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Institute for Ethics and Emerging Technologies

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Can Synthetic Biology Cure Bad Air? (It’s not what you think)

Randall Mayes

Ethical Technology

June 15, 2009

Treatments for some of the world’s biggest killers, such as malaria, can’t earn enough profits for pharmaceutical companies to attract research investments. The people they kill are just too poor to be worth the investment. Fortunately scientist-activists are attempting to find ways to support vital research through the non-profit sector.

Vitalists believe forces flow through the air and particles through our bodies which are responsible for diseases and catastrophic events sometimes through curses from the gods. Malaria’s etymology has its roots in vitalism as mala aria is Italian for bad air. Prior to Pasteur’s discovery that plagues are caused by microorganisms, the prevailing wisdom was malaria, a deadly disease that has flu like symptoms, originated from swamp air. In 1880, French Army doctor Charles Leveran discovered parasites in the red blood cells of malaria patients are responsible.

Although the medical community has used a number of methods to prevent malaria, it remains a major world health problem. Malaria infects an estimated 300-500 million people annually, and it is fatal to roughly 1.5 million of those. Children under five in African and pregnant women are the most vulnerable. Mosquito nets, head coverings, drainage of marshy areas where mosquitoes lay their eggs, and spraying their habitat with the insecticide DDT, which is now banned, were used until malarial drugs were developed.

The first effective drug treatment for malaria was quinine which is from the bark of the cinchona tree in the Andes of South America. A synthetic form of quinine was synthesized by Robert Woodward of Harvard in the 1940s called Chloroquine. The parasite developed resistance to quinine through a mutation resulting in a change in one amino acid. In some regions, sulfur drugs replaced quinine; however, the parasite developed resistance in even a shorter time. 

During the Chinese Cultural Revolution in the 1960s, the Chinese government launched a project to investigate the properties of plants used in traditional herbal medicines. Chinese Herbalists use Qing hao also known as Artemisia annua or sweet wormwood which is indigenous to China and Vietnam to treat fevers. Its dried leaves are soaked and the active ingredient artemisinin is extracted. Artemisinin releases oxygen based free radicals that destroys the Plasmodium parasite while in the red blood cells of the host.

Overcoming Resistance to Drugs

The Plasmodium parasite that infects humans is transmitted by the saliva of the female Anopheles mosquitoes that feeds at night. Both sexes live on nectar, but blood is needed by the female for egg production because the protein content of nectar is very low. The parasite travels to the liver where it is shielded and replicates. After entering into the bloodstream, the parasite invades red blood cells to feed on iron rich hemoglobin. Infected blood cells are destroyed in the spleen; however, the parasites have adapted the ability to display surface proteins on the surface of red blood cells, causing the red blood cells to stick to the walls of small blood vessels blocking the circulatory system. 

Artemisia annua has a nearly 90 percent efficacy rate against parasites resistant to other anti-malarial drugs. But, isolating and extracting artemisinin from plants is an expensive and laborious process. Also, the parasite could develop resistance to one artemisinin drug, so time is a factor in finding a treatment. In 2004, the World Health Organization endorsed artemisinin combination therapy (ACT), the use of several anti-malarial drugs, which scientists devised in order to outsmart the parasite. To develop resistance, it would require that parasites acquire simultaneous mutations which is highly unlikely.

The combination therapy treatment is more expensive and the supply is not meeting the demand (Hale et. al. 2007). Some reports estimate up to 50 percent of the drugs sold in Africa and Asia are counterfeit and speculators are stockpiling the wild plant. If scientists can develop a low cost artemisimin drug, the black market business will disappear. 

The Free Rider Problem

Most patients in need of anti-malarial drugs are from developing countries and unable to afford them. A criticism of patenting pharmaceuticals is that companies lack an incentive to invest in and produce drugs for those who are not able to afford them since they are not profitable. If producers do not supply public goods or services because they are susceptible to the free rider problem, a market failure occurs.

Victoria Hale, a former FDA analyst, noticed that only 10 percent of FDA’s budget went to diseases of the developing world which accounts for 90 percent of infectious diseases. Without private drug manufacturers, investors, or paying customers to effectively fight malaria, an outside the box solution is needed. Hale created the non-profit Institute One World Health which already has success with three drugs including paromomycin, an antibiotic for black fever.

With backing from the Gates Foundation through a $42.6 million grant, synthetic biology may provide a non-profit solution to treating malaria. The goal is to develop a novel and less expensive process to manufacture artemisimin. According to a OneWorld Health spokesperson, “The project aims to create a stable, second source of artemisinin to supplement existing natural sources. It is hoped that this complementary source of semisynthetic artemisinin will be more affordable for drug manufacturers. In turn, this will help reduce the price of ACTs, making them more accessible to people in malaria afflicted countries.”

Jay Keasling, a synthetic biologist at the University of California at Berkeley, is redesigning the genetic circuits in the metabolic pathways of E. coli to code for all of the enzymes to produce the precursors to artemisinin. Sanofi Aventis has agreed to build a bioreactor, a vessel which provides favorable conditions and provides a high rate of success, to mass produce the drug by growing gene cassettes in fermenting vats in a process similar to brewing beer

Hale negotiated with patent holders, drug manufacturers, and scientists to form an innovative partnership. The University of California at Berkeley has waived its royalties on the process. When the process is refined, Amyris will take Keasling’s research to a commercial process to grow the bacteria and will produce them at cost. OneWorld Health will take the new process through the clinical trials regulatory process and FDA approval, and make the product available for drug makers.

Once a proof of principle prototype is established for bio-engineering gene networks, with a combination of profitable process and product patents Keasling’s start-up company Amyris Biotechnologies hopes to use the same technique to produce other drugs and more useful products.

Randall Mayes served as a 2009 IEET Fellow. He is a science writer and policy analyst with a focus on enhancement and emerging biotechnologies.


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