[tt] visions of drummers or half-a-megabase genome assembled

[Alejandro Dubrovsky]

(
might as well cnp the full article. biggest news of the day
)

January 24, 2008
Scientists Take New Step Toward Man-Made Life
By ANDREW POLLACK

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 M. 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, Mr. 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, Md., 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.


On Fri, 2008-01-25 at 08:35 +0100, Eugen Leitl wrote:
> ----- Forwarded message from coderman <coderman at gmail.com> -----
> 
> From: coderman <coderman at gmail.com>
> Date: Thu, 24 Jan 2008 15:03:37 -0800
> To: cypherpunks at al-qaeda.net
> Subject: visions of drummers
> 
> http://www.nytimes.com/2008/01/24/science/24cnd-genome.html?ei=5087&em=&en=2da45a7dc351c849&ex=1201323600&pagewanted=print
> """
> 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.
> """
> 
> 
> i await the paper, "low latency signalling via coded influenza medium:
> bandwidth estimates and congestion avoidance"
> 
> ----- End forwarded message -----