LIFE FROM SCRATCH? Scientists concoct longest strand of synthetic DNA to date
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Scientists today announced that they have crafted a bacterial genome from scratch, moving one step closer to creating entirely synthetic life forms--living cells designed and built by humans to carry out a diverse set of tasks ranging from manufacturing biofuels to sequestering carbon dioxide.
Researchers at the J. Craig Venter Institute (JCVI) in Rockville, Md., report in the online edition of Science that they pieced together the genes of Mycoplasma genitalium, the smallest free-living bacterium that can be grown in the laboratory and a common culprit in urinary tract infections.
"The 582,970 base pair M. genitalium bacterial genome is the largest chemically defined structure synthesized in the lab," lead author Daniel Gibson told ScientificAmerican.com via e-mail. (Base pairs are complementary linked nucleotide bases, such as adenine–thymine.)
"It's the first time a genome the size of a bacterium has chemically been synthesized that's about 20 times longer than [any DNA molecule] synthesized before," adds Christopher Voigt, an assistant professor of bioengineering at the University of California, San Francisco, who was not involved in the study.
The research team, led by Nobel laureate Hamilton Smith, ordered short strands of genetic code from commercial DNA synthesis companies in the U.S. and Germany and stitched them into longer and longer strands using standard molecular biology techniques. To assemble the largest pieces of DNA, they inserted them into yeast cells and exploited a natural process called "homologous recombination," which is used by yeast to repair damaged DNA. The experiment's final product is equivalent to the naturally occurring genetic code of M. genitalium, with two minor exceptions: The scientists disabled the gene that gave the bug power to infect human cells, and they added a few "watermarks," short strips of signature genetic code that identify the product as man-made.
"This completes the second step of a three-step process in creating a synthetic organism," Gibson says. The first step came last summer when JCVI scientists transformed one species of bacteria into another with a DNA transplant, switching the identity of one bug by impregnating it with another's genetic code. The second step, constructing a synthetic bacterial genome, has now been accomplished with this study. The final step will involve inserting the synthetic genome into a cell and bringing it to life; Gibson says experiments with this goal are currently underway.
"We want to emphasize that we have not yet booted up the synthetic chromosome," JCVI founder Craig Venter said in a conference call with journalists this morning. There are multiple steps that must be overcome, the biologist explained, but "we are confident that they can be overcome."
"The ultimate step is proving what they have synthesized is biologically active," says Eckard Wimmer, a molecular biologist at Stony Brook University in Long Island, N.Y., who led the effort to construct synthetic polio, the first synthetically built virus. "Unfortunately, this very critical point is missing here."
If the researchers succeed in creating their synthetic bacteria, they will be closer to conceiving artificial creatures that could be used to mitigate some of society's greatest problems, among them climate change and overdependence on fossil fuels. Venter's team belongs to a cadre of scientists practicing synthetic biology, a burgeoning discipline that aims to design and build living things from the raw materials of life (organic chemicals) and nature's blueprints (genetic codes). Synthetic biologists also draw up their own blueprints, designing genetic sequences that nature never fathomed; the idea is to create novel functions for living things. Man-made microbes that manufacture pharmaceuticals, crank out cheap biofuels, mop up pollutants and oil spills or invade and destroy cancer cells may be just a decade or two away.
Venter's group is trying to create a completely synthetic bare-bones version of M. genitalium with a genome stripped of all but the most vital genes. The goal is to use this organism as chassis into which new genes can be added--perhaps ones that would give the germ the ability to spin silk, detect toxins or manufacture drugs. The possibilities seem endless, albeit not all rosy.
Critics have pointed out that the same synthetic biology know-how and technologies could be used by terrorists or rogue states to engineer a bacterium that churns out a neurotoxin or, perhaps, a deadly flu virus with resistance to vaccines and antiviral medications. Leaders in the field recognize the potential for misuse, both accidental and intentional, and have begun to address the issue. In October, members of JCVI, the Center for Strategic & International Studies and the Massachusetts Institute of Technology released a report offering policy options for oversight, and several leading synthetic biologists have published papers on the matter in peer-reviewed journals.
Looking at potential applications, not everyone agrees on the best strategy for manufacturing these promising organisms. The sleekest bug is not necessarily the best, points out George Church, a geneticist at the Harvard Medical School in Cambridge, Mass., and director of the Lipper Center for Computational Genetics. "Simplicity is overrated. E. Coli, with all its so-called junk DNA, is way more efficient than Mycoplasma," he says, noting that E. Coli's genome is about eight times bigger but grows about 50 times faster.
A company called LS9, Inc., in San Carlos, Calif., has already taken advantage of E. coli’s productivity, engineering the bug to churn out DesignerBiofuels, "a family of fuels that has properties indistinguishable from those of gasoline, diesel, and jet fuel," according to the company's Web site. Instead of rebuilding E. Coli from scratch, LS9 has taken the organism from nature and modified it by inserting fragments of synthetic DNA, an approach that, Church notes, is much less costly and easy to scale up for industrial purposes.
Regardless of what approach yields the most return, synthetic biology is, no doubt, racing forward. In the last few years DNA synthesis techniques have become faster, cheaper and accessible to more people. Ordering DNA from commercial outfits has become as easy as ordering pizza, according to Voigt, who projects that in upcoming decades scientists will be able to whip up much larger segments of DNA: synthetic genomes for yeast, animals--perhaps even humans.
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10 Comments
Add CommentThis article is just the kind SciAm will print in its 50, 100 and 150 years ago section. I wonder what it will sound like then.
Reply | Report Abuse | Link to thisGod is the Creator. GOD created man as His vicegerent. As a vicegerent man is expected to acquire all powers to carry out God's wish.
Reply | Report Abuse | Link to thisSo we are confident that mankind would indeed succeed in creating new life forms. What needs to be borne in mind is that man cannot - should not - compete with God. That is man should not aim to produce life forms that would override mankind and evolve into independent species consuming the resources of the universe and denying mankind the right of existence.
In the event such species emerge - by intentional design or by accident - that event would indicate the start of "the end of the universe" - the Day of Judgment expected by Muslims.
We hope computer simulation of large interacting populations would help mankind avoid the possibility of creating artificial life forms that would eliminate mankind.
By that we are assigning a major responsibility to Computer Scientists.
With the rapid advancement of scientific learning, it is not surprising to learn that life can now be created in a test tube. It is now time for our bible thumping pals and not such intelligent intelligent design disciples to get out their red pencils and begin to either significantly alter or better yet discard Genesis entirely.
Reply | Report Abuse | Link to thisSome people think that the formation of a living organism in the laboratory would disprove the idea that God created life. Not so. Making life in a test tube would prove that great intelligence and vast resources are necessary for the production of life. John LaShell
Reply | Report Abuse | Link to thisThe speculation of how we came to be is useless... there is no point to understanding why. All we can do is learn as much as we can about what is so that we may research the possibilities of what may be. We used to create all powerful deities to explain the unexplainable... now we just figure it out through researching what is. "GOD" is a redundant term.
Reply | Report Abuse | Link to thisNot to get off the subject ,but where is the story on the hybrid polar/grizzle bear? This is much more important than anyone, except me ,realizes! The bear,half breed, represents the evolution of the polar to a more adapted position in it 's environment-I mean as the polar bears ice pack hunting environment vanishes via earth heating up , the polar bear females start breeding with the grizzle bears so the off spring are more adapted to the land type hunting that is characteristic to the grizzle bear. gunondeer
Reply | Report Abuse | Link to thisThis is on par with the discovery of electromagnetism. If you combine this advance with Moores's Law the exponential development of this area of science over the next 5 to 10 years will be astounding. The implications are like nothing human beings have ever faced....well, yes they did. It was call Aushwitz.
Reply | Report Abuse | Link to thisAmazing how quickly some who read an article like this are to dismiss God as a result. The article starts, "Scientists today announced that they have crafted a bacterial genome from scratch." But "scratch" is later explained as "the research team, led by Nobel laureate Hamilton Smith, ordered short strands of genetic code from commercial DNA synthesis companies in the U.S. and Germany." So saying that they crafted the bacterial genome from scratch is like saying that I made home-made biscuits from scratch. Well, I had the recipe [template], the ingredients [short strands of genetic code - and have you seen how many processes go into making those?], the oven [controlled heat necessary to make the strands of genetic code], the kitchen [laboratory], and I was the baker [scientists]. And some how that proves there was not a designer? Leave flour, shortening, milk, salt, and baking powder on your kitchen counter next to a warm oven for say 100,000,000 years and come back to see how your bisquits are doing!
Reply | Report Abuse | Link to thisanybody looking at or discussing the ethics or ecologic impact of synthetic organisms?
Reply | Report Abuse | Link to thisWhat you fail to comprehend is that scientists have created DNA. No human off branched species has been made. This is simply a component of Genetic Engineering research that could, one day, cure genetic diseases, and possibly bacterial diseases, as well as allowing the food industry to become more efficient and productive. I do not think God would mind if we saved lives or took care of the planet. It is not necessary to speculate that scientists will take advantage of the research to make a sub-human species, simply because they have recreated DNA; it is possible to use recombinant gene technology to grow organs (rendering transplants unnecessary) with synthetic human DNA. Again, we aren't making another human.
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