How Much Is That Molecule in the Window?

Note: This article appeared in the fall 2010 Quadrangle Magazine (see pdf version)

The Science and Ethics of Creating Synthetic Molecules

by Hal Jacobs

In May, genetic pioneer and entrepreneur Craig Venter made headlines worldwide when he proclaimed (most scientists report, Venter proclaims) the existence of the “first self-replicating cell we’ve had on the planet whose parent is a computer.”

It’s “a new era in biology,” wrote the Wall Street Journal. “This invention and others like it in the field of synthetic life could rival or surpass the invention of the internal combustion engine, or the microchip,” said Fortune.

A bioethicist in Nature said the discovery was “likely to prove as momentous to our view of ourselves and our place in the universe as the discoveries of Galileo, Copernicus, Darwin, and Einstein.”

As a result of the attention, President Obama asked the Presidential Commission for the Study of Bioethical Issues, with Emory President James Wagner as vice chair, to focus on synthetic biology. Among the first experts to speak at a commission hearing was Paul Wolpe, director of the Emory Center for Ethics, who delivered a thoughtful talk on science, religion and the ways they inform one another.

It’s only fitting that Emory have a seat at the table for such an important conversation. Chemists and biologists here are recognized nationally for their research and work with students. Informed by collaborations with ethicists, social scientists, artists and others, Emory scientists are at the forefront of a field that is rapidly making advances into uncharted territory.

Not Your Grandfather’s Molecules

From where David Lynn sits, Venter’s discovery was more of a technological feat than a major turning point in history. “The press picked it up because it involved synthetic life,” says Lynn, Asa Griggs Candler Professor of Chemistry and Biology.

“But scientists have been moving genes from one organism to another for decades. What Venter did was make a whole genome, with all the components and all the information, and then move it into an existing bacterium.” Lynn smiles. “It was a testosterone-based show of technology.”

Because of the discovery and the work that Lynn and others are doing, however, we can expect to see the pace of evolution accelerate. What might have taken thousands of years to change in the ecosystem may take months in the laboratory. Lynn’s research group looks at the mechanics of how life works: the structures and forces that enable molecules to assemble, and how chemical information can be stored and translated into new molecular entities. His lab is one of fifteen sharing a $20 million grant from the National Science Foundation and the National Aeronautics and Space Administration to see how the forces of evolution can be harnessed to new structures and functions.

Lynn collaborates with other leading researchers at Emory like Ichiro Matsuma, associate professor of biochemistry, whose group applies the new tools of synthetic biology to longstanding questions about how complex systems such as proteins and cells originate and evolve.

Thousands of years ago, humans selectively bred horses and dogs in order to benefit from certain traits they found useful. Now scientists like Matsuma are studying how we can manipulate proteins and cells—he calls them “sophisticated nano-scale machines”—to benefit humans by, say, creating cost-effective, environmentally friendly biofuels. Or by re-tooling bacteria so that it can be turned loose in a cornfield to clean up toxic herbicides.

That’s exactly what Justin Gallivan, associate professor of biomolecular chemistry, has done. He leads a research group that is reprogramming existing bacteria to chase down atrazine and render it nontoxic. He’s also working on bacteria that can function like smoke detectors in tracking down “bad stuff” in drinking water or in buildings. In the near future, research like Gallivan’s may lead to an oil-eating microbe that could be used to combat the kind of spill we saw in the Gulf of Mexico this summer.

Thanks to Venter’s technological tour de force, Gallivan believes it may not be long before it will be cost-effective for his group and others to use synthetic genomes rather than reprogramming existing organisms.

The modern pharmaceutical industry testifies to the power of chemistry to synthesize drugs rather than produce everything from nature. Chemists Dennis Liotta and Huw Davies have made substantial contributions in this area while coming at it from different directions.

Liotta, a professor of organic chemistry at Emory for more than 30 years, has worked on several important antiviral drugs, including Emtriva, which made headlines in 2005 when it brought $540 million in royalty sales to Emory and its inventors. He is currently testing a synthetic equivalent of curcumin, which is found in turmeric and gives curry its yellow coloring.

Liotta first became intrigued by turmeric after hearing stories of its long history as a folk medicine in India. He heard stories from friends whose mothers gave it to them in their milk for an upset stomach. After closer study, he found that curcumin has properties that make it effective as an antioxidant and anti-inflammatory. The only downside is that for it to be really effective, you would need to take an enormous amount.

“Imagine twelve horse pills a day,” Liotta says. With a synthetic version, Liotta can fine-tune it for better results. He’s just begun early-stage clinical trials to measure its effects on human subjects for the first time.

Liotta’s research in drug discovery is complemented by the drug development program at Emory directed by Davies, who joined Emory in 2008 as Asa Griggs Candler Professor of Organic Chemistry. Davies’ group uses chemical synthesis to create the tools necessary to develop cost-effective medications. Students and postdoctoral fellows in his lab are speeding up and simplifying the synthesis of new classes of pharmaceuticals, bringing down the costs.

“We’re developing more efficient ways of cooking,” Davies says. “By finding new ways to streamline the production of chemicals and drugs, we’re able to make compounds in the laboratory that have never been made before. We can also make them in easier, safer and more environmentally friendly ways.”

He sees these new techniques as underpinning future technology and economic development. The National Science Foundation agrees: last year it awarded him $1.5 million to lead a team of scientists from four universities to develop a Center for Chemical Innovation.

The next source for new molecules might be the next galaxy. Susanna Widicus Weaver, assistant professor of chemistry, heads one of the few labs in the world that can identify (with a little help from NASA and the latest generation of high-tech observatories) molecules located in other galaxies. She and her students create new ways to make “little unstable molecules that you can’t buy in a bottle,” then look for those molecules in space. It’s like trying to match fingerprints from millions of miles away.

Her group is at the far end of the spectrum from the other Emory chemists. While they look at large, complex molecules, she looks at the building blocks that went into forming those molecules on earth. “We’re trying to get an idea what could’ve been around our neighborhood in the solar system when earth was forming, and what might’ve been delivered to earth from comets and other forces.”

Physics plays an important role in synthetic biology as well. For example, Ilya Nemenman, associate professor of physics and biology, analyzes (theoretically and computationally) the function of various natural, constructed, and proposed biological designs. Earlier this year he and several colleagues identified a way to neatly distill the entire behavior of complex biological systems to a few simple features. Simplifying the representation of biochemical systems “from about 3,000 steps to three steps,” Nemenman says, may shed light on the processes of immune cells and streamline the development of drugs and diagnostic tools.

Who’s Minding the Store?

How should we think about technology that re-creates us? How do we handle sped-up evolution and the possible impact on the environment? How do we slow things down to allow for reflection or guideposts?

At the Presidential Commission, Paul Wolpe raised these and other ethical issues related to synthetic biology. In conversations at Emory, scientists often mention the safeguards being used to prevent synthetic organisms from spinning out of control. They also bring up the point that all technology has the potential for good and bad.

“Synthetic biology isn’t new, but the pace of ethical conversations hasn’t kept pace with technological innovations,” says Arri Eisen, a senior lecturer in biology for Emory’s Center for Ethics and co-editor of Science, Religion, and Society: History, Cultures, and Controversies. “Ironically, evolution hasn’t prepared us cognitively for such rapid changes.”

This technology will force us to ask basic questions that humans have always dealt with, and that’s not a bad thing, Eisen says. What does it mean to be human? If life is sacred or defined by the rules of sentience as the Buddhists believe, then what happens when that life is created by man in the laboratory instead of by nature or God?

These questions are spilling over into a project that Deboleena Roy, associate professor of women’s studies and neuroscience and behavioral biology, is collaborating on with the help of Eisen, Matsuma and others. The project seeks to examine the bioethical implications of synthetic biology before the field takes off, not after.

“The idea is that stakeholders such as scientists, pharmaceuticals and politicians are not the only interested parties when it comes to the development of synthetic biology,” Roy says. “Rather than developing the technology first, and then seeing how the non-traditional stakeholders react, this model takes seriously the task of incorporating their concerns in the process of developing the field of synthetic biology in the first place.”

Concerns and problems are sure to arise. When David Lynn is asked how to address these issues, he is quiet for a moment, then says, “We are going to make mistakes. But the more we educate others the better we’ll be able to deal with mistakes.

“You can’t put restrictions on gaining new knowledge. The only advantage humans have in terms of competing with biology is using our brains.”


Astrochemist Weaver wins deep space time

Emory astrochemist Susanna Widicus Weaver will soon begin one of the first broad spectral surveys of small organic molecules in deep space. Her lab’s research proposal – to search for the raw materials of life in star-forming regions – recently won 42 hours of observing time on the Herschel Space Observatory.

Read more at eScienceCommons