Proposal for second Human Genome Project draws mix of criticism and acclaim

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A group of leading experts in synthetic biology along with a few life science entrepreneurs have proposed one of the most ambitious and controversial projects since the effort to decode the human genome was launched close to three decades ago. Now scientists want to write the code for human life themselves.

Called Human Genome Project-Write (HGP-Write), the primary goal is to “reduce the costs of engineering and testing large (0.1 to 100 billion base pairs) genomes in cell lines by over 1000-fold within 10 years. This will include whole-genome engineering of human cell lines and other organisms of agricultural and public health significance” according to noted researchers Jef Boeke, George Church and colleagues writing in the journal Science.

Controversy surrounding the project made headlines a few weeks ago, when it was reported that an invite-only meeting that was closed to the press was held to discuss the proposal. A critical commentary by Stanford synthetic biologist Drew Endy and Laurie Zoloth, a bioethicist from Northwestern University chided the organizers of the meeting for discussing something as ethically important as making a human genome in a secretive atmosphere and without really asking the question of whether such a project should be conducted in the first place.

Perhaps after recognizing the concerns surrounding this endeavor, in the current Perspectives article the authors stated right up front the need for ‘responsible innovation’ that includes but is not limited to addressing the ethical, legal and social implications (ELSI) of HGP-Write. The project, they noted, would “enable broad public discourse on HGP-write; having such conversations well in advance of project implementation will guide emerging capabilities in science and contribute to societal decision-making.”

HGP-Write is set to progress in phases, with pilot projects attempting to build build larger and larger genomes from scratch, while simultaneously improving the technology and lowering the cost needed to synthesize long strands of DNA molecules. The project could have great potential if successful, the authors wrote, from growing transplantable human organs to engineering therapeutic cells that are cancer resistant and identifying and developing new bio-based energy sources.

Scientists commenting to the Genetic Expert News Service and the UK Science Media Centre, (including some who were involved in the meeting) called the project ambitious and complex but indicated that the payoffs could benefit society immensely.

Dr. Samuel Deutsch, Head of DNA Synthesis and Assembly at the DOE Joint Genome Institute said “Accomplishing such a milestone will require transformative advances in DNA synthesis technologies relative to current state-of-the-art.” He pointed out that while it is unclear what the immediate applications would be, the ones proposed by the authors would have “clear societal benefits”

Professor Richard Kitney, Co-Director and Co-Founder of the Centre for Synthetic Biology and Innovation at Imperial College London highlighted the emphasis the project placed on global impact, saying “There is a strong emphasis in both the paper and the more general field towards applying any technology which is developed to problems in the developing world as well as the developed world, in the context of responsible research innovation.”

No taxpayer funding, yet.

HGP-Write could cost as much as $1 billion, according to Andrew Hessel who was interviewed by BuzzFeed news. Hessel is a distinguished researcher at San Francisco based software firm Autodesk and one of HGP-Write’s organizers. For its part, Autodesk has committed to $250,000 of the initial $100 million that the organizers think would be needed to kickstart the effort. “HGP-write is just the sort of potentially world-changing endeavor that Autodesk is proud to stand behind,” wrote Autodesk’s chief technology officer in a Medium blog post announcing the move.  

Francis Collins, director of the NIH, confirmed that at this point there was no intention to fund a project like HGP-Write on the scale of the Human Genome Project. According to the New York Times:

Dr. Collins said in a statement that while N.I.H. was interested in encouraging advances in DNA synthesis, it “has not considered the time to be right for funding a large-scale production-oriented” project like the one being proposed.

He added that “whole-genome, whole-organism synthesis projects extend far beyond current scientific capabilities, and immediately raise numerous ethical and philosophical red flags.”

Red flags

The ‘red flags’ have been brought up by other experts as well, most stridently by Drew Endy who posted the initial criticism of the project. Responding to questions from BuzzFeed news, he said “Boeke et al.’s current proposal should be broadly rejected and not now pursued.” In a statement reported by the New York Times, Endy and Zoloth said “Before launching into such a momentous project, with such enormous ethical and theological implications, a basic ethical question still needs to be asked — starting with whether and under what circumstances we should make such technologies real,” said a statement issued by Drew Endy, a bioengineer at Stanford, and Laurie Zoloth

Commenting to the Genetic Expert News Service, Megan Palmer, the William J. Perry Fellow in International Security, Center for International Security and Cooperation (CISAC) at Stanford University said “It’s admirable that the authors state a need for an early, ongoing and participatory approach to the societal aspects of their work. However, it’s not clear how such work will proceed. To use their own language – how they will go from observation to action?”

However, other scientists have pointed out that the project only aims to create cell lines, and is nowhere close to being able to create humans.

Paul Freemont, Co-Director of the Centre for Synthetic Biology and Innovation at Imperial College London and one of the meeting’s attendees said “It’s important to note that the human genome synthesis project, if started, will be implemented in a non-reproducing laboratory cell line.”

Sriram Kosuri, an assistant professor of Chemistry and Biochemistry at the University of California Los Angeles and a former member of George Church’s lab said in response to the earlier news about the closed-door meeting “my understanding is that there is no real technical ability nor desire to work on making genetically engineered humans, so I’m not sure what all the controversy is about.”

Despite the criticism, it remains that the project has some strong backing from some of the world’s leading experts and is likely to move forward, unless explicitly prohibited by a government regulator. It may be have been the best move to start the conversations early, given the contentious nature of the research and its global impact. Sharon Begley and Ike Swetlitz of STAT may have put it best in saying “the train has left the station.”

Arvind Suresh is a Science Media Liaison at the Genetic Expert News Service, a freelance science communicator and a former laboratory biologist. Follow him @suresh_arvind

  • David Ashton

    Amazing that for some people the “artificial” creation of human beings, and the extermination of human beings before or soon after they are born, is great progress, whereas painless eugenics and “scientific racism” remain taboo.

  • Roy Williams

    This will be a very cool project – better if coupled with parallel advances in our ability to computationally predict protein function. Instead of being limited to existing genetics we can find in samples, being able to generate a much larger array of genetic variants for investigation would seem likely to greatly improve our ability to test hypotheses about gene function, and determine the potential outcomes of various possible genetic modifications. The use of language to describe this as “synthesizing the human genome” is inappropriate, and not helpful in the public relations arena. The point is not to “synthesize a human”, but to be able to synthesize any arbitrary segment of human DNA for research purposes. Hopefully this project will not get caught up debates over ethics