford to pay for insecticides or bed nets, Scott says.

"We are at the point now where we need to assess the use of transgenic mosquitoes and come to a conclusion in the next five to ten years on whether or not it's feasible," he says. "If it's not feasible, we need to drop it and move on. If it is, we need to pursue it in an aggressive way. Enough of the ground work has already been done."

Jenkins finds it “particularly disturbing” that the federal government doesn't have any clear cut regulatory guidelines to ensure that all GM insects are reviewed for potential environmental, food safety, and public health risks.

"Researchers want some clear direction on what's required and what's not," Jenkins says. "The agencies are in a shameful position because they are not responding to responsible researchers who want some direction. The different agencies keep dropping the ball and nobody takes it."

Jenkins is concerned that the lack of direction from the government creates confusion. He notes, "There's very little outside review happening. It's all happening in the dark in a lot of ways and we are trying to shed some light on it."

For more information, please visit:

http://www.centerforfoodsafety.org
Center For Food Safety

http://www.entomology.ucr.edu/people/miller.html
Thomas Miller's Page

http://www.usda.gov
USDA

http://publichealth.yale.edu/faculty/durvasula.html Ravi Durvasula's Page

entomology.ucdavis.edu/faculty/scott.cfm
Thomas Scott's Page

http://www.who.int/en/
World Health Organization online.