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Synthetic Biology Is What, Exactly?

Posted by Pete Shanks on October 1st, 2014


Synthetic biology is about, well, living things that are manufactured. Or something.

The European Commission is the latest body to struggle with defining the term synthetic biology, and has produced a 65-page report. In the end, the Scientific Committees punted. (Their full names are here, which links to the Opinion, pdf, as well as comments on an earlier draft, pdf.) This is what they came up with:

SynBio is the application of science, technology and engineering to facilitate and accelerate the design, manufacture and/or modification of genetic materials in living organisms.

The Committees' rationale makes sense, up to a point: They came up with an "operational definition” that "has the advantage that it does not exclude the relevant and large body of risk assessment and safety guidelines developed over the past 40 years for GM work.” But their approach fails to include what the report acknowledges are key elements of most current definitions: "modularisation and engineering concepts.” In fact, their formulation is pretty close to the more succinct title the ETC Group came up with in January 2007:

Extreme genetic engineering

Which in turn is really not so far from what synthetic biologist Drew Endy said (video), also in 2007:

“Synthetic biology is an approach to engineering biology. … Synthetic biology isn’t making a specific thing, it’s how you make something.”

In the same five-minute video, however, Endy distinguishes the then-new field from genetic engineering by saying that it adds to the older technologies (recombinant DNA, PCR, automated sequencing) three new elements: automated construction, standards and abstraction. Taken together, he said, "they define a new process for engineering biological systems.”

The Committees’ Report is a useful survey. Along the way, it lists 35 different attempts at definitions and appraises the field, including the regulatory position in the European Union, United States, Canada, China, Latin America and internationally. It will be followed in due course by two other Opinions that will "focus on the methodology to determine what, if any, risks SynBio may potentially pose to public health and what type of further research in this field is required."

Meanwhile, you know it when you see it, right?

Previously on Biopolitical Times:





The Collapse of a Dangerous Analogy: Or, why mitochondria are much more than batteries

Posted by Jessica Cussins on September 29th, 2014


The editors at New Scientist have made a “U-turn” on “three-parent babies.” Their new conclusion: “It’s more messy than we thought."

Untitled Document

If you’ve read anything at all promoting 3-person IVF, you’ve no doubt seen the analogy that the cellular organelles called mitochondria “just” produce energy, and that the biologically extreme technique often misleadingly called “mitochondrial replacement,” which would combine genetic material from three people into an embryo, is comparable to merely “changing a battery.”

The connotation is immediate: Just as changing a battery in a computer doesn’t affect the hard disk, so too, the logic goes, would this technique – more accurately termed nuclear genome transfer – merely provide the resulting person with a healthy new source of energy (from the second woman’s mitochondria.)

The mitochondria-as-batteries analogy has always been spurious, and for numerous reasons. But it has now, thankfully, collapsed.

A new article in New Scientist lays out the evidence. It reviews case after case that supports a “new paradigm” whereby mitochondria are understood not merely as energy sources, but as important actors in and of themselves, greatly influencing numerous complex traits that do in fact make people who they are.

In short, this is because mitochondrial DNA “generates thousands of distinct small non-coding RNAs,” which “are able to influence how the nuclear genetic code is expressed through processes such as methylation, which alters gene activity, thus modifying which proteins are produced.”

And what does this mean?

The author explains that “the picture of the enslaved organelle seems to be precisely the wrong way around – in many ways, these bacterial “slaves” are in fact “masters of our fates.” In fact, he continues, this “suggests that the mitochondrion isn’t an evolutionary bystander, but a bona fide second genome.” (Emphasis mine.)

And as the article spells out, this suggests serious trouble for the safety and efficacy of nuclear genome transfer or 3-person IVF.

Most debate around the issue has worked on the assumption that mitochondria are simply cellular powerhouses. However, given their new-found influence over our bodies the implications of this technology may be far more radical than we have assumed.

No doubt about it, this article is a game changer. Along with its publication, New Scientist put out an editorial in which it admitted that the creation of “three-parent babies” is “more messy than we thought.” This was a necessary corrective, given that the editors confidently told their readers last year that “the mitochondrial genome is tiny, so the changes involved are minimal,” and that therefore there was no need to “fear babies made with genes from three parents.”

The editors’ new statement is a good one, and its importance in this ongoing debate could be critical. But they might have acknowledged that they are not the first in the scientific community to raise these concerns. Instead, they include the assertion that critics of nuclear genome transfer “may be right – albeit for the wrong reasons.” (They give no explanation of what those “wrong reasons” are.)

Did New Scientists’ editors not notice when evolutionary biologists published a report in Science last year arguing that mitochondrial DNA influences a range of important traits? Or when one of the authors later wrote in his blog that this “evidence indicates that the battery analogy is really an inaccurate simplification of how the mitochondrial genome exerts its influence”?

Where were they when a New York Medical College cell biologist pointed out in an article at the Huffington Post that if a nucleus is moved into a different egg, that egg and the mitochondria it contains are absolutely essential to the development of a resulting child because this information will direct the expression of genes at the earliest stages of development?

The New Scientist may have missed its moment to offer a hat tip to those who have been right on this point for years, but at least there is now no excuse for the UK House of Commons to make the same mistake. When its Science and Technology Committee meets on October 22 for a final inquiry into the science of what it calls “mitochondrial donation,” it will have to contend with the expanding evidence that mitochondria are not just batteries for the important genes, but that the genes they contain exert powerful influences of their own on traits ranging from memory, to aging, adaptation and obesity.

That also means acknowledging just how drastic toying with the mitochondrial genome would be. The “new paradigm” changes the safety profile of the proposed techniques, as well as the ethical and practical calculus of evaluating them: even if they may be able to reduce the risk of inheriting mitochondrial disorders, they will also alter the phenotype of the resulting child in unknowable ways.

The accumulating evidence about mitochondrial function makes it clear that issues of critical scientific importance were either overlooked or minimized in recent reports on safety and efficacy from the Human Fertilisation and Embryology Authority (HFEA) and the Department of Health. Will anyone now have enough faith in the merits of their conclusions to actually change UK law based upon their recommendations?

With the UK Parliamentary vote planned for this fall, we will soon find out. In the meantime, let’s put this dangerous analogy to rest.

Creating embryos or children with 3-person IVF is not like changing a battery at all. It’s more like suddenly realizing that the pages of your cookbook were stuck together and you just accidentally combined two different recipes in one bowl. It could end up all working out, but you probably wouldn’t want to bet your child’s life on it.

Previously on Biopolitical Times:





An End to Sterilization Abuses in California Prisons

Posted by Jessica Cussins on September 26th, 2014


Untitled Document

California Governor Jerry Brown signed SB 1135 into law Thursday night, banning unnecessary coercive sterilizations in the state's prisons - a happy victory for advocates of reproductive and criminal justice as well as of human and women’s rights.

The bill’s sponsor, Sen. Hannah-Beth Jackson (D), identified the need for the change:

Pressuring a vulnerable population into making permanent reproductive choices without informed consent is unacceptable, and violates our most basic human rights.

The bill was inspired by the efforts of Justice Now, an advocacy organization working to challenge the prison industrial complex, which originally uncovered evidence of these abuses and started a petition last year to demand that they end, as well as by the important journalism of Corey Johnson of the Center for Investigative Reporting, who documented evidence of 148 illegal sterilizations taking place in California prisons between 2006 and 2010.

California bears the shameful history of having sterilized more people under 20th century eugenic laws than any other state. Over 20,000 people lost their reproductive rights because the state considered them “unfit” to reproduce. These laws disproportionately impacted communities of color, people with disabilities, and people living in poverty. It is critical to know this history so that problematic resurgences of these same ideologies do not creep back under new auspices. SB 1135 is an important victory in the fight for the remembrance of our eugenic history and its ongoing implications.

We are absolutely thrilled to see this policy become law. Thank you, Jerry Brown!

Previously on Biopolitical Times:





Drew Endy's Hollywood Dreams for Synthetic Biology

Posted by Pete Shanks on September 18th, 2014


Drew Endy

Drew Endy, Stanford professor and synthetic biology evangelist, gave an interesting overview of the subject in general and "The iGEM Revolution" in particular at a Long Now seminar on September 16 in San Francisco. A summary will be posted soon, as well as complete video.

Endy is convinced that this is the century of biology, and in particular of making things with biology. He even invoked "Steve & Steve" (Jobs & Wozniak) — a common trope among synthetic biology types — claiming that the technology he started with was even cruder than the first Apple (which didn't even have a screen). The implication is, of course, that these new tools will lead to an equivalent technical, economic and social revolution.

Some DiY biotech initiatives do struggle along on a shoestring, but the analogy is misleading. iGEM has 20,000 alumni, Endy said, scattered among labs worldwide. Stanford's department of bioengineering alone has two dozen core faculty, plus associates and consultants; this is not a small operation, nor are those in Cambridge and elsewhere. Allied Market Research is hawking a report claiming that the global synthetic biology market will reach $38.7 billion by 2020.

Yet Endy admitted, in the Q&A, that "we need to figure out what we wish for." Which might help to explain why (as he complained) movies always seem to show biologists as villains, although he and others in the field seem to view themselves, sincerely though not always humbly, as white knights and revolutionary heroes bringing salvation and transcendence to the planet. Sadly for them, Hollywood has not yet come up with the "realistic heroic narratives" that Endy thinks are needed to promote biotech to the general public.

Previously on Biopolitical Times:






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