Jay Keasling is a pioneer
synthetic biology, the process of hacking microbial DNA to produce ultra-low cost fuel and drugs. His talk, in part, is about just how difficult this hacking process is.
In building computers, we can go to Fry’s, buy some components and plug them in together. They work because we’ve got standard connectors, standard protocols. These devices function independently, and we choose to put them together in new configurations.
The same thing, he tells us, is true in the chemical industry. If you want to synthesize styrene, it’s possible to build a factory from “off-the-shelf” evaporators and fermenters, connected with pipes. Those pipes work together because someone took the time to set the pitch on pipe threads, establishing a protocol.
This is not how we manufacture biologicals, unfortunately.
Keasling is interested in manufacturing Artemisinin. Artemisinin is the latest weapon in the battle against malaria, a disease that effects 300 to 500 million people a year, killing 1-3 million of them. 90% of the people the disease kills are children under five years old. The economic impact of malaria is profound – nations effected are estimated to lose up to 50% of their GDP due to productivity losses from the disease.
For 400 years, quinine drugs have been how we combatted malaria. Wars have been fought over quinine supplies, and crazy plans have been put into place to put quinine in table salt. (We’ve settled for putting it in tonic water instead.) But the widespread use of quinine means it’s no longer effective in most of the world. The successor drug, chloroquine, now also experiences widespread resistance.
Artemisinin is a compound that comes from sweet wormwood, or Artemisia Annua, a plan that literally grows like a weed. It’s been used in China from 168 BC to cure hemorrhoids, and since 300AD to cure fevers connected to malaria. It was largely forgotten until the Chinese found themselves involved in Vietnam, and searched their ancient medical literature for malarial treatments.
Artemisinin is incredibly effective against drug-resistant malaria, but it’s not cheap – it might cost $20 for a traveller to malarial areas. In negotiation with manufacturers, some developing nations have gotten access to combination therapies at $1-2.50 per dose, which is still very expensive for a developing world government. There are wild price fluctuations in the product – as growers have seen the market, they control the supply very tightly. And some rogue manufacturers sell artemesinin with little or no active compounds in it.
Keasling’s plan is to destroy the market for fake artemisinin by selling high quality products at the lowest possible cost. This involves synthesizing the drug not via chemical synthesis – which is inefficient and expensive – but by coaxing microbes into growing it. If you have a microbe that can produce the substance, you just feed it sugar and it gives you the drug.
But making that microbe isn’t that easy. You need about 12 genes to make Artemisinin, and about 40 compounds in total to make it possible. You’ve love to go to Fry’s Biologicals and buy what you need, but that’s not how it works. Instead, you write to your colleagues and say, “Hey, I read your paper, please send me your gene.”
Your colleague responds in a couple of weeks, sends you a vial and says, “Please use as described in my paper.” You do, and it doesn’t work. You write him back and say so. He says, “Well, it worked for me. Did you follow my instructions exactly?” It’s not an efficient process. To produce Artemisnin, you need to isolate some genes, model some others mathematically, and learn how to put these genes together without having the genes kill the cells. But his lab is getting much better at doing this, improving seven orders of magnitude in producing this compound in six years. He points out that, if there were the biological Fry’s, it would have taken about six months.
Keasling is now partnering with Amyris Biotech and Institute for OneWorld Health to scale up production, get the drug manufactured and distributed. The most radical aspect of the work is the intellectual property part. These biological components are generally patented, and you need to license each of them – usually for huge fees – to build something out of components. Keasling is patenting his components – defensively – but making them available in an open license. You can use his technology to produce artemisinin on a nonprofit basis, or to produce something that contains artemisnin on a for-profit basis. This is an amazing step forward towards a world in which scientists are able to put components together and produce new solutions without entering into a legal nightmare.
He hopes to have cheap Artemisinin in people’s hands in two years. But some of this other projects are even more impressive. He’s looking at Taxol, a chemical found in the bark of Pacific Yew trees which is an effective cancer drug. The bark of one hundred-year old tree equals one dose, and there are fewer trees in the world than cancer patients. What if we could use biological synthesis to produce Taxol? Or Prostratin, a compound found in the Mamala tree from Samoa, which can be used to treat hepatitis, or to inhibit HIV infection? We could mow down rainforests, or we could synthesize this compound from sugar and microbes.
The holy grail of biological synthesis might be motor fuel. Keasling points out that we’ve increased energy consumption 85% from between 1970 and 1999, and that we’re literally running out of fuel. While it’s exciting that we’re starting to use ethanol – which is basically a process of biological synthesis, using microbes to produce ethanol from sugar – it’s a lousy fuel. “Ethanol is for drinking, not driving.” The chemical kills the microbes that produce it, which means you end up with 85% water and 15% ethanol. And most cars can use only 10% ethanol. What we really want to do is produce oil from microbes and simply skim it off the top of a vat. If Keasling can figure out how to do this, he’s likely to have a lot of money to play with to pursue drugs for all sorts of diseases.
Our morning’s session ends with a talk and performance by musician John Legend. Legend has begun using his music as a platform for social activism, trying to get his fans interested in an issue that he’s focused on: extreme poverty. Legend is trying to support the Millenium Promise Organization – he visited a Millenium Village in Ghana, and has been working since then to “put a face on extreme poverty.”
Legend acknowledges that most of his fans may not know or care about these issues, and that they may not know what to do even if they do care. He just shot a video for a song called “Show Me” in Tanzania – that video should drop in a few weeks and will help expose his fans to the reality of life in a developing world. He’s beginning “The Show Me Campaign”, which is his charitable project to raise awareness for this issue.
Whether or not you’re into Legend’s music – and you have to acknowledge the power of his voice no matter what – and whether or not you think that Jeff Sachs’s Millenium Villages are the right way to address global poverty, it’s incredibly exciting to see a prominent musician using his fame to introduce his fans to critical global issues.
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