Life from Scratch?

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

No more ambitious goal than mapping the human genome could tantalize a pair of pioneers who guided that project through to its completed encyclopedia. But Dr. Craig Venter, one of the map’s most prolific contributors, and Dr. Hamilton Smith, a Nobel laureate, researcher and physician, have announced an even grander plan.

Winning a three-year, $3-million (U.S.) Energy Department grant, the pair plan to create a single-celled organism with the minimum number of genes necessary to sustain life. To begin the plan, computer simulations will attempt to mimic what genetic starting materials might be needed for life, mainly feeding, reproduction, and death.

Their 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. According to the scientists’ interview with the Washington Post: "We are wondering if we can come up with a molecular definition of life," Venter said. "The goal is to fundamentally understand the components of the most basic living cell."

If successful 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.

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.

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.

While the tiniest bacteria measure 200 nanometers across, nanobes are even smaller. They can range anywhere from 20 to 150 nanometers long.

What first caught the attention of some scientists was the way nanobes are shaped. They look remarkably like bacteria, forming spheres, chains of beads, filaments, or bean- or sausage-like shapes.

Nanobes seem to share other important qualities with bacteria. For one thing, nanobes are often found grouped together in clusters. Also, some scientists claim they can grow colonies of nanobes by culturing them in the lab. The nanobes seem to spontaneously grow on metal, glass, plastic or organic surfaces which are left in water or exposed to oxygen for a few days or weeks.

Baking a Cake Needs a Mold

One scientist who firmly believes that nanobes are alive is Robert Folk of the University of Texas at Austin. In 1990, Folk discovered bacteria-like structures about 100 nanometers in size in Italian hot-spring deposits. He went public about his findings at a Geological Society of America meeting in 1992.

A ribosome is usually 25-30 nanometers wide. According to the expert panel, 200 nanometers is the smallest size for life as we know it.
Credit: AIP

An organism able to live and reproduce on its own needs certain equipment to accomplish these tasks – and that equipment takes up space. For instance, a single ribosome, a tiny factory that cells use to make proteins, is usually 25 to 30 nanometers wide. A typical modern cell can house several hundred thousand ribosomes. Based on such life requirements, the 18 experts on the panel concluded that 200 nanometers probably marked the lowest size limit. In other words, anything smaller than 200 nanometers could not be considered "life" as we know it.

"Several lines of evidence suggest that the volume of a sphere about 200 nanometers across is needed to house the chemistry of a cell that has a biology familiar to us," says Andrew Knoll, paleobiologist from Harvard University, member of the NASA Astrobiology Institute, and one of the editors of the report. "As long as molecules have volume there will be a lower limit to organism size."

However, the panel also said it was possible that primitive microbes could once have been as small as 50 nanometers in diameter.

"Simpler forms of life are conceivable and probably existed early in the history of life," says Knoll. "One might envision a simple cell with only one class of informational macromolecule that would fit into a 50 nanometer sphere. The key, of course, is making the distinction between cells of familiar biochemistry and cells that may exist but for which we have no direct observational knowledge."

Folk disagrees with the determination of the panel, however. He believes the nanobe structures, which he says commonly range between 50 and 100 nanometers across, are viable life forms.

"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," says Folk. "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."

Proof of Life?

Four years ago, scientists at the University of Queensland discovered nanobes in ancient Australian sandstones. Although some of the structures were as small as 20 nanometers across, the fuzzy tangles of filaments looked a lot like fungi. They also appeared to reproduce quickly, spontaneously forming dense colonies of tendrils, on Petri dishes that were exposed to oxygen and kept at 22 degrees Celsius (72 F). Laboratory analysis of the filaments repeatedly found signs of DNA (deoxyribonucleic acid).

According to Philippa J.R. Uwins, one of the lead scientists of the Queensland team, all the nanobes they discovered seem to have the enzymatic and genetic material considered essential for life.

Folk believes this research should have made other scientists accept the idea that life could be smaller than previously thought.

"Uwins, of course, should have broken the life-barrier for biologists," says Folk.

But Knoll doesn’t find this example of possible nanometer-sized life to be especially compelling. Although the Queensland structures stain positively for DNA, Knoll says there are other substances that can give a "false positive" for DNA.

Learning from Nature

If nanobes are ever proven to be alive, they would challenge our understanding of life on Earth. Based on everything we know about biology, it does not seem possible for modern living organisms to be smaller than 200 nanometers.

"If current nanobes can be shown to be living entities, then Earth harbors life forms whose chemistry we do not understand," says Knoll. "That would be interesting."

Although such a revelation would change our comprehension of life, Knoll doesn’t think it would dramatically affect astrobiology.

"We already acknowledge that unfamiliar life is possible," says Knoll. "I don’t think that it would change the philosophy or search strategy for life detection."

"Until more advanced forms are discovered, nanobacteria are astrobiology," says Folk. "Nanobacteria are the primordial life form on Earth, as well."

Since his discovery of nanobes in Italian hot spring deposits, Folk says he has found nanobes in such things as bird bath scum, decayed leaves in streams, brownish water from old flower bouquets, air filters, tap and well water, hair, feces, blood, gallstones, chicken egg shells, clam shells, and teeth. He says that nanobes are virtually everywhere – one only need look for them.

Nanobes at 35000x magnification. The debate continues– Are these structures living entities fully capable of self replication?
Credit: Nanoworld

"I would say, cattily, that those who say NO [to the existence of nanobes] simply have not looked for small life forms," says Folk. "All those who have looked, have found them. Over half a dozen labs have succeeded in culturing colonies of organisms of this minute size, and some of these labs have succeeded in obtaining DNA, detecting the organic chemistry of living tissue, and even revealing structure of cell walls or membranes."

Despite such assertions, Knoll maintains that those who insist nanobes are alive have yet to prove their claims.

"No one has as yet convinced a skeptical microbiological community that the very small structures under discussion are living entities fully capable of self-replication," says Knoll. "Or that if they are, what novel biochemistry makes this possible."

What’s Next

While the issue of nanobes continues to be debated, the Queensland group is trying to determine the exact nature of nanobe genetic material. They also plan to analyze the growth rates of their nanobe cultures.

Folk, meanwhile, is working hard to prove that the structures are widespread in nature. He is currently studying both modern and ancient rocks and minerals, as well as samples of Martian meteors, for evidence of nanobes. Folk is also conducting studies to see how nanobes may play important biological roles.

"[I'm studying] the possible role of nanobacteria in symbiotically precipitating hard parts of organisms, from clam shells to dinosaur teeth," says Folk. "Also, in a joint project with the Mayo clinic, [I'm conducting] an intense study with Dr. Brenda Kirkland on [the role of nanobes in] human arterial plaque and diseased heart tissue."

As Venter and Smith start up their own ambitious project, the three year target would be for a new human-made species to appear sometime after 2006.

Related Web Pages

Miller-Urey Experiment: Amino Acids from Scratch
Overview: Size Limits on Very Small Organisms
Robert Folk’s UT Austin nannobacteria web page
University of Queensland nanobe research and findings