杏吧原创

鈥淲HAT I cannot create, I do not understand.鈥� Last week, 25 leading synthetic biologists decided it was time to follow Richard Feynman鈥檚 famous credo.

After nearly two decades spent poring over the 3 billion letters or base pairs that make up the human genome, they announced a 10-year plan to chemically synthesise one. 鈥淩eading the genome can only get you so far. At some point you have to build it,鈥� says Susan Rosser of the Mammalian Synthetic Biology Research Centre at the University of Edinburgh, UK, and a co-author on the paper outlining the plan.

The team, which counts among its leaders the maverick geneticist George Church, says it is aiming to launch the ambitious initiative this year, depending on raising an initial 拢100 million.

鈥淵ou could use this plain yogurt of humanity to slot in different genes and find out what they do鈥�

The primary goal of the Human Genome Project-Write, as it is known, is to engineer large genomes of up to 100 billion base pairs, including 鈥渨hole genome engineering of human cell lines and other organisms of agricultural and public health significance鈥�, the team writes. This will require technological development early on in the project 鈥渢o propel large-scale genome design and engineering鈥� (Science, ).

The artificial genome won鈥檛 be derived from any one person, but will be created using computer-aided design 鈥� one of the main players is software company Autodesk. Chunks of synthetic DNA could then be put into cell lines, like those used to test drugs, or into E.coli bacteria, the workhorse of the research lab, with the host genetic material 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鈥檚 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 鈥� but this is also a characteristic shared by cancer cells, so a therapeutic injection of stem cells turning cancerous has long been a concern. 鈥淎 synthetic biology variant encoded to never become cancerous would be preferable,鈥� he says.

Other projects include finding the minimal human genome 鈥� the tiniest possible stash of DNA capable of supporting life 鈥� and adapting the pig genome so it becomes a better source of organs for human transplants.

There鈥檚 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.

Church calls the genome this would create a totally plain human. 鈥淚f 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鈥檛 know if the variants are causal, or how many it takes [to cause disease],鈥� he says. 鈥淵ou could use this blank slate, this plain yogurt of humanity, to slot in the different genes and find out鈥�.

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. 鈥淭his would be a way of finding out why,鈥� says Freemont.

Some see darker applications, however. 鈥淪ome of the speculative goals of this project sound innocuous or benign鈥� Others would be dangerously unacceptable,鈥� said Marcy Darnovsky, who heads the California-based Center for Genetics and Society, in a statement. In an interview with US radio station NPR, she said: 鈥淭he worry is that 鈥� manufacturing chromosomes that could be used ultimately to produce synthetic human beings that they see as improved models.鈥�

鈥淭he worry is that it could be used to produce synthetic humans they see as improved models鈥�

While there is no suggestion that the artificial DNA sequence created by the project would be put into a human egg or embryo, allowing the creation of a human from scratch, the paper doesn鈥檛 do much to allay these fears. While it mentions ethical considerations, it doesn鈥檛 state clearly what potential risks or ethical quandaries the project might raise, says Baojun Wang, also at the University of Edinburgh. More justifiable reasons than those given in the paper 鈥� namely that it would deliver important scientific advances and reduce the cost of genetic engineering 鈥� are needed to start the HGP-Write project, he says. 鈥淭he investment is huge and long-term and will involve governmental taxpayers money.鈥�

Francis Collins, director of the US National Institutes of Health, agrees. 鈥淣IH has not considered the time to be right for funding a large-scale production-oriented 鈥楬GP-Write鈥� effort,鈥� he said in a statement.

Then there鈥檚 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. 鈥淚f you process it in your lab, it is yours, you can patent it,鈥� says Laurie Zoloth, a bioethicist at Northwestern University in Evanston, Illinois.

Genome owner

鈥淚n the first Human Genome Project, it was clear that the knowledge gained would be owned by everyone 鈥� anyone can download and use the information,鈥� says Freemont. 鈥淏ut it鈥檚 less clear how that will work with this project 鈥� this will not be digital information, this will be a physical entity鈥� It鈥檚 an issue that hasn鈥檛 been sorted out.鈥�

Rosser says that is exactly the discussion the team鈥檚 paper is intended to catalyse.

But not everyone is placated by the authors鈥� talk of 鈥渞esponsible innovation鈥�. Zoloth and Drew Endy, a synthetic biologist at Stanford University, say the authors fail to pose essential questions in their proposal. 鈥淣or do they detail specific limits about what should not be done.鈥� This raises the question of whether the group is well equipped to organise and lead such a project, the pair say.

Church says that people are working to make sure certain actions cannot be carried out. As an example, he points to the now widely implemented safety standards he devised in 2004 to .

What is certain is that there is still plenty of time to get things in order. With just a few groups capable of writing genomes with millions of bases, the synthetic human is a long way off.

This article appeared in print under the headline 鈥淪ynthetic humans are go鈥�