Will the flu vaccine give my child narcolepsy?

As my last research job involved vaccine development and safety, I get a lot of emails and Facebook posts relating to the safety of particular vaccines. I often get sent links from Natural News, which is renowned for its biased and inaccurate reporting of anything scientific. In particular, there was a lot of chatter about the H1N1 vaccine and its link to narcolepsy in Europe (http://www.naturalnews.com/039732_flu_vaccines_narcolepsy_children.html). The truth of the situation is, of course, a bit murky and the nuances of how science has pulled apart this issue get lost. A recent retraction of a key paper in the story is complicating the situation.

Soon after the 2009 H1N1 outbreak, medical authorities in Sweden and Finland documented an increase in the number of cases of narcolepsy. Narcolepsy is a disorder in which the sleep-regulation hormone hypocretin is too low, resulting in sleepiness, cataplexy (sudden loss of muscle tone) and disordered sleep. The reason for the increase in Sweden and Finland, (subsequently also seen in the UK) was associated with the use of Pandemrix, a particular formulation of the H1N1 vaccine made by Glaxo-Smith-Kline. Importantly, this particular vaccine was not used in Canada or the US.

In this case, the risk of developing narcolepsy for children who received pandemrix was around 0.36  (Science, 345(6196):498) to 6.67 per 100,000. In contrast, the risk of hospitalization for all types of flu run between 66 and 99 per 100,000 cases . In other words, the increased risk of narcolepsy from is negligible compared to the risk of developing complications from the flu, a relatively common disease during Canadian winters.

Still, a side-effect from vaccine is a serious issue. The association between Pandemrix administration and the rise of narcolepsy in Europe suggests that Pandemrix was a likely cause, but much work needs to be done in order to determine why, including an examination of the molecular mechanisms behind the side effect. Vaccines induce immunity against an infectious organism by presenting your body with a tiny bit of that bug such as a bit of a cell wall or a bit of a protein. This is called an antigen, and presentation of just the antigen allows your immune system to mount a response against it without you having to suffer the illness. In the case of Pandemrix, it’s increasingly looking like narcolepsy was induced by an auto-immune reaction: somehow, the small bit of the flu particle included in the Pandemrix vaccine looked like the hypocretin molecule. Thus the immune system of susceptible kids who received Pandemrix would suddenly attack the hypocretin producing cells, thinking that they were the flu.

However, one of the key papers demonstrating this phenomenon was retracted this week because the key experiments could not be replicated (Science, 345(6196): 498). The original paper (Herran-Arita, 2013. “CD4+ T Cell Autoimmunity to Hypocretin/Orexin and Cross-Reactivity to a 2009 H1N1 Influenza A Epitope in Narcolepsy.” Sci. Trans. Med. 5(216): 216ra176) demonstrated how particular immune cells attack hypocretin. It was a key paper supporting the hypothesis that narcolepsy is an auto-immune disorder, and that Pandemrix triggered this reaction in susceptible kids.

What does this mean for parents trying to decide if vaccines are safe? It is still accepted that Pandemrix contributed to the rise of narcolepsy, and that the antigen in Pandemrix was the cause. However, it will take years to understand all the molecular details. In the meantime, vaccine designers are increasingly aware of the potential for side effects if the chosen antigen is too similar to a host protein, though now that the Mignot and Mellins paper has been retracted there are no documented cases of an antigen triggering an autoimmune reaction. The story of Pandemrix does show how vaccines can have side effects. However, the rate of those side effects is still far lower than the rate of complications with vaccine preventable diseases.

There are risks to any medical intervention; the job of the parent is to knowingly weigh those risks, which is very difficult. We like to think that we behave in rational ways, but we don’t. We are extremely poor at understanding risk, and because of this people are much more comfortable committing a sin of omission than commission. When applied to vaccination, it is much easier for parents to accept making a mistake by not vaccinating their children, than by vaccinating them and risking a side-effect. That’s why it’s so important to quantify risks. In this case, it’s clear that the risks of developing narcolepsy is roughly 11-300 times lower than the risk of complications from the flu, and furthermore, those risks are only for one type of vaccine. H1N1 vaccines in Canada and the US did not have the same side effect. Meanwhile, the discovery of a side effect can hit the media full force, generating fears among the public. It’s extremely common for the media to report the results of “an important new study,” as if it is definitive on any subject. The retraction of the Mignot and Mellins paper demonstrates how dangerous this is; science is a slow and careful practice. It’s important to remember that demonstrating cause can take years of difficult and complicated study and require multiple verifiable experiments. Nearly 100 years of use have shown that vaccines are safe and effective. When reports of side effects surface, weigh the risks, and remember that one study is never enough.

 Why Retractions?

Websites like Retraction Watch (retractionwatch.com) have shown that the rates of retraction have been increasing in recent years. Part of the reason for this increase is the high pressure for investigators to publish or perish, particularly for young investigators for whom a high profile publication can set up their career. But this retraction is particularly interesting: the original authors themselves could not replicate their experiment. The authors of the paper (corresponding authors Emmanuel Mignot and Elizabeth Mellins, both at Stanford) deserve commendation for their honesty. The immunological assays that they were working with are notoriously tricky; when, after publishing the first paper they returned to the experiment to build on the results, they couldn’t get it to work again (http://retractionwatch.com/2014/07/30/authors-retract-paper-confirming-that-narcolepsy-is-an-autoimmune-disease/). Where other scientists may have thrown up their hands, they notified Science Translational Medicine and retracted their work.


Metal Mining Effluent Regulations Review


Mountain stream on Grotto Mountain, Alberta

Some disturbing statistics were presented in a guest column in the New York Times: “Welcome to the Age of Denial,” by the University of Rochester physics professor Adam Frank. Roughly half of Americans are creationists, and only 58% are concerned about climate change. These numbers are slightly worse than they were 30 years ago. In Canada, creationism is not as big a concern (in 2008, 22% of Canadians think God created humans in the last 10,000 years, and 20% are unsure and surprisingly, according to a 2012 poll, 98% of Canadians believe that climate change is real, and most believe that humans are at least partly responsible (86%)). Though in Canada science literacy is slightly better than in the states, we still have a government that systematically undermines science in policy, and in the oil in gas community in Calgary people are far less willing to hold humans accountable for the state of our climate. The dissonance between the conclusions of science and the economic imperative of the resource economy have made working in my field, science consulting, an interesting place to be.

Why should we rely so heavily on science when developing policy? Because our brains are notoriously biased. We are so good at finding patterns where there are none, that scientists working with the multitude of images from the Hubble Space Telescope crowd sourced basic image analysis because they could not write software as good as finding patterns as the human eye. We also have a nasty habit of discounting facts that challenge comfortable ways of thinking. Science, at its root, is a method for trying to understand the natural world, without falling prey to the easy tricks of our minds. You think that a black cat crossing your path is bad luck? Prove it. Walk down the same street 10 times in a row. Have someone release a black cat in your path randomly. See what happens. You think that echinaceae prevents colds? Prove it. Show it to me. Let me prove it. By rigorously testing the world, we can show ourselves and each other how things work. For a country that is as heavily dependent on our environment and natural resources as Canada, good science is imperative for managing our resources, and thus the economy which relies so heavily on them.

Good science is extremely important in environmental regulations. This last week I participated in the 10-year review of the Metal Mining Effluent Regulations. In particular, we were looking at the Environmental Effects Monitoring Regulations. These rules dictate to mines how they have to monitor the environment for damage due to contaminants in effluent. In the late spring, Environment Canada brought together a number of stake-holders to review proposed changes to the regulations. The Alberta Environmental Network contacted Sustainability Resources Ltd, the non-profit society with which Endeavour Scientific is associated, to inquire whether we were interested in participating for the eNGO sector. I naively said yes.

Environmental regulations like the guidelines for Environmental Effects Monitoring (EEM) balance a bewildering number of considerations. Metal mines can include mines for uranium, base metals like nickel, iron and zinc, and precious metals. They operate in every province and territory but PEI, and are situated in various environments. Some release effluent into large rivers, but most are remote and release into small headwater areas. One mine has the potential to have no effluent released at all. As a result of differing ore bodies, technologies and water sources, the types and amounts of effluents from mine to mine are wildly different. With all these considerations, designing a scientifically defensible program to detect problems is tricky, to say the least. The solution taken by EEM is to test fish and the tiny organisms living in the river bottom, and compare them to similar communities of fish and river bottom dwellers nearby. The monitoring studies are done on three year intervals. If two studies showed that there was an effect on the environment, the mines are required to investigate why, and how it can be fixed. The elegance of the program is that it does not require an understanding of what compounds may be coming out of the effluent (though these are monitored as well), so that problems can be detected even if mines are in compliance. Simple and elegant, but fiendishly difficult to do in the field. A number of operators discovered the hard way that doing cheap studies in early monitoring efforts required them to do expensive investigative studies that showed only that their sites were variable, something that more thorough monitoring earlier on would have shown. Improvements in the regulations to make detecting real problems were proposed.

I expected for my participation to be a learning experience: I would read the material, go to the meeting, and largely keep my mouth shut. I expected that there would be practitioners with years of experience discussing the fine points of statistics and ecology. What I didn’t expect is that none of them would be representing the environmental sector. For this process, Environment Canada paid for the travel expenses and a small stipend for representatives of environmental organizations. The hours allotted by Environment Canada to review materials was woefully inadequate. As a result, the members of the environmental sector didn’t have the support to spend the time with the documents, much less the extra time to read anything else in the scientific literature. First Nations and Metis communities have the same challenges. By the time August rolled around, it became clear that I was the only eNGO participant for our committee with a science background, and because a number of my clients were on holidays, I took the time to dive in and prepare a position paper, find time on the agenda to discuss our concerns, and put together a presentation. I felt an enormous burden of responsibility, and no small amount of frustration at the willingness of some participants to go to these proceedings with all guns blazing, but without spending the time to really understand the issues.

Indeed as we prepared, I had misgivings about the type of meeting I would be walking into. Years of distrust have developed between the environmental sector and industry, and mining, in particular, is widely felt to be among the most polluting industries internationally. Some members had less time than others to prepare, but brought years of frustration to the process. Too often, on both sides, people are prepared to fight over any small detail that suggests a double cross. At the same time, subtle changes to the regulations can result in dangerous loss of protection to the environment, or huge costs to industry that do nothing but generate ill will. Dealing with these issues require honesty, preparation, and making absolutely sure that your objections are substantive.

At Endeavour Scientific, I work hard to find the middle ground between the imperatives of the economy and the need to protect the environment. I work hard to make sure that a group of people in a divided room can find the common ground to discuss the issues. The best way to start to break down barriers? Humour. That’s tricky. I started my presentation with a picture from Dr. Seuss and said that I spoke for the trees. Then asked if anyone was a fan of the Lorax. And then listened to the crickets. I swear to God, mid-morning in Ontario, in the middle of a large government building, I heard crickets. I gamely fought on. By the end of my talk, some members were smiling, some were thoughtful, some shifted uncomfortably. But as the day wore on, we found that discussing the science provided a way to really address the issues. By the end of the day, participants were commenting on the lack of tension and progress we’d made.

This process would be improved immeasurably if Environment Canada had approached the eNGO and Aboriginal sector earlier, provided capacity funding so that these sectors could be on an even playing field with industry in terms of the time and resources they could bring to the proceedings. Sustainability Resources and I donated our time to make sure our understanding of the issues was thorough and we were prepared; and without our commitment to the process and to building consensus, the meeting could easily have been tense, full of conflict and ultimately unproductive. Both the environmental and industrial sectors have for too long neglected the complexities of the science in order to emphasize easily digestible talking points. As a result, the environment suffers.

Balancing priorities is difficult. True consensus is possible when you’re clear on what issues are truly important, and where you can find compromise. Science not only gives policy makers tools for really measuring and understanding the impact of policy on the natural world, but allows stake-holders to have discussions that, if not completely free of posturing, at least are based on what’s real. When we talk about what can be proven, we find that we can actually start to talk.