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Breakthroughs, Briefly

Matt Van Rooijen

Efficient Eating

Blue whales 
(Balaenoptera musculus) can grow to 100 feet, rostrum to fluke, and weigh more than 150 tons, making them one of the largest creatures ever to have lived on Earth. Scientists have postulated that their unusual manner of feeding—characterized by high-speed lunges with their mouths open, allowing them to take in enormous volumes of prey-laden water—may account for their massive size. "There's no other animal that feeds like it," says Jeremy Goldbogen. "It's thought to be why baleen whales have been able to get so big. They're able to be energetically efficient so they can process and eat a lot . . . in a small amount of time."

To gain a better understanding of how so-called lunge feeding may have evolved, Goldbogen, an assistant professor of biology at Stanford's Hopkins Marine Station, and collaborators from Oregon State, Duke and the Australian Department of the Environment, Antarctic Division, looked to the blue's much smaller cousin, the minke (B. bonaerensis). Using noninvasive, multi-sensor digital tags, the researchers tracked two whales for a combined 27 hours and recorded 2,831 feeding events. Their data showed an inverse relationship between the number of lunges per foraging dive and body size—a minke may ram-feed five to eight times more frequently than a blue or fin whale—which suggests an energetic trade-off.

Poppy Disruption

Currently, the sole source of opiates such as the analgesic morphine, the cough-suppressant codeine, the vasodilator papaverine and the drug precursor thebaine is the poppy Papaver somniferum. Due to the complexity of the chemical reactions involved, commercial-scale synthesis of these molecules is not feasible by traditional means. Thus, the global supply of these medically essential compounds is subject to the vicissitudes of climate, crop pathogens and international trade—to say nothing of the potential for diversion to illicit use as opium or refined heroin. (Worldwide, illegal cultivation of the flowers dwarfs legitimate production by greater than tenfold.)

Christina Smolke envisions a novel alternative. Marshaling the tools of synthetic biology to reprogram common baker's yeast, she hopes to manufacture various opioid drugs from sugars in industrial-sized fermentation vats. As far-fetched as it may sound, in the past decade Smolke, an associate professor of bioengineering, has made significant progress toward that goal.

In the first phase of the project, she and a Caltech collaborator successfully modified the microorganism to produce an intermediate product in the opiate biosynthetic pathway. Now, with Stanford colleagues Kate Thodey, a postdoctoral scholar, and Stephanie Galanie, MS '13, a doctoral student, Smolke has altered yeast, using genes from P. somniferum, to turn thebaine into morphine and codeine. They further demonstrated that the addition of a gene from a bacterium that feeds on dead poppy stalks facilitated the conversion of thebaine into oxycodone and hydrocodone—semi-synthetic drugs sold under the brand names OxyContin and Vicodin.

"We are now very close to replicating the entire opioid production process in a way that eliminates the need to grow poppies, allowing us to reliably manufacture essential medicines while mitigating the potential for diversion to illegal use," says Smolke. However, she acknowledges that it may take several more years to combine the two innovations in a single strain of yeast, fine-tune the process to optimize yield, and scale it up. Ultimately, though, she estimates that a 260-gallon vat could produce as much morphine as a 2.5-acre poppy field.


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