Comments on That CRISPR Paper

If you’ve got a pulse and are interested in biology, you’ve probably heard that a team of scientists have reported successfully (well, kinda) conducting germ line editing on human embryos using the CRISPR-Cas9 technique. I started hearing rumors of this study around the time that a moratorium on germ line experiments in humans was being proposed by some Very Big Deals. With confirmation that the study is real, the bioethics and life sciences worlds are all a-twitter (somewhat literally).

There’s an ugly side to the current furor, and a lot of it has to do with the nationality of the research team. Apparently the fact that Chinese researchers conducted the study has given people cause for alarm. That there is straight up racism, seasoned liberally with some vintage Cold War nonsense; Kelly has gone over this in a lot more detail. I won’t say any more on this, except to remind that people that when I teach about unethical research, Nazi Germany and the United States of America account for the overwhelming majority of my examples. So let’s all keep a bit of perspective.

Risks, Benefits, and Arguments

Instead, I want to talk about this paper in the context of risks and benefits, and proposed regulatory action around CRISPR. Let me be clear: I think we need to proceed very carefully with CRISPR technologies, particularly as we approach clinical applications. There was a worry that a group had used CRISPR on human embryos. That worry was vindicated yesterday.

Well, sort of. Almost. Not really?

From where I sit, the central concern is best expressed in terms of the risks of using CRISPR techniques on potentially viable human embryos. Commentary in Nature News highlights this concern perfectly:

Others say that such work crosses an ethical line: researchers warned in Nature in March that because the genetic changes to embryos, known as germ line modification, are heritable, they could have an unpredictable effect on future generations. 

The central premises are that 1) CRISPR studies on viable human embryos could lead to significant genetic changes to the resulting live humans; 2) these genetic changes could have unpredictable effects on those humans; 3) the changes could be propagated through human reproduction; and 4) this propagation of changes could have an unpredictable effect on future generations. The conclusion is that we shouldn’t be conducting studies on viable human embryos until we’ve done a lot more research, and have a better mechanism for ethically conducting such research. I support this argument.

The conclusion doesn’t obtain in this case, however, because these embryos weren’t viable. As in, they are never going to result in human beings, and never were. They are “potential human beings” to about the same degree that the Miller-Urey experiment is a potential human being.

Above: not a potential human being.

What the study does show—conclusively— is that the clinical applications for germ line editing require substantial research before they are safe and effective, and this research should be approached with incredible care. The sequence the scientists attempted to introduce into the embryos only took hold in a subset of the embryos tested. Those embryos that did take the change, also produced many off-target mutations (unwanted mutations in the wrong places on the genome). And even when the embryos did show the right mutation, it was only in some cells —the resulting embryos were chimeras, in which some cells possessed the mutation, and others didn’t.

This experiment shows that you can use CRISPR-Cas9 on a human embryo. But that isn’t really a revolutionary result. What is important is just how marginal the success was in terms of a clinically relevant outcome. The conclusion we should draw is that even starting in vivo testing with viable embryos is not only hazardous (for reasons Very Big Deals have noted), but totally futile relative to less risky, more basic scientific inquiry.

Rather than an ethical firestorm, I view this research as an opportunity. This study is, more or less, proof that a robust, community-centered deliberative process is needed to determine what the goals of future CRISPR research are, and what science is needed, in what order, to get there safely. A moratorium on in vivo testing in viable embryos is a valuable part of this process.

What am I reading? 15 June 2014

This week involved some heavy reading. I’ve got a series of writing tasks ahead of me, and the last week has involved a lot of citation collection. I find that unless I’ve got most—if not all—my citations at hand, my writing is really inefficient. Lots of scratching my head going “I know that’s a Thing… where did I read it?!” and so on.

Bioethics/STS

Evans, Sam Weiss. 2014. “Synthetic Biology: Missing the Point.” Nature 510: 218.

Sam Evans—no relation—continues to fight the (one of the) good fight(s). Corresponding on behalf of 21 other correspondents, Evans reminds the readers of Nature that:

the point of supporting synthetic biology is not about making sure that science can go wherever it wants: it is about making the type of society people want to live in.

This, I think, nails down the objection I have to a lot of public debates about science and ethics. In a staggering number of contexts—everything from synthetic biology to sexual harassment—there is a tendency for some groups to wring their hands about how a particular movement, regulation, or concern will “stifle” innovation or creativity. I’m happy to see Evans calling bullshit on this particular rhetorical sleight of hand. Serial killers and terrorists can be innovative and creative; an appeal to innovation isn’t valid unless it points to more substantive values.

Glerup, Cecilie, and Maja Horst. 2014. “Mapping ‘Social Responsibility’ in Science.” Journal of Responsible Innovation 1(1): 31–50.

An analysis of different conceptions of responsibility in science, as it relates to the social impact of scientific research.

The article has an important point to make: that there are a number of different ways we understand the relationship between science and society, and that all of these conceptions are active and engaged in contemporary discourse. Unfortunately, for all the time the authors spend on unpacking the governance of science in its varied forms, they don’t unpack the concept of responsibility. Which—considering the article’s title—might be important. The problems intensify in that the review is based around a set of distinctions that aren’t hard or fast rules. This is acknowledged by the authors towards the end of the paper, but it might have been better to proceed with that as a part of the review, rather than an afterthought.

Also, if you’re going to do a review? Being a bit more transparent in one’s methodology. Looking through the references I identified dozens of papers that probably could have been included, but without better knowledge of how the authors structured their search criteria, I don’t know whether those papers were found and rejected, or just never found.

National Research Council. 2014. Emerging and Readily Available Technologies and National Security. Washington, DC: National Academy Press.

Another Big Government Report on science policy and ethics. I’m about 30 pages in, so don’t spoil the ending for me.

Murphy, Brad, and Jennifer S Reath. 2014. “The Imperative for Investment in Aboriginal and Torres Strait Islander Health.” Medical Journal of Australia 200 (11): 615–16. doi:10.5694/mja14.00632.

An important article about the investment priorities for Indigenous health in Australia. This is an issue that is really close to my heart (my grandfather was a GP, and spent half a century working in rural South Australia), and one that the current Australian Government has compromised in defunding primary care and Indigenous health.

Part of an entire issue of the MJA devoted to Indigenous health.

Infectious Diseases

Almazán, Fernando, Marta L DeDiego, Isabel Sola, Sonia Zuñiga, Jose L Nieto-Torres, Silvia Marquez-Jurado, German Andrés, and Luis Enjuanes. 2013. “Engineering a Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate.” mBio 4 (5): e00650–13. doi:10.1128/mBio.00650–13.

A “loss-of-function” study, in which the researchers engineered the Middle Eastern Respiratory Syndrome Coronavirus (MERS) to lose its transmissibility. The studies I’ve been arguing against, typically, are “gain-of-function,” and so a loss-of-function study is very interesting. Near as I can tell, the mutations the study makes use of are common to coronaviruses, and don’t correspond to extra properties—so this isn’t a gain-of-function study masquerading as loss-of-function. By interrupting how the virus transcribes its own genetic material, they were able to create a variant of the virus which can replicate, but can’t propagate. Unlike an attenuated virus—which runs the risk of reactivating—this virus appears unable to do so. The authors argue, from this, that their virus presents a better option for study and vaccine development.

Webster, Robert G, William J Bean, Owen T Gorman, Thomas M Chambers, and Yoshihiro Kawaoka. 1992. “Evolution and Ecology of Influenza A Viruses.” Microbiological Reviews 56 (1). Am Soc Microbiol: 152–79.

Wertheim, Joel O. 2010. “The Re-Emergence of H1N1 Influenza Virus in 1977: a Cautionary Tale for Estimating Divergence Times Using Biologically Unrealistic Sampling Dates.” PLoS One 5 (6). Public Library of Science: e11184. doi:10.1371/journal.pone.0011184.

Nakajima, Katsuhisa, Ulrich Desselberger, and Peter Palese. 1978. “Recent Human Influenza A (H1N1) Viruses Are Closely Related Genetically to Strains Isolated in 1950.” Nature 274 (5669): 334–39. doi:10.1038/274334a0.

Interesting papers on the evolution of the influenza viruses. My particular interest was the evolution of the 1977 influenza virus, which—according to the above papers—matches a 1950 strain so closely that researchers concluded it was likely the 1977 escaped from a laboratory sample.

Racaniello, Vincent R. 2010. “Social Media and Microbiology Education.” PLoS Pathogens 6 (10). Public Library of Science: e1001095.

I’ve a series of bones to pick with Vincent, and this was part of my research. More on that next week.

Tokiko Watanabe, Gongxun Zhong, Colin A Russell, Noriko Nakajima, Masato Hatta, Anthony Hanson, Ryan McBride, et al. 2014. “Circulating Avian Influenza Viruses Closely Related to the 1918 Virus Have Pandemic Potential.” Cell Host & Microbe 15 (692–705). doi:10.1016/j.chom.2014.05.006.

No surprise—I’ve blogged about this paper twice this week (here and here).

History of Science

Foerstel, Herbert N. 1993. Secret Science. Praeger Publishers.

A book I was unable to get my hands on during my PhD, but always wished I could. Foerstel gives some incredible history about censorship and secrecy in science. The chapter I was interested in was the nuclear sciences, as befitting my background. The highlight of the chapter was Foerstel’s retelling of the Office of Censorship requesting the writers of Superman in 1942 cease and desist in a storyline that involved an “atom smasher,” for fear that enemies of the state would infer from the story that something was up (i.e. the race for the bomb). This, mind you, while TIME was reporting that there were zero physics of chemistry papers in the annual meeting of the American Philosophical Society, inferring that something must be up behind the veil of military secrecy.

Philosophy

Kvanvig, Jonathan L. 2003. The Value of Knowledge and the Pursuit of Understanding. Cambridge University Press.

For an article I’m writing on the “ethics of knowledge.” Kvanvig investigates the idea that knowledge has some kind of normative value—in simplest terms, utility—that sets it apart, and makes it more important, than other types of beliefs. The value of meaning has received some attention regarding the internal features of knowledge that make it valuable over, say, a mere true belief, but work in philosophy on the value of knowledge through external appeal, and as a holistic concept, is sparse in the Western analytic tradition. Kvanvig is after that. I read through the introduction and first chapter, as I don’t yet have borrowing privileges at the University of Pennsylvania Library.

Kagan, S. 1992. “The Limits of Well-Being.” Social Philosophy and Policy 9 (2): 169–89.

Kagan, S. 1994. “Me and My Life.” Proceedings of the Aristotelian Society 94: 309–24.

Two articles by one of my favourite philosophers. Kagan addresses the same problem in both articles: to what extent is well-being—not the amount of it one has, but how one conceives of it—something that relies entirely on one’s internal state, and to what extent is it something that relates to external properties of the world. Kagan’s writing is nice and conversational, and (unlike a lot of analytic philosophers) he’s less worried about grinding his particular conceptual axe, as he is exploring a series of concepts.

Put another way, there are no answers in these papers. There are, however, a lot of questions.

(Kagan also has an awesome set of lectures on death on YouTube)

Economics/Law

Cheng, Cheng, and Mark Hoekstra. 2013. “Does Strengthening Self-Defense Law Deter Crime or Escalate Violence? Evidence From Expansions to Castle Doctrine.” Journal of Human Resources 48 (3). University of Wisconsin Press: 821–54.

McClellan, Chandler B, and Erdal Tekin. 2012. Stand Your Ground Laws and Homicides. IZA Discussion Paper 6705.

Cook, Philip J. 2013. “Why Stand Your Ground Laws Are Dangerous.” Scholars Strategy Network. Scholars Strategy Network.

A series or articles provided to my by Philip Cook (author of the third article) on the “stand your ground” gun laws that have emerged since Florida introduced theirs in 2005. I’m starting some work on gun control and regulation in the United States, and Philip was kind enough to correspond with me and provide me with some starting points.

Coase, Ronald Harry. 1974. “The Market for Goods and the Market for Ideas.” The American Economic Review. JSTOR: 384–91.

One of the classics of the vast literature on the right to freedom of speech. Central to Coase’s argument is that the market of goods and the “marketplace of ideas” (the quotes acknowledging that, as Sparrow and Goodin argue persuasively, the market metaphor doesn’t apply cleanly to ideas) are treated in divergent ways. Coase points out that this either means that something is wrong with our laws and philosophy, and argues that it is likely we’ve got both types of markets wrong (but in different ways). This is a reread; it’s been about five years since I last read this article.

Fiction

Preston, Richard. 1998. The Cobra Event. Ballantine Books

Excellent novel about a bioterror attack. Yes, I study bioterrorism for a living, and when I finish my work for the day I like to relax with a little light reading about fictional bioterrorism. Hits some of the most important aspects—as far as I’m concerned—of bioterrorism, and the incredibly difficulty of policing and tracking such an attack. Preston’s occasional interludes about the politics and science behind bioweapons (at least as understood in the 1990s) give serious plausibility to the novel. The science is a little dated—biology has come a long way in 16 years—but I don’t think that detracts from the novel at all.

Health concerns with 3D printing

Smartplanet is reporting that current models of 3D printers are emitting concerning quantities of ultrafine particles (UFPs). The news comes on the back of a recent study in Atmospheric Environment on the topic.[1] The study reported emission ranges of 20–200 billion UFPs per minute, depending on the feedstock used.

These levels of emissions are a cause for concern, but come with two caveats. The first is that there isn’t a lot of toxicology information on feedstocks studied, polylactic acid or acrylonitrile butadiene styrene. Second, there are coagulation effects that may reduce the reactivity of the emitted UFPs.

Though these qualifications are signs that we need more research on the topic, the article serves as an important reminder that distributing scientific and manufacturing power also distributes the health and safety issues that come with those tools. There isn’t yet good evidence that with the gradual erosion of economies of scale in manufacturing comes a reduction in the impact of manufacturing. Even if it does, there are still important health issues to be considered when it comes to 3D printing, of which current consumers may not be aware.

This is only going to get more serious. As 3D printing expands, along with DNA synthesis and chemical micro-process devices (subject of a recent, excellent paper by Amy E. Smithson),[2] chemical and biological foundries will continue to miniaturise and find their way into homes. It is alarming that we’re already seeing health concerns with 3D printers, much less these more advanced applications.

We should continue to investigate the health and security impacts of citizen manufacturing, and how we approach the design and sale of these devices in the future. We should also look to consumer education about filtration and air ventilation as these devices continue to device to proliferate. 3D printers and their ilk are likely here to stay, but we should work to make them as safe to use as possible.

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1. B. Stephens, P. Azimi, Z.E. Orch, and T. Ramos, “Ultrafine particle emissions from desktop 3D printers,” Atmospheric Environment 79 (2013): 334–339.  ↩
2. For those interested, the updated version of this paper and its companions was published in J.B. Tucker (2012) Innovation, Dual Use, and Security: Managing the Risks of Emerging Biological and Chemical Technologies (Cambridge, MA: MIT Press).  ↩