Artificial life a step closer with bacterium genome synthesis

Jan. 25 (Bloomberg) — Scientists at the J. Craig Venter
Institute, a research group thats trying to create artificial
life, moved one step closer to their goal by synthesizing the
complete set of genes of a bacterium.

The researchers built the longest artificial genome ever
made using four chemicals that make up DNA, according to the
study published yesterday by the journal Science. Comparisons of
the sequences of the four bases — adenine, cytosine, guanine
and thymine — are used to identify genetic differences among
living creatures from bacteria to humans.

The goal is to use artificial genomes to create bacteria
designed to take on specific jobs, such as converting
underground coal into a more easily extracted gas. The
scientists previously inserted the genes of one type of bacteria
into the cells of another. If they can use that method to insert
the artificial genome into a cell, theyll have created the
first new life form controlled by man-made DNA.

A genome “is the operating system of the cell, said
Hamilton Smith, the author and a Nobel Prize-winning researcher,
in an audio interview published by Science. As with computers,
“You have an operating system which by itself doesnt do
anything, but when you install it on a computer, then you have a
working computer system. Its the same with the genome. The two
together make a living, reproducing cell.

New Technique

The new technique may help to construct even bigger DNA
molecules from chemically created pieces, according to the
report. The scientists designed bits of DNA to build 101
segments of 5,000 to 7,000 base pairs, the molecules that form
the rungs of the DNA ladder. They connected the segments into
four strands, which they inserted into yeast for the final
connections.

The final chromosome was then checked against the sequence
of the natural DNA to confirm that it was an accurate replica.
The bacterial genome uses 582,970 base pairs. The longest
previous stretch of artificial DNA was 32,000 base pairs.

“Scientists are one step closer to constructing a living,
synthetic organism that has the potential for social, economic,
and ecological disruption — and society is not at all prepared
for that, said Kathy Jo Wetter, a Carrboro, North Carolina-
based researcher with ETC Group, an environmental advocacy group
in Ottawa.

Venter, 61, founded Synthetic Genomics Inc. in 2005 to find
ways to use artificial genes to build new organisms that could
turn sunlight and plant matter into fuel, clean up industrial
waste, or monitor patients for the first signs of disease.

The Venter Institute, which engages in a wide range of
genetic research, has made virus genomes, which are much
smaller, in previous studies. The Rockville, Maryland-based lab
was originally named the Institute for Genomic Research.

`Wonderful Breakthrough

“Its a wonderful breakthrough that could change the way
we think about gene therapy, said David Magnus, co-director of
Stanford Universitys Center for Biomedical Ethics. “It would
allow us potentially to create chromosomes exactly the same as a
patients chromosome but with genes that have been corrected.
This could be a future treatment for disease.

The potential to profit from creating so-called designer
organisms like this is sparking both excitement and debate among
scientists and venture capital investors.

“Venter is claiming bragging rights to the worlds longest
length of synthetic DNA, but size isnt everything, said Jim
Thomas, a program manager at ETC Group, in an e-mail. “The
important question isnt `How long? but `How wise?

Already, scientists are producing strings of man-made DNA,
short for deoxyribonucleic acid, which directs the functions of
all living cells. They then splice the manufactured DNA into the
genes of existing organisms, reprogramming bacteria to act like
microscopic factories churning out biofuels.

No Regulatory Oversight

Venters experiments are taking synthetic biology a step
further by building new organisms from the ground up with wholly
artificial genes. The ETC Group called for “a moratorium on the
release and commercialization of synthetic organisms,
according to a statement released on its Web site yesterday.

“Regulatory oversight is stalled, and there has been no
meaningful or inclusive discussion on how to govern synthetic
biology in a safe and just way, ETC Groups Thomas said.

Venter, who rocked the scientific world in 2000 by
designing a new way to map the collection of human genes in
record time, is no stranger to big ideas, or controversy.

In 2002, he was ousted as president of Foster City,
California-based Celera Genomics, which he helped start to
decode the human genome, after the board decided to concentrate
on drug development instead of selling genetic data. Later that
year, Venter revealed on CBSs 60 Minutes II that his own genes
made up most of Celeras database.

Re-engineered microorganisms may inherit all sorts of jobs.
For now, top gene researchers are particularly excited about the
potential for energy-producing microbes that may become single-
celled refineries for ethanol, biodiesel or other petroleum
substitutes without using food crops such as corn.

Synthetic biology builds on the more than three decades of
genetic engineering behind trailblazing biotechnology companies
such as Amgen Inc. and Genentech Inc.

Gene Swap Changes Organism's Species

Fig.:E.coli bacteria, not the kind that had its genome swapped.


WASHINGTON- Talk about identity theft: Scientists changed one species of bacteria into another by performing a complete gene swap.

It's a step in the quest to one day create artificial organisms, part of a bigger project to custom-design microbes that could produce cleaner fuels.

But the way it was performed, dubbed a "genome transplant," has genetics specialists buzzing.

"This is equivalent to changing a Macintosh computer to a PC by inserting a new piece of software," declared genome-mapping pioneer J. Craig Venter, senior author of the new research published Thursday by the journal Science.

For years, scientists have moved single genes and even large chunks of DNA from one species to another. But Venter's team transplanted an entire genome, all of an organism's genes, from one bacterium into another in one fell swoop.

These weren't complex bacteria, but cousins from a family of small, simple microbes known as Mycoplasma. Nor do the researchers know exactly how the transplant took hold.

But somehow the new genes cleanly replaced the old and started working correctly — not very often, but in just enough cells to prove the concept.

The experiment "is a landmark in biological engineering," said Dr. Barbara Jasny, a deputy editor of Science.

Beyond pushing scientific boundaries, why would switching a goat germ into a cattle germ be useful?

That's not the real aim. It's part of a broader field called "synthetic biology" or "synthetic genomics" that aims to build new organisms that work in ways totally different from what nature intended — and scientists are divided about whether the Venter approach will really play a big role.

"There are people doing some important synthetic engineering efforts with other approaches," cautioned Dr. David Relman, a microbiologist and infectious disease specialist at Stanford University. "This is a different one that is a little more daring, and perhaps dramatic."

"One could wonder whether this method will be used for more than a tiny research community," added Dr. George Church, a genetics professor at Harvard Medical School. "Most people find it easier to work with pieces" of DNA.

Church points to the most popular synthetic biology method under study, genetically modifying existing organisms, such as E. coli bacteria, to make them do such things as churn out medications.

In contrast, Venter's self-named institute in Rockville, Md., is trying to create an artificial chromosome — the structure that carries DNA — that contains industrially useful genes such as ones that could help produce alternative fuels.

That work is far from complete, but to make it work, they'd have to put the artificial chromosome into a living cell and it would have to jump-start that host. Thursday's experiment was designed just to prove an entire-genome switch is possible, with regular bacteria DNA.

The Venter team picked two Mycoplasma species, simple germs that contain a single chromosome and lack the cell walls that form barriers in other bacteria.

First, they added genes to turn the donor bacteria an easy-to-spot bright blue, and to make it resist an antibiotic used to kill off any host germ that retained its own genes.

Then they stripped off the donor chromosome's proteins, to see if naked DNA alone could "reboot" a foreign cell.

Blue germs appeared within days of dropping the genome into lab dishes containing the second bacteria. Not many — only about one in every 150,000 cells took up the donor genome and grew — but they bore no evidence of the original DNA.

"That's extremely inefficient," acknowledged lead scientist John Glass, a Venter Institute microbiologist. "We think we can steadily improve this."

"Synthetic genomics still remains to be proven, but now we are much closer to knowing it's actually theoretically possible," added Venter.

It's not clear that the method would work on larger, more complicated bacteria, other specialists cautioned. Nor does the work automatically mean an artificial chromosome alone could activate a living cell.

"It's going to be much more complicated to do with synthetic organisms," said Dr. Jonathan Eisen, an evolutionary biologist at the University of California, Davis. Still, "it's a great first step."

Artificial life likely in 3-10 years

WASHINGTON (AP) -- Around the world, a handful of scientists are trying to create life from scratch and they're getting closer.

Experts expect an announcement within three to 10 years from someone in the now little-known field of "wet artificial life."

"It's going to be a big deal and everybody's going to know about it," said Mark Bedau, chief operating officer of ProtoLife of Venice, Italy, one of those in the race. "We're talking about a technology that could change our world in pretty fundamental ways -- in fact, in ways that are impossible to predict."

That first cell of synthetic life -- made from the basic chemicals in DNA -- may not seem like much to non-scientists. For one thing, you'll have to look in a microscope to see it.

"Creating protocells has the potential to shed new life on our place in the universe," Bedau said. "This will remove one of the few fundamental mysteries about creation in the universe and our role."

And several scientists believe man-made life forms will one day offer the potential for solving a variety of problems, from fighting diseases to locking up greenhouse gases to eating toxic waste.

Bedau figures there are three major hurdles to creating synthetic life:


A container, or membrane, for the cell to keep bad molecules out, allow good ones, and the ability to multiply.


A genetic system that controls the functions of the cell, enabling it to reproduce and mutate in response to environmental changes.


A metabolism that extracts raw materials from the environment as food and then changes it into energy.

One of the leaders in the field, Jack Szostak at Harvard Medical School, predicts that within the next six months, scientists will report evidence that the first step -- creating a cell membrane -- is "not a big problem." Scientists are using fatty acids in that effort.

Szostak is also optimistic about the next step -- getting nucleotides, the building blocks of DNA, to form a working genetic system.

His idea is that once the container is made, if scientists add nucleotides in the right proportions, then Darwinian evolution could simply take over.

"We aren't smart enough to design things, we just let evolution do the hard work and then we figure out what happened," Szostak said.

In Gainesville, Florida, Steve Benner, a biological chemist at the Foundation for Applied Molecular Evolution is attacking that problem by going outside of natural genetics. Normal DNA consists of four bases -- adenine, cytosine, guanine and thymine (known as A,C,G,T) -- molecules that spell out the genetic code in pairs. Benner is trying to add eight new bases to the genetic alphabet.

Bedau said there are legitimate worries about creating life that could "run amok," but there are ways of addressing it, and it will be a very long time before that is a problem.

"When these things are created, they're going to be so weak, it'll be a huge achievement if you can keep them alive for an hour in the lab," he said. "But them getting out and taking over, never in our imagination could this happen."



Frens this is an article published in the TOI a few weeks back..

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