Scientists are often accused of trying to play God. Cloning experts, genetic engineers and atomic physicists have all fiddled with aspects of the world that many believe should remain the preserve of some higher power. But for one group of scientists in particular, playing is a serious business. They are seeking to create life itself, and in doing so could push God aside.
They are making astonishing progress. According to the Bible it took six days to create heaven, Earth and everything in them; the scientists already need only a fortnight to produce a totally synthetic organism. They are also figuring out how to expand life's genetic code, which has acted as a barrier to new forms of creation since time immemorial. "I don't think there's anything wrong with playing God," says Clyde Hutchison, one of the new breed of scientists learning to master creation. "As long as it's just playing."
Before tackling the creation of new life, the scientists have been forced to ask a more fundamental question: what, precisely, is it? What are the bare essentials life requires, the building blocks needed to make the most basic living organism? The answer has an almost profound significance, for it is these components that form the common denominator that links every living thing on Earth, from aardvarks to amoebae, zooplankton to zebras.
The common denominator for life is a package of genes that together do the bare minimum necessary to produce a living organism; enough to produce life, but no more. All other genes are add-ons, tweaks that nudge an organism into one species or other, that help grow fins or feet, trunks or tails.
At his lab at the University of North Carolina at Chapel Hill, Hutchison is trying to find the essentials for life by playing what seems a macabre game. He begins by taking a clutch of the most basic forms of life known to man, a bacterium called Mycoplasma genitalium. The bacterium has only 500 or so genes, compared with an estimated 42,000 genes found in humans.
Because M. genitalium has fewer genes than any other living organism, Hutchison says it is the closest nature has to the simplest possible life form. Most of the genes inside the bacterium are vital for its survival, helping the bacterium to grow its body, divide and convert nutrients around it into energy. But to find out the bare minimum required for life, Hutchison is systematically whittling down the bacterium by knocking out genes to find the point at which life becomes impossible. So far, he believes he's found up to 215 genes that are strictly superfluous for the microbe's survival, meaning that a cassette of fewer than 300 genes is required for life.
Stripping life down to its essentials has more than curiosity appeal. While scientists like to think they know all the processes essential for life, a simple organism would allow them to work out precisely how life works. "The exciting possibility is that there may be some essential biological functions that are vital for life that we just don't know about," says Hutchison.
In the grand tradition of taking things apart and putting them back together again, scientists are also keen to rebuild life from its basic components. By starting with a stripped down, basic life form, a designer organism could be made by simply adding genes, says Hutchison. It would allow organisms to be designed for specific tasks, like breaking down pollutants. "We believe it will get to the stage where we can sit down at a computer and design the organism we want just by ordering in the parts. It won't be fundamentally different to genetic modification, but it's a lot more flexible," he says. While the motivations at this stage are essentially scientific curiosity, stronger urges are also at work. "Part of it is definitely a desire to play God," he says.
More ambitious than making new organisms from stripped-down life forms is the prospect of creating new life from scratch. In 2002, a team of scientists led by Eckard Wimmer at the State University of New York at Stony Brook caused a stir when they created the polio virus by chemically stitching together strands of DNA ordered from the internet.
Although viruses are not technically alive - since they need to hijack other living cells to replicate - the techniques used pave the way to making living cells. Last year, Hutchison, in collaboration with Craig Venter's group at the Institute for Biological Energy Alternatives, disclosed that they had produced a virus of their own, a harmless strain called phi-x. Having recreated the virus's DNA using a similar technique to Wimmer, Hutchison injected it into E coli. The virus replicated and broke out of the cells and was able to infect new bacteria.
Venter sees designer organisms as the saviour of the planet. His aim is to create new microbes that can strip carbon dioxide from our polluted atmosphere or churn out hydrogen so it can be used as a new power source.
Before embarking on the work, Venter's institute convened a bioethics committee to see if their plans were likely to raise objections from certain quarters of society. The committee, led by Mildred Cho at the centre for biomedical ethics at Stanford University, had no objections to the work, but pointed out that scientists must take responsibility for any impact their new organisms had if they got out of the lab. "Even if you're not intending to release them, you can't have the view that it's not your problem if they do get out," she says. Hutchison argues that designer organisms will be so specialised that they can be designed to die as soon as they leave laboratory conditions.
Strictly speaking, these scientists are not playing God, but copying God. At present they can only build synthetic versions of organisms that already exist, using their decoded genomes as instructions. Even designer organisms built from scratch will be stitched together from synthetic versions of genes that already exist. Is this truly the creation of artificial life? If not, will scientists ever be able to design and synthesise new genes, creating life the like of which has never been seen before?
Not according to Wimmer. "Sitting down at a desk and constructing an entirely new virus from scratch that doesn't exist on Earth is totally impossible," he says. "By shuffling things around that exist already you could get something with different properties, such as a bacterium that eats up oil much faster, but this is very different from saying I create a new form of life."
Life is just too complex to invent from scratch. Wimmer and Venter may have been able to produce the viral equivalents of fake Mona Lisas by copying every brushstroke, but they have as much chance of painting a new masterpiece as a three-year-old using potato prints. Even a virus - something so primitive that it does not earn the right to be called alive - relies on a bewildering series of hidden chemical reactions and biological interactions that are not revealed in the sparse language of its genes. Scientists can only work with what already exists. Genes are life's playing cards, and however many ways they devise to shuffle them, they must always use the same deck.
But what if new cards could be introduced to the game? The set of genes may be fixed, but what about the proteins they produce - which bend, fold and combine to give every cell, every organ and every living thing their distinctive features?
Since life began, all creatures have been based on the same set of biological building blocks: 20 amino acids from which all proteins are made. No longer. If you are looking for scientists who are truly learning to play God then start your search at the Scripps research institute in California. And they are not biologists, but chemists.
Biologists may be unable to devise new genes, but chemists have no problem making new amino acids. Nature has limited itself to using just 20 (and nobody knows why) but chemistry labs the world over have synthesised hundreds. Swirl these unnatural amino acids around in a test tube and you can get interesting results. Design a living organism capable of using them and you create bona-fide new forms of life. And that is exactly what the Scripps scientists are doing.
"There are potential ethical issues with this if you're creating new forms of life, which I think in one sense that is," says Jason Chin, who worked at the Scripps centre and is now at the MRC's laboratory for molecular biology in Cambridge.
In January last year, the team said they had created an E coli bacterium capable of incorporating a 21st amino acid into its proteins, and in August they repeated the trick in yeast. They are now investigating how it might work in worms and cultured human kidney cells. Living mice will probably follow, and in principle there is nothing to stop the same technique being used to redesign a person.
This clever chemistry goes way beyond shifting genes around between organisms. The unnatural amino acids have never been available to living things in millions of years of evolution, so who knows the benefits or dangers they could bring? "The big question is whether life with 21 amino acids can do anything that life with 20 amino acids can't," says Chin. Perhaps they could allow life to flourish where previously impossible by withstanding poisons or surviving extreme temperatures - or make diseases immune to existing cures.
The Scripps team is currently trying to find out what their new bug - dubbed an Un Coli - is capable of. Uniquely, it has been given the cellular machinery it needs to synthesise the unnatural amino acid itself (the research with yeast and worms requires the amino acid to be made in a lab and then supplied). Could it be dangerous? The team has taken no chances and has crippled its ability to make a different, essential amino acid it needs to live. "Outside the laboratory it would starve and that's how they controlled letting the thing live," Chin says. Being able to create new proteins raises the possibility of introducing new traits on demand. Some of the unnatural amino acids have hooks to which other molecules like dyes can be hung. Get an organism to incorporate these and researchers can track the proteins produced to see what they do inside cells. Other chemicals could be added to make the bugs manufacture designer proteins used as medicines.
Chemists have also made more bizarre amino acids that glow in the dark, or change shape when light shines on them. Design a mouse that incorporates these in the right place in the right proteins, and you could produce an animal with fluorescent fur that switches from straight to curly in the dark.
"You could certainly do that if someone gave you the money," Chin says. "It's a fuzzy line whether you call it a new form of life but in principle you have the ability to control a lot of things."
But because scientists have the ability, should they use it? In theory the Scripps team's work could one day lead to freakish creatures, but that seems unlikely, and right now they are working to understand fundamental processes and develop better medicines. Ashton Cropp, a researcher with the Scripps institute, says ethics is not yet an issue because they are dealing with microbes and cultured cells, but he accepts that they will have to be more careful when the work moves to mice.
Even then, there may be fewer objections to the idea of scientists creating new life than some people think.
When it assessed Venter's plans, Mildred Cho's ethics team also looked at whether religious groups were likely to take issue with scientists openly admitting to "playing God". Although not every religion was represented on the committee, those that were, including Judaism and Christianity, had no problem.
"The idea that playing God is wrong is not supported by religious texts. It's a popular notion of religion, but not one that is backed up," Cho says. "All our religious advisers used the same metaphor: God gives us the keys to the car, saying, you have the keys, just don't crash the car."
Further reading
http://schultz.scripps.edu/ research.htm
More on Peter Schultz's efforts to expand the genetic code
www.bioenergyalts.org
Craig Venter's Institute for Biological Energy Alternatives
http://gels.ethics.ubc.ca
Analysing the ethics of genomics
www.thehastingscenter.org/pdf/publications/in_brief_nov_dec_2003.pdf
Further analysis of the ethics of using genetics to create new life
