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Abstract
Biologists can take genes from one species and make them part of another, can clone animals, and can even design brand new creatures. But one major achievement still eludes them. No one can take a bunch of chemicals and make a living being. No one can create life from scratch.
| What are the minimum requirements for creating life? |
Several major labs, however, are trying - working to develop pared-down artificial cells in an attempt to understand how life first evolved. These labs include David Bartel's lab in the Department of Biology at MIT, Jack Szostaka's lab at the Howard Hughes Medical Institute in Boston, and David Deamer's group in the Chemistry Department at the University of California at Santa Cruz.
Before the early 1980s, biologists were hard-pressed even to explain how life's power trio of DNA, RNA, and protein could ever have developed. Proteins are needed to catalyze the reactions that send the genetic message from DNA to RNA, but without this genetic information, proteins wouldn't exist. In 1981, however, Thomas Cech, in the Department of Molecular, Cellular, and Developmental Biology at the University of Colorado at Boulder, published a paper in Cell showing that some RNA molecules can catalyze reactions by themselves [1]. Cech won the Nobel Prize in chemistry in 1989 along with Sidney Altman, in the Department of Molecular, Cellular, and Developmental Biology at Yale, who published another seminal paper on these kinds of reactions in Science in 1984 [2].
| RNA would be a good starting place. |
Their work could mean that the first life used RNA both to catalyze reactions and to reproduce itself, or at least that perhaps self-replicating RNA would be a good starting place in trying to make life. The complexity of the RNA molecule suggests that there may have been an earlier precursor, which has since vanished, that started the process. "We're pretty far away from RNA self-replication, but at the same time, we've come pretty far." says Bartel, an associate professor of biology at MIT.
In a paper published in the May 18 issue of Science, Bartel and his colleagues describe how they synthesized an RNA molecule that can use another piece of RNA as a template and copy it with 95 percent accuracy [3]. The new molecule, says Bartel, "uses information from the template to extend another strand. That's the kind of reaction needed to get an RNA to replicate RNA molecules identical to itself, as well as replicate other RNAs." This particular RNA, however, cannot completely duplicate itself, but Bartel is continuing to work on synthesizing such a molecule. He adds, "Even if we had self-replicating RNA, it wouldn't be alive because in order for it to be alive, it would have to be capable of evolving."
| "The problem is compartmentalization. You need membranes." |
Free-floating, self-replicating RNA wouldn't do the trick. Even if a molecule mutated to perform the reaction twice as fast, it wouldn't be able to replicate itself preferentially. For topological reasons, the same RNA molecule can't serve simultaneously as an enzyme and a template. "You wouldn't get a higher concentration of [the faster] RNA molecule because it would just replicate all its crappy neighbors," says Bartel. "The problem is compartmentalization. You need membranes."
Which are exactly what David Deamer, professor emeritus of chemistry at the University of California at Santa Cruz, is trying to develop. "We're interested in membrane formation and how membranes could self-assemble from plausible prebiotic organic compounds," he says. Deamer has studied samples from the Murchison meteorite, which landed in Australia in 1969. "Four billion years ago, there was a continuing infall of dust, comets, and meteorites that carried organic compounds to Earth, and it's still occurring," he says.
| Amphiphiles are crucial to the working of most membranes. |
The Murchison meteorite contains amphiphiles - molecules that attract water on one side and repel it on another side. They are crucial to the workings of most membranes.
Under conditions similar to those found on early Earth, Deamer's group found that these amphiphiles "can self-assemble into membranes [4]." Deamer compares the process to the formation of soap bubbles. "When you think about it, soap bubbles are miraculous. Why would they 'want' to self assemble into these marvelous structures?"
The membranes that can develop from the material in the meteorite, however, are more stable than bubbles. "They can pop osmotically but can heal the hole, unlike soap bubbles. If you pop them at a microscopic level, they come back to haunt you. . . . This makes a plausible membrane available predating the origin of life," says Deamer, who believes that membranes evolved before genetic material like RNA because "it's easy to make bubbles and hard to make RNA."
| "Now we can transcribe a gene into RNA in a membrane." |
Deamer has been able to make a simple cell-like system work. "We encapsulated an enzyme that can make RNA from ADP, and it could have access to substrates by diffusion through the membrane." He has also made systems containing a substance called T7 polymerase (an enzyme made by some viruses) that can transcribe information from DNA to RNA. "Now we can transcribe a gene into RNA in a membrane," he says.
Deamer doesn't think he's created life, however. "These systems are a long way from being alive because they are not metabolizing. I want a system that can take simple compounds and use a source of energy to self-assemble and reproduce," he says. Deamer's genetic systems are further from what early life would have been like than Bartel's, but easier to work with because the enzymes are much faster and already perform the desired function.
| TIGR works backward, creating a minimal genome by removing genes. |
Another step further from early life - but closer to real life - is The Institute for Genetic Research's (TIGR) Minimal Genome Project. This group, led by J. Craig Venter, who founded TIGR and then Celera Genomics, and Clyde Hutchison, professor of microbiology in the Department of Microbiology and Immunology at the University of North Carolina at Chapel Hill, started with the cell currently known to have the smallest genome (which, oddly, is a bacterium, Mycoplasma genitalium, that lives around pubic hair and may cause inflammation of the urethra). They worked backward, trying to take out every possible extraneous gene and still have a functioning organism [5].
This is unlikely to be a true model of early life because a concise genome may actually take more evolution than a lengthy one - just as a longer article may be faster and easier to write than a tight, short piece. "I'd be surprised if they could get something as simple as what might come out of experiments like ours," says Bartel, "but at least they are starting with something that is alive, and that's a real advantage."
So what would the ethical implications be if any of these scientists did create life?
| Is life nothing more than a bunch of chemicals? |
David Magnus, graduate studies director and professor of bioethics at the Center for Bioethics at the University of Pennsylvania, was one of the authors of a 1999 paper published in Science on the ethical implications of the minimal genome project [6]. He says, "I think there are two levels of implications. The first is what this means for the way we conceive of the meaning of life. Does this suggest that life is nothing more than a bunch of chemicals? Does it mean that all of life is reducible to genes?
"That idea has worrisome implications for religion, and I think that it contributes to the overemphasis on genes as determinants of who we are." He adds, "It could lead to the abandonment of the idea of free will because we could see ourselves as just determined by genes and our chemical makeup. And I do think that people are likely to go there. Some of the scientists involved in the minimal genome program have already gone in that direction. [One of the scientists] said when he first presented his data to us that this shows that there is no soul and religion is false."
| "He's Jose's identical twin, he must be good." |
Magnus believes that such conclusions are unwarranted and points to the recent discovery that there are far fewer human genes than expected in order to show some of the limits of genetic determinism. He also gives a human example. "[Baseball's Chicago White Sox slugger] Jose Canseco has an identical twin brother who stinks at baseball. And in spite of the fact that he had no ability, he got promoted through the minor leagues and even to the major leagues even though his batting average was .200 or less. You could just see the coaches thinking, 'He's Jose's identical twin, he must be good.'"
Magnus is wary of a genomic definition of life - the idea that life is the presence or absence of certain genes. "It's hard to draw the line between what is life and what isn't," he says. "For example, the question of whether viruses are alive. If you emphasize the role of genes and replication, then they are alive, but if you put the focus on metabolism, [they aren't]. There's a cytological answer, a metabolic answer, and a religious answer," he adds, "and it's important that the genomic answer isn't the only one."
| The definition of life becomes a very practical matter. |
The second set of implications of creating artificial life is practical. "What will happen if, base pair by base pair, we can create the nucleus of an organism?" asks Magnus, considering the potential of this technology to improve existing genetic engineering efforts for good or ill. He also expresses concerns about the potential ecological impact if artificial cells escaped from the lab.
However, given the enormous technical challenge required just to create and nurture the most simple organism, the chances that such artificial life would pose any threat to real life are extremely remote. Just keeping the cells alive in the sheltered confines of a lab would be hard enough.
Maia Szalavitz is a health/science journalist who has written for the New York Times, the Washington Post, Newsday, New York Magazine, Salon, and other major publications.
Susan Wolsborn is Web designer of HMS Beagle.
Constructing an RNA World - a recent review coauthored by Bartel and Unrau. From Trends in Biochemical Sciences, 24: M9-12. Full text available from BioMedNet.
Artificial Ribozymes and Deoxyribozymes - highlights recent contributions made in the field. From Current Opinion in Structural Biology, 2001, 11:3:321-326. Full text available from BioMedNet.
Man-Made Enzymes: From Design to In Vitro Compartmentalization - reviews the central features of in vitro evolution: genetic diversity, genotype-phenotype linkage and selection. From Current Opinion in Biotechnology, 2000, 11:4:338-353. Full text available from BioMedNet.
Evolution of DNA and RNA as Catalysts for Chemical Reactions - reviews progress in the field of artificial ribozymes and deoxyribozymes. From Current Opinion in Chemical Biology, 2000, 4:257-262. Full text available from BioMedNet.
Boundaries for an RNA World - discusses selection/amplification experiments that potentially constrain important evolutionary events. From Current Opinion in Chemical Biology, 1999, 3:260-267. Full text available from BioMedNet.
Making Catalytic DNAs, A Simpler Nucleic Acid, and Making Copies in the RNA World - several recent articles from Science.
RNA World Website - provides an extensive collection of links on RNA related topics. From the Institut für Molekulare Biotechnologie Jena Biocomputing Group.
From Primordial Soup to the Prebiotic Beach - an interview with Stanley L.Miller, whose early experiments with amino acids gave rise to the term "prebiotic soup." From Access Excellence.
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