Life’s Recipe Card

Life’s Recipe Card

Wet Ingredients-to-Table-top Takes Two Weeks

Scientists announced significant progress toward creating an artificial organism that one day may have uses ranging from pollution control to clean energy production.

"… some warm little pond, with all sorts of ammonia and phosphoric salts, light, heat, electricity etc…", Charles Darwin, on the origins of life in tidal pools

Scientists using commercially available DNA took only two weeks to build from scratch an artificial virus with the identical genetic code of a simple virus already known to infect and kill bacterial cells.

The research at the Institute of Biological Energy Alternatives in Rockville, Md., was detailed in a paper to be published in the Proceedings of the National Academy of Sciences and at a news conference by the Energy Department, which funded the three-year research effort.

While the project was based on widely known molecular biology principles, the breakthrough was in the short time — days instead of months or years — it took to construct the virus, said institute founder J. Craig Venter, one of the lead researchers.

Researchers previously synthesized the polio virus from enzymes that naturally occurred in cells, but that process took three years and produced viruses with defects.

The biomolecule, DNA, that twists throughout the cell nucleus

The effort last summer by Venter and his colleagues took only two weeks from start to finish and created a viral DNA identical to the known genetic code, the researchers said. The team used enzymes to glue the oligonucleotides together accurately into the complete 5,386-base genetic strand, and to copy it many times.

The synthetic virus ‘had the ability to infect and kill bacterial cells,’ the authors wrote in the paper. Even though the experiment involved a simple organism, the researchers suggested their work demonstrated the ability to quickly and accurately synthesize long segments of DNA that can serve as ‘a stepping stone to manipulating more complex organisms.’

At a news conference, Energy Secretary Spencer Abraham called the accomplishment ‘an extraordinary and exciting development’ that will speed up ‘our ability to develop biology-based solutions for some of our most pressing energy and environmental challenges.’

As a result of the scientists’ progress, Abraham said it is now ‘easier to imagine in the not-too-distance future a colony of specially designed microbes living within the emission-control system of a coal-fired plant, consuming its pollution and its carbon dioxide, or employing microbes to radically reduce water pollution or to reduce the toxic effects of radioactive water.’

Their project is part of a three-year, $3-million (U.S.) Energy Department grant, to create a single-celled organism with the minimum number of genes necessary to sustain life. To begin the plan, computer simulations attempted to mimic what genetic starting materials might be needed for life, mainly feeding, reproduction, and death. Eventually in a petri dish, their experiment would then have spawned a new human-made species on Earth.

For astrobiologists, such a prospect offers up an intriguing kind of milestone- one not unlike how first creating amino acids from simpler biochemicals shaped the subsequent origin of life debate. As the Astrobiology roadmap for this new field states: "A golden age has begun for the life sciences, an age in which science and technology will benefit enormously from a fundamental understanding of the full potential of living systems…This is an agenda for inspiring the next generation of planetary explorers and stewards to sustain the NASA vision and mission." NASA’s Astrobiology Institute has recently initiated a Working Group specifically devoted to studying the role of viruses and primordial life.

The molecular definition of life

Several years ago, Venter first looked at this mycoplasma as the best such model, because the organism is a record-holder of sorts: the self-replicating life form with the smallest known complement of genetic material. Unlike the human genome with its 30,000 to 50,000 genes, M. genitalium gets by with only 517. But remarkably, nearly half of even that minimal set is extra baggage. Under some laboratory conditions, as few as 300 of the genes can fulfill its definition as a lifeform that feeds and divides.

Nanobes can be as much as 10 times smaller than the smallest of these bacteria.
Credit: Conneticut Food Protection Program

As it turns out, what is the definition of life itself? and also exactly what is its minimal genetic set? have been hotly contested. Gene size is one of the main limits to what could be the final and minimal cell size, and thus may set a limit on possible targets for creating life from scratch.

But what structures are too small or too simple to be considered "life"?

To answer this question, NASA earlier asked the National Research Council of the National Academy of Sciences to convene an expert panel. It met in late 1998 and published the report, "Size Limits of Very Small Micro-organisms."

Some scientists believe that life can be very small indeed. If mycoplasma’s small gene set is too challenging for laboratory ‘synthesis’, then there are even more radical choices to consider. Called nanobes, nanobacteria, or nano-organisms, these miniscule structures borrow their name from their unit of measurement, the nanometer. A nanometer is one billionth of a meter. That’s about the length of 10 hydrogen atoms laid out side by side. The period at the end of this sentence is approximately one million nanometers in diameter.

Computerised image of the foot-and-mouth virus, the second virus discovered after the initial Russian observations of tobacco mosaic virus. Credit: Oxford Univ.

While the tiniest bacteria measure 200 nanometers across, nanobes are even smaller. They can range anywhere from 20 to 150 nanometers long. "The limit adopted by biologists is 200 to 250 nanometers on the basis that [the structures] must be large enough to contain a DNA or RNA strand, and have the ribosomes, etc., necessary to carry on metabolism," said Robert Folk of the University of Texas at Austin. "My opinion is that scientists do not know enough to set arbitrary limits on life. After all, pre-Pasteur, nobody even thought there were things such as germs, and pre-1890 nobody knew there were viruses."

Century of Struggle and Discovery

The Latin name itself for virus means ‘poison’. The collection labs have identified thousands (approx. 3500) so far. The basic modus operandi of a virus is to take over another organism’s cellular machinery. The virus thus ties its fate intimately with the internal –and not external– ecosystem of another species. Since the first virus was isolated one-hundred and eleven years ago (1892, by Russian Dimitrii Ivanovsky), the number of questions centering on their transmission and lifecycle seem to have ballooned: how do viruses move from host-to-host, how does the host’s immune system try to check their replication, and even more simply, what do they look like?

One question that arises in this context but without consensus is whether viruses are living at all–or just living with us?

The problem with this question is how one defines life.

Viruses do seemingly have ‘a plan’, thus satisfying the earliest definitions for life offered by Aristotle. Viruses do furthermore offer a surprising and radical set of Darwinian choices; indeed high mutation rates are often credited with their robust survival strategies. A clean separation of viruses from the continuum of biochemistry seems unlikely. There is evidence that human DNA has many viral vestiges, thus elevating the virus kingdom to much more than some kind of biological passenger status. From generation to generation, viruses have introduced new genetic information into their victims and hosts.

The debate on defining life rarely has reached scientific consensus, despite volumes written cataloguing the various qualifications for being ‘alive’. Of note however, the presence of similar molecules like DNA and RNA, even in the simplest life forms like viruses, is often suggestive of a single origin event–or at least, a whittling away of inferior encoding molecules from a multitude of less fit alternatives.

What’s Next

To continue this research, Venter’s recipe is not entirely one constructed from scratch. First all genetic material will be removed from an existing organism called Mycoplasma genitalium, a tiny organism that lives in human genital tracts. The 25-person research team led by Venter and Smith will then synthesize an artificial string of genetic material, resembling a naturally occurring chromosome. If the project goes according to their outline, this basic biochemical soup will then contain the minimum number of M. genitalium genes needed to sustain life.

By first ‘gutting’ their mycoplasma to its minimal genetic needs, they will then try to stitch the pieces back together and see if they can reassemble the whole. A hollowed-out cell membrane will encase the simplified chromosome, and its basic life-sustaining capabilities will become the new and never-before-seen organism.

But Venter, among the scientists who first produced a map of the complete human genetic code, said much research is needed to produce such a significantly larger artificial organism.

‘It’s an interim step. Now we have the enabling technology to take us to these next exciting frontiers,’ Venter said. For now, ‘This is basic science at the most basic level with lots of unknowns.’

Still, he said, ‘the ability to construct synthetic genomes may lead to extraordinary advances in our ability to engineer microorganisms for many vital energy and environmental purposes.’

Venter said all the research details would be included in the paper to be published in the scientific journal and that at this time, his company has no plans to file for any patents.

In addition to Venter, the lead scientists involved in the research were Hamilton Smith, the institute’s science director who in 1978 shared a Nobel Prize for his genetic research; Clyde A. Hutchison of the University of North Carolina at Chapel Hill, and Cynthia Pfannkoch of the institute.

Related Web Pages

Miller-Urey Experiment: Amino Acids from Scratch
Life’s Working Definition
Overview: Size Limits on Very Small Organisms
A Perfect World IV: Venter
Minimalist Life
Life from Scratch?
Polio virus – reproducing virus from scratch, Eckard Wimmer
phi-X174 – Venter, et al. virus synthesis accelerated
Human Genome Project
Genetics Book of Life