Engineering Biology for Drugs and Fuels

I'M GOING TO TALK about plug-and-play biology. And I'm g oing to first introduce it by talking about a problem, a problem many of you may know about. It's malaria. It actually affects about Ia quarter of the world's population; 2.4 billion people are at risk of getting malaria at any one time; between 300 and 500 million people have the disease, and every year between one and three million people die of the disease. Ninety percent are children under the age of five.And of those countries most affected by malaria, economists have noted that it reduces their GDP by roughly half. So it's a hugely debilitating disease. The drugs that are currently available are based largely on quinine. Quinine has been around for four hundred years; wars were fought for access to quinine. And it's been so widely used and abused that Plasmodium, which causes malaria, has grown resistant to it. So, widely available, inexpensive, and no longer effective.This is artemisinin (fig. 1). It comes from this plant Artemisia annua and it's a miracle cure, really, for malaria. It's been around for literally centuries. It was discovered in about 168 BC by the Chinese. There are some writings about its use, first for treating hemorrhoids and later for treating fevers. It was largely forgotten until the 1960s, when the Chinese were fighting in Vietnam and they needed a cure for the severe malaria there. They went back to their literature; they purified the active ingredient, and the rest is history.Now, here's how we get artemisinin. It's actually produced by this plant Artemisia annua in sacs called trichomes on the surface of the leaves. So there are basal cells in these trichomes and they push this oil, this artemisinin, up into these bags, and when you rub the leaf, you actually get it off.Now we get artemisinin from farmers who grow plants. There are a lot of plantations, primarily in Southeast Asia, where they grow the plant. They then purify it, from the plant; they purify it using the only solvent they have available-gasoline. There's a big problem. A few years ago when they were using leaded gasoline, the lead was contaminating the artemisinin supply, and then that's sold to the farmer for conversion into the various derivatives that are currently in use for treating malaria. Artesanate looks like it's going to be the best derivative of artemisinin because it's water soluble and it can be formulated in IVs.In 2005 the World Health Organization recommended artemisinin combination therapies as the drug of choice for treating malaria. These bars here (fig. 2) show artemisinin combination therapies delivered over that period. You can see there's a huge ramp-up primarily around 2006 and 2007. It takes about eighteen months to two years to get seeds in the field and artemisinin delivered to the farmers, so you need a very long lag time.Now here's where we project the demand will go. This is largely due to the Gates Foundation, the Clinton Global Fund, and the World Bank's making these drugs available. So there's going to be a huge demand for them. We're going to need on the order of 300 million treatments every year for malaria.Now when artemisinin was recommended as the drug of choice for treating malaria in 2005, the price spiked. This is one of the severe problems with artemisinin: the price fluctuates while there is an open market.So the price spiked and farmers started planting it like crazy, and that is shown right here (fig. 3). By 2007 there was a huge over-supply of artemisinin. What happened? They stopped planting it. The price of food went up, and they are no longer planting artemisinin. You can see that the prices are sitting down here because we have this over-supply, but the problem is that we're living on that over-supply from 2007.And guess what? Next year that supply runs out. And in fact we have a deficit. And if you look forward, there's going to be a huge u nder-supply by about 250 million treatments, which means the prices are going to go back up. …