Is a synthetic human genome project a step too far?

Philippa Brice

14 June 2016

Debate continues to rage following the leaked news that scientific experts had convened a ‘secret’ meeting to discuss plans to create an artificial human genome – the ‘next chapter in our understanding of the blueprint of life’. The idea appears to be the brainchild of renowned geneticist George Church and colleagues, building on progress in genetic engineering and synthetic biology that yielded the first synthetic bacterial cell in 2010.

From HGP-read to HGP -write

Initial secrecy surrounding the meeting no doubt fuelled press speculation. It may even have been a shrewd PR move by the meeting organisers who subsequently have been (relatively) swift to release details of their proposals.

Arguing that the original Human Genome Project should be renamed ‘HGP-read’ Jef Boeke, George Church and colleagues contend we should convene a fresh, $100 million global consortium to scale the next genomic peak: the Human Genome Project-write or ‘HGP-write’, would seek to massively expand existing capacity to synthesise DNA.

A scientific endeavour to ‘understand, discuss, and apply large-genome engineering technologies’ for human genome-scale synthesis is, they say, timely and should catalyse game-changing falls in cost. The primary goal of HGP-write would be to reduce the costs of engineering and testing large genomes in cell lines (including, but not limited to, human cells) by over 1000-fold within 10 years.

Such efforts, they claim, would aim to address human health challenges such as growing human organs for transplant, engineering viral immunity or cancer resistance in cell lines and ‘accelerating high-productivity, cost-efficient vaccine and pharmaceutical development using human cells and organoids’. The project would clearly have considerable commercial interest, but proposers say it would be feasible to encourage broad intellectual property access via patent pooling

The rights and wrongs of HGP-write

Not surprisingly, alarm bells have been ringing. Stanford’s Drew Endy, himself a bioengineer (and an invitee to the original HGP-write meeting) co-authored a response  with bioethicist Laurie Zolof in which they argue greater research and health benefits would derive from ‘synthesis of less controversial and more immediately useful genomes along with greatly improved sub-genomic synthesis capacities’. This would, they say, reduce the risk of an own goal for science, should adverse public reaction to the HGP-write concept deter wider fields of research. They also raise ethical concerns over simultaneous proposals for changing the human genome, such as to resist viral infection, suggesting it could spur a ‘genome-engineering arms race’.

Proposers of the project are keen to stress that the HGP-write would involve public consultation and scrutiny of ethical, legal and social issues (ELSI) and even the dedication of a proportion of its research funding for ‘inclusive decision-making’. However, they also claim that responsible innovation requires the identification of ‘common goals important to scientists and the wider public’ via stakeholder consultation. 

This sounds good, but could it lead to the relentless promotion of goals framed solely as life-saving medical intervention? It is difficult to object to impassioned proposals to save the lives of innocent children, for example, without seeming callous, even if there are reasonable ethical, social or other objections or concerns. This dilemma was typified by UK debate on proposals for legal changes (now enacted) to permit mitochondrial transfer procedures.

More fundamental concerns are outlined by Endy and Zolof, who observe: ”When the first people at the table mostly have significant and direct material interests in proceeding, everyone, not just those in the room, risk out-of-control competition between public and private interests, ethical conflicts of interest, and temptations to manipulate human subject consent”. They caution that to create an artificial human genome “would be an enormous moral gesture”. 

Endy later reiterated that he personally would draw the line at the synthesis of a human genome, observing: “The human genome is special to me — it’s the thing that connects us”.

Towards new scientific – and ethical - frontiers

Proponents of HGP-write are clearly keen to encourage public dialogue, but they also assume the project will go ahead, and that given international variation in regulations ‘a major burden of responsibility of setting standards’ rests with the scientists themselves. Whether the public will agree remains to be seen. 

Church has reportedly claimed that synthetic biology will rapidly overtake CRISPR as the go-to genomic technique of modern science; if so, perhaps the ethical debate over gene editing was merely essential preparation for bigger challenges to come. How soon human genome synthesis could be possible, in scientific terms, remains unclear. Whilst the project proposers aim for a ten-year timescale, it could take longer. The technical challenges are at least as vast as those at outset of the HGP. Sequencing pioneer Craig Venter himself has said that “I don’t think anybody is going to make synthetic humans any time soon”. But perhaps it will be rather sooner than we might have expected.