Scientist Creates Designer Microbe From Scratch

 

By Fiona Macrae
on 21st May 2010

Scientists today lined up to air their fears over a genome pioneer’s claims that he has created artificial life in the laboratory.

In a world first, which has alarmed many, maverick biologist and billionaire entrepreneur Craig Venter, built a synthetic cell from scratch.

The creation of the new life form, which has been nicknamed ‘Synthia’, paves the way for customised bugs that could revolutionise healthcare and fuel production, according to its maker.

But there are fears that the research, detailed in the journal Science, could be abused to create the ultimate biological weapon, or that one mistake in a lab could lead to millions being wiped out by a plague, in scenes reminiscent of the Will Smith film I Am Legend.

artificial
artificial

While some hailed the research as ‘a defining moment in the history of biology’, others attacked it as ‘a shot in the dark’, with ‘unparalleled risks’. The team involved have been accused of ‘playing God’ and tampering ‘with the essence of life’.

Dr Venter created the lifeform by synthesising a DNA code and injecting it into a single bacteria cell. The cell containing the man-made DNA then grew and divided, creating a hitherto unseen lifeform.

Kenneth Oye, a social scientist at the Massachusetts Institute of Technology in the U.S., said: ‘Right now, we are shooting in the dark as to what the long-term benefits and long-term risks will be.’

synthetic life
This picture shows the colonies of the artificial lifeform nicknamed ‘Synthia’

Pat Mooney, of the ETC group, a technology watchdog with a special interest in synthetic biology, said: ‘This is a Pandora’s box moment – like the splitting of the atom or the cloning of Dolly the sheep, we will all have to deal with the fall-out from this alarming experiment.’

Dr David King, of the Human Genetics Alert watchdog, said: ‘What is really dangerous is these scientists’ ambitions for total and unrestrained control over nature, which many people describe as ‘playing God’.

‘Scientists’ understanding of biology falls far short of their technical capabilities. We have learned to our cost the risks that gap brings, for the environment, animal welfare and human health.’

Professor Julian Savulescu, an Oxford University ethicist, 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 by genetic engineering. He is going towards the role of God: Creating artificial life that could never have existed.’

He said the creation of the first designer bug was a step towards ‘the creation of living beings with capacities and a nature that could never have naturally evolved’. The risks were ‘unparalleled’,’ he added.

And he warned: ‘This could be used in the future to make the most powerful bioweapons imaginable. The challenge is to eat the fruit without the worm.’ 

Dr Venter, who was instrumental in sequencing the human genome, had previously succeeded in transplanting one bug’s genome – its entire cache of DNA – into another bacterium, effectively changing its species.

He has taken this one step further, transplanting not a natural genome but a man-made one. To do this, he read the DNA of Mycoplasma mycoides, a bug that infects goats, and recreated it piece by piece.

The fragments were then ‘stitched together’ and inserted into a bacterium from a different species.

There, it sprang to life, allowing the bug to grow and multiply, producing generations that were entirely artificial.

The transferred DNA contained around 850 genes – a fraction of the 20,000 or so contained in a human’s genetic blueprint.

 
  aggregated M. mycoides

In future, bacterial ‘factories’ could be set up to manufacture artificial organisms designed for specific tasks such as medicines or producing clean biofuels.

The technology could also be harnessed to create environmentally friendly bugs capable of mopping up carbon dioxide or toxic waste.

Dr Venter, a 63-year-old Vietnam War veteran known for his showman tendencies, said last night: ‘We are entering a new era where we’re limited mostly by our imaginations.’

But the breakthrough, which took 15 years and £27.7million to achieve, opens an ethical Pandora’s box. Ethicists said he is ‘creaking open the most profound door in humanity’s history’ – with unparalleled risks.

Dr Venter, whose team of 20 scientists includes a Nobel laureate, likens the process to booting-up a computer.

Like a program without a hard drive, the DNA doesn’t do anything by itself. But, when the software is loaded into the computer – in this case the second bacterium – amazing things are possible, he said.

‘WATERMARKING’ DNA

This dramatic development naturally raises fears of the dangers these organisms pose. So one idea, which has been followed through by Venter and his team, is to ‘watermark’ them.

By weaving these hidden codes in it enables scientists to trace the organisms to their laboratories and prove the recipient bacteria contained the synthetic genome.

Researchers used the ‘alphabet’ of genes and proteins to spell out messages.

The team created a code that spells out the 26 letters of the alphabet, the numbers 0 to 9 and several punctuation marks. They then wrote a message which reveals the code. A second missive was a string of ‘letters’ corresponding to the names of 46 people involved in the project. A third gave an e-mail address where people can write once they crack the code and the fourth listed three philosophical quotes.

Now that the scientist, whose J Craig Venter Institute has labs in California and Maryland, has proved the concept, the path is open for him to alter the ‘recipe’ to create any sort of organism he chooses.

At the top of his wishlist are bugs capable of producing clean biofuels and of sucking carbon dioxide out of the atmosphere. Other possibilities include designer microbes that can mop up oil slicks or generate huge quantities of drugs, including the flu vaccine.

Any such organisms would be deliberately ‘crippled’ so that they cannot survive outside the lab, he claimed.

Brushing aside the ethical concerns of his work, Dr Venter wrote in his autobiography that it would allow ‘a new creature to enter the world’.

‘We have often been asked if this will be a step too far,’ he said. ‘I always reply that – so far at least – we are only reconstructing a diminished version of what is out there in nature.’

Last night, he claimed the breakthrough had changed his views on the definition of life. ‘We have ended up with the first synthetic cell powered and controlled by a synthetic chromosome and made from four bottles of chemicals,’ he said.

‘It is pretty stunning when you just replace the DNA software in a cell and the cell instantly starts reading that new software and starts making a whole new set of proteins, and within a short while all the characteristics of the first species disappear and a new species emerges.

‘That’s a pretty important change in how we approach and think about life.’

The process was carried out on one of the simplest types of bacteria, under strict ethical guidelines. The research team insist that they cannot think of a day when the technology could be used to create animals or people from scratch.

Has he created a monster?

By Michael Hanlon, Science Editor

The creation of a living being in a laboratory is one of the staples of science fiction.

Now it is a scientific fact. Yesterday’s announcement of the birth of a ‘synthetic cell’ – made by injecting a bacterium shell with genetic material created from scratch by scientists – raises many questions.

There are fears the research could be abused and lead to millions being wiped out by a plague like in the Will Smith film I Am LegendThere are fears the research could be abused and lead to millions being wiped out by a plague like in the Will Smith film I Am Legend

These range from the mundanely practical – how will this be useful? – to the profoundly philosophical – will we have to redefine what life is? 

Depending on your viewpoint, it is either a powerful testament to human ingenuity or a terrible example of hubris – and the first step on a very dangerous road.

To understand what this development means, we need to discover who the team behind this innovation is.

It is led by Craig Venter, the world’s greatest scientific provocateur, a 63-year-old Utah-born genius, a Vietnam veteran, billionaire, yachtsman, and an explorer. Above all he is a showman.

A master of self-publicity, he does not do things by halves; he led the private team which competed with scores of publicly funded scientists in the U.S. and UK to ‘crack’ the human genome by sequencing our DNA.

His rapid, innovative approach led to the possibility he would beat the scientific establishment.

So, to save face all round, the human genome was presented as a joint achievement. At around the same time, he began talking about making an artificial lifeform in the lab.

Not a Frankenstein’s monster, or even a mouse, but a bacterium, one of the simplest living organisms. His blueprint was to be an unassuming and harmless little germ with only 485 genes (humans have around 25,000).

Venter talks grandly of a supercharged biotech revolution, with synthetic bacteria designed to produce biofuels, to mine precious metals from rocks and industrial waste, to digest oil slicks and render toxic spills harmless.

WHO IS CRAIG VENTER?

Craig Venter is a controversial biologist and entrepreneur who led the effort by the private sector to sequence the human genome.

He was vilified by the scientific community for turning the project into a competitive race but his efforts did mean that the human genome was mapped three years earlier than expected.

J. Craig VenterBorn in 1946, Dr Venter was an average scholar with a keen interest in surfing.

It was while serving in Vietnam and tending to wounded comrades that he was inspired to become a doctor.

During his medical training he excelled in research and was quick to realise the importance of decoding genes. In 1992 he set up the private Institute for Genomic Research. Then a mere three years later he stunned the scientific establishment by revealing the first complete genome of a free-living organism that causes childhood ear infections and meningitis.

In 2005 he founded the private company Synthetic Genomics, with the aim of engineering new life forms the would produce alternative fuels.

He was listed on Time Magazine’s 100 list of the most influential people in both 2007 and 2008.

Scientists could even create bacteria which can produce novel drugs and vaccines, or organisms engineered to live on Mars and other planets.

The potential is huge – but so are the dangers. An artificial species, created in the lab, might not ‘obey the rules’ of the natural world – after all, every living being on Earth has evolved over three billion years, when a myriad of competing species have had to share the same increasingly crowded environment.

It is possible to imagine a synthetic microbe going on the rampage, perhaps wiping out all the world’s crop plants or even humanity itself.

Synthetic biology also challenges our most cherished notions of what life itself actually is. Non-scientists might not realise that we have, as yet, no proper definition of life.

A diamond is not alive; a baboon clearly is. But what about a virus? Viruses, which are even simpler than bacteria, have a genetic code written in DNA (or its cousin RNA).

The stuff viruses are made from is the stuff of life – protein coats and so on – yet they cannot reproduce independently.

Like diamonds, they can be grown into crystals – and you certainly cannot crystallise baboons. Most biologists say viruses are not alive, and that true biology begins with bacteria.

So is Synthia, Venter’s tentative name for his new critter, alive? It is certainly not the result of Darwinian evolution, one of the (many) definitions of life. It is more ‘alive’ than any virus but it is the product of Man, not of evolution. Its genetic code is simple enough to be stored on a computer (but then again, so is ours).

Whatever the answer to this fundamental question, Venter’s breakthrough is certainly the final rebuttal to the old notion of a vital spark – a mysterious essence that divides the quick from the dead. If you can carry around a genome on a computer memory stick and make a cell using a few simple chemicals, then the old idea of ‘vitalism’ is truly dead.

Of course, this is early days. It is not yet clear if Venter can negotiate the final step – creating a whole cell from scratch, using no bits of existing living organisms at all.

His bacterium is likely to be weak and feeble; we are a long way from synthetic super-plagues, and even further from an artificial animal or plant. But it is hard to escape the feeling that a boundary has been crossed. The problem is, it is far from clear where we go from here.

 

 

 

 

‘Artificial life’ breakthrough announced by scientists

By Victoria Gill Science reporter, BBC News

 Synthetic cell (Science)

The synthetic cell looks identical to the ‘wild type’

Scientists in the US have succeeded in developing the first living cell to be controlled entirely by synthetic DNA.

The researchers constructed a bacterium’s “genetic software” and transplanted it into a host cell.

The resulting microbe then looked and behaved like the species “dictated” by the synthetic DNA.

The advance, published in Science, has been hailed as a scientific landmark, but critics say there are dangers posed by synthetic organisms.

Some also suggest that the potential benefits of the technology have been over-stated.

But the researchers hope eventually to design bacterial cells that will produce medicines and fuels and even absorb greenhouse gases.

The team was led by Dr Craig Venter of the J Craig Venter Institute (JCVI) in Maryland and California.

Craig Venter defends the synthetic living cell

He and his colleagues had previously made a synthetic bacterial genome, and transplanted the genome of one bacterium into another.

Now, the scientists have put both methods together, to create what they call a “synthetic cell”, although only its genome is truly synthetic.

Dr Venter likened the advance to making new software for the cell.

The researchers copied an existing bacterial genome. They sequenced its genetic code and then used “synthesis machines” to chemically construct a copy.

How a synthetic cell
was created

Thaksin Shinawatra in 2001
The scientists “decoded” the chromosome of an existing bacterial cell – using a computer to read each of the letters of genetic code.
Thaksin Shinawatra in 2006
They copied this code and chemically constructed a new synthetic chromosome, piecing together blocks of DNA.
A Thai soldier stands guard in front of the Government House in Bangkok on 19 September 2006
The team inserted this chromosome into a bacterial cell which replicated itself. Synthetic bacteria might be used to make new fuels and drugs.
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Dr Venter told BBC News: “We’ve now been able to take our synthetic chromosome and transplant it into a recipient cell – a different organism.

“As soon as this new software goes into the cell, the cell reads [it] and converts into the species specified in that genetic code.”

The new bacteria replicated over a billion times, producing copies that contained and were controlled by the constructed, synthetic DNA.

“This is the first time any synthetic DNA has been in complete control of a cell,” said Dr Venter.

‘New industrial revolution’

Dr Venter and his colleagues hope eventually to design and build new bacteria that will perform useful functions.

“I think they’re going to potentially create a new industrial revolution,” he said.

“If we can really get cells to do the production that we want, they could help wean us off oil and reverse some of the damage to the environment by capturing carbon dioxide.”

Even some scientists worry we lack the means to weigh up the risks such novel organisms might represent, once set loose

Susan Watts BBC Newsnight science editor Read Susan Watts’s thoughts Analysis from around the world Send us your comments

Dr Venter and his colleagues are already collaborating with pharmaceutical and fuel companies to design and develop chromosomes for bacteria that would produce useful fuels and new vaccines.

But critics say that the potential benefits of synthetic organisms have been overstated.

Dr Helen Wallace from Genewatch UK, an organisation that monitors developments in genetic technologies, told BBC News that synthetic bacteria could be dangerous.

“If you release new organisms into the environment, you can do more harm than good,” she said.

“By releasing them into areas of pollution, [with the aim of cleaning it up], you’re actually releasing a new kind of pollution.

“We don’t know how these organisms will behave in the environment.”

Continue reading the main story

The risks are unparalleled, we need safety evaluation for this kind of radical research and protections from military or terrorist misuse

Julian Savulescu Oxford University ethics professor Profile: Craig Venter Q&A: The meaning of synthetic life Ethics concern over synthetic cell

Dr Wallace accused Dr Venter of playing down the potential drawbacks.

“He isn’t God,” she said, “he’s actually being very human; trying to get money invested in his technology and avoid regulation that would restrict its use.”

But Dr Venter said that he was “driving the discussions” about the regulations governing this relatively new scientific field and about the ethical implications of the work.

He said: “In 2003, when we made the first synthetic virus, it underwent an extensive ethical review that went all the way up to the level of the White House.

“And there have been extensive reviews including from the National Academy of Sciences, which has done a comprehensive report on this new field.

“We think these are important issues and we urge continued discussion that we want to take part in.”

Ethical discussions

Dr Gos Micklem, a geneticist from the University of Cambridge, said that the advance was “undoubtedly a landmark” study.

But, he said, “there is already a wealth of simple, cheap, powerful and mature techniques for genetically engineering a range of organisms. Therefore, for the time being, this approach is unlikely to supplant existing methods for genetic engineering”.

The ethical discussions surrounding the creation of synthetic or artificial life are set to continue.

Professor Julian Savulescu, from the Oxford Uehiro Centre for Practical Ethics at the University of Oxford, said the potential of this science was “in the far future, but real and significant”.

“But the risks are also unparalleled,” he continued. “We need new standards of safety evaluation for this kind of radical research and protections from military or terrorist misuse and abuse.

“These could be used in the future to make the most powerful bioweapons imaginable. The challenge is to eat the fruit without the worm.”

The advance did not pose a danger in the form of bio-terrorism, Dr Venter said.

“That was reviewed extensively in the US in a report from Massachusetts Institute of Technology (MIT) and a Washington defence think tank, indicating that there were very small new dangers from this.

“Most people are in agreement that there is a slight increase in the potential for harm. But there’s an exponential increase in the potential benefit to society,” he told BBC’s Newsnight.

“The flu vaccine you’ll get next year could be developed by these processes,” he added.

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