Drug resistance, Berkeley, and the biobuckaroos

By Richard Brenneman, cross-posted from Eats Shoots ‘n Leaves

2012 April 7 – When Bill Gates bankrolled UC Berkelely “bioengineer” Jay Keasling to launch corporate genetic engineering firm Amyris, Gates’s professed goal was the creation of a cheap antimalarial drug to replace the plant derivative armtemisin.

Produced from the wormwood plant Artemisia, the drug is the most widely used compound to clear the body of the parasite which causes the devastating tropical killer.

Gates and Amyris founder Jay Keasling announced they would create the drug from a genetically tweaked intestinal microbe, producing a product that would radically reduce the price to consumers in Africa and Asia.

By the time they had turned over the process to pharmaceutical giant Sanofi-Aventis for non-profit commercial production, any thought of “cheaper” had vanished. The chemical will sell for the same price as the naturally derived product, while potentially devastating the lives of peasant farmers who currently produce enough of the crop to meet all current needs.

But the Big Pharma player would get access to more markets, and their representatives could peddle other for-profit drugs — a win for Sanofi-Aventis, but a loss for thousands of peasant farmers.

Amyris went on to repurpose itself as an agrofuel company, partnering with French oil giant Total to launch pilot programs in Brazil, where sugar cane is the feedstock of choice — a crop that relies of massive land-clearing efforts, including newly designated sites in the Amazon rain forest.

While Keasling promised that “scaling up” programs from the realm of the experimental to full-scale refineries wouldn’t be a problem, reality intervened, and production plans have been, er, scaled down, leaving the company for now in the role of a supplier of chemicals to the cosmetics industry while Amyris stock has plunged from a high of $33.85 last year to as low as $4 on Thursday.

And now comes word of an alarming development that could be bad news both for the Amyris not-so-cheap artmesinin as well as for the Third World’s wormwood farmers.

Resistance discovered in Southeast Asia

A new study by a team of medical scientists from Thailand, Britain, and the United States just published in The Lancet, Britain’s premiere medical journal, reports that strains of Plasmodium falciparum — the parasite responsible for the ravages of malaria — have emerged in Cambodia and are spreading to Western Thailand and Myanmar.

To quote from the report’s conclusion:

Genetically determined artemisinin resistance in P falciparum emerged along the Thailand—Myanmar border at least 8 years ago and has since increased substantially. At this rate of increase, resistance will reach rates reported in western Cambodia in 2—6 years.

The World Health Organization reported on the emergence of resistance two years ago:

“If we do not put a stop to the drug-resistant malaria situation that has been documented in the Thai-Cambodia border, it could spread rapidly to neighbouring countries and threaten our efforts to control this deadly disease,” said Dr Hiroki Nakatani, Assistant Director-General of WHO.

Resistance along the Thai-Cambodia border started with chloroquine, followed by resistance to sulfadoxine-pyrimethamine and mefloquine, drugs used in malaria control several years ago.

Malaria poses a risk to half of the world’s population and more than one million people die of the disease each year. The malaria map, or the area where it is prevalent, has been reduced considerably over the past 50 years, but the disease has defied elimination in areas of intense transmission.

Bryan Walsh of Time has more on the latest developments:

In another study published in Science, researchers at Texas Biomed and their colleagues managed to get close to isolating the genes in the malaria parasite that convey resistance to artemisinin. That will help scientists understand how artemisinin interacts with the parasite, and how resistance takes place over time. In the future, it may even offer clues on how to alter treatment to cancel out resistance — to adapt to the parasite’s adaptation. “Mapping the geographical spread of resistance can be particularly challenging using existing clinical and parasitological tools,” Texas Biomed’s Dr. Tim Anderson said in a statement. “If we can identify the genetic determinants of artemisinin resistance, we should be able to confirm potential cases of resistance more rapidly. This could be critically importing for limiting further spread of resistance.”

Drug resistance is inevitable — the more a treatment is used, the faster resistance will often develop, and the fact is that there are some 250 million cases of malaria a year. The only hope is to try to root out resistant-malaria where it occurs, and stop the chain of resistant transmission. That was hard enough in Cambodia, but with drug-resistant malaria spreading to Thailand and likely Burma as well — a desperately poor nation with a threadbare medical system — it will only get tougher. And if resistant malaria spreads to Africa, where the disease is still a catastrophe, perhaps millions more could die, as Francois Nosten of the Shoklo Malaria Research Unit in Thailand put it:

We are in a race against time to control malaria in these regions before drug resistance worsens and develops and spreads further. The effect of that happening could be devastating. Malaria already kills hundreds of thousands of people a year — if our drugs become ineffective, this figure will rise dramatically.

Read the rest.

So what’s the takeaway?

One clear conclusion from all this is that the panglossian pronouncements of the “bioengineers” and their financial backers must always be taken with a grain or ten of sodium chloride.

Consider this from Jay Keasling, reported by Megan Molteni in Richmond Confidential:

Keasling’s lab recently used yeast that would normally produce ethanol (like the yeast used in beer brewing) and engineered it to instead produce artemisinin—an effective anti-malarial drug currently produced from expensive plant sources. Through partnerships and licensing agreements with drug and chemical companies Sanofi-Aventis and Amyris, Keasling said more than 100 million people per year will get access to the drug that otherwise wouldn’t have it available.

A hundred million people who don’t have access?

While supply and demand of artemisin are almost equally matched at the moment, the price of the drug has been falling, which is one reason higher than predicted costs for the Amyris-created product won’t have any impact on the consumer but could have devastating impacts on farmers.

A2S2, the Assured Amyris Supply System, was created specifically to support the farming system which still produces all the world’s supply of the drug to ensure that current needs are met.

Bill Gates, the sugar daddy behind Amyris, is also a major player in the agrofuels industry — and had major holdings in another company which has partnered with another enterprise founded by Keasling, the Joint BioEnergy Institute [JBEI], created by the Department of Energy and run by UC Berkeley in partnership with a joint partnership of UC Berkeley with Lawrence Berkeley, Lawrence Livermore, and Sandia national laboratories and the Carnegie Institute.

Pacific Ethanol is a corporate partner of of JBEI, and Gates held 20 percent of the stock in the Sacramento-based ethanol refiner until the shares tanked in 2008.

Gates hasn’t bought into Amyris since the stock went public. Perhaps he learned something.

JBEI continues to run at full steam, but its venue would change from its current location in Emeryville [upstairs from the headquarters of Amyris] to the new Lawrence Berkeley National Laboratory billion-dollar-plus complex in nearby Richmond if the lab wins approval at the site — which has a century-long history of contamination by toxic industrial waste, another subject we reported on extensively back in our days with the Berkeley Daily Planet.

Oh, and by the way, UC Berkeley fought a successful call by the Richmond City Council for oversight of the toxic waste cleanup of the site by the state Department of Toxic Substances Control.

 

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