In a feat of genetic engineering heralded by philosophic quotations and dark fears of a Frankenstein future, a team of scientists in a Maryland laboratory have brought to life the world’s first synthetic cells.
The microbes — a tiny clump of blue cells — came to life about a month ago. They are controlled by a chromosome made by a team led by maverick geneticist Craig Venter, who has dreamed of creating artificial life for 15 years.
Mr. Venter and his colleagues have now accomplished the feat and inscribed their names — along with a few lines of philosophy — in the life-giving chromosome.
“We ended up with the world’s first synthetic cell powered and controlled totally by a synthetic chromosome, made from four bottles of chemicals,” says Mr. Venter.
The genetic whiz, who is also working with some of the world’s biggest companies to try to put synthetic microbes to work, has taken to describing life as “a software process” that can be “booted up.”
“It’s certainly changed my views of the definition of life and how life works,” says Mr. Venter, who unveiled his synthetic cells Thursday in the journal Science.
He described the cells as “the first self-replicating species we’ve had on the planet whose parent is a computer.”
The creation is inspiring both awe and angst.
“It is a remarkable technological feat,” says University of Toronto bioengineer Elizabeth Edwards.
“It’s paradigm-shifting,” says University of Calgary bioethicist and biochemist Gregor Wolbring, adding the fast-moving field of synthetic biology is ushering in “cyber” cells and life.
It could be as “transformative” as the computer revolution, says Andrew Hessel, of the Pink Army Cooperative, an Alberta-based initiative promoting do-it-yourself bioengineering. Mr. Hessel says Mr. Venter deserves the Nobel Prize for his pioneering work in creating “a new branch on the evolutionary tree” — one where humans shape and control new species.
While Hessel foresees great things, others see looming disaster.
The arrival of the synthetic microbes “should be a wake-up call that a technological step-change of historic and alarming proportions has now occurred,” says Pat Mooney, the Ottawa-based executive director of the watchdog agency ETC Group, which follows Mr. Venter’s work closely.
“Like splitting the atom or cloning Dolly, the world is now going to have to deal with the social, economic and political fallout from commercially-driven scientific hubris in ways we can’t yet imagine,” says Mr. Mooney.
He raises the spectre of “new forms of living pollution and bioweapons” and says Mr. Venter’s partnership with companies such as BP and ExxonMobil “threatens biodiversity on a large scale.”
Synthetic microbes and cells could consume large amounts of plant life as feedstock for the next generation of biofuels and bio-based chemicals, says Mr. Mooney, who is calling for a moratorium on synthetic biology until oversight mechanisms are in place.
The new synthetic genome includes designed segments of DNA that use the genetic “alphabet” of genes and proteins to spell out words and phrases. In addition to the new code, the new genome includes a web address to send emails to — if you manage to read the code — plus the names of 46 authors and other key contributors, and three quotations:
“To live, to err, to fall, to triumph, to recreate life out of life.” — James Joyce, author.
“See things not as they are, but as they might be.” — Felix Adler, ethical philosopher, as quoted in the Robert Oppenheimer biography, American Prometheus.
“What I cannot build, I cannot understand.” — Richard Feynman, physicist.
Meanwhile, Mr. Mooney and his colleagues say the synthetic microbes should not be allowed out of the lab.
Mr. Venter has big plans for synthetic life, and has filed for patents on some of the techniques his team is using. He is collaborating with Exxon Mobil to create algae to capture CO2 and construct hydrocarbons “to try and replace taking oil out of the ground.”
New organisms could be designed to make chemicals and “food substances” and clean up water supplies, he says, noting that the most immediate application is a project to speed up flu vaccine production.
“We are entering a new era,” says Mr. Venter. “We are limited mostly by our imaginations.”
His team of 20 scientists at the J. Craig Venter Institute in Maryland is said to have spent close to $40-million on the project to provide “proof of principle for producing cells based upon genome sequences designed in the computer.”
They had hoped to bring their synthetic chromosome to life years ago, but Mr. Venter says they ran in serious “roadblocks” stringing the DNA together and getting the chromosome to work.
They designed the chromosome from a DNA sequence for a simple species of bacteria. It was stored in a computer and used as instructions for assembly of the chromosome, which was made of four compounds that are the basic building blocks of DNA.
Mr. Venter likens it to building something out of Lego pieces. They made short bits of the DNA and then inserted them into yeast cells, where DNA-repair enzymes linked the strings together. After three rounds of assembly, they had a synthetic genome that was more than a million building blocks long.
Then they inserted the synthetic chromosome into cells of naturally occurring bacteria. One tiny mistake in the synthetic genome caused a weeks-long delay, but last month the genome “booted up” some recipient cells. It took control of the cells, which began to replicate and generated a colony of blue bacteria — a blue marker turns on in cells using the new genome.
Mr. Venter’s team has been publishing reports on their progress over the years, and observers like Ms. Edwards in Toronto note that they haven’t create a truly synthetic life form because the genome was inserted into existing cells.
“It is important to note that they synthesized a genome, not a whole cell,” says Ms. Edwards.
But she says it’s still a remarkable accomplishment as they have devised “clever ways of assembling and manipulating large molecules of DNA without breaking them up.”
And as Mr. Venter notes, the artificial genome took control of the cells to create what he calls “synthetic cells.”
Mr. Venter says “it’s pretty stunning” to replace the DNA software in a cell. “The cell instantly starts reading that new software, starts making a whole different set of proteins, and within a short while all the characteristics of the first species disappear and a new species emerges from the software that controls that cell going forward.”
He says the new synthetic cells are based on a “minor” pathogen that can infect goats. He says they tried to eliminate the disease-causing genes.
“It will not grow outside of the laboratory unless it is deliberately injected or sprayed into a goat,” he says, noting the project underwent an extensive bioethical review before it began.
The synthetic chromosome includes several “watermarks” that make it clear that it was made in a lab. The names of all the scientists involved are encoded in the gene sequence along with three quotations — “adding a little philosophy into the genetic code,” says Mr. Venter.
As synthetic biology advances, he says, more sophisticated containment systems will develop, such as “suicide” genes — genetic fail-safes that would limit the organisms’ life spans or kill them off if they should leave a controlled environment. “There are a number of approaches we and other labs are developing to guarantee absolute containment,” he says.
While this first creation is a simple bacteria, he expects to make more complex synthetic cells.
“Higher animals, multi-cellular systems are, I think, projects for the much more distant future,” says Mr. Venter.
While some critics want a moratorium, Ms. Edwards says the work is “not really anymore concerning than the kinds of DNA manipulations one can already do.
“And it is great that this kind of research is done openly so that we can have intelligent dialogue about what it means,” she says.
Scientists reported Thursday that they have created a cell controlled entirely by man-made genetic instructions — the latest step toward creating life from scratch. The achievement is a landmark in the emerging field of “synthetic biology,” which aims to control the behavior of organisms by manipulating their genes.
Although the ultimate goal of creating artificial organisms is still far off, the experiment points to a future in which microbes could be manufactured with novel functions, such as the ability to digest pollutants or produce fuels. Some ethicists fear that the strategy could also be used to produce biological weapons and other dangerous life forms.
In a paper published online by the journal Science, researchers from the J. Craig Venter Institute described using off-the-shelf chemicals and the DNA sequence of Mycoplasma mycoides’s genes to make an artificial copy of the bacterium’s genome. The scientists then transplanted that genome into the cell of a different (but closely related) microbe.
The donor genome reprogrammed the recipient cell, which went on to replicate and divide. The result was new colonies of Mycoplasma mycoides.
“We think these are the first synthetic cells that are self-replicating and whose genetic heritage started in the computer. That changes conceptually how I think about life,” said J. Craig Venter, 63, who gained fame a decade ago as the co-sequencer of the human genome. His institute has laboratories and offices in Rockville and San Diego.
Other scientists characterize the experiment in less revolutionary terms. They say that only the genome was synthetic; the recipient cell was equipped by nature and billions of years of evolution to make sense of the genes it received and turn them on. Still, they praised Venter’s 24-member team for showing that such a transplant was feasible.
“From a technical standpoint, this is clearly a very important advance,” said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
“It is a milestone in synthetic biology,” said Gregory Stephanopoulos, a professor of chemical and engineering and biotechnology at MIT. “Over the long term, it will have an impact, although over the short term, not so much.”
The Venter team stopped short of creating new cells with new functions. Instead, it manufactured a Mycoplasma mycoides genome that was virtually identical to the natural one and used it to make cells that were also nearly indistinguishable from the natural cells.
In that sense, the experiment’s success is more symbolic than practical. It is unlikely to have any immediate effect on the biotech world, which for more than two decades has used various methods of recombinant DNA technology to manipulate to manufacture drugs, produce pest-resistant crops and enhance the nutritional value of food.
The development nonetheless engaged the attention of President Obama, who on Thursday asked the Presidential Commission for the Study of Bioethical Issues to “undertake, as its first order of business, a study of the implications of this scientific milestone, as well as other advances that may lie ahead in this field of research.”
The early consensus is that Venter’s achievement poses no hazards beyond those that exist with current modes of moving or tweaking genes.
It does not represent an additional threat for biological weapons,” said Paul S. Keim, a molecular biologist at Northern Arizona University who chairs the National Science Advisory Board for Biosecurity, a 17-member committee of academic scientists and federal officials that advises the government on “dual use” technologies that can be employed for both good and harmful purposes. Keim said that Venter has been transparent about the direction of his research and had provided the board with a copy of the new paper before it was published.
Under current methods of gene manipulation, scientists harvest a gene from one cell through a process called “cloning” and put it into a transfer vehicle. That vehicle (often a subcellular structure called a plasmid) is then inserted into a different cell, which activates the gene, leading to the production of a scientifically or commercially useful protein.
Venter’s project was more ambitious. The scientists knew the order of the 1,089,202 DNA letters (“nucleotides”) of Mycoplasma mycoides’s genome. They built it in pieces, nucleotide-by-nucleotide. Then they stitched the pieces together.
The result was a man-made copy of the genome that Mycoplasma mycoides produces naturally. However, it was not an exact duplicate. Fourteen of the bacterium’s 850 genes were altered or deleted during the experiment — 12 intentionally, two accidentally. None of those was essential for the bacterium’s survival.
Parts of the process remain mysterious even to the scientists. For example, the cells receiving the synthetic genome also contained a natural genome, and the two genomes were sent into different “daughter” cells when the bacterium divided.
“We don’t know exactly what happens during the genome transplantation experiment,” said Daniel Gibson, 33, a molecular biologist at the Venter Institute who did much of the work.
We have now accomplished the last piece on the list that was required to do what ethicists called “playing God”. What that literally means is the capacity to be a creator.
There are a number of people who will find that very fact in itself terrifying. Many believe there ought to be certain areas that ought to be left alone. This is one of those areas where you can do things vastly before you consider their implications.
There are obviously very important ethical issues. This work has proceeded without any real regulation at all. The bad guys are out there. Weaponising all sorts of things will be much, much easier.
The science is flying 30,000 feet over the public’s understanding of the ethics. Scientists can be their own worst enemy by using words like “clone” or “synthetic life”.
This isn’t a case of rogue scientists, this is a group that is extremely well known, incredibly well respected.
You are going to have to help scientists with education so this thing doesn’t become a national or international threat.
[That is] the way to fend off the Luddites that would say this and any other genetic research is awful – these people will be harder to fend off because more safeguards haven’t been made.
PROF JULIAN SAVULESCU, HEAD OF OXFORD UEHIRO CENTRE FOR PRACTICAL ETHICS
A lot of people will think that the main ethical concern is that this is playing God. But the main issue for me is that this has profound and unparalleled potential benefits – developing new biofuels, being able to deal with pollution, new medical treatments – but it also has almost unimaginable potential risks.
So far we have seen [elsewhere] the construction of polio and mouse pox but these are just small fry compared to what might happen when you can go down the path of engineering organisms that could never naturally exist.
I don’t think people appreciate the power of this revolution. I don’t think the scientists are behaving unethically but this is potentially so powerful we have to think now how we are going to realise the benefits before exposing ourselves to the risk.
If this research goes in one direction Dr Venter may get the Nobel prize, but if it goes in another direction there will be no Nobel prizes to give because there will be no people to give them.