Policy

The CRISPR gene-edited babies: a technological breakthrough or a brave new future?

  He Jiankui announcing the birth of the gene-edited twins on Youtube

He Jiankui announcing the birth of the gene-edited twins on Youtube

The announcement of the first CRISPR gene-edited babies has sparked a major polemic in the scientific community, but also in the media and the public. The research was discreetly carried by a Chinese team lead by He Jiankui at the Southern University of Science and Technology (SUST), in Shenzhen. He announced in a Youtube video: “Two beautiful little Chinese girls, Lulu and Nana, came crying into the world as healthy as any other babies a few weeks ago”. The research team have used CRISPR to deactivate the CCR5 gene in the embryos, which were then implanted into the mother. The CCR5 gene encodes for a protein that enables the HIV virus to enter in human cells. The aim was to deactivate it to reduce the risk of HIV infection, as the father was HIV-positive. This procedure has been apparently applied to eight couples. However, its success is still unclear, as no data or details were publicly released yet.

 

  Deletion/insertion in genome by CRISPR Source: Wikimedia

Deletion/insertion in genome by CRISPR Source: Wikimedia

In response to this announcement, many researchers in China and abroad condemned this experiment. Feng Zeng, the pioneer researcher in the application of CRISPR in mammalian cells, called for a global moratorium. Feng insisted that he was “deeply concerned” of the fact that the project was secretly undertaken. More than a 100 Chinese scientists have also signed a letter condemning the experiment. This announcement also coincides with the Second International Summit on Human Genome Editing in Honk Kong, where many researchers reiterated the condemnations against the experiment. It was highlighted by Qiu Renzong (Chinese Academy of Social Science) that this violates the regulation in China, which is however not penalized. In opposition, George Church (Harvard University) defended it saying that HIV was “a major and growing public health threat” and “I think this is justifiable”.

The whole story is not fully known yet, and we still need to wait a few days to have more information to find out how the experiment was conducted. However, this story puts at risk the near future of gene editing, due to the way it was carried, with the secrecy around the project and the non-respect of ethical procedures.

  Off-target effects of CRISPR Source: Wikimedia

Off-target effects of CRISPR Source: Wikimedia

At first, the issues with off targets in CRISPR gene-editing means that there are still high risks of inducing unwanted modifications in the genome. So, the babies risk irreversible damage in their genomes, potentially transmitting these to their offspring. Secondly, the way the team carried this experiment creates multiple ethical and practical issues. If the public see that scientists can decide to “engineer babies” in secret without any safety check, we risk to end up banning or restricting CRISPR even more. From an ethical point of view, using CRISPR was not a last resort solution here; other safer options exist to avoid HIV transmission from parents to their children. In practice, the cost of an IVF is not accessible to the vulnerable populations where HIV spreads. The CCR5 gene was probably an “easy” target, giving the opportunity to be the first one in the race to apply CRISPR in humans. But, the attention that this story attracts can negatively impact the public (and policy-makers’) perception of scientists and CRISPR. If the technology lacks a wide public understanding and support, it could delay the release of validated lifesaving treatments for many years.

Even if one day humanity decides to modify itself to prevent diseases, it is still too early and it is not the choice of a single person or a small group of academics. In the end, as scientists, we should do our best to bring life changing solutions, like human gene-editing, in a responsible way to make sure of the best positive impact possible.

“All conditioning aims at that: making people like their unescapable social destiny”

Aldous Huxley, Brave New World


Posted by courtesy of the PLOS Synbio Community blog, where this was originally published.

Written by: Adam Amara

Disclaimer: Views and opinions expressed in EUSynBioS Pulse articles belong solely to the writer(s). They do not reflect the opinion of the Community, the Advisory Board or the Steering Committee.

Geoengineering and synthetic biology

This September, as part of our annual symposium, EUSynBioS will hold an Open Discussion on the topic, "Synthetic Biology and Environmental Engineering", at the National Center for Biotechnology, Madrid, Spain. We will host experts in the field to talk about the science and the more difficult aspects of public acceptance and bioethics surrounding geoengineering and synthetic biology. 

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Geoengineering is a word that means many things to many people. Formally defined as the "deliberate intervention in the climate system to counteract man-made global warming", for some scientists it represents a cheap and effective way to protect our planet from the ravages of climate change. To others it's symptomatic of technological hubris: a grand, doomed plan to control every aspect of our ecosystem. Dig past the rhetoric though and you find a science that's still in infancy, being developed by scientists around the globe, almost as a last resort in the (now very possible) event that on-going efforts to avert climate catastrophe by reducing global emissions fail.

Current research on geoengineering is focused on either removing carbon dioxide from the Earth's atmosphere or reducing global warming by reflecting more solar radiation away from the planet. Most proposals to achieve these goals rely on physical engineering solutions, cloud seeding for instance. A more expansive reading of "geoengineering"though, leads to several intriguing ideas on using synthetic biology to remedy the effects of intensive industrialisation/pollution on the environment.

i. pale blue dot

In 1980, the US Supreme Court issued a ruling that changed the status of living organisms forever. In Diamond v. Chakrabarty the court affirmed the right of inventors to patent living organisms that had been modified for some purpose. In this case, the patent was granted to a genetically engineered creature called the Superbug. The Superbug was a strain of Pseudonomas putida that could break down crude oil, and was posited as a tool to deal with oil spills. Since then, there's been a lot of work in developing such organisms, spawning a field of science called bioremediation that seeks to undo the damage human industry causes the environment. 

Now, a group of scientists are advocating the use of such organisms on a global scale to help mitigate the effects of climate change. Their, very SciFi-ish, ideas include: modifying particular species of bacteria that exist in harsh environments like deserts and equipping them with water harvesting capabilities; releasing entire stretches of DNA into a biosphere and allowing them to spread, equipping any host creature with water/temperature sensing capabilities, or releasing bacteria into the oceans that can cause pieces of plastic to stick to each other, solving the scourge of microplastic pollution. 

biologists are ever-aware of the conceit involved in predicting biological futures

These and other ideas find few takers though, and carry some real risks. We would have to be prepared to deal with the fact that any man-made bacteria released into a particular part of the world might escape a particular ecosystem, potentially wreaking havoc in others. Biological entities evolve, and evolution might change released modified bacteria in unpredictable ways. 

These are concerns synthetic biologists are tackling head on. In the last five years, we've made tremendous progress in engineering 'kill-switches' that could allow us to precisely control engineered bacteria in natural ecosystems. We've also developed bacteria which have been so extensively engineered that they cannot interact with other life-forms very well, or cannot reproduce, hence limiting the potential spread of synthetic DNA. Yet, biologists are ever-aware of the conceit involved in predicting biological futures and for the moment these bacteria will remain in petri dishes in labs around the world. 

ii. the red planet

The largest concern with biological geo-engineering is the fact that we might cause dangerously irreversible changes to the only habitable planet we know of. This is why, a group of scientists including NASA researchers are exploring biological options in terraforming Mars. The hopes are many, ranging from making Mars human-habitable (paving the way for eventual human colonisation), to using the red planet as a test-bed for ecosystem engineering whose lessons might then rescue the Earth from climate catastrophe. Less futuristic scenarios include the possibility of employing bacteria to harvest resources directly from Mars, or recycling consumable resources like waste-water, making manned Mars-missions a cheaper and easier endeavour. Most experts agree though that terraforming, the process of completely changing Mars' atmosphere is a process that could take centuries. A nearer-term option is something called para-terraforming. Paraterraforming envisions making smaller, enclosed spaces on Mars habitable for humans. Previous experiments in paraterraforming conducted on Earth have met with little success; however the prospect of engineering organisms specifically for terraforming makes this a more feasible proposition. 

Some however, question the ethics of using Mars as a lab-bench. One argument is that any human attempt at terraforming Mars might destroy or alter any remnant, hitherto undiscovered life on the planet. Another, that seeding Mars with terrestrial life may change a potential independent development of biological life on the planet in the distant future. These are minority opinions however. A view that, in my opinion, holds more merit suggests that the creation of Mars as a back-up planet might hinder attempts to mitigate anthropogenic climate change and pollution here on Earth.

iii. a last resort

There are two forms of climate change mitigation on the table at the moment, passive and active. Passive mitigation uses methods that are easier to swallow for most, reducing global consumption, stricter pollution controls, and switching to low-carbon sources of energy. The problem however lies in the fact that passive mitigation alone might not be enough to limit global warming to the 2°C threshold set by the Paris Agreement. Indeed, experts are highly sceptical that limiting warming to even 4°C is feasible given current trends. And the difference between a 2°C and 4°C limit is that the latter will result in massive droughts, flooding on an unprecedented scale and food shortages.

In this scenario, several climate experts have called for more drastic measures including non-biological geoengineering technologies cloud-seeding. In fact some estimates claim that cloud-seeding on a large enough scale might even bring global temperatures down to below pre-industrial levels. In this scenario then, would we even need a biological solution that might carry more risk? 

A possible benefit of biological remediation is of course that we might be able to rescue ecosystems that are on the brink of collapse, something that physical solutions like cloud seeding might never be able to achieve. Biological solutions can address biological problems in a manner that purely physical measures might struggle to. Another aspect of synthetic biology, the de-extinction of extinct species, is something that might supplement the reduction in global warming with the restoration of lost biospheres. 

On the policy front geoengineering is a topic that's often scoffed at or neglected in favour of discussions such as emissions reduction. The reasons for this are legitimate, though given the current political climate with the US backing out of climate accords, the dream of a 2°C reduction in global warming seems to be growing ever more distant. Science agencies across the world are waking up to this fact, and just a couple of months ago China announced the world's largest geoengineering research program. As of now, geoengineering remains a last resort, and biological measures even more so.

This isn't stopping scientists from experimenting with it though, and nor should it. 


Written by: Devang Mehta
Devang is currently a PhD student in Plant Biotechnology and Science & Policy at ETH Zurich. He also serves on the EUSynBioS Steering Committee as Policy Officer. Follow him on twitter at @_devangm or check out his blog at www.devang.bio

Photos: All photos used under CC0 license. 

UN CBD COP13: Outcomes relevant to Synthetic Biology

COP13.jpeg
 

Dear Synbio enthusiasts,

three weeks ago, we invited you to follow and contribute to our participation in the 13th Conference of the Parties to the UN Convention on Biological Diversity (COP13) and the parallel Meetings of the Parties to the Cartagena Protocol on Biosafety (CP-MOP8) and the Nagoya Protocol on Access and Benefit-sharing (NP-MOP2). 

Following conclusion of this year's UN CBD events on December 17th, we would like to share with you the below draft outcomes which will have an impact on the future regulation of our discipline.

In case you do not have a particularly keen interest in science policy and governance (yet) or you simply lack the time to read through all of the below bullet points, here is a -considerably simplified- summary:

Synthetic biology may be subject to the same regulatory framework which already exists for classical biotechnology. However, a precautionary approach to synthetic biology has been encouraged, and methodologies for risk assessment of synthetic biology may be updated as new developments emerge.

 

More details are given below:


  • it has been reaffirmed that Parties and other Governments are urged and invited, respectively, to take a precautionary approach when addressing threats of significant reduction or loss of biological diversity posed by organisms, components, and products resulting from synthetic biology.

  • the draft operational definition "synthetic biology is a further development and new dimension of modern biotechnology that combines science, technology and engineering to facilitate and accelerate the understanding, design, redesign, manufacture and/or modification of genetic materials, living organisms and biological systems" has been acknowledged, yet further refinement of this definition has been noted as neccessary.

  • it has been noted that living organisms developed or being developed through current applications of synthetic biology are similar to living modified organisms (LMOs) as defined in the Cartagena Protocol, and that general principles and methodologies for risk assessment under this Protocol and existing biosafety frameworks provide a good basis for risk assessment regarding such LMOs. However, it has also been noted that such methodologies may need to be updated and adapted for current and future developments and applications of synthetic biology.

  • it has been noted that it remains unclear whether or not some organisms created through synthetic biology would fall under the definition of LMOs under the Cartagena Protocol, and whether or not some results of a synthetic biology application are living.

  • Parties have been invited to take into account socio-economic, cultural, and ethical considerations when identifying the potential benefits and potential adverse effects of organisms, components, and products resulting from synthetic biology techniques.

  • Parties, other Governments, relevant organizations, and indigenous peoples have been invited to share experiences and fill knowledge gaps related to potential benefits and potential adverse effects of synthetic biology products as outlined above, to promote public and multi-stakeholder dialogue, and to cooperate in developing guidance and capacity.

  • it has been decided to extend the mandate of the Ad Hoc Technical Expert Group (AHTEG) on Synthetic Biology to make recommendations relevant to the above unresolved issues.

  • it has been decided that, at its next meeting, the Convention will consider any potential implications of the use of digital sequence information on genetic resources for (i) the conservation of biological diversity, (ii) the sustainable use of its components, and (iii) the fair and equitable sharing of the benefits arising out of the utilization of genetic resources. As with potential benefits and potential adverse effects of synthetic biology, relevant information and experiences have been invited from stakeholders, and establishment of a dedicated AHTEG has been decided.


In case you would like to dig deeper into the material, the official meeting documents can be found here.

We, the EUSynBioS Steering Committee, will make an effort to stay involved in this process, and to represent your opinion at future meetings of the UN Convention on Biological Diversity. It is for the sake of a future which allows us to freely and responsibly pursue our scientific careers in an appropriate regulatory environment.

All the best,

-Christian

 

We are an Observer to UN CBD COP13/CP-MOP8/NP-MOP2

 
COP13

Dear SynBio enthusiasts,

in three days' time, the Parties to the UN Convention on Biological Diversity will come together in Cancun, Mexico for their 13th conference (COP13). In parallel,  Meetings of the Parties to the Cartagena Protocol on Biosafety (CP-MOP8) and the Nagoya Protocol on Access and Benefit-sharing (NP-MOP2) will take place.

At this event, an internationally agreed operational definition of synthetic biology shall be finalized, with wide implications for the nascent discipline’s future regulation. Related key decisions to be made include the status of digital DNA sequence information in scope of the Nagoya Protocol’s Access and Benefit-sharing (ABS) rules, and the extent of Socio-Economic, Cultural, and Ethical considerations (SECE) being encouraged as key part of research efforts. We feel that it is imperative for the next generation of young scientists to have a voice in these decisions.

The CBD Secretariat has kindly admitted EUSynBioS as an Observer organization to this event, which gives you, the EUSynBioS community, a unique opportunity to have a voice. Even though Observers have no formal right to vote, the opinion of the next generation of synthetic biology researchers does count, and will on site be communicated in collaboration with partner organizations such as the Public Research & Regulation Initiative.

I would hence like to invite you to share your opinion, your suggestions, and concerns related to the Cancun negotiations with us. You can do so either via our twitter channel @EUSynBioS, or directly by email to sc@eusynbios.org.

You can also follow the official webcast here.

We are looking forward to hearing from you!

Christian, on behalf of the EUSynBioS Steering Committee

 

Scientific opinions needed for CBD documents on synthetic biology

This article by EUSynBioS staff writer Josephine Buerger looks at recent documents prepared by the Convention on Biological Diversity. The EUSynBioS Steering Committee urges members and partner organisations to review these documents to reflect scientific opinion. The documents can be found at www.cbd.int/emerging 

 

Call for contributions from synthetic biologists by August 13th

The Convention on Biological Diversity (CBD) is a treaty created in 1992 to promote biodiversity, highlight the interplay between politics and environment, and raise awareness on an international scale. Each country that ratifies the Convention plays an active role in shaping its official stance, so the CBD is uniquely situated between governments and grassroot movements and directly impacts legislation, biodiversity, and conservation. The EU, in addition to one hundred and ninety-five nations (excepting the United States) are parties to the CBD.

An important initiative of the Convention is to apprehend “new and emerging issues” within the scientific community. Within a public context, the CBD has prepared two extensive documents outlining the impact of synthetic biology on conservation and sustainable use of biodiversity. These documents provide a detailed account of the benefits, hazards, and research breakthroughs generated by the manipulation of genomic information; examples range from bacterial genome shuffling to utilising bats as synthetic vaccine carriers. The initiative’s statements cover some well-discussed aspects of bioethical discourse: the potential threat of releasing genetically modified organisms into fragile ecosystems, the danger of hazardous mutations arising within synthetic strains, or the misuse of open-source knowledge for bioterror activity.

Issues pointed out by multiple reviewers include lack of clarity regarding terms such as “synthetic biology” and “genetic engineering” or the difference between a self-replicating plasmid versus a genetically modified live organism

The CBD documents point out the disparity between the synthetic biology of pop-science and the reality of creating genetically modified organisms in a laboratory setting. It emphasises that scaremongering does not procure productive interactions between scientists, the public, and interest groups, and should be avoided.

The summary presented by the CBD also highlights future complexities that merit discussion. For example, “de-extinction”, i.e. reconstructing genomes of lost species, is a crowd-pleaser, yet the CBD points out that such “sci-fi science” could ultimately diminish funds available for ongoing conservation projects. Second-generation biofuels have huge energy potential, yet the biomass requirement may propagate an exploitative trade-off between technology and nature reserves. The production of pharmaceuticals or chemicals using cell factories could displace economies dependent on agriculture. Synthetic biology has the power to transform our world - but transformation begets complexity.


The documents as prepared by the Convention have already been subject to two rounds of peer-review. Preceding the 12th Conference of the CBD, an additional round of peer-review has been requested and previous comments from funding bodies and research groups are available for inspection. The comments published so far praise the comprehensive nature of the documents, but criticisms have also arisen. Issues pointed out by multiple reviewers include lack of clarity regarding terms such as “synthetic biology” and “genetic engineering” or the difference between a self-replicating plasmid versus a genetically modified live organism. Funding applications and ethical guidelines may adopt the CBD’s definitions in the future. Though such terms can be contentious even between experts, it is important that the CBD documents utilise nuanced terminology to reflect the complexity of extant research.

Finally, a repeated criticism towards the CBD documents is their tendency to over-interpret views presented within the literature. Bioethicists have published on the nature of risk posed by synthetic biology in a highly abstract manner which may or may not reflect actual risks, yet this is not made clear in the summaries. In addition, comments point out that claims from scientific articles are used in an incorrect context. The distinction between data from peer-reviewed papers and opinions prepared by parties with vested interest is not presented clearly which at times paints a biased picture of the field.

The current peer-review process is open to all contributors and a number of groups have stepped forward with strong views against the technology of synthetic biology. As the CBD documents aim to provide an unbiased overview of the field, all reviews may be incorporated into the body of text. Amongst the commenters so far, researchers of synthetic biology and related fields are under-represented.  It is imperative that opinions grounded in scientific fact balance out the views presented thus far, especially in light of the criticisms already emerging against the potential mis-representation of journal articles as well as the future impact of the CBD documents.

The final round of peer-review will end on August 13th.  The official CBD statement on synthetic biology and risk recommendations will set a strong precedent for future policy. This is a unique opportunity for research groups to step forward, contribute their expertise, and help shape the language which will determine the future of the field.


Written by:

Josephine Buerger

Josephine is a postgraduate student at Imperial College London with an avid interest in synthetic biology and metabolic engineering, as well as their impact on scientific research and public outreach. Find her on twitter 

Edited by: Devang Mehta

Disclaimer: Views and opinions expressed in EUSynBioS Pulse articles belong solely to the writer(s). They do not reflect the opinion of the Community, the Advisory Board or the Steering Committee