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About this Article
Written by: Christopher Romero
Written on: April 4th, 2003
Tags: biomedical engineering, health & medicine
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About the Author
In the spring of 2003, Christopher was an engineering student at the University of Southern California.
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Volume V Issue III > A Genetic Solution to Malaria: More Harm Than Good?
Malaria continues to plague peoples worldwide, transmitted by a viral parasite carried by mosquitoes. Vaccines and pesticides have combated the disease in the past, but the disease adapts and becomes resistant to drugs, and pesticides such as DDT hurt the environment while killing mosquitoes. Geneticists have developed a new solution to this age-old quandary-a genetic alteration of the mosquito's physiology that keeps it from transmitting the disease and passes this characteristic to its offspring. However, overwhelming ethical questions in testing and implementing this innovation deserve careful consideration by society.

Introduction

Illumin
Figure 1: Parasite-carrying mosquitoes are the cause behind millions of deaths a year.
Every year, up to 2 million people are killed by malaria worldwide. Typically transmitted by parasite-carrying mosquitoes in underdeveloped countries where sanitation is poor and preventative strategies are failing, malaria, which was once "eliminated or largely controlled for 90 percent of the world's population, now threatens more than 40 percent" of all humans [1].

Ineffectiveness of Drugs, Vaccines, and Pesticides

So, what has been done to harness this powerful epidemic? Anti-malarial drugs, vaccines and pesticides have been developed, but both the host (i.e. the mosquito) and the protozoan parasite, one of four disease-causing species of the viral genus Plasmodium, have grown resistant to these technologies, demonstrating why malaria is one of the most dangerous diseases.
One pesticide, known as DDT, was very effective in eliminating mosquito populations; however, its natural degradation is very slow and its toxicity to all organisms is high. DDT accumulates in biosystems, increasing in concentration through the food chain and cumulating into a fatally toxic dosage, as evidenced by diminished bald eagle populations of North America. Furthermore, many species of mosquitoes have become resistant to this insecticide. Due to this, the World Health Organization (WHO) no longer uses DDT, and no other environmentally safe pesticide has been discovered.
After "research to create a [permanent] vaccine for malaria failed in the 1980s," very few methods of controlling malaria remained. Without any effective pesticide to limit large mosquito populations, geneticists suggested an alternative strategy. Believing that the resistance of Plasmodium to anti-malarial drugs would ultimately hinder vaccine research, geneticists such as UC Irvine's Anthony James turned their focus to the possibility of genetically altering mosquitoes, thereby making them incapable of transmitting the disease.

Genetically-Altered Mosquitoes

While the technology to effectively activate and inactivate specific genes is very complex and currently being refined, the concept of this strategy is simple. Say, for example, geneticists did build such a mosquito and released it into an environment affected by malaria. If the genetically altered mosquito were to mate with wild-type mosquitoes (i.e. mosquitoes that have not been genetically mutated) and successfully pass on its genes to its progeny, then, theoretically, nearly the entire population would eventually be incapable of transmitting malaria. The benefits of such a technology would be enormous: millions of lives would be saved, and governments need only purchase a handful of mosquitoes rather than meet the high cost of anti-malarial drugs or negotiate compulsory licenses (i.e. contracts allowing poorer nations to generically manufacture drugs). The greatest long-term benefit, of course, would be the eventual containment and possible elimination of malaria'a goal the WHO deemed impossible in 1969 [1].
Although the rewards of introducing a genetically mutated mosquito would clearly benefit mankind, there are also potential drawbacks. Michael D'Antonio of Los Angeles Times magazine states voices an obvious, but significant concern: "If only the real world were the same as a laboratory"[2]. Although tropical-like conditions (e.g. high humidity and temperature) are necessary even in the laboratory for successful breeding, many variables present in a natural environment cannot be duplicated. For example, in James' experiments, "male and female mosquitoes were placed in covered paper cups...[and] mice were anesthetized and laid on the mesh covers of the cups" to provide a constant food source necessary for the nourishment of the eggs. Such a guarantee of food to the desired mosquito populations may not occur in nature.
Other factors that are not accounted for during many of the experiments conducted in James' and other laboratories include variations in the chemical characteristics of the environment, types of animals present, and the possibility of different species of mosquitoes inhabiting the same area. This factor in particular generates more hypotheticals. Will the transgenic mosquitoes be fit to compete with other indigenous species? Can they successfully breed with wild-types of varying species-will the altered genes be preserved in each successive generation? This problem known as genetic consistency commonly occurs in genetic engineering. What may be even worse is the possibility of a more dangerous mosquito that could spawn from mating between transgenic and wild-type mosquitoes. Would this unexpected mutant be more capable of transmitting mosquito-borne diseases or other pathogens such as HIV? With so many ambiguities, how does one justify the release of a genetically modified mosquito when so many lives are involved?
Advocates of genetic manipulation have, undoubtedly, taken these questions into consideration and offer both practical and ethical solutions. Taking into consideration the problems posed by the idealized environment used in the laboratory to enhance research, one suggestion is to first study transgenic species released into an isolated environment, such as an uninhabited island [2]. This allows the mutated mosquitoes to interact with indigenous species while providing geographical containment if a problem should arise. Field-studies could then be conducted to determine the probability of successful mating of transgenic species with various wild-type mosquitoes while concomitantly observing the possibility of eliminating malaria. In addition, offspring could be obtained to study any changes in the mosquito's natural ability to harbor pathogens. Gathered data could also provide valuable insight regarding which genetic traits should be expressed or amplified to optimize population growth and the successful passing of genes. For example, to increase the size of a population, geneticists suggest using the satyr effect, which makes males "aggressively mate with every female they encounter" [2]. This suggestion of first studying an isolated environment offers a sound solution to the question of idealized laboratory conditions, which would not involve the loss of human life.
History has shown that both the host and parasite can develop a resistance to other technologies such as insecticides and drugs. Drugs such as quinine, once used during the Vietnam conflict by U.S. soldiers are now ineffective in preventing parasitic transmittance; moreover, mosquitoes are now resistant to many pesticides, including DDT [1]. So the question remains: what would prevent either the parasite or mosquito from developing a resistance to any technology? Since the mosquito's genome is being chemically altered, the only challenge regarding the development of resistance in the mosquito lies in ensuring that the effective genes are dominant and that the modified traits are expressed in each daughter cell that receives them.

Passing on Genes

Nature utilizes two methods to ensure the passing of genes. One involves the use of transposons, referred to as "jumping genes", while another method, called cytoplasmic incompatability, uses bacterial infections of mosquitoes to insert genes in targeted populations. Both approaches offer promising results. However, to account for the possibility of the parasite overcoming genetic modifications, geneticists would like for transgenic mosquitoes to carry several "parasite-blocking mechanisms...[to] lessen the risk that the parasite would eventually outwit the engineers" [3]. These parasite-blocking techniques include different genetic alterations that prevent the passing of parasites to other organisms. Examples could include inducing the formation of antibodies in mosquitoes that degrade parasites or adjusting the passage of saliva (where parasites often reside) to the bloodstream of a potential new host.
After considering the many technical problems that could arise, geneticists feel that social problems, such as the acceptance of the introduction of a man-made insect, constitute a greater opposition to the implementation of this technology. Dr. Andrew Spielman of the Harvard School of Public Health is one of the most well known scientists opposing this approach to malaria. He asks:
What about the people-most likely villagers in Africa or Asia-who live where these mosquitoes would be released? Would they be asked for their informed consent? How could we be sure they really understand the risk? What about those who don't want to participate? Would they be allowed to use insecticides or bed nets to protect themselves from biting? [2].
Furthermore, would advocates of genetic engineering only require the consent of the majority of a specific population before introducing such an insect? To this, James claims that after being exposed to so much disease and misery, villagers might try anything to eradicate mosquito-borne diseases. While this may carry some truth to it, this proposed statement by an inhabitant of an infected area seems irrational, implying that villagers are willing to risk the possibility of more death if anything were to go wrong. Generally, when questioning the use of a new pharmaceutical, approval for its release to the public is given only when life is not considered to be at risk. While this is typically the policy of developed countries, its objective should not be compromised when genetically modified mosquitoes are being considered in an underdeveloped region. Unfortunately, the inventor is enthusiastic to promote the use of a new, but potentially hazardous and catastrophic technology when his life is not at risk.
Spielman furthers his argument regarding social acceptance, recalling a plan in the 1970s to release sterile male mosquitoes into an Indian region to help reduce the mosquito population responsible for yellow fever. The project never started because of a few local politicians who "spread rumors that it was a sinister American experiment to study the use of mosquitoes and yellow fever virus for biological warfare against India" [2]. Similarly, how would local communities respond to the idea of releasing a genetically mutated species, when even sterile mosquitos were feared in previous cases? Accurate information, from both genetic engineers and local governments, must be provided for indigenous people to make rational decisions regarding the use of mutant mosquitoes.
Another consideration involves funding decisions-whether the money invested in genetics research would be better spent developing alternative, and generally less expensive methods to contain malaria. Examples of this include using the money to develop affected areas, which would reduce mosquito breeding grounds. Additionally, window screening could be provided to prevent mosquitoes from entering households. Medical entomologist Chris Curtis of the London School of Hygiene and Tropical Medicine, one of the oldest mosquito labs in the world, pleaded with donors to "keep in mind that every million dollars given to a few molecular biologists... trying to engineer mosquitoes could pay instead for lifesaving drugs and insecticides" [2].
With such monumental benefits offered by this technology, regardless of some of the questions that remain, many find it increasingly difficult not to employ this approach to malaria. After all, the elimination of malaria-one of the deadliest diseases ever known-would qualify as an amazing victory for mankind, one that could lead to genetic solutions for other devastating diseases. Yet, opponents to this cite the questionable success rate of this technology, as well as its social acceptance by local governments and inhabitants of affected areas. Perhaps what is really underlying their argument, however, is this: vaccines, pharmaceuticals and pesticides, though expensive, are immobile. Humans allocate these resources, and if some unexpected result were to occur after distribution, containment of any of these technologies would be quick and effective. On the other hand, while geneticists hail the cost advantages of the transgenic mosquito's natural ability to reproduce, a treatment problem in such a situation could potentially be catastrophic. The spread would be difficult to control, especially since no known pesticides are effective in eliminating mosquito populations.

Conclusion

Although a "good" mosquito would save countless lives and eliminate one of the worst diseases affecting humans, the millions of dollars spent will probably never ensure that the "perfect" mosquito has been created. With so many questions remaining about how this man-made mosquito will adapt to an ever-changing environment, the potential for disaster could outweigh our hopes of eradicating malaria. Skeptics of genetic engineering must remember that with science, there will always be some risk involved or some unanticipated flaw that could arise. So the real question becomes: is taking some risk reasonable and, if so, how much? Advocates of this questionable technology feel similar to Curtis, who states, "If we had in our hands a way of saving a lot of sickness and death, and we turned it down for some clever-clever argument about what it might do-that's not being quite so ethical as you might think" [3]. With so many lives at stake, coupled with the mobility of man-made mosquitoes, how do geneticists justify the risk involved with the above statement? Richard Feynman, the Nobel Prize-winning American Physicist, once stated, "For a successful technology, reality must take precedence over public relations, for Nature cannot be fooled." Perhaps we have not reached such a point as of yet.

References

    • [1] P. Brown. "Who Cares About Malaria?" New Scientist, pp. 37-41, October 31, 1992.
    • [2] M. D'Antonio. "Building a Better Mosquito." Los Angeles Times, pp. 10-13, 30-32, September 2, 2001.
    • [3] S. Young. "Mosquitoes That Kill Malaria." New Scientist, pp. 36-9, August 5, 1995.