One of the Nobel Prize winners at The Scripps Research Institute in San Diego has been saying for a decade that chemists would be better off doing the simple thing instead of the hard thing. Now quite a few of the world’s top academic scientists and Big Pharma companies are starting to adopt K. Barry Sharpless‘ philosophy of “click chemistry.”
This is the concept that Sharpless has been advocating a long time, along with a couple like-minded faculty members at Scripps, MG Finn and Valery Fokin. I met with Sharpless, Finn and Scripps’ tech transfer leader, Scott Forrest, a few weeks ago to talk about the boom they are seeing in scientific publications, patents, and some new technology licenses that are taking advantage of “click chemistry” principles.
What’s the big idea? It’s about using small chemical building blocks that you put in water or some other solvent, until they naturally “click” together. Sort of like a plastic buckle on a backpack, these molecules join together in the easiest, cheapest, most reliable, and most durable reactions possible, according to the laws of Mother Nature. These are fundamental reactions that tightly bind molecules together and could be useful as oral pills, industrial adhesives, stable coatings for implantable medical devices, or any number of valuable products. It sounds simple, and Sharpless and Finn say it is. What’s surprising is how strange it might appear to the modern lab with its state-of-the-art tools and its efforts to constantly strive for the leading edge and peer approval that goes with it.
Sharpless has been applying this idea for about 20 years, but he says he was really inspired by Kevin Kelly’s 1995 book “Out of Control.” Kelly, the founding editor of Wired, wrote that scientists should recognize they’re playing “God games.” In the case of a chemist, he or she is trying to do things that are more complicated any human can fully understand, so they should listen carefully to what Mother Nature says. It’s a more humble approach than what you often see in pharmaland.
“We are going toward an unknown target. Even if we think we know the target, we say we know what’s best. That was big-scale hubris. It’s like Cinderella and her sisters, with a shoehorn. Our intellect is saying we can shoehorn what we say works into the shoe. It’s not close to the truth,” Sharpless says. “If you want to be God, you have to allow your objects to have free will. You have to relinquish control.”
Instead of trying to do things the way nature wants, chemistry and other fields of science are really more of a game of “hey, can you top this?” to hear Finn and Sharpless describe it. The click philosophy, they say, strikes a lot of peers as mundane.
“We are trained as most experts to do the hardest things and do them well. That’s how you get praise and learn,” Finn says. “You want to do the hardest chemical reactions and make them work. It’s weird to say ‘We’re not going to do the hardest reactions.’ We’re going to find or create the easiest reactions.’ But if you think about it, it’s a lot harder to invent a process that works all the time, than it is to make the process that’s really difficult work a few times.”
Yet more and more scientists and companies are seeking to apply the click philosophy. One example is Seattle-based Integrated Diagnostics, a company co-founded by Leroy Hood of the Institute for Systems Biology and Caltech’s Jim Heath. Their idea is to create a diagnostic tool that can perform binding reactions cheaply and reliably enough to usher in an era in which physicians will be able to spot proteins that are early warning signs of cancer or neurodegenerative diseases in a pinprick of blood.
Hood loves to tell the story about how the prototype, and the tight binding reactions it performs inside, were rugged enough to produce reliable results even when Heath left the machine in the truck of his car near Caltech in Pasadena, CA.
That’s just one example. Carlsbad, CA-based Life Technologies (NASDAQ: [[ticker:LIFE]]) markets a kit that performs a click reaction to take quantitative measures of DNA in cells, Finn says. Tampa, FL-based Intezyne, whom Finn advises, is using the click principles to attach polymers to drug candidates in a cheap, strong, consistent way to make chemotherapies active only inside tumors, not other tissues where they cause side effects. Hundreds of drug candidates that use the principle are now working their way
