What Are We Thinking When We (Try to) Solve Problems?

What Are We Thinking When We (Try to) Solve Problems?

New research indicates what happens in the brain when we're faced with a dilemma
 

 
I'VE GOT IT: Two new studies address what goes on in the mind while one is trying to tease apart a difficult problem.

Aha! Eureka! Bingo! "By George, I think she's got it!" Everyone knows what it's like to finally figure out a seemingly impossible problem. But what on Earth is happening in the brain while we're driving toward mental pay dirt? Researchers eager to find out have long been on the hunt, knowing that such information could one day provide priceless clues in uncovering and fixing faulty neural systems believed to be behind some mental illnesses and learning disabilities.

Researchers at Goldsmiths, University of London report in the journal PLoS ONE that they monitored action in the brains of 21 volunteers with electroencephalography (EEG) as they tackled verbal problems in an attempt to uncover what goes through the mind—literally—in order to observe what happens in the brain during an "aha!" moment of problem solving.

"This insight is at the core of human intelligence … this is a key cognitive function that the human can boast to have," says Joydeep Bhattacharya, an assistant professor in Goldsmiths's psychology department. "We're interested [in finding out] whether—there is a sudden change that takes place or something that changes gradually [that] we're not consciously aware of," he says. The researchers believed they could pin down brain signals that would enable them to predict whether a person could solve a particular problem or not.

In many cases, the subjects hit a wall, or what researchers refer to as a "mental impasse." If the participants arrived at this point, they could press a button for a clue to help them untangle a problem. Bhattacharya says blocks correlated with strong gamma rhythms (a pattern of brain wave activity associated with selective attention) in the parietal cortex, a region in the upper rear of the brain that has been implicated in integrating information coming from the senses. The research team noticed an interesting phenomenon taking place in the brains of participants given hints: The clues were less likely to help if subjects had an especially high gamma rhythm pattern. The reason, Bhattacharya speculates, is that these participants were, in essence, locked into an inflexible way of thinking and less able to free their minds, and thereby restructure the problem before them.

"If there's excessive attention, it somehow creates mental fixation," he notes. "Your brain is not in a receptive condition."

At the end of each trial, subjects reported whether or not they had a strong "Aha!" moment. Interestingly, researchers found that subjects who were aware that they had found a new way to tackle the problem (and so, had consciously restructured their thinking) were less likely to feel as if they'd had eureka moment compared to more clueless candidates.

"People experience the "Aha!" feeling when they are not consciously monitoring what they are thinking," Bhattacharya says, adding that the sentiment is more of an emotional experience he likens to relief. "If you're applying your conscious brain information processing ability, then you're alpha." (Alpha brain rhythms are associated with a relaxed and open mind; volunteers who unwittingly solved problems showed more robust alpha rhythms than those who knowingly adjusted their thinking to come up with the answer.)

He says the findings indicate that it's better to tackle problems with an open mind than by concentrating too hard on them. In the future, Bhattacharya says, his team will attempt to predict in real-time whether a stumped subject will be able to solve a vexing problem and, also, whether they can manipulate brain rhythms to aid in finding a solution.

The second probe into problem-solving focused on the anterior cingulate cortex (ACC), a region in the front of the brain tied to functions such as decision making, conflict monitoring and reward feedback. A team at the University of Lyon's Stem Cell and Brain Research Institute in Bron, France reports in Neuron that it verified that the ACC helps detect errors during problem solving (as previously discovered), but also that it does so by acting more as a general guide, monitoring and scoring the steps involved in problem solving, pointing out miscalculations as well as success. 

The team discovered this by recording electrical activity in the brains of two male rhesus monkeys as they tried to determine which targets on a screen would result in a tasty drink of juice. "When you're trying to solve a problem, you need to search; when you discover the solution, you need to stop searching," says study co-author Emmanuel Procyk, coordinator of the Institute's Department of Integrative Neurobiology. "We need brain areas to do that."

He says that researchers observed increased neuronal activity in the animals' ACCs when they began searching. When the monkeys hit the jackpot, there was still heightened activity in the ACC (though only a selective population of nerve cells remained hopped up), indicating that the region is responsible for more than simply alerting the rest of the brain when errors are made. Once the monkeys got the hang of it—and routinely pressed the correct target—ACC activity slowed.

"What we think based on this experiment and other experiments," Procyk says, "is that this structure is very important in valuing things." It essentially scores each of the monkey's behaviors as successful or not successful. "It is an area," he adds, "that will help to decide when to shift from the functioning that goes on when [the brain is] learning to when the learning [is] done."

Procyk says that if this system is compromised, it could have implications for issues such as drug dependency. If the ACC is functioning abnormally, he says, it could overvalue drugs, leading to addiction. (Other studies have shown that an impaired cingulate cortex can result in maladaptive social behavior and disrupted cognitive abilities.)

Alas, the ultimate "Aha!" moment for researchers probing problem solving is likely is far off, but at least the latest research may help them avoid an impasse.

Longest Piece of Synthetic DNA Yet

Longest Piece of Synthetic DNA Yet

Scientists have created an entire bacterial genome with off-the-shelf chemicals

 
LIFE FROM SCRATCH? Scientists concoct longest strand of DNA to date

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.

Blood Flow May Be Key Player in Neural Processing

Blood Flow May Be Key Player in Neural Processing

An M.I.T. scientist believes that if blood flow actually impacts neuronal behavior, the fMRI would be an even more powerful tool for diagnosing disorders such as Alzheimer's and schizophrenia

 
A MORE ROBUST ROLE: An M.I.T. professor believes that blood flow may do more than just serve oxygen to neurons in the brain. It may also be key to information processing.

Blood racing through a brain region's web of vessels is a sign that nerve cells in that locale have kicked into action. The blood rushes to active areas to supply firing neurons with the oxygen and glucose they need for energy.

It is this blood flow, which can last up to a minute, that scientists track in functional magnetic resonance imaging (fMRI) to determine which brain areas are responding to different stimuli. But a new theory could pave the way for a reinterpretation of fMRI images, elevating their measurements to the evaluation of actual neuronal processing rather than the subsequent blood flow that indirectly indicates it, and thereby enhancing the fMRI's usefulness in diagnosing neurological problems.

Christopher Moore, an assistant neuroscience professor at the Massachusetts Institute of Technology's McGovern Institute for Brain Research, detailed his hypothesis in a recent article published in the Journal of Neurophysiology. In essence, it suggests blood's role in the cortex (a key brain processing center), specifically, is more than just bringing nutrients to the cell, it can also alter the activity of local neuronal circuits. For instance, in experiments in his lab, Moore has seen that there is more blood flow can arrive in an area that processes information from a presented stimulus to a certain sense (e.g. touch, visual, auditory) prior to the appearance of the stimulus, implying that the flow can prime a circuit for activity, as well.

Researchers estimate that blood flow in areas of the brain increases by 40 percent when neurons start to fire (or send out electronic impulses), whereas the corresponding metabolic rate of the cells only increases by 4 percent, meaning the cell only needs a tenth of the blood it is supplied to reenergize. "[Neuroscientists] call this discrepancy an 'uncoupling' between flow and metabolism," says Kenneth Kwong, an associate professor in radiology at Harvard Medical School and the researcher, along with Seiji Ogawa, who is generally credited with developing fMRI.

Moore believes that the reason for the discrepancy could be that blood not only nourishes cells but may be intimately involved in the information processing.

If true, Moore says, blood should be factored into any model of neuronal processing—how nerve cells in the brain are activated, how impulses are transmitted between them, how long activity lasts, and how it is terminated. In addition to changing what fMRI is actually measuring, such models could potentially provide new clues to causes of enigmatic disorders such as Alzheimer's disease, multiple sclerosis and schziophrenia—potentially paving the way for treatments that involve correcting blood flow as well as (or rather than) chemical deficiencies.

"Historically, fMRI researchers have to be a little apologetic because they're not looking [directly] at the neuron," Moore says. "fMRI would stop being a second-class citizen; instead it would make fMRI a much more interesting tool…a Heisenberg sort of thing [referring to how the act of observing a quantum state changes it], where what you're looking at is actually a part of the computation going on." Further, scans taken over a number of years could help predict neurodegeneration, if vasculature in a particular brain region begins to weaken. Preliminary data already suggest this is the case for many neurological disorders such as schizophrenia.

The so-called hemo-neural hypothesis plays out in three tissue types: neurons, the blood vessels that feed them, and astrocytes, the star-shaped nerve cells that support and maintain neurons. (Astrocytes, the feet of which are splayed on blood vessels, also help maintain the endothelial cells that line the vessels as well as make up the semipermeable blood–brain barrier responsible for keeping chemicals in the blood from seeping into the brain unless they are needed for metabolism or some other function.)

According to Moore, the vasculature thus directly or indirectly (via astrocytes) influences neurons. He notes that substances in blood may modulate neuron activity. The most likely candidate, he says, is nitric oxide (NO), which easily crosses the blood–brain barrier and has been shown both in brain slices and in animal models to excite (and in some cases dampen) neuronal action. Blood vessels also affect neurons via thermal and mechanical stress. Increased blood flow can alter the local temperature in a brain region. For instance, a decrease of just one degree Celsius can lead to suppressed firing rates, in some circumstances. As a rule, blood flow changes increase the temperature in outer brain areas, while decreasing the temperature of more central regions. Pressure and volume, meanwhile, within the blood vessels can change the amount that the vessels physically impact the membranes of brain cells. If pressure or volume were to increase, a vessel could bulge, blocking receptors or ion channels and thereby causing a decrease in a neuron's electrical activity.

A change in blood flow could also trigger astrocytes to release certain hormones or neurotransmitters. "If anything is going on in the blood vessel," Moore says, "the glia (astrocytes and other nonneuronal nerve cells) is in a great position to sense it." For instance, astrocytes might secrete the excitatory neurotransmitter glutamate, which binds to neurons and allows ion exchanges that cause cells to fire.

Preliminary data from Moore's lab, involving a drug that selectively binds to receptors on blood vessels (and can open or close them), has shown neurons may become more active when blood flow increases. The M.I.T. group is now trying to develop light-activated ion channels on muscle cells, which they could then selectively control to induce changes in blood flow.

The theory "brings up something that a lot of people have been ignoring—thinking that blood vessels are tubes," says Edith Hamel, a professor of neurology at McGill University in Montreal, who believes that Moore's theory will one day prove true. "But, they are live cells…like neurons." She likens the vasculature interaction within the nervous system to that of the infrastructure of a highway system. "We have always been looking at the highway going out of the city," she says. "We need to look at the one coming into the city, as well."

Rick Buxton, a radiology professor at the University of California, San Diego, finds the idea intriguing, but he is "skeptical that blood flow is really an important modulator." In his interpretation, the rush of blood is necessary to maintain oxygen levels in the tissue, because neurons may take in oxygen at a slower rate than normal when blood is gushing by; therefore, more is needed to properly nourish the cells. Another possible way to account for the excess blood flow, according to some researchers, is that it may help carry away some of the heat generated by neuronal firing. "If there's some low level of neuromodulation in there, [as well], that's good," Buxton adds.

Moore notes that if the blood is responsible for a relatively low level of neuromodulation, it could still be significant. "Let's say that blood flow accounts for 5 percent of the variance of activity in cortical neurons," he supposes. "Five percent of the neuron's work—that's huge, if it's pushing around excitability by that scale."

Moore's theory is supported by research into neurodegenerative and mental disorders. Constantino Iadecola, a professor of neurology and neuroscience at Weill Cornell Medical College in New York City, for instance, has found a link between blood vessels and neurons in his work on Alzheimer's disease.

"We have provided evidence that the vasculature is the first thing that goes," he says, noting that Alzheimer's-associated dementia was previously split into two groups: vascular-induced (in which neurons die due to improper blood flow) and neurodegeneration-induced (with vasculature collapse following nerve cell death). "What's emerging from the literature now is that the [vessel changes occur] at least as early or earlier than the neuronal changes."

Abnormal blood flow has also been linked to epilepsy, which is caused by overactive neurons. And, according to Moore, an impoverished blood supply is usually noted in the areas of schizophrenia sufferers' brains that go awry in the disorder.

Moore envisions that in the future research on treatments for mental disorders will focus on potential drugs designed to maintain proper neuronal function by targeting vasculature. "It would be beneficial to upregulate and downregulate blood flow," he says, "the same way as it's beneficial to upregulate or downregulate [the neurotransmitter] dopamine in schizophrenics."

1,000 Genomes Project: Expanding the Map of Human Genetics

1,000 Genomes Project: Expanding the Map of Human Genetics

Researchers hope the effort will speed up the discovery of many diseases's genetic roots

 
1,000 GENOMES: By sequencing several genomes in depth and hundreds lightly, scientists will create a map of human genetic diversity, which may provide a road map for uncovering the potential genetic roots of disease.

The number of sequenced human genomes will soon swell to more than 1,000 as part of a new international research consortium's effort to trace the potential genetic origins of disease. But first the mother, father and adult child of a European-ancestry family from Utah and a Yoruba-ancestry family from Nigeria will join an anonymous individual as well as famous geneticists Craig Venter and James Watson as part of the handful of humans to have on record a complete readout of their roughly three billion pairs of DNA. And these six will also each have their genetic codes examined at least 20 times, providing 10 times the accuracy of existing genetic sequences as well as paving the way for the ambitious effort dubbed the 1,000 Genomes Project, which will comprehensively map humanity's genetic variation.

"The reference sequence that we obtained in 2003 [from the anonymous individual] is just a human genome sequence, but there are six billion humans and it is the sequence of all of us that is important," says project co-chair Richard Durbin of the Wellcome Trust Sanger Institute in Cambridge, England. "We can't get that, but the output of the 1,000 Genomes Project will be a lot closer."

The project will proceed in three steps, according to the consortium. The first, currently underway and expected to be completed by year's end, is the detailed scanning of the six individuals. This will be followed by less detailed genome scans of 180 anonymous people from around the world and then partial scans of an additional 1,000 people. "If we look at about 1,000 individuals, we'll get genetic variants in those samples that are somewhere around 1 percent or lower frequency" in the human population, says geneticist Lisa Brooks, director of the Bethesda, Md.–based National Human Genome Research Institute's Genetic Variation Program.

The researchers plan to use common genetic sequences from the initial six individuals to allow less rigorous scanning as the project accelerates. For example, a shared stretch of DNA from one of the detailed individual scans could fill in the blanks for a less rigorously scanned later individual. "This all needs to be tested," Brooks says. "Is doing these scans 2x [twice] sufficient?"

Blood samples for the final project have already been collected from the first six candidates as well as randomly selected populations from throughout the world: Japanese from Tokyo, Chinese from Beijing, Luhya and Masai from Kenya, Toscani from Italy, Gujarati Asian Indians from Houston, Chinese from Denver, Mexican-Americans from Los Angeles and African-Americans from the southwestern U.S. "We wanted to look at a couple of populations, two or three from each of the major Old World continents. That gives you the variety of people but no one population is needed," Brooks notes. "We don't know exactly who these people are."

The researchers collected no identifying individual information, such as medical histories or basic height and weight data, because the study is not looking for specific diseases but rather the range of human genetic variation. "How many individuals with autism would be in 100 samples from a community?" Brooks says. "It's not a very good disease study but this is going to support a zillion disease studies that are properly designed."

For example, once complete, the 1,000-genome resource will allow researchers to pinpoint genes, structural variants in chromosomes and other individual genomic variations that are associated with diseases ranging from autism to cancer. Researchers using the incomplete genetic information presently available have already identified at least 100 regions of the genome associated with various diseases by comparing the DNA variation between healthy and ill subjects. "This project is talking about a hundred times as much data" as existing genetic resources, Durbin says.

It will also shed light on humanity's shared evolutionary history. "We will learn some more about…the period of a few hundred thousand years or so in which modern humans evolved before they spread from Africa," Durbin says. "This can be studied by looking for evidence of selection in the pattern of variation seen in the genome."

It is already clear that 99 percent of DNA is the same in all humans. But by mapping variations in the other 1 percent, the 1,000 Genomes Project may help reveal the genetic underpinnings of some disease. "Once you have those elements fingered, then you can figure out how to do therapies," Brooks says. "It's not going to tell you the causal ones, but it's going to give you the list of suspects."

In a first, scientists manufacture genome of a bacteria

In a first, scientists manufacture genome of a bacteria

Taking a significant step toward the creation of man-made forms of life, researchers reported Thursday that they had manufactured the entire genome of a bacterium by painstakingly stitching together its chemical components.

While scientists had previously synthesized the complete DNA of viruses, this is the first time it has been done for bacteria, which are much more complex. The genome is more than 10 times as long as the longest piece of DNA ever previously synthesized.

The feat is a watershed for the emerging field called synthetic biology, which involves the design of organisms to perform particular tasks, such as making biofuels. Synthetic biologists envision being able one day to design an organism on a computer, press the "print" button to have the necessary DNA made, and then put that DNA into a cell to produce a custom-made creature.

"What we are doing with the synthetic chromosome is going to be the design process of the future," said Dr. J. Craig Venter, the boundary-pushing gene scientist. He assembled the team that made the bacterial genome as part of his well publicized quest to create the first synthetic organism. The work was published online Thursday by the journal Science.

But there are concerns that synthetic biology could be used to make pathogens, or that errors by well-intended scientists could produce organisms that run amok. The genome of the smallpox virus can in theory now be synthesized using the techniques reported on Thursday, since it is only about one-third the size of the genome manufactured by Dr. Venter's group.

In any case, there are many hurdles to overcome before Dr. Venter's vision of "life by design" is realized. The synthetic genome made by Dr. Venter's team was not designed from scratch, but rather was a copy, with only a few changes, of the genetic sequence of a tiny natural bacterium called Mycoplasma genitalium.

Moreover, Dr. Venter's team, led by a Nobel laureate, Hamilton Smith, has so far failed to accomplish the next - and biggest - step. That would be to insert the synthetic chromosome into a living microbe and have it "boot up" and take control of the organism's functioning.

If that happened, it would be considered by some to be the creation of the first synthetic organism. The failure to achieve that so far has tempered the reception of some outside scientists.

"No matter how they praise the quality of the synthetic DNA, they have no idea whether it is biologically active," said Eckard Wimmer, a professor at Stony Brook University who created live polio virus in 2002 using synthetic DNA and the publicly available genome sequence.

George Church, a professor of genetics at Harvard Medical School, said, "Right now, all they've done is shown they can buy a bunch of DNA and put it together." Dr. Venter's team reported successfully doing such a chromosome transplant last year, but it involved the natural genome of one type of Mycoplasma being put into another species of that bacterium.

Dr. Venter said each pair of donor genome and recipient cell presents unique problems. The scientists also think they interrupted the functioning of one crucial gene by their assembly process, a correctable problem.

"It's not a slam dunk, or we would be announcing it today," he told reporters. Still, he expressed confidence, saying, "I will be equally surprised and disappointed if we can't do it in 2008."

The bacterial genome that was synthesized consisted of 582,970 base pairs, the chemical units of the genetic code that are represented by the letters A, C, G, and T. The longest stretch of synthetic DNA previously reported in a scientific paper was about 32,000 bases long, though some gene synthesis companies say they can attach about 50,000 bases.

The machines that can string together bases make lots of errors, so it is not practical to make a string of more than 50 to 100 bases at a time. But some companies - the foundries of the biotechnology era - now make genes thousands of bases long by splicing those shorter strings together.

The Venter team ordered 101 such sequences, each 5,000 to 7,000 bases long, from these companies. They then joined them together into bigger pieces and still bigger pieces. In the final step, four big pieces were put into yeast, which hooked them together using a natural gene-repair mechanism.

The process was started in late 2002, Dr. Venter said, and undoubtedly cost millions of dollars. That led some scientists to question why someone would want to synthesize an entire organism. Scientists can already make useful organisms - including some that are now starting to be make biofuels - by modifying existing ones using genetic engineering.

"It's not entirely clear to me what the immediate purpose of doing something like this is," said Jeremy Minshull, chief executive of DNA 2.0, a company that supplied some of the DNA stretches to the Venter team. "To some extent, it's something that was driven by 'I want to be the first person to do it.' " Right now, Minshull said, scientists do not know enough about how living things work to design an entire genome: "Now our synthetic capability way outpaces our understanding of what we want to do."

For now, that is the case, Dr. Venter concedes. He has a company, Synthetic Genomics, that is using genetic engineering to produce biofuels. It is using organisms other than Mycoplasma genitalium, which was chosen for the synthetic genome project because its genome is tiny, one-tenth the size of the genomes of some other bacteria. But Mycoplasma is not suited to industrial production.

Still, Dr. Venter and some other scientists say that DNA synthesis is following the path of computer chips, with capability rising rapidly and cost - now about $1 per base - falling swiftly. At some point, they say, it will become faster and cheaper for scientists to design and synthesize an organism from scratch rather than cut and paste genes from one organism to another, just as it is sometimes easier for a writer to type a fresh draft rather than edit an existing one.

The ability to synthesize genomes would allow for more scientific experimentation. Dr. Venter said he would now be able to create organisms missing dozens of genes to answer the initial question that sparked the research ten years ago: What is the minimum set of genes needed for life?

Dr. Venter, who runs the nonprofit J. Craig Venter Institute in Rockville, Maryland, has been a pioneer in genomics. He is best known for sequencing the human genome in a race with the publicly funded Human Genome Project. The method his team used was novel at the time, but is now widely accepted. It turned out that the genome his team sequenced was his own, making Dr. Venter the first person to have his complete DNA sequence published.

Some activist groups say Dr. Venter is going too far, too fast, this time, and that the entire field of synthetic biology needs outside regulation to prevent the introduction of dangerous organisms, created either by evil intent or by innocent error.

"The fact that he's pushing ahead with this without any societal oversight is very worrying," said Jim Thomas, a program manager at the ETC Group, an activist group based in Canada. He also said it was worrisome that Dr. Venter was applying for very broad patents that could give him a near monopoly over the field of synthetic organisms.

Dr. Venter said the synthetic biology field has been discussing ethics and safety steps since it started and that his work had been reviewed by ethicists.

In the new genome, he said, one gene was changed to make any resulting organism non-infective. (Mycoplasma genitalium, which can be transmitted sexually, is associated with inflammation, though its exact role in causing disease is not well understood.) The team also added some DNA segments to the genome to serve as "watermarks," allowing scientists to distinguish the synthetic genome from the natural one.

That raises new possibilities of using microbes as a method of communication. Dr. Venter said the watermarks contain coded messages. Sleuths will have to determine the amino acid sequence coded for by the watermarks, in order to decipher the message. "It's a fun thing that has a practical application," he said.