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From Ambitions To Markets: Richard Kitney And More Synthetic Bio Views

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to mate with females and pass along a gene that causes the offspring to die as larvae. Trials have shown a sharp reduction in the dengue-carrying mosquito population, but as a Brazilian researcher in this article pointed out, a reduction of mosquitoes doesn’t necessarily equal a reduction of transmission.

An even more powerful mosquito “product” could soon be here, via an extremely controversial technique called gene drive, making a genetic trait of one organism heritable by its offspring all the time, not just half the time—and now possible using the CRISPR-Cas9 gene editing system.

Stanford bioethicist Hank Greely generally resides on the laissez-faire end of the spectrum regarding altering the human genome. But as he described at Xconomy’s biotech forum last month, gene drive—with the power to sweep unalterable genomic changes through a broad population of a species—keeps him up at night, even if those changes are meant to do good, like creating mosquitoes that don’t transmit malaria. No one has proposed commercializing a gene drive organism yet.

Vanillin

The Swiss firm Evolva has re-engineered yeast to produce a form of vanillin. With that product, Evolva is aiming to compete with the widely used artificial vanilla flavor, not the natural flavor extracted from the vanilla bean. There are environmental and fair-trade concerns, voiced here by Friends of the Earth, many of which are rebutted here by a synthetic biologist at Arizona State University.

Evolva’s synbio vanillin came to market in 2014. Jamie Bacher, CEO of Pareto Biotechnologies in San Francisco, is also trying to create flavors using synthetic biology techniques spun out of the Salk Institute. He said Evolva’s form of vanillin was important to the field “because it started a discussion about the role of synthetic biology in the public and in the general press that is now becoming sophisticated.”

My query returned several other examples, including carpet fiber, pain killers, meat and dairy substitutes, and animal feed ingredients. It also prompted thoughts from synthetic biology leaders on what the field needs most in the coming year and beyond. “Broadly educating the public,” said Twist Bioscience CEO Emily Leproust, citing the challenge of “the small minority who carry an irrational fear of science.”

Bacher said education can come by making products that matter: “We’re past the point where technophiles can just say that this sounds cool. The field has to deliver real innovation.”

Endy, meanwhile, also warned against complacency, but from a different point of view. “We need to keep synthetic biology weird and wonderful,” he said. “The field has been mostly captured over the last eight years by an abundance of boring people and programs. Synthetic biology needs to renew its ambitions and capacities.”

Let’s finish with part two of the conversation with Kitney. (It has been edited for length and clarity.) Part one ended with Kitney saying that the perceived messiness of human biology will eventually come to seem far more rational, broken down into understandable parts—or “modularized,” in engineer speak. “It might take 50 or 100 years, but there’s a wave front moving through,” he said.

Xconomy: Besides artemisinin, where has that wave had an impact so far in human therapeutics?

Dick Kitney: One area to single out is biosensors. We and others have built sensors that do things like detect urinary tract infections. In patients with an in-dwelling catheter, the infection starts to build up on the outside of the catheter, spreads into the bladder, and causes a massive infection. A lot of people in hospital are elderly or frail, and the infection kills them. Sometimes the antibiotics kill them.

To get around this you need a biosensor that detects the infection before it gets into the catheter. The bacteria Pseudomonas aeruginosa like to congregate into a colony by releasing a small signaling molecule called AHL. We figured if you could detect the AHL, you would know the colony is coming together. So we developed a [cell that is a] three-stage biosensor: It detects the AHL, amplifies the signal, and [activates] a fluorescent protein.

It works in a lab. Now we’re starting to seek industrial partners to work out a delivery mechanism. In simple terms you can imagine putting the biosensors in some kind of suspension like shaving foam. You then spray that suspension onto the end of the catheter. If you’ve got infection starting, it would fluoresce green to the human eye. A nurse could spray it on and come back 20 minutes later and wipe clean the catheter.

X: A preventive measure?

DK: Sure, you could do it two or three times a day. It takes about 24 hours for urinary tract infection to develop from the end of the catheter.

We and others are also working on a combination of a biosensor and therapeutic device, looking at liver cancer. You can introduce … Next Page »

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