A new article in Nature, Malaria breakthrough raises spectre of drug resistance: Yeast engineered to produce potent drug, manages to simultaneously announce exciting scientific progress that will reduce the cost of artemisinin combination therapy (ACTs) for malaria while addressing the potential impact on drug resistance in the same breath :
The 'miracle' malaria drug artemisinin is a step closer to being produced plentifully and cheaply. Synthetic chemists have put plant genes into yeast to make it churn out large amounts of the precursor artemisinic acid. The discovery brings hope to areas such as sub-Saharan Africa, where those who need the drug most can ill afford it.
Researchers have praised the work and are excited that it may soon be possible to get artemisinin to the 300 million to 500 million people infected with malaria each year. But many are also concerned that this will trigger the emergence of resistance to the drug, thus destroying our most effective weapon against the disease.
Jay Keasling's bioengineering team at Berkeley had already found a way to insert yeast and plant genes into E. coli bacteria that will produce a precursor to artemisinin; now, they have achieved the critical step of identifying the enzyme that can convert that precursor into artemisinic acid, which can be chemically synthesized into the drug. Currently, a course of treatment costs $2.40 due to a long and expensive manufacturing process that relies on extracting the active ingredient from the wormwood plant. By reducing the costs of production, this discovery has the potential to slash the price of treatment to less than 25 cents within just a few years.
While this is an unequivally exciting and important milestone in increasing access to malarial treatment in the developing world, it also poses a new set of challenges to the global health community. As the price of ACTs falls and adoption rises, drug resistance is almost certain to follow. As Ramanan Laxminarayan, Mead Over and David Smith have shown in their economic analysis of a potential global subsidy for antimalarials, effective price has a huge impact on the rate of resistance over time (which varies immensely under different financing scenarios). The market implications of this scientific breakthrough suggest that more research should be done on this front.
In general, the reaction to resistance is simply to develop more and newer products to replace those that have been rendered ineffective. But in the case of malaria, there are no obvious 'next line' drugs on the development horizon if the parasite becomes resistant to artemisinin. Now the health community needs to begin shifting its focus to find ways to make the existing drugs last longer through proper usage. The TB community has already begun to address this issue with the adoption of Directly Observed Treatment Short-Course (DOTS) strategy to ensure that patients take their medication correctly; another approach is to increase the use of diagnostics so that only infected individuals are receiving treatment in the first place (which is a particular problem given the frequent overdiagnosis of malaria). If we will soon be treating malaria for pennies in the short term, we should not let it come at a higher long-term cost.