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The controversy over a “secret” meeting on synthetic human genomes?

Reports of a “secret” meeting on synthetic human genomes have caused quite the uproar online. Some of the headlines and comments conjured up sci-fi plots of new artificial humans. While many predictably overhyped the meeting, there are still open questions for the synthetic biology community and society as a whole to answer. The possibility of synthetic genomes reminds us of the balance and pace of pushing science into areas in which policy and bioethics may not always keep up. Similar discussions of societal values and policies are ongoing for genetic screening and gene editing. While we can’t answer all of these questions here we can try to address some of the big questions that this meeting and its controversy raised in the larger conversation on bioethics and transparency in science.

First, we need some basics on what happened. Last week roughly 150 invited guests discussed the possibility of synthesizing huge amounts of DNA up to an entire human genome. For the record, as a lowly graduate student I was not on that list. Organizers included Harvard professor George Church, NYU professor Jef Boeke, and Autodesk researcher Andrew Hessel. Church, known for his scientific contributions to reading/writing/editing DNA and his public facing role including visits to Stephen Colbert at the Colbert Report and the Late Show, has been particularly in the spotlight as questions over the meeting swirled on the internet. Guests seem to have included people from academic research, industry, law, and policy who all met to discuss a DNA synthesis project that could rival the sequencing efforts of the Human Genome Project.

DNA synthesis means building up a new DNA molecule using chemical means instead of modifying an existing DNA molecule. Synthesis is getting cheaper and more efficient but is not yet ready for the scale of the humane genome which is about 3 BILLION base pairs of As to Ts and Cs to Gs. 3 billion is the kind of number that’s difficult for our brains to even grasp. So for reference, companies offering gene synthesis services can regularly make sequences of hundreds to a couple thousand base pairs for a few hundred dollars. In 2008, the J. Craig Venter Institute achieved the milestone of the first synthetic bacterial genome with 580,000 base pairs and in 2010 they synthesized and assembled the 1.08 million base pairs of the Mycoplasma mycoides genome. Currently, the Sc2.0 international consortium is working to build synthetic yeast chromosomes totaling about 12 million base pairs of DNA. A human genome would be quite the feat since it is ~250 times larger than the yeast genome. A successful human genome would include the correct 3 billion base pairs of DNA and be able to function in cells which would require proper packaging and DNA modifications. It would NOT mean creating an artificial human, so leave that in your sci-fi thriller for now.

Jane Ades, NHGRI - source: https://www.genome.gov/dmd/img.cfm?node=Photos/Graphics&id=85335
Jane Ades, NHGRI – source: https://www.genome.gov/dmd/img.cfm?node=Photos/Graphics&id=85335

If we can’t yet synthesize a human genome then why have the meeting now?

Because a project of this size would take planning and obviously not everyone agrees that we should even do it. The meeting reportedly had the goal to “synthesize a complete human genome in a cell line within a period of 10 years.” This goal would require ethical and technical discussions on the goals, policies, and funding to guide such an ambitious project. Synthetic genomics is certainly not new, but applying it to the human genome would be. In fact, a criticism has been that such meetings would need to include even more perspectives before moving forward. Simply put, this would be a big deal for science and the ethical questions of what biotechnology should do.

So why would the meeting be secret?

Let’s start with the fact that the event was not actually secret but more like closed. There were always plans to share outcomes from the meeting, but the organizers asked attendees to avoid media/publicity during the meeting. This still rubbed some people the wrong way and the perception of secrecy certainly did not come off well. I first heard of the meeting as Stanford synthetic biologist Drew Endy tweeted out a screenshot of the invitation with obvious disapproval of the closed door nature of the meeting.

Wait, I still don’t know why it would be closed. Why wait to share?

Apparently, it was not originally intended to be closed but a journal had an embargo on the subject matter since a related manuscript was under review. This rationale for closing the meeting brought in more controversy over the role of big name journals in disseminating science. While the organizers will be publishing a paper, the pace of information is slowed and depending on the journal it may be behind a paywall.

Ok. Then what does this say about the pace of open science?

There was already a raging debate in science communities over the pace and nature of sharing scientific results and ideas. Open access vs subscription journals continues as the economic models for journals and metrics for judging academic scientists evolve. More recently for biological science, preprint versions of articles have been debated and adopted by many as a way to more quickly and openly communicate scientific results. Open science advocates want to see all work made available to the public as soon as possible to promote scientific progress and public access. The embargo enforced by a journal certainly speaks to the power of major journals and the metrics that academics are judged on. However, the meeting was originally meant to be more open, and a video of the meeting is still supposed to be made public along with the peer reviewed article that’s under review. This was not the secret meeting of nefarious scientists that some headlines might promote, but rather an important scientific discussion that got bogged down by the clunky nature of the current scientific publishing environment and priorities.

But why would we even want to synthesize a human genome?

Well the project really aims to push DNA synthesis forward in general and a human genome could be a grand challenge like the Human Genome was for sequencing. DNA synthesis will play a large role in biotechnology going forward, but the question of attempting a human genome is far from settled. Building a genome may teach us more than just the sequence alone as there are more aspects than just DNA sequence that go into packaging DNA into functional chromosomes. However, some such as Drew Endy and bioethicist Laurie Zoloth have questioned the ethical implications of doing this for a human genome and pointed toward synthesizing less controversial DNA that may have more immediate uses (see Should We Synthesize A Human Genome?).

It seems like everyone has been discussing this meeting. Even the satirical twitter account Bored George Church had to poke fun at the meeting.

If you want to read more on the meeting and the implications synthesizing a human genome you should check out the early reporting and analysis from STAT, the insightful blog post from Rob Carlson, the previously mentioned paper from Endy and Zoloth, Andy Balmer’s post on secrecy in science and synthetic biology, and the NY Times coverage. We’ll also be sure to link to the organizers’ article and meeting video once those become available. Have more resources or opinions that the community should know about? Let us know in the comments or on Twitter.

 

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