Saturday, October 25, 2014
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Understanding the Frankenstein Tradition

PALO ALTO – “It’s alive, it’s moving, it’s alive... IT’S ALIVE!” So said Dr. Victor Frankenstein when his “creation” was complete. Researchers have long been fascinated with trying to create life, but mainly they have had to settle for crafting variations of living organisms via mutation or other techniques of genetic engineering.amp#160;

In May, researchers at the J. Craig Venter Institute, led by Venter himself, synthesized the genome of a bacterium from scratch using chemical building blocks, and inserted it into the cell of a different variety of bacteria. The new genetic information “rebooted” its host cell and got it to function, replicate, and take on the characteristics of the “donor.” In other words, a sort of synthetic organism had been created.

Reactions in the scientific community ranged from “slight novelty” to “looming apocalypse.” The former is more apt: Venter’s creation is evolutionary, not revolutionary.

The goal of “synthetic biology,” as the field is known, is to move microbiology and cell biology closer to the approach of engineering, so that standardized parts can be mixed, matched, and assembled – just as off-the-shelf chassis, engines, transmissions, and so on can be combined to build a hot-rod.

Achieving this goal could offer scientists unprecedented opportunities for innovation, and better enable them to craft bespoke microorganisms and plants that produce pharmaceuticals, clean up toxic wastes, and obtain (or “fix”) nitrogen from the air (obviating the need for chemical fertilizers).

During the past half-century, genetic engineers, using increasingly powerful and precise tools and resources, have achieved breakthroughs that are opening up new opportunities in a broad array of fields. The Venter lab’s achievement builds on similar work that began decades ago.amp#160; In 1967, a research group from Stanford Medical School and Caltech demonstrated the infectiousness of the genome of a bacterial virus called ΦΧ174, whose DNA had been synthesized with an enzyme using the intact viral DNA as a template, or blueprint. That feat was hailed as “life in a test tube.”

In 2002, a research group at the State University of New York, Stony Brook, created a functional, infectious poliovirus solely from basic, off-the-shelf chemical building blocks.amp#160;Their only blueprint for engineering the genome was the known sequence of RNA (which comprises the viral genome and is chemically very similar to DNA). Similar to the 1967 experiments, the infectious RNA was synthesized enzymatically. It was able to direct the synthesis of viral proteins in the absence of a natural template. Once again, scientists had, in effect, created life in a test tube.

Venter’s group did much the same thing in the recently reported research, except that they used chemical synthesis instead of enzymes to make the DNA. But some of the hype that surrounded the publication of the ensuing article in the journal Nature was disproportionate.amp#160;

Along with the Venter paper, Nature published eight commentaries on the significance of the work. The “real” scientists were aware of the incremental nature of the work, and questioned whether the Venter group had created a genuine “synthetic cell,” while the social scientists tended to exaggerate the implications of the work.

Mark Bedau, a professor of philosophy at Reed College, wrote that the technology’s “new powers create new responsibilities. Nobody can be sure about the consequences of making new forms of life, and we must expect the unexpected and the unintended. This calls for fundamental innovations in precautionary thinking and risk analysis.”

But, with increasing sophistication, genetic engineers using old and new techniques have been creating organisms with novel or enhanced properties for decades. Regulations and standards of good practice already effectively address organisms that may be pathogenic or that threaten the natural environment. (If anything, these standards are excessively burdensome.)

On the other hand, Swiss bioengineer Martin Fussenegger correctly observed that the Venter achievement “is a technical advance, not a conceptual one.” Other scientists noted that the organism is really only “semi-synthetic,” because the synthetic DNA (which comprises only about 1% of the dry weight of the cell) was introduced into a normal, or non-synthetic, bacterium.

Understanding the history of synthetic biology is important, because recognizing the correct paradigm has critical implications for how governments regulate it, which in turn affects the potential application and diffusion of the technology. Thirty-five years ago, the US National Institutes of Health adopted overly risk-averse guidelines for research using recombinant DNA, or “genetic engineering,” techniques. Those guidelines, based on what has proved to be an idiosyncratic and largely invalid set of assumptions, sent a powerful message that scientists and the federal government were taking seriously speculative, exaggerated risk scenarios – a message that has afflicted the technology’s development worldwide ever since.

Synthetic biology offers the prospect of powerful new tools for research and development in innumerable fields. But its potential can be fulfilled only if regulatory oversight is based on science, sound risk analysis, and an appreciation of the mistakes of history.

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