Midsummer Madness: A News Roundup of Synbio Moonshoots

“Why, this is very midsummer madness.” Shakespeare, Twelfth Night

In the fast moving field of synthetic biology, things have been speeding up over the last couple of months. Control of infectious disease is a hot topic with concern about the transmission of the Zika virus. The outbreak has spread from South America, with the first confirmed cases in the US in recent months, and there is talk that the virus could reach Europe this summer. Release of genetically modified mosquitoes has been proposed as part of the solution, and Oxitec who commercialized the process, announced expansion of their vector control project in Brazil in April.

Fast forward, and excitement about the potential of genetic tools to combat disease led to a meeting on Nantucket last week. The purpose was to gauge opinion about using a gene drive involving transgenic mice to counteract the spread of Lyme disease, an affliction which affects up to 40% of the island’s residents.

However the technology remains highly controversial as it has the potential to wipe out entire species. Gene drives are currently prohibited, and policy makers have been struggling to keep pace with scientific developments. The National Academy of Sciences, Engineering and Medicine began to address the issue with the release a much anticipated report into ‘Gene Drive Research In non-Humans’ on the 8th of June. The authors found that:

“There is insufficient evidence available at this time to support the release of gene-drive modified organisms into the environment.”

But went on to say:

“The potential of gene drives for basic and applied research are significant and justify proceeding with laboratory research and highly-controlled field trials.”

Which means it is not clear how effective gene drives are, but they suggest proceeding with field trials to test them out. The report was followed up by an excellent opinion piece from a range of leading experts, where concerns were raised that ecological science is not yet at a stage to predict the consequences of gene drives, that the infrastructure to conduct field trials is lacking and that a ‘one size fits all’ approach to regulation is unsuitable.

In response to the report Kevin Esvelt, a professor at MIT, made an impassioned call for open-science. He argued that researchers should start adopting the default position that any gene drive will get out into the environment, and as a result scientists should be completely transparent about their plans from the beginning because of the potential to effect the wider community.

Further calls for caution could be found elsewhere, with involvement of the US military department DARPA causing particular unease about the possibility of weaponization of synbio. The NAS report is not the final word on the issue, and it is important the debate continues.

Editing with style

Developments in gene editing tech are never out of the headlines for long. May 26th provided a notable highlight when researchers apparently inspired by German philosophy, produced GESTALT – a neat approach that uses CRISPR to create DNA barcodes to facilitate tracking of cell lineages. This could help our understanding of organisms as they grow from single cells, or follow the progression of tumors (I can highly recommend the infographic accompanying the science editorial for further explanation).

Additionally, if editing DNA with CRISPR/Cas9 isn’t enough for you, the Zhang lab published the first programmable CRISPR system able to cleave RNA, known as C2c2 – firing the starting gun on a rush for smart applications in RNA regulation.

Give me some mo‘

The seemingly insatiable demand for DNA synthesis started at the end of April, when Microsoft announced the purchase of 10 million bp of DNA from Twist Bioscience to drive their DNA storage program. The idea has been around for a while, with the first successful encoding of information in DNA by George Church and co. in 2012, followed by researchers at the EBI in 2013 who wrote Shakespeare’s 154 sonnets in the script of life.

The reason for this is simple, data storage centers are costly to run and eat electricity, so much so, Amazon is using a hydroelectric dam to power their new cloud computing facilities. This is a problem that will only grow, Microsoft predict global data storage demand will be 17 zetabytes by 2017.

Just try and imagine this:  1ZB= 1000⁷bytes = 10²¹bytes = 1000000000000000000000bytes = 1000exabytes
= 1millionpetabytes =1billionterabytes = 1trilliongigabytes!!! – a number that even the starry eyed Prof. Brian Cox would struggle to articulate.

By Microsoft’s own calculations, using DNA they can store up to 1 exabyte per cubic millimeter… that would mean we could store the global annual data requirements in a Falcon Tube!

However, there are many challenges to overcome before this becomes a reality, and as MIT’s Jake Beal wrote on his blog back in April, it is likely that DNA hard drives will be best suited for long term data storage.

If Microsoft’s appetite for DNA seemed big, this week’s announcements make synbio startup Ginkgo Bioworks look positively greedy. Ginkgo raised $100 million dollars to build on last year’s purchase of 100 million base pairs – ordering 300 million base pairs from both Gen9 and Twist Bioscience. The DNA among will be put to use, among other things to synthesize fragrances for expensive perfumes.

At a cool 600 million base pairs, this is equal to ~60% of the total amount of synthetic DNA sold in 2015. What the deals show, is that the fall in cost of DNA synthesis is quickly changing the way molecular biology is done. Jason Kelly, Ginkgo’s co-founder was quoted as saying:

“If your company is still cloning by hand you’re missing out on a big opportunity.”

However, all this has merely preparation for the main act: As the saying goes – if you are going to dream, dream big – and that’s certainly what the folks in Boston have been doing recently.

‘The Future Belongs to those who believe in their dreams’  – Eleanor Roosevelt 

Things started a bit cloak-and-dagger with the secret-not-so-secret closed door meeting at MIT, in which 150 guests were invited to speak about possibility of synthesizing the human genome. Perhaps understandably this had many up in arms about the need for openness in science to maintain public trust. The meeting was quickly followed by a publication in Science introducing idea of Human Genome Project write (HGPwrite).

The proposal is to ‘move from observation to action’ as a a follow on from the successful Human Genome Project (HGP) to create a synthetic human genome. The scientific justification is to provide foundational tools for the engineering of biological organisms.  The authors propose to create a standard human cell line for experimentation, allowing investigation of the causes of human disease and cancer, in addition to giving a boost to gene therapy and the study of enigmatic parts of non-coding DNA. The authors estimate it will cost less than the $3 billion cost of HGP-read.

One of the motivations behind the idea is that the cost of gene synthesis can be brought down by adopting a grand challenge which would create an overwhelming demand for DNA. Such a price drop would likely revolutionize molecular biology, making laborious cloning a thing of the past – thereby rapidly increasing the pace of development.

However, there is far from unanimous agreement in the scientific community that the proposal is justified. Drew Endy, a long time champion if synbio, wrote a piece criticizing the aims of the project along with bioethicist Laurie Zoloth. Firstly they argued that focusing on such a controversial topic will cause strong moral or religious objections from many sections of society, suggesting that the resulting backlash could actually cause harm to the field as a whole. To address this they called for an open discussion beyond scientific circles to ask if synthesizing the human genome this is morally acceptable. They went on to question if efforts could be better spent on less controversial sub-genome engineering projects such as direct printing of plasmids, and pointed out concerns that people involved in the project have material interests in its success, through links to gene synthesis companies.

Things are happening at such a rate there is hardly time to catch breath. This matters, as these developments have the potential to fundamentally change our relationship to both the environment and to ourselves as a species. As Kevin Esvelt said, ‘regulation will always be too slow’. The question is how do we deal with this?

The opinions expressed in this article are personal and not representative of PLOS. For more information about gene drives we recommend visiting http://www.sculptingevolution.org/genedrives