Tag Archives: bioethics

Comments on the NSABB Meeting on Gain of Function

On May 5, 2015, the National Science Advisory Board for Biosecurity held a meeting to review the gain-of-function deliberative process, and solicit feedback on their draft framework on the process (published April 6).

As part of that meeting, I am presenting public comment on the ethics of the deliberative process. A copy of the handout I provided to the members of the NSABB—updated to correct a couple of typographical errors—is available here.

You can also view the webcast of my comments live. I am not sure when I’ll be speaking—the public comment sessions are planned for 2:00pm-2:30pm, and again at 3:30pm-3:50pm. However, if you want to watch me give comment (or the rest of the meeting) the webcast is available here.

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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.

[The Miller–Urey experiment (or Miller experiment) was a chemical experiment that simulated the conditions thought at the time to be present on the early Earth, and tested the chemical origin of life.]

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.

Book Interest: A Straw Poll

A question for readers of this blog, and followers on Twitter. If I and two co-editors were to release an interdisciplinary edited collection on the 2013-2015 Ebola Virus Disease Outbreak, would you read it? This collection would cover topics including:

  • Virology;
  • Clinical Medicine;
  • Epidemiology;
  • Ecology;
  • Political Science;
  • Anthropology;
  • Journalism;
  • Health Law;
  • Bioethics.

If this is something that interests you, leave a comment, reply to me on Twitter, or drop me an email at neva9257 [at] Gmail dot com. If you can, please note your country of residence, field that you work in (research discipline, teaching/policy/research/public health, etc.) , and what you’d use such a volume for (reference, scholarship, teaching, general interest, coffee table, doorstop, etc.)

This is a project I’ve had in the works for some time, and my colleagues and I are almost at a contract. Demonstrating some interest will get us over that line.

Fetishizing science in a time of Ebola

It didn’t matter to me – I was in it for the science. –GLaDOS.

Science provides us knowledge. But—for most—science and the knowledge it brings isn’t the only or most important thing out there. Modern biomedical ethics is built upon, among other seminal statements, the Declaration of Helsinki, which states that:

While the primary purpose of medical research is to generate new knowledge, this goal can never take precedence over the rights and interests of individual research subjects.

That’s one of the reasons it was so concerning to stumble across a new article on Scientia Salon, brainchild of CUNY Professor of Philosophy Massimo Pigliucci, in which it was argued that anyone who wants to receive an experimental treatment for the Ebola virus must enroll in a placebo-controlled, randomized clinical trial. The author, evolutionary biologist Joanna Monti-Masel, claims that

The unethical behavior here…is not doing an experiment, but doing an experiment without using a control group. There should be no compassionate use exceptions. Everybody who wants these treatments should have to enter a randomized trial to have a chance of getting them.

…At least five patients have received a potentially effective treatment, but nobody has yet been assigned to a control group. This is the ethical travesty, and it needs to stop.

For those catching up, the Ebola outbreak that is believed to have started in December of 2013 has infected 1,975 people, and killed 1,069. Last week, the WHO declared that the outbreak constituted an Public Health Emergency of International Concern; this week, a WHO ethics advisory committee released a statement approving the use of unregistered interventions for Ebola. Kelly Hills and I have written on the ethics of latter part here.

Monti-Masel, however, thinks that the WHO is acting unethically by allowing for “compassionate use,” which the WHO is defining here as access to an unapproved drug outside of a clinical trial. Rather, she argues, anyone who wants access to these new drugs must be part of a clinical trial.

And not just any trial. Monti-Masel believes that the only way we ought to collect data about these experimental interventions is by setting up a double-blind, randomized clinical trial in the middle of an epidemic in West Africa. That is, we offer those suffering from Ebola—which is primarily killing vulnerable members of the nations of Sierra Leone, Guinea, Liberia, and Nigeria—something, which may or may not be a drug that may or may not work, or might be a sugar pill. We don’t tell them which one it is, because we won’t know which it was until after the fact. We then determine who gets better, and which ones get worse. And if that isn’t what the patient wants, then they get nothing.

Science for the sake of science

It is worth noting, first up, that Monti-Masel is reacting to a hypothetical storm in a nonexistent teacup. Aside from the WHO ethics committee’s general recommendations that data collection is necessary, but must be collected and shared ethically and equitably, there’s nothing else to suggest what types of data collection, and study design, might be permissible. Moving immediately to the need for control groups and randomized trials presumes a lot about the WHO’s mild statement, and jumps the gun on a lot of serious ethics that has to happen before—and has to involve the countries that are actually in the middle of this outbreak.

But more importantly, Monti-Masel fetishizes data collection above and beyond any other consideration. The main benefits she cites is the power of the studies that could be achieved through a randomized trial. All other concerns are secondary, it seems, to the possibility of doing accurate—not good—science.

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But that’s wrongheaded; more, it is paternalistic and racist—to say nothing of deeply myopic—to presume that the central purpose of these interventions ought to be to collect data. Collecting data is necessary; collecting data is good. But the ways in which collect that data, and the quality of data we should aim for, must be subject to the central aim of these interventions: “to try to save the lives of patients and to curb the epidemic.”

Requiring participation in a randomized, placebo-controlled clinical trial in order to access these drugs is deeply paternalistic. It presumes that the priorities defined by Monti-Masel’s hypothetical study are not only the best for the scientist, but the best for everyone. It doesn’t even consider that the people of a country embroiled in an Ebola epidemic might not want to participate in a placebo-controlled trial. Indeed, Monti-Masel claims that compassionate use outside of a clinical trial would be “an ethical travesty” because it would give us lower quality data for lack of a suitable (placebo) control group.

That reduces the patient to a mere data point. Considering the lengthy history of drug testing in African countries that leave the communities in which they are tested worse off, it is not hard to detect the racism implicit in such an extreme study design. History is rife with contributions “to the legacy of black bodies being manipulated and violated for ‘the benefit of all.’” To be ethical, research—even in small samples such as must occur with the limited experimental agents present for this outbreak of Ebola—must take into account practices that respect the agency and priorities of the participant. People are not simply data points; vulnerable populations are not simply a convenient supply of test subjects.

Finally, advocating placebo controls simply misses the ethical forest for the trees. Monti-Masel claims:

One final concern is that many Africans are suspicious of Western doctors and experiments, and that their fears will keep them away. That’s fine, at least for now. That’s what the ethical principle of autonomy is about, crystallized in the notion of informed consent.

Rather, we should simply let those prospective patients know that if they want a chance at accessing an intervention, they have to enroll. If not, they are just out of luck—a move that is, as already discussed, paternalistic and racist. This doesn’t concern Monti-Masel, however:

Plenty of infected Africans will probably refuse to take part in the trial. That’s okay, because we don’t have enough treatments to go around anyway.

This completely misses the point of the “suspicion of Western doctors” about which people are concerned. To know why, ask this question instead: what happens when it becomes clear that Western doctors are only offering the hope of drugs if you’ll sign up to their trials? In an outbreak in which people are already avoiding reporting cases, or hiding loved ones that are infected with the virus; for a disease that, historically, has generated mistrust in Western interventions; what does Monti-Masel think the impact of a placebo-controlled trial will be for the outbreak as a whole? I know there are no RCTs on that topic, but any student of history would be able to tell you that things will go downhill fast. Trust is a vital element in a public health intervention. Jeopardizing that trust in the name of a small trial values the data above the lives of everyone in the outbreak.

This is a disappointing article in Scientia Salon. The submission itself is problematic; the comments are horrific. One hopes that in the future the site will look closely at submissions, in light of the enthusiastic endorsement of enforced autopsies that has resulted from this post. There is power in the platform, and in the middle of an outbreak this is not a productive contribution.

Doing better means asking, not telling

Hills and I have already argued, at length, about the ethics of distributing these drugs. We’ve advocated that those “who have traditionally and unjustly held power over African nations, step back and accept our role as people to provide assistance, rather than determine it.” It isn’t surprising that Monti-Masel’s reply has struck the worst possible chord.

Moreover, there is still good science that we should be doing, in partnership with the countries that are the site of this outbreak. Giving up the fetish of the placebo control group doesn’t mean giving up on trials, or good research. It just recognizes that certain kinds of study are unethical to pursue in the context of a dangerous disease outbreak, among a vulnerable population that are prone to exploitation by Western powers.

At the end of the day, we want science to be commensurate with other important values. Making science—one type of science—the be-all and end-all of our ethical considerations takes the very important role of knowledge in promoting human health, wealth, and security, and perverts it. We do not want to be like GLaDOS, the super-intelligent, passive aggressive antagonist of the Portal franchise.

Our motto should never be:

I’ve experiments to run,

There is research to be done;

On the people who are still alive.

Paternalism, Procedure, Precedent: The Ethics of Using Unproven Therapies in an Ebola Outbreak

The World Health Organization convened an ethics panel on Monday to discuss the ethics of using experimental treatments in the current Ebola outbreak in—so far—Guinea, Liberia, Sierra Leone, and Nigeria. The panel has, thankfully, concluded that “it is ethical to offer unproven interventions with as yet unknown efficacy and adverse effects, as potential treatment or prevention.”

Nonetheless, the reasons for this decision aren’t necessarily clear; statements like the one issued today are typically light on the details. My own experience on social media is that there isn’t a lot of clarity on the range of decisions we might take into account in coming to such a decision, and how we decide what’s important. And—believing, as I do, that ethics is as much a conversation as it is a set of decisions—that leaves open significant potential for misunderstanding and misrepresentation.

Kelly and I wrote the following over the weekend, but were sidetracked in posting it by pesky things like scientific accuracy, and the controversy that followed the announcement that a Spanish priest had also received the Zmapp treatment. We post this, as Kelly so beautifully put it, in the hope that it will be “is useful for answering the questions people who don’t have much background in ethics may have, as well as getting into the cultural zeitgeist for discussions not only about future pandemic situations but also discussions about disparate treatment of people from the Developed vs Developing World.”

[Cross-posted at Life as an Extreme Sport]

A “secret serum.” A vaccine. A cure. A miracle. With the announcement of the use of ZMapp to treat two Americans sick with the Ebola virus with apparently no ill effect, the hum and buzz on social media, commentary websites, and even the 24/7 news cycle, has become one of “should the serum be given to Africa? Will it?” The question has dominated for more than a week, and become something that the World Health Organization feels it needs to address by convening a panel of medical ethics experts to offer an analysis of what should be done.

And the general question about untested cures/vaccines in the event of a disease pandemic is an important one; there are already guidelines for what kind of treatments can and will be made available during a flu pandemic, and it seems quite sensible that a guideline be developed for all potential pandemic pathogens. However, it isn’t a question that is relevant in the current context, because we are already past that.

While people may be stating “should the serum be made available?” that’s not the question being asked.

It isn’t the question being asked, because we already know the answer: yes. In this last week, the serum has been made available—to Kent Brantly and Nancy Writebol. The pair of American health care workers have received the ZMapp serum, which, until this past week, had not been tested on any human subjects. We already know that the answer to whether or not the serum should be made available is “yes”–or at least, “yes, to people like us.” [1]

Instead, more specifically, the implicit (and at times very explicit) question being asked is: “should the serum be made available to the West African countries suffering from the current Ebola outbreak?”

Your instinctive response to this might be “yes! This is clearly a matter of equality and justice; the lives of those people suffering from Ebola in Sierra Leone, Guinea, Liberia, and Nigeria[2] are just as important as the Americans who were given the serum.” If so, good reader, then this essay is not addressed to you. After all, you have clearly reached the same conclusion we have: Why shouldn’t—assuming that Mapp can make good on its claims that it can manufacture sufficient quantities of their serum—those who are suffering have care made available? There are risks, to be sure. But those risks were clearly outweighed by the urgency of the situation in which Brantly and Writebol found themselves, and in which hundreds (if not thousands) of people across the Atlantic find themselves now.

And why not? If it is in our power to help those suffering, we ought to do so. Justice and equality are traditions upon which civilizations are based. Adam Smith, better known for his “invisible hand” of the market, believed that societies are only worthy when they are just. Peter Singer has argued that if we can help those in need at no cost to ourselves, we simply must do so. And Thomas Pogge has, for more then a decade now, argued that the historical injustices faced by countries who were preyed on by the West obligate those living today to assist in supporting the health systems of those countries, and bettering the lives of their citizens.

Indeed, the responses to “why not,” which attempt to justify not sharing a treatment already given to two people, has an uncomfortable relationship to the historical injustices that Pogge references. These objections, often made with good intentions, can be broadly broken down into three categories: paternalism; procedure; and precedent.

Paternalism

With paternalistic objections to proving experimental Ebola treatments to Western African nations in need, it’s common to hear concern about corruption, ability to consent, or even a call-back to previous, unethical testing on vulnerable human subjects. Perhaps the most common of these is the belief that all governments in Africa are corrupt maws that inhale non-governmental organization money and aid to prop up an exclusive elite at the expense of the rest of the country. The history of corruption, from the power voids left by colonial government departures, to the actual problems created by colonialism (complete with unnatural country delineations) are broadly recognized and, importantly, well beyond the scope of a post arguing that it is ethical to allow these countries self-determination.

A more specific ethical concern is that people who are gravely ill are often viewed as being unable to give consent, let alone informed consent. Much of the current outbreak has occurred outside of city areas, in rural and remote areas of the affected countries. There are some valid questions about whether or not people can genuinely understand the risks and benefits of using a completely experimental vaccine if they don’t have anything that easily maps onto the “basic education” system common in the developed world. There is also the fact that when people are gravely ill, they may not be cognizant and aware enough to grant consent, or that their family is so desperate for a cure that they will do anything, regardless of risk.

Neither of these issues, though, means that it is impossible for infected patients or their families to made determinations about what kind of care they would like to receive. An aspect of receiving informed consent is to make sure risk and benefit is described in a way that makes sense and is understandable to the people making the choices; in this, the reverence for autonomy of the individual should be respected, rather than the paternalistic instincts of those in positions of power.

Informed consent also ties into specific and ugly histories involving pharmaceutical testing and African countries. There is a history of many countries in Africa, like Zimbabwe and South Africa, being exploited for AZT trials, experimental hormonal contraceptive, and other drugs and devices. These trials are frequently coercive, and have contributed to the legacy of black bodies being manipulated and violated for “the benefit of all.”

Fears about consent and testing on vulnerable populations are valid; no one is saying to parachute the ZMapp serum down in little chilled coolers for willy-nilly application. Merely that, given the history of testing on vulnerable people and exploiting the populations of African countries, rather than standing in a position of authority saying “let us decide whether or not we will let you make your own decision,” the West should step aside and say “this is your choice.”

The difference here is stark: it’s a matter of forcing an option vs. accepting that the choice is to be made by someone not you (where “you” is “the West”), and that these countries are full-fledged countries who have their own systems and own choices.

Procedure

Others believe that there is an ethical issue in distributing the serum on a broad scale. Some people claim that the outbreak provides the perfect opportunity to conduct a large, randomized control trial (RCT)—the “gold standard” of medical research—of ZMapp. Others believe that such a trial is impossible in the context of a pandemic, and we should thus hold off from making the drug available for lack of ability to monitor the drug’s efficacy.

We believe both positions are false. By fetishizing the gold standard, we—the USA and developed world—miss the point of our role as participants in solving this disease outbreak. Standards of evidence required for drug use are different from country to country, even in the developed world. They are also different in different contexts, and levels of urgency. An RCT would introduce an element of testing to treatment that, given what we know about the justified mistrust that people in developing nations have of the developed world and their experiments, would creating more tensions in countries wary of Western medical interventions. The potential of an RCT to backfire and jeopardize the provision of care makes it unwise—without changing our conclusion that assistance must be rendered.

But the lack of wisdom in conducting an RCT doesn’t mean we should just throw up our hands and not assist. If the countries responsible for managing the outbreak thought it opportune, a large cohort study could be done where everyone who is able receives treatment, and the results are compared to the history of the virus over time. This might not allow researchers to control every factor, but it would go a long way to showing the efficacy of ZMapp the next time Ebola surfaces.

Talk of trials, however, misses the point of our role in participation in a more fundamental way. If you aid someone, you do so for their benefit on their terms. We don’t want to mandate data collection “for the good of West Africa.” We should ask the decision makers inside Guinea, Sierra Leone, Nigeria, and Liberia how we can best collect data with them, for them and their benefit as they see it.

The WHO has developed frameworks for this in other disease contexts, such as pandemic influenza.[3] While these need not define the scope of cooperation, the past can serve to guide deliberation on how best to assist. The WHO’s policies, by virtue of being reached through international consensus, gives extra weight to the global nature of this cooperation.

Precedent

The WHO can play an extra role in countering the paternalism of intervention by developed nations, while beginning the process to set a good precedent for future outbreaks. Jeremy Farrar, David Heynmann, and Peter Piot have argued that:

“The [WHO] could assist African countries with developing rigorous protocols for the use and study of experimental approaches to treatment and prevention, while coordinating more traditional containment measures. As the only body with the necessary international authority, it must take on this greater leadership role.” [5; emphasis added]

The capacity of the WHO to provide oversight, while still enabling African countries to enact their own protocols and treatment plans, is our best chance to address concerns over oversight of the outbreak. There is no denying that this outbreak is international, and without proper management more countries could see cases of Ebola arise. An international body is better equipped to do this with legitimacy, and without paternalism, than any one country alone. The recent declaration by the WHO that the Ebola outbreak is a Public Health Emergency of International Concern, and their accompanying recommendations, is the perfect backdrop for this type of action.

Compassion, or Colonialism

We have to ask ourselves if we want to continue inflicting the wounds of colonialism on African nations. Insisting that Americans are a “special case” when it comes to a disease with a current CFR of 56% only underscores a persistent mistrust: that people in the West get better treatment and care, because those lives are valued more than the lives in developing parts of the world. This fear can be seen in previous Ebola outbreaks: During the 2000-2001 Ugandan outbreak of Sudan ebolavirus, an existing pervasive belief that Euro-Americans visit Central Africa to harvest body parts for profit was amplified by infectious disease control efforts, resulting in infected individuals and their family running and hiding from medical treatment, magnifying the extent of the outbreak. Many local people during the 2002 outbreak of Zaire ebolavirus in the border areas of Gabon and the Republic of Congo believed that Ebola was a disease invented by the French to eliminate African populations (allowing the French unfettered access to their lands and materials).[4] Currently, people in Liberia are already asking why, if there is no cure for Ebola (the standard response on the ground), the Americans are being cured. [5]

The choice to use the experimental vaccine was already made; that genie is well and truly out of the bottle. The question you have to ask yourself is this: can you live with supporting the idea that the lives of Brantly and Writebol are more important than the life of Shiekh Umarr Kahn, the only virologist in Sierra Leone? What about Dr. Samuel Brisbane, the chief medical officer of one of Liberia’s medical centers? How about the other approximately 800 people spread between Nigeria, Sierra Leone, Guinea, and Liberia, all of whom are certainly valued by the people within their lives.

Is this an appeal to emotion? Certainly. Sometimes decisions about what is moral, ethical, right, requires seeing the people you’re talking about as people, rather than numbers and statistics on the other side of an ocean. But that emotion can and should build into our conception of ethics and justice. Returning to the legacy of Adam Smith, “the relief of misery for its own sake is an impulse whose justification is a core intuition…of any plausible theory of moral thought.”[6]

We know that Ebola is a disease of missing infrastructure, poverty, and minimal health care systems. No one is suggesting that these countries not be given the help that they are asking for, in containing the disease, in implementing public health strategies, or in having access to any experimental cures and vaccines available. No one denies that there are ethical issues at stake. Nor are we stating a belief that ZMapp–or Tekmira, or any other unproven intervention–will stop the current outbreak. What we are advocating is merely that we, who have traditionally and unjustly held power over African nations, step back and accept our role as people to provide assistance, rather than determine it.

Kelly Hills and Nicholas Evans

[1]: While some light debate may have questioned whether or not Brantly and Writebol had the ability to consent, there has never been a serious question here in the USA of not giving them the serum.

[2]: Not “Africa.”

[3]: World Health Organization. Pandemic influenza preparedness Framework for the sharing of influenza viruses and access to vaccines and other benefits. Geneva, 2011. http://www.who.int/influenza/resources/pip_framework/en/ Accessed 8 August 2014.

[4] Hewlett BS, Hewlett BL. “Ebola, Culture and Politics: The Anthropology of an Emerging Disease,” pp 57;77. Thomson Wadsworth; Belmont, California; 2008.

[5] Farrar J, Heymann D, Piot P. Experimental Medicine in a Time of Ebola. Published 6 August 2014: http://online.wsj.com/articles/experimental-medicine-and-african-ebola-1407258551 Accessed 7 August 2014.

[6] Campbell, T. “Poverty as a Violation of Human Rights: Inhumanity, or Injustice?” in Pogge, T., Freedom from Poverty as a Human Right: Who Owes What to the Very Poor? (Oxford, UK: Oxford University Press, 2007)

A Risk-Benefit Analysis is not a Death Sentence

As is stated by Marc Lipsitch on the Cambridge Working Group site, the CWG reflects a consensus. My personal views do not reflect the views of the group. When you build a consensus, you often don’t end up with everything you wanted. When a group of very different people forms around a common issue, the outcomes that get devised are heavily moderated by the competing priorities and backgrounds of the participants. Sometimes that leads to a stagnation.[1] Other times, it leads to a more reasonable and practical set of priorities. In the case of the Cambridge Working Group, in which I participated as a founding member last month, our Consensus Statement on the Creation of Potential Pandemic Pathogens (PPPs) was the product of deliberation on the types of steps the eighteen founding members could agree on. For those of you who are just arriving, PPP studies involve the creation of a novel pathogen that could, if released, cause a disease pandemic. In my line of work, PPP studies are a type of “gain of function” study, and associated with dual-use research—scientific research that can be used to benefit or harm humanity. When it comes to PPP studies, the CWG stated one ultimate goal:

Experiments involving the creation of potential pandemic pathogens should be curtailed until there has been a quantitative, objective and credible assessment of the risks, potential benefits, and opportunities for risk mitigation, as well as comparison against safer experimental approaches.

And one proximate goal in the pursuit of that ultimate goal:

A modern version of the Asilomar process, which engaged scientists in proposing rules to manage research on recombinant DNA, could be a starting point to identify the best approaches to achieve the global public health goals of defeating pandemic disease and assuring the highest level of safety.

In short, we want to ask a question: what are the risks and benefits of PPP studies? To ask that question, we want to convene a meeting. And though we’ve no ability to stop them, we’d really like it if scientists could just, I don’t know, not make any new and improved strains of influenza before we have that meeting. Simple, right? Well, I thought so. Which is why I was surprised when colleague said this:

Wait what?!

Hyperbole is Not Helping

NewProf is right: *if* we shut down (all) BSL-3/4 labs, there would be nowhere (safe) for people to work on dangerous pathogens like Ebola, or train new people to do the same. The only problem is that no-one—that I know of—is saying that.

First: the CWG statement says nothing about shutting down laboratories. As a consensus statement, it is necessarily limited by pragmatic considerations. The CWG calls for a risk assessment. It calls for collecting data. That data collection is focused on PPP studies, and primarily in the context of influenza research. Even if the CWG were to be looking at Ebola, PPP studies would (I really, really hope) be a very small subset of Ebola research. Of course, NewProd is not concerned only about individual research, but whole labs:

That is, NewProf claims that a CWG-inspired risk assessment would lead to labs shutting down, which would lead to there being “no scientists trained to study/treat/find cures for Ebola.” But that’s equally ludicrous. A risk assessment of a small set of experiments would be unlikely to result in an entire field being unable to perform. In fact, that would be a really bad thing. The risk of that bad thing would—ought—to be something that informs the risk-benefit analysis of research in the life sciences. Regulation that unduly limits the progress of genuinely (or even plausibly) beneficial research, without providing any additional benefit, would be bad regulation.

Grind Your Axe on Your Own Time

What is most frustrating, however, is how mercenary the whole thing feels. If you are concerned about the Ebola virus, you should be concerned that the public health effort to stem the tide of the virus in West Africa is failing. That a combination of poverty, civil unrest, environmental degradation,, failing healthcare, traditional practices, and a (historically justified) mistrust of western healthcare workers is again the perfect breeding ground for the Ebola virus. You shouldn’t be concerned about a risk-benefit analysis that has been advocated for a particular subset of scientific experiments—with a focus on influenza—that may or may not lead to some outcome in the future. Dual-use research and the Ebola virus, right now, have very little to do with each other. If there comes a time where researchers decide they want to augment the already fearsome pathology caused by the virus with, say, a new and improved transmission mechanism, we should definitely have a discussion about that. That, I think it is uncontroversial to say, would probably be a very bad idea.

A Personal View of Moving Forward

I’ve been present the last few days talking about Ebola, primarily on Twitter (and on other platforms whenever someone asks). I’ve not had a lot of time to talk about the CWG’s statement, or my views on the types of questions we need to ask in putting together a comprehensive picture of the types of risks and benefits posed by PPP studies. So here’s a few thoughts, because it is apparently weighing on people’s minds quite heavily. I don’t know how many high-containment labs are needed to study the things we need to study in order to improve public health. I know Richard Ebright, in the recent Congressional Subcommittee Hearing on the CDC Anthrax Lab “incident” mentioned a figure of 50, but I don’t know of the basis on which he made that claim. As such, I, personally, wouldn’t back such a number without more information. I do know that the question of risk and benefits of PPP studies—and other dual-use research—has been a decade in the making. The purported benefits to health and welfare of gain-of-function research, time and again, fail to meet scrutiny Something needs to happen. The next step is an empirical, multi-disciplinary analysis of the benefits and risks of the research. It has to be empirical because we need to ground policy in rigorous evidence. It has to be multi-disciplinary because first, the question itself can’t be answered by one group; second, the values into which we are inquiring cover more than one set of interests. That, as I understand it, is what the CWG is moving towards. That’s certainly why I put my name to the Consensus Statement. I’m coming into that risk-assessment process looking for an answer, not presuming one. I’m not looking to undermine any single field of research wholesale. And frankly, I find the use of the current tragedy in West Africa as an argumentative tool pretty distasteful.


  1. The twists and turns of consensus-building are playing out on a grand scale at the current experts meeting of the Biological and Toxins Weapons Convention in Geneva. My colleagues are participating as academics and members of NGOs at the meeting, and you can follow them at #BWCMX. And yes, I’m terribly sad to not be there. Next time, folks.  ↩

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.