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Synthetic humans are go
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Synthetic humans are go “WHAT I cannot create, I do not base pairs, including “whole understand.” Last week, 25 leading genome engineering of human synthetic biologists decided it was cell lines and other organisms time to follow Richard Feynman’s of agricultural and public famous credo. health significance”, the team After nearly two decades spent writes. This will require poring over the 3 billion letters technological development or base pairs that make up the early on in the project “to propel human genome, they announced “You could use this plain a 10-year plan to chemically yogurt of humanity to synthesise one. “Reading the slot in different genes genome can only get you so far. and find out what they do” At some point you have to build it,” says Susan Rosser of the Mammalian Synthetic Biology large-scale genome design Research Centre at the University and engineering” (Science, of Edinburgh, UK, and a co-author doi.org/bjmv). on the paper outlining the plan. The artificial genome won’t The team, which counts among be derived from any one person, its leaders the maverick geneticist but will be created using George Church, says it is aiming computer-aided design – one of to launch the ambitious initiative the main players is software this year, depending on raising company Autodesk. Chunks of an initial £100 million. synthetic DNA could then be put The primary goal of the Human into cell lines, like those used to Genome Project-Write, as it is test drugs, or into E.coli bacteria, the workhorse of the research lab, known, is to engineer large with the host genetic material genomes of up to 100 billion
an almighty leap The project to create an artificial human genome will build on previous work to construct synthetic genomes Rewriting baker’s yeast Sc2.0 is an international attempt to recreate the genome of baker’s yeast, Saccharomyces cerevisiae, one of the first organisms to be sequenced. The yeast genome is tiny: just 12 million base pairs on 16 chromosomes, compared with the 3 billion base pairs of the human genome spread over 23 chromosomes. The project should address some previously unanswerable questions, such as how transposons – “jumping genes” that insert themselves in DNA – evolve. The project is expected to finish in 2018. 16 | NewScientist | 11 June 2016
Craig Venter’s artificial bacteria In 2010, a team led by Craig Venter reported that it had synthesised the only chromosome of the bacterium Mycoplasma mycoides and transplanted it into an empty chassis of a separate strain of Mycoplasma. Earlier this year, the team announced that it had whittled down the 901 genes of the synthetic bacterium to the minimum needed to support life. Of these essential genes, we have no idea what 31 per cent of them do.
gradually being replaced. While difficult to put a figure on the cost at this stage, the team says it expects the final bill to be less than the $3-billion cost of the first Human Genome Project. But what’s the point of such a lofty proposal? To entice funders, the team has outlined several pilot projects that will take advantage of the progress as it is made. Those discussed in the paper include the development of an ultra-safe line of cells that would be virus resistant, cancer resistant and free of potentially harmful genes that could lead, for example, to prion diseases. That would be a boon for stem cell medicine, says Paul Freemont, who runs the synthetic biology centre at Imperial College London. One of the benefits of stem-cell therapies is that the cells can multiply rapidly – but this is also a characteristic shared by cancer cells, so a therapeutic injection of stem cells turning cancerous has long been a concern. “A synthetic biology variant encoded to never become cancerous would be preferable,” he says. Other projects include finding the minimal human genome – the tiniest possible stash of DNA capable of supporting life – and adapting the pig genome so it becomes a better source of organs for human transplants. There’s also a proposal to develop a reference human genome. This would consist of the most common gene variants that humans carry at every single position of the genome. It could be used to make a cell that has a generalised genome that most accurately represents the baseline genetic code of the majority of the human race.
EPA/MICHAEL REYNOLDS
What’s the point of building the entire human genome from scratch? Sally Adee investigates
Church calls the genome this would create a totally plain human. “If you had this, you can introduce variants of unknown significance one at a time. These are turning up constantly in genome research but you don’t know if the variants are causal, or how many it takes [to cause disease],” he says. “You could use this blank slate, this plain yogurt of humanity, to slot in the different genes and find out”. This could help identify why some populations are more susceptible to certain diseases, for example sickle cell anaemia, which is more common in people of African, African American or Mediterranean heritage. “This would be a way of finding out why,” says Freemont. Some see darker applications, however. “Some of the speculative
large-scale production-oriented ‘HGP-Write’ effort,” he said in a statement. Then there’s the question of who would own the synthesised genome. Unlike existing DNA that has been manipulated, a wholly synthetic cell could be owned outright. This could benefit any corporations involved. “If you process it in your lab, it is yours, you can patent it,” says Laurie Zoloth, a bioethicist at Northwestern University in Evanston, Illinois.
Genome owner “In the first Human Genome Project, it was clear that the knowledge gained would be owned by everyone – anyone can download and use the information,” says Freemont. “But it’s less clear how that will work with this project – this will not be digital information, this will be a physical entity… It’s an issue that hasn’t been sorted out.” Rosser says that is exactly the discussion the team’s paper is intended to catalyse. But not everyone is placated by –No easy task, ethically or technically the authors’ talk of “responsible innovation”. Zoloth and Drew goals of this project sound it doesn’t state clearly what Endy, a synthetic biologist at innocuous or benign… potential risks or ethical Stanford University, say the Others would be dangerously quandaries the project might authors fail to pose essential unacceptable,” said Marcy raise, says Baojun Wang, also at questions in their proposal. Darnovsky, who heads the the University of Edinburgh. More “Nor do they detail specific California-based Center for justifiable reasons than those limits about what should not Genetics and Society, in a given in the paper – namely that it be done.” This raises the question statement. In an interview with would deliver important scientific of whether the group is well US radio station NPR, she said: equipped to organise and lead “The worry is that we’re going to “The worry is that it could such a project, the pair say. be used to produce be synthesising entire optimised Church says that people are human genomes – manufacturing synthetic humans they working to make sure certain see as improved models” chromosomes that could be used actions cannot be carried out. ultimately to produce synthetic As an example, he points to the advances and reduce the cost of human beings that they see as now widely implemented safety genetic engineering – are needed improved models.” standards he devised in 2004 to to start the HGP-Write project, While there is no suggestion prevent DNA being used to make he says. “The investment is huge that the artificial DNA sequence biohazardous material. and long-term and will involve created by the project would be What is certain is that there is governmental taxpayers money.” still plenty of time to get things put into a human egg or embryo, Francis Collins, director of the allowing the creation of a human in order. With just a few groups from scratch, the paper doesn’t do US National Institutes of Health, capable of writing genomes with much to allay these fears. While it agrees. “NIH has not considered millions of bases, the synthetic the time to be right for funding a mentions ethical considerations, human is a long way off. n
uncertain ambition The Human Genome Project–Write was generating controversy before it was even officially announced. On 10 May, team members held an invitation-only meeting at Harvard University. Attendees were barred from speaking with the press, leaving people to guess at the applications of the rumoured project. This led to suggestions of using “the synthetic genome to create human beings without biological parents”. The reality will be less sensational but just as radical, says geneticist George Church at Harvard, one of the leaders of the project. “We are not well suited to 60-mile commutes, a super-abundance of food, and certainly not for being astronauts,” says Church. Knowledge gleaned from this project could, for example, switch off the genes that make us susceptible to type 2 diabetes. While the descriptions of the applications (see main story) seem uncontroversial enough, greater ambitions may lurk behind them. “There has been a ratcheting down of the rhetoric of the project [since 10 May],” says Hank Greely of the Stanford Centre for Law and the Biosciences. “But whether there’s been a ratcheting down of the plans, I don’t know”. Clues may lie in its leaders’ wider interests. During presentations, for example, Church likes to show a slide on which he lists naturally occurring variants of around 10 genes that give people extraordinary qualities or resistance to disease. Andrew Hessel of software company Autodesk, who first proposed the human genome synthesis project in 2012, is a lecturer at think-tank Singularity University, which explicitly tries to adapt to a future in which technology outpaces biology. Hessel has often spoken of his plans to make genetic engineering into an accessible “programming language”, using Autodesk software.
11 June 2016 | NewScientist | 17
Synthetic humans are go “WHAT I cannot create, I do not base pairs, including “whole understand.” Last week, 25 leading genome engineering of human synthetic biologists decided it was cell lines and other organisms time to follow Richard Feynman’s of agricultural and public famous credo. health significance”, the team After nearly two decades spent writes. This will require poring over the 3 billion letters technological development or base pairs that make up the early on in the project “to propel human genome, they announced “You could use this plain a 10-year plan to chemically yogurt of humanity to synthesise one. “Reading the slot in different genes genome can only get you so far. and find out what they do” At some point you have to build it,” says Susan Rosser of the Mammalian Synthetic Biology large-scale genome design Research Centre at the University and engineering” (Science, of Edinburgh, UK, and a co-author doi.org/bjmv). on the paper outlining the plan. The artificial genome won’t The team, which counts among be derived from any one person, its leaders the maverick geneticist but will be created using George Church, says it is aiming computer-aided design – one of to launch the ambitious initiative the main players is software this year, depending on raising company Autodesk. Chunks of an initial £100 million. synthetic DNA could then be put The primary goal of the Human into cell lines, like those used to Genome Project-Write, as it is test drugs, or into E.coli bacteria, the workhorse of the research lab, known, is to engineer large with the host genetic material genomes of up to 100 billion
an almighty leap The project to create an artificial human genome will build on previous work to construct synthetic genomes Rewriting baker’s yeast Sc2.0 is an international attempt to recreate the genome of baker’s yeast, Saccharomyces cerevisiae, one of the first organisms to be sequenced. The yeast genome is tiny: just 12 million base pairs on 16 chromosomes, compared with the 3 billion base pairs of the human genome spread over 23 chromosomes. The project should address some previously unanswerable questions, such as how transposons – “jumping genes” that insert themselves in DNA – evolve. The project is expected to finish in 2018. 16 | NewScientist | 11 June 2016
Craig Venter’s artificial bacteria In 2010, a team led by Craig Venter reported that it had synthesised the only chromosome of the bacterium Mycoplasma mycoides and transplanted it into an empty chassis of a separate strain of Mycoplasma. Earlier this year, the team announced that it had whittled down the 901 genes of the synthetic bacterium to the minimum needed to support life. Of these essential genes, we have no idea what 31 per cent of them do.
gradually being replaced. While difficult to put a figure on the cost at this stage, the team says it expects the final bill to be less than the $3-billion cost of the first Human Genome Project. But what’s the point of such a lofty proposal? To entice funders, the team has outlined several pilot projects that will take advantage of the progress as it is made. Those discussed in the paper include the development of an ultra-safe line of cells that would be virus resistant, cancer resistant and free of potentially harmful genes that could lead, for example, to prion diseases. That would be a boon for stem cell medicine, says Paul Freemont, who runs the synthetic biology centre at Imperial College London. One of the benefits of stem-cell therapies is that the cells can multiply rapidly – but this is also a characteristic shared by cancer cells, so a therapeutic injection of stem cells turning cancerous has long been a concern. “A synthetic biology variant encoded to never become cancerous would be preferable,” he says. Other projects include finding the minimal human genome – the tiniest possible stash of DNA capable of supporting life – and adapting the pig genome so it becomes a better source of organs for human transplants. There’s also a proposal to develop a reference human genome. This would consist of the most common gene variants that humans carry at every single position of the genome. It could be used to make a cell that has a generalised genome that most accurately represents the baseline genetic code of the majority of the human race.
EPA/MICHAEL REYNOLDS
What’s the point of building the entire human genome from scratch? Sally Adee investigates
Church calls the genome this would create a totally plain human. “If you had this, you can introduce variants of unknown significance one at a time. These are turning up constantly in genome research but you don’t know if the variants are causal, or how many it takes [to cause disease],” he says. “You could use this blank slate, this plain yogurt of humanity, to slot in the different genes and find out”. This could help identify why some populations are more susceptible to certain diseases, for example sickle cell anaemia, which is more common in people of African, African American or Mediterranean heritage. “This would be a way of finding out why,” says Freemont. Some see darker applications, however. “Some of the speculative
large-scale production-oriented ‘HGP-Write’ effort,” he said in a statement. Then there’s the question of who would own the synthesised genome. Unlike existing DNA that has been manipulated, a wholly synthetic cell could be owned outright. This could benefit any corporations involved. “If you process it in your lab, it is yours, you can patent it,” says Laurie Zoloth, a bioethicist at Northwestern University in Evanston, Illinois.
Genome owner “In the first Human Genome Project, it was clear that the knowledge gained would be owned by everyone – anyone can download and use the information,” says Freemont. “But it’s less clear how that will work with this project – this will not be digital information, this will be a physical entity… It’s an issue that hasn’t been sorted out.” Rosser says that is exactly the discussion the team’s paper is intended to catalyse. But not everyone is placated by –No easy task, ethically or technically the authors’ talk of “responsible innovation”. Zoloth and Drew goals of this project sound it doesn’t state clearly what Endy, a synthetic biologist at innocuous or benign… potential risks or ethical Stanford University, say the Others would be dangerously quandaries the project might authors fail to pose essential unacceptable,” said Marcy raise, says Baojun Wang, also at questions in their proposal. Darnovsky, who heads the the University of Edinburgh. More “Nor do they detail specific California-based Center for justifiable reasons than those limits about what should not Genetics and Society, in a given in the paper – namely that it be done.” This raises the question statement. In an interview with would deliver important scientific of whether the group is well US radio station NPR, she said: equipped to organise and lead “The worry is that we’re going to “The worry is that it could such a project, the pair say. be used to produce be synthesising entire optimised Church says that people are human genomes – manufacturing synthetic humans they working to make sure certain see as improved models” chromosomes that could be used actions cannot be carried out. ultimately to produce synthetic As an example, he points to the advances and reduce the cost of human beings that they see as now widely implemented safety genetic engineering – are needed improved models.” standards he devised in 2004 to to start the HGP-Write project, While there is no suggestion prevent DNA being used to make he says. “The investment is huge that the artificial DNA sequence biohazardous material. and long-term and will involve created by the project would be What is certain is that there is governmental taxpayers money.” still plenty of time to get things put into a human egg or embryo, Francis Collins, director of the allowing the creation of a human in order. With just a few groups from scratch, the paper doesn’t do US National Institutes of Health, capable of writing genomes with much to allay these fears. While it agrees. “NIH has not considered millions of bases, the synthetic the time to be right for funding a mentions ethical considerations, human is a long way off. n
uncertain ambition The Human Genome Project–Write was generating controversy before it was even officially announced. On 10 May, team members held an invitation-only meeting at Harvard University. Attendees were barred from speaking with the press, leaving people to guess at the applications of the rumoured project. This led to suggestions of using “the synthetic genome to create human beings without biological parents”. The reality will be less sensational but just as radical, says geneticist George Church at Harvard, one of the leaders of the project. “We are not well suited to 60-mile commutes, a super-abundance of food, and certainly not for being astronauts,” says Church. Knowledge gleaned from this project could, for example, switch off the genes that make us susceptible to type 2 diabetes. While the descriptions of the applications (see main story) seem uncontroversial enough, greater ambitions may lurk behind them. “There has been a ratcheting down of the rhetoric of the project [since 10 May],” says Hank Greely of the Stanford Centre for Law and the Biosciences. “But whether there’s been a ratcheting down of the plans, I don’t know”. Clues may lie in its leaders’ wider interests. During presentations, for example, Church likes to show a slide on which he lists naturally occurring variants of around 10 genes that give people extraordinary qualities or resistance to disease. Andrew Hessel of software company Autodesk, who first proposed the human genome synthesis project in 2012, is a lecturer at think-tank Singularity University, which explicitly tries to adapt to a future in which technology outpaces biology. Hessel has often spoken of his plans to make genetic engineering into an accessible “programming language”, using Autodesk software.
11 June 2016 | NewScientist | 17