In what is being hailed as "a defining moment in biology," a team of scientists working for Craig Venter's company, Synthetic Genomics Inc., has created from scratch a complete DNA genome, inserted it into a cell, and booted it up to function and reproduce, thus creating "the world's first synthetic life form," the London Guardian reported Thursday.[1]  --  By inserting identifiable "watermarks" into the genetic material of the cell, (including a coded email address and "three apt quotations from James Joyce and others"[3]), Venter said that he had created "a living species . . . part of our planet's inventory of life."  --  Julian Savulescu of Oxford University said Venter "is going towards the role of a god."  --  Mark Bedau of Reed College in Portland called it "a defining moment in the history of biology and biotechnology."  --  The New York Times said that at a press conference Venter called it "a philosophical advance as much as a technical advance" and called his cell "the first self-replicating species we’ve had on the planet whose parent is a computer.”[2]  --  Venter's company "ordered pieces of DNA 1,000 units in length . . . and developed a technique for assembling the shorter lengths into a complete genome," Nicholas Wade reported.  --  "The cost of the project was $40 million."  --  Molecular biologist Richard Ebright of Rutgers University called it "literally a turning point in the relationship between man and nature," the Wall Street Journal said.[3]  --  Robert Lee Hotz said that the 1,000-unit pieces of DNA that were assembled were made by a DNA-sequencing company called Blue Heron Bio in Bothell, Wash.  --  A link to the scientific paper announcing the advance is posted below.[4]  --  Thanks to Roger Erickson for sending a link to the Guardian....


1.

News

Science

CRAIG VENTER CREATES SYNTHETIC LIFE FORM

By Ian Sample

** Craig Venter and his team have built the genome of a bacterium from scratch and incorporated it into a cell to make what they call the world's first synthetic life form **

Guardian (London)
May 20, 2010

Scientists have created the world's first synthetic life form in a landmark experiment that paves the way for designer organisms that are built rather than evolved.

The controversial feat, which has occupied 20 scientists for more than 10 years at an estimated cost of $40m, was described by one researcher as "a defining moment in biology."

Craig Venter, the pioneering U.S. geneticist behind the experiment, said the achievement heralds the dawn of a new era in which new life is made to benefit humanity, starting with bacteria that churn out biofuels, soak up carbon dioxide from the atmosphere, and even manufacture vaccines.

However critics, including some religious groups, condemned the work, with one organization warning that artificial organisms could escape into the wild and cause environmental havoc or be turned into biological weapons.  Others said Venter was playing God.

The new organism is based on an existing bacterium that causes mastitis in goats, but at its core is an entirely synthetic genome that was constructed from chemicals in the laboratory.

The single-celled organism has four "watermarks" written into its DNA to identify it as synthetic and help trace its descendants back to their creator, should they go astray.

"We were ecstatic when the cells booted up with all the watermarks in place," Dr. Venter told the Guardian.  "It's a living species now, part of our planet's inventory of life."

Dr. Venter's team developed a new code based on the four letters of the genetic code, G, T, C and A, that allowed them to draw on the whole alphabet, numbers, and punctuation marks to write the watermarks.  Anyone who cracks the code is invited to email an address written into the DNA.

The research is reported online today in the journal Science.

"This is an important step both scientifically and philosophically," Dr. Venter told the journal.  "It has certainly changed my views of definitions of life and how life works."

The team now plans to use the synthetic organism to work out the minimum number of genes needed for life to exist.  From this, new microorganisms could be made by bolting on additional genes to produce useful chemicals, break down pollutants, or produce proteins for use in vaccines.

Julian Savulescu, professor of practical ethics at Oxford University, said:  "Venter is creaking open the most profound door in humanity's history, potentially peeking into its destiny.  He is not merely copying life artificially . . . or modifying it radically by genetic engineering.  He is going towards the role of a god:  creating artificial life that could never have existed naturally."

This is "a defining moment in the history of biology and biotechnology", Mark Bedau, a philosopher at Reed College in Portland, Oregon, told Science.

Dr. Venter became a controversial figure in the 1990s when he pitted his former company, Celera Genomics, against the publicly funded effort to sequence the human genome, the Human Genome Project.  Venter had already applied for patents on more than 300 genes, raising concerns that the company might claim intellectual rights to the building blocks of life.

2.

Science

RESEARCHERS SAY THEY CREATED A 'SYNTHETIC CELL'

By Nicholas Wade

http://www.nytimes.com/2010/05/21/science/21cell.html


The genome pioneer J. Craig Venter has taken another step in his quest to create synthetic life, by synthesizing an entire bacterial genome and using it to take over a cell.

Dr. Venter calls the result a “synthetic cell” and is presenting the research as a landmark achievement that will open the way to creating useful microbes from scratch to make products like vaccines and biofuels.  At a press conference Thursday, Dr. Venter described the converted cell as “the first self-replicating species we’ve had on the planet whose parent is a computer.”

“This is a philosophical advance as much as a technical advance,” he said, suggesting that the “synthetic cell” raised new questions about the nature of life

Other scientists agree that he has achieved a technical feat in synthesizing the largest piece of DNA so far -- a million units in length -- and in making it accurate enough to substitute for the cell’s own DNA.

But some regard this approach as unpromising because it will take years to design new organisms, and meanwhile progress toward making biofuels is already being achieved with conventional genetic engineering approaches in which existing organisms are modified a few genes at a time.

Dr. Venter’s aim is to achieve total control over a bacterium’s genome, first by synthesizing its DNA in a laboratory and then by designing a new genome stripped of many natural functions and equipped with new genes that govern production of useful chemicals.

“It’s very powerful to be able to reconstruct and own every letter in a genome because that means you can put in different genes,” said Gerald Joyce, a biologist at the Scripps Research Institute in La Jolla, Calif.

In response to the scientific report, President Obama asked the White House bioethics commission on Thursday to complete a study of the issues raised by synthetic biology within six months and report back to him on its findings.  He said the new development raised “genuine concerns,” though he did not specify them further.

Dr. Venter took a first step toward this goal three years ago, showing that the natural DNA from one bacterium could be inserted into another and that it would take over the host cell’s operation.  Last year, his team synthesized a piece of DNA with 1,080,000 bases, the chemical units of which DNA is composed.

In a final step, a team led by Daniel G. Gibson, Hamilton O. Smith and Dr. Venter report in Thursday’s issue of the journal Science that the synthetic DNA takes over a bacterial cell just as the natural DNA did, making the cell generate the proteins specified by the new DNA’s genetic information in preference to those of its own genome.

The team ordered pieces of DNA 1,000 units in length from Blue Heron, a company that specializes in synthesizing DNA, and developed a technique for assembling the shorter lengths into a complete genome.  The cost of the project was $40 million, most of it paid for by Synthetic Genomics, a company Dr. Venter founded.

But the bacterium used by the Venter group is unsuitable for biofuel production, and Dr. Venter said he would move to different organisms.  Synthetic Genomics has a contract from Exxon to generate biofuels from algae.  Exxon is prepared to spend  up to $600 million if all its milestones are met.  Dr. Venter said he would try to build “an entire algae genome so we can vary the 50 to 60 different parameters for algae growth to make superproductive organisms.”

On his yacht trips round the world, Dr. Venter has analyzed the DNA of the many microbes in seawater and now has a library of about 40 million genes, mostly from algae.  These genes will be a resource to make captive algae produce useful chemicals, he said.

Some other scientists said that aside from assembling a large piece of DNA, Dr. Venter has not broken new ground.  “To my mind Craig has somewhat overplayed the importance of this,” said David Baltimore, a geneticist at Caltech.  He described the result as “a technical tour de force,” a matter of scale rather than a scientific breakthrough.

“He has not created life, only mimicked it,” Dr. Baltimore said.

Dr. Venter’s approach “is not necessarily on the path” to produce useful microorganisms, said George Church, a genome researcher at Harvard Medical School.  Leroy Hood, of the Institute for Systems Biology in Seattle, described Dr. Venter’s report as “glitzy” but said lower-level genes and networks had to be understood first before it would be worth trying to design whole organisms from scratch.

In 2002 Eckard Wimmer, of the State University of New York at Stony Brook, synthesized the genome of the polio virus.  The genome constructed a live polio virus that infected and killed mice.  Dr. Venter’s work on the bacterium is similar in principle, except that the polio virus genome is only 7,500 units in length, and the bacteria’s genome is more than 100 times longer.

Friends of the Earth, an environmental group, denounced the synthetic genome as “dangerous new technology,” saying that “Mr. Venter should stop all further research until sufficient regulations are in place.”

The genome Dr. Venter synthesized is copied from a natural bacterium that infects goats.  He said that before copying the DNA, he excised 14 genes likely to be pathogenic, so the new bacterium, even if it escaped, would be unlikely to cause goats harm.

Dr. Venter’s assertion that he has created a “synthetic cell” has alarmed people who think that means he has created a new life form or an artificial cell.  “Of course that’s not right -- its ancestor is a biological life form,” said Dr. Joyce of Scripps.

Dr. Venter copied the DNA from one species of bacteria and inserted it into another.  The second bacteria made all the proteins and organelles in the so-called “synthetic cell,” by following the specifications implicit in the structure of the inserted DNA.

“My worry is that some people are going to draw the conclusion that they have created a new life form,” said Jim Collins, a bioengineer at Boston University.  “What they have created is an organism with a synthesized natural genome.  But it doesn’t represent the creation of life from scratch or the creation of a new life form,” he said.

3.

Environment & science

SCIENTISTS CREATE SYNTHETIC ORGANISM

By Robert Lee Hotz

Wall Street Journal

May 21, 2010

http://online.wsj.com/article/SB10001424052748703559004575256470152341984.html

Heralding a potential new era in biology, scientists for the first time have created a synthetic cell, completely controlled by man-made genetic instructions, researchers at the private J. Craig Venter Institute announced Thursday.

"We call it the first synthetic cell," said genomics pioneer Craig Venter, who oversaw the project. "These are very much real cells."

Created at a cost of $40 million, this experimental one-cell organism, which can reproduce, opens the way to the manipulation of life on a previously unattainable scale, several researchers and ethics experts said.  Scientists have been altering DNA piecemeal for a generation, producing a menagerie of genetically engineered plants and animals.  But the ability to craft an entire organism offers a new power over life, they said.

The development, documented in the peer-reviewed journal *Science*, may stir anew nagging questions of ethics, law, and public safety about artificial life that biomedical experts have been debating for more than a decade.

"This is literally a turning point in the relationship between man and nature," said molecular biologist Richard Ebright at Rutgers University, who wasn't involved in the project.  "For the first time, someone has generated an entire artificial cell with predetermined properties."

David Magnus, director of the Stanford University Center for Biomedical Ethics, said, "It has the potential to transform genetic engineering. The research is going to explode."

Leery of previous moral and ethical debates about whether it is right to manipulate life forms -- which arose with the advent of cloning, stem-cell technology, and genetic engineering -- some researchers chose neutral terms to describe the experimental cell.  Some played down the development.

"I don't think it represents the creation of an artificial life form," said biomedical engineer James Collins at Boston University.  "I view this as an organism with a synthetic genome, not as a synthetic organism.  It is tough to draw where the line is."

The new cell, a bacterium, was conceived solely as a demonstration project.  But several biologists said they believed that the laboratory technique used to birth it would soon be applied to other strains of bacteria with commercial potential.

"I think this quickly will be applied to all the most important industrial bacteria," said biologist Christopher Voigt at the University of California, San Francisco, who is developing microbes that help make gasoline.

Several companies are already seeking to take advantage of the new field, called synthetic biology, which combines chemistry, computer science, molecular biology, genetics, and cell biology to breed industrial life forms that can secrete fuels, vaccines or other commercial products.

Synthetic Genomics Inc., a company founded by Dr. Venter, provided $30 million to fund the experiments and owns the intellectual-property rights to the cell-creation techniques.  The company has a $600 million contract with Exxon Mobil Corp. to design algae that can capture carbon dioxide and make fuel.

At least three other companies -- Amyris Biotechnologies in Emeryville, Calif.; LS9 Inc. in San Francisco; and Joule Unlimited in Cambridge, Mass. -- are working on synthetic cells to produce renewable fuels.

Although patents on single genes now face legal challenges, Dr. Venter said he intends to patent his experimental cells.  "They are pretty clearly human inventions," he said.

Before making their work public, the researchers said, they briefed White House officials, members of Congress and officials from several government agencies.  Within minutes of Thursday's announcement, the House Energy and Commerce Committee announced it would hold a public hearing on the new technology next week.

Environmental groups also reacted quickly.  Friends of the Earth issued a statement asking the Environmental Protection Agency and the Food and Drug Administration "to fully regulate all synthetic biology experiments and products," while ETC Group, a group based in Canada, called for a global moratorium on synthetic biology.

There was no immediate reaction from Roman Catholic and Protestant groups that have questioned such developments in the past.  There was some support.  "It is very much within divine mandate that we do these things," said theologian Nancey Murphy, who studies Christianity and science at the Fuller Theological Seminary, a multidenominational Christian seminary in Pasadena, Calif.

The announcement Thursday was the culmination of a project Dr. Venter and his colleagues have pursued since 1995.  In a series of peer-reviewed papers, the group has published the interim technical steps.  So far, that research has withstood scrutiny.

The latest research was reviewed by a panel of independent scientists, but no one has duplicated the team's experiment.  Other researchers working on different approaches in the field found the report credible and said it combined a series of prior advances.

"They are pulling all the pieces together," said Drew Endy, a biologist at Stanford University who is president of the BioBricks Foundation, a nonprofit consortium organized by researchers from Harvard University, the Massachusetts Institute of Technology and the University of California to make the DNA tools of synthetic biology freely available.

To make the synthetic cell, a team of 25 researchers at labs in Rockville, Md., and San Diego, led by bioengineer Daniel Gibson and Mr. Venter, essentially turned computer code into a new life form.  They started with a species of bacteria called Mycoplasma capricolum and, by replacing its genome with one they wrote themselves, turned it into a customized variant of a second existing species, called Mycoplasma mycoides, they reported.

To begin, they wrote out the creature's entire genetic code as a digital computer file, documenting more than one million base pairs of DNA in a biochemical alphabet of adenine, cytosine, guanine, and thymine.  They edited that file, adding new code, and then sent that electronic data to a DNA sequencing company called Blue Heron Bio in Bothell, Wash., where it was transformed into hundreds of small pieces of chemical DNA, they reported.

To assemble the strips of DNA, the researchers said they took advantage of the natural capacities of yeast and other bacteria to meld genes and chromosomes in order to stitch those short sequences into ever-longer fragments until they had assembled the complete genome, as the entire set of an organism's genetic instructions is called.

They transplanted that master set of genes into an emptied cell, where it converted the cell into a different species.

"We make a genome from four bottles of chemicals; we put that synthetic genome into a cell; that synthetic genome takes over the cell," said Dr. Gibson.  "The cell is entirely controlled by that new genome."

The scientists didn't give the new organism its own species name, but they did give its synthetic genome an official version number, Mycoplasma mycoides JCVI-syn1.0.

To set this novel bacterium -- and all its descendants -- apart from any natural creation, Dr. Venter and his colleagues wrote their names into its chemical DNA code, along with three apt quotations from James Joyce and others.  These genetic watermarks will, eventually, allow the researchers to assert ownership of the cells.  "You have to have a way of tracking it," said Stanford ethicist Mildred Cho, who has studied the issues posed by the creation of such organisms.

--Write to Robert Lee Hotz at This email address is being protected from spambots. You need JavaScript enabled to view it.


4.

Research articles

CREATION OF A BACTERIAL CELL CONTROLLED BY A CHEMICALLY SYNTHESIZED GENOME

By Daniel G. Gibson,1 John I. Glass,1 Carole Lartigue,1 Vladimir N. Noskov,1 Ray-Yuan Chuang,1 Mikkel A. Algire,1 Gwynedd A. Benders,2 Michael G. Montague,1 Li Ma,1 Monzia M. Moodie,1 Chuck Merryman,1 Sanjay Vashee,1 Radha Krishnakumar,1 Nacyra Assad-Garcia,1 Cynthia Andrews-Pfannkoch,1 Evgeniya A. Denisova,1 Lei Young,1 Zhi-Qing Qi,1 Thomas H. Segall-Shapiro,1 Christopher H. Calvey,1 Prashanth P. Parmar,1 Clyde A. Hutchison, III,2 Hamilton O. Smith,2 J. Craig Venter1,2,*

http://www.guardian.co.uk/science/2010/may/20/creation-bacterial-cell-craig-venter

or
http://www.sciencemag.org/cgi/rapidpdf/science.1190719v1.pdf


** We report the design, synthesis, and assembly of the 1.08-Mbp Mycoplasma mycoides JCVI-syn1.0 genome starting from digitized genome sequence information and its transplantation into a Mycoplasma capricolum recipient cell to create new Mycoplasma mycoides cells that are controlled only by the synthetic chromosome.  The only DNA in the cells is the designed synthetic DNA sequence, including "watermark" sequences and other designed gene deletions and polymorphisms, and mutations acquired during the building process.  The new cells have expected phenotypic properties and are capable of continuous self-replication.

1 The J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD 20850, USA.
2 The J. Craig Venter Institute, 10355 Science Center Drive, San Diego, CA 92121, USA.

* To whom correspondence should be addressed. E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.