But today I have to admit the wind has been temporarily removed from my sails as the world finally got an idea of what went down on May 10th, 2016 at Harvard. Dr. George Church, world-renowned geneticist, held a closed-door meeting with numerous other geneticists, bioethicists, lawyers, and industrialists about the emerging field of synthetic biology - specifically whether it was worth building a human genome from scratch. The media caught word of this and a few days later several articles were published, with rampant speculation as to what was discussed. Research opinion articles started to come out from others in the field (not invited to the discussion) with some very valid talking points about feasibility, practicality, and important societal, moral, and ethical considerations. I have since learned that the entire meeting was videotaped and will be put up live online in the coming days. It was only withheld (apparently) because the corresponding peer-reviewed article calling for a new initiative to synthesize the human genome was still under consideration.
I have to admit I think Drs. Boeke, Church, Hessel, and Kelley (referenced here as BCHK, the co-first authors of the article summarizing this May 10th meeting) really handled this poorly. There should never be a closed-door discussion about the use of new technologies in molecular biology, especially without the involvement of the general public and press. All of this secrecy leaves a bad taste in my mouth. For something like this, where so many people have an opinion to contribute, doing it this way does not cast the endeavor in a good light. And in addition, there were other meetings back in October 2015 at NYU (which didn't get much press) that also contributed to the paper put out yesterday. This is cited at the end of the article, which I link to below.
OK, so what the hell is going on here?
In a nutshell, Drs. BCHK and others published a Science Perspectives article promoting the launch of the so called Human Genome Project - Write (HGP-Write). A publicly-and privately-funded initiative to synthesize a complete human genome from scratch in order to push forward several areas of biomedical research. The idea is to build a synthetic human genome (using natural DNA bases) to work within a living cell and address fundamental questions about development, immunity, disease, and other biological questions about genetics. I'm not going to get into the scientific merits of the proposal today (I will soon). But I will mention that the technology to do something like this, and on this scale, needs to be refined. This technology has been utilized to synthetically engineer the genomes of select bacterial and viral species, but this is small potatoes compared to the human genome.
I'm bringing this up here because my immediate reaction to his was very skeptical and there are some outstanding issues that aren't raised in the paper that I think need to be immediately addressed:
1. BCHK conveniently use acronyms to mush together several essential topics in this discussion. They say in the article, "HGP-Write will require public involvement and consideration of ethical, legal, and social implications (ELSI) from the start. Responsible innovation requires more than ELSI, though, and involves identifying common goals important to scientists and the wider public through timely and detailed consultation among diverse stakeholders."
This is all well and good, but when your first substantial meetings on this topic are closed-door, this kind of blows all credibility out of the water....not to mention ELSI is a convenient way to shrug off some of the vital roles these topics by clumping them all together and conveniently under one umbrella concept.
This is immediately followed with, "We will 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."
Again, all well and good on its own. Except at the end of the article they also say, "The goal is to launch HGP-Write in 2016 with $100 million in committed support, from public, private, philanthropic, industry, and academic sources from around the world."
If the goal is to launch in 2016, how can any discussion be "well in advance", as suggested earlier? In science a 'well-advanced' time frame often means a year or two out, not in the coming months. This is especially true for the academic, extramural peer review program used by most institutions. This isn't enough time, especially because the debate about CRISPR is still ongoing.
2. Francis Collins, Director of the NIH, has already stated in response that the NIH, "has not considered the time to be right for funding large-scale production-oriented [projects]...whole-genome, whole-organism synthesis projects extend far beyond current scientific capabilities, and immediately raise numerous ethical and philosophical red flags."
Not quite a ringing endorsement is it? I think this is an important response that shouldn't be ignored. To be fair, Dr. Collins was the spearhead of the Human Genome Project, and may feel some personal protection over the human genome since he sequenced it (credit goes to Dr. Venter too, for spurring the government along from a sluggish start). Dr. Venter is the guy from industry who helped contribute to the sequencing of the human genome AND he's the guy that built one of the first bacterial genomes (like what I mentioned above) at his own company. I can already see this turning into Part 2 of the 'Publicly-funded vs. Venture capital-funded' battle royale that waged two decades ago during the Human Genome Project.
Yes folks, scientists are all about the drama, too.
3. A few other very important tidbits that haven't been addressed:
-Once this thing gets built (which will certainly take a long time), who then owns it? Can the entire human genome be patented? What about huge stretches of DNA sequence surrounding a single gene? I shudder at the thought.
-Several of the authors have financial stakes and considerations with companies that perform genome synthesis or work with related technologies. While these relationships have been disclosed in the Science article, I can't help but think many of these scientists could financially benefit from a massive endeavor in this area. I'm not saying that's already happened, but it's a possibility that makes me a little curious and that certainly could happen.
-There was an appalling lack of concern, scientifically-speaking, in two key biological areas:
i. There are still parts of the human chromosomes, including sequences at the telomeres, centromeres, and within long CpG stretches, that are still a little ambiguous with respect to a streamlined, definitive sequence. This will need to be resolved to make an accurate and functional genome.
ii. More importantly, there was no mention at all about epigenetics. The human genome is heavily chemically modified along the backbone and the nucleotides themselves. These modifications govern how the genome is 'read' by the molecular machinery and how genes are expressed. The chemical signature of the human genome, often called the epigenome, is essential to proper function of our DNA on a variety of levels, and also includes the tens of thousands of copies of proteins that help structure the chromosomes and maintain its integrity. If we are just stringing together some base pairs, without the context of the nucleus and the epigenome, what biological value can really be obtained that makes this worth doing? I'm not convinced yet and the lack of any discussion about this troubles me. The epigenome is incredibly complex, maybe even more so than our actual DNA sequence. Changes in the epigenome are heritable and contribute to a variety of processes in our body and in disease states. This has to be addressed.
So, I'll leave it at that for now. Enjoy this little quote from Mary Shelley's Frankenstein and a nice picture of Gene Wilder as Dr. Frankenstein.
"Man," I cried, "how ignorant art thou in thy pride of wisdom!"
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