I read with a great deal of interest a report on Vox by their science and health reporter Julia Belluz (@juliaoftoronto on Twitter) on the recently publicized story of Pandemrix, an H1N1 pandemic influenza (a.k.a. “Swine Flu”) vaccine manufactured by GlaxoSmithKline (GSK), and the condition of narcolepsy (a debilitating sleep disorder) that affected a small fraction of individuals who received this vaccine.
The facts of the story are not in dispute. During the 2009-10 Swine Flu pandemic in Europe, GSK’s Pandemrix was given to more than 30 million people in Europe, including about 6 million in the UK. A small proportion of people, about 1300, of those who received the vaccine developed narcolepsy, a chronic, incurable condition marked by overwhelming urge to sleep during daytime, as well as cataplexy (total loss of muscle control during heightened emotions), terrifying nightmares, and sleep paralysis (temporary loss of ability to move upon waking up).
For reasons that were possibly primarily more political/fiscal than guided by science, the UK government initially appeared hostile to the idea of the narcolepsy being traced back to the Pandemrix vaccine, because acknowledging this link would mean an automatic, lump sum payment of £120,000 to anyone with “severe and permanent” disability adjudged to be due to a vaccine under the Department for Work and Pensions’ (DWP) vaccine compensation scheme; in addition, because of an indemnity signed between the UK government and GSK, the total cost arising out of litigation brought against GSK by vaccine-compensation claimants and resultant financial settlements would likely devolve upon the taxpayers eventually.
There are about 80 such individual claimants in the UK, and despite acknowledging the Pandemrix-narcolepsy link in 2013, the DWP has been refusing payment claiming that the condition in these patients was not serious enough. Last month (June 2015), following a protracted 3-year court battle, a 12-year old who developed narcolepsy after being vaccinated with Pandemrix was awarded the full compensation by an upper tribunal court – a decision that the UK government may yet challenge. The overall situation decidedly took a turn for the worse, when last year a 23-year old woman, one of the 80 narcolepsy patients, committed suicide after struggling with the devastating effects of narcolepsy on the quality of her life. Her family has applied to DWP for compensation, but has received no response yet.
Belluz’s essay has adequately highlighted these facts, as well as the scientific research that helped uncover the epidemiological association between narcolepsy and Pandemrix. Belluz spoke to Elizabeth Miller, epidemiologist with the UK Health Protection Agency and lead member of the team which trawled through clinical records and sleep test results from UK pediatric neurology hospitals, to determine the causal association between the Pandemrix vaccine and increased narcolepsy risk (which was published in the British Medical Journal in early 2013). Belluz also spoke to Hanna Nohynek, a vaccine researcher with Finland government’s National Institute for Health and Welfare, who studied the 46 vaccinated Finnish individuals with narcolepsy whose condition could be definitively traced to Pandemrix received by close to 700,000 in Finland; these results were corroborated by similar observations from Sweden.
However, in writing the report, Belluz focused on certain perspectives – those of science journalists – that I ordinarily find valuable, but which were rather disappointing in this case. Apparently, some journalists, including Belluz, “shied away” from reporting on the negative consequences of the Pandemrix vaccine. It is likely that this was a rather US- or North America-centric situation, because Finnish media – according to Nohynek’s statement in their PLOS ONE paper – devoted attention to post-vaccination narcolepsy right in the Fall of 2010. Belluz justified this conduct on the basis of the fact that much of the current anti-vaccine frenzy stems from uncritical media reports on Andrew Wakefield’s flawed and ethically-questionable paper in Lancet linking vaccines with occurrences of autism (Belluz has an excellent summary of the Wakefield debacle in her Vox column); in fact, her current Vox report under discussion is titled expressively “How anti-vaxxers have scared reporters away from covering vaccine side effects“. This may not be untrue. And yet, I think that such abstinence, practised as a journalistic conduct, does a great disservice to the reading public as well as the cause of public health, to which health and science reporters ought to have a duty. Allow me to explain why I think so.
Such conduct enables precisely what Belluz is trying to avoid; since news never remains hidden, especially in this age of information and social media, journalistic silence on an important public health issue inevitably gives rise to conspiracy theories and ammunition to the rather vocal and vituperative anti-vaccine activists to spread further fear, uncertainty and doubt – maligning vaccines which have overall saved millions upon millions of lives.
Belluz’s account also glosses over an important idea that Nohynek brought forth; rare events such as the narcolepsy side-effect may never surface easily with the current phases of clinical trials, until at the post-marketing phase (Phase 4) when the therapeutic agent in question has been given to a sufficiently large number of people thereby allowing those rare events to be observed and recorded. This is not a matter of vaccine “uncertainty”. Recording and reporting of such events, by scientists as well as journalists, will allow the agent to be further investigated and refined if necessary, and harm:benefit ratios can be more effectively and accurately estimated and recorded. As Nohynek rightly points out, the Finnish media was instrumental in pushing the scientific community to investigate the rare events associated with Pandermrix.
The fact that Nohynek’s paper was initially rejected by the NEJM, the Lancet, and the BMJ, as well as the publication problems faced by Miller, point to an abysmally myopic vision of the decision-makers at these prestigious, top-tier medical journals. Journals, like everyone else, ought to learn from their mistakes: if the Lancet published Wakefield’s fraudulent work in 1998, Nature published Benveniste’s ‘Water Memory’ paper in 1988; Lancet eventually retracted the paper, and Benveniste’s extraordinary claims were thoroughly eviscerated by subsequent scientific work. Therefore, there is no reason why medical journals cannot lead the charge and pick up a well-researched paper, even if its subject matter engenders controversy – if there is even a remote possibility that the subject matter is relevant to public health. This is how science progresses, by trials, by adversarial interactions, by rigorous testing of hypotheses. To hide behind the “Wakefield effect” is just plain lazy, not to mention, unethical, for these journals, as well as science journalists.
In fact, what left me most disappointed with Belluz’s account was the egregious omission of the most exciting aspect of this otherwise deplorable Pandemrix-Narcolepsy situation: further scientific work has actually uncovered a possible reason why the narcolepsy was triggered in a relatively small number of people by the vaccine. Independent lines of evidence (read an excellent summary by Gretchen Vogel) suggested that certain people were genetically predisposed towards making a variant of a brain protein involved in regulation of sleep-wakefulness, a variant that coincidentally shared a structural similarity with an H1N1 protein; this may have led to generation of antibodies, as a part of their anti-influenza immune response, that attacked their own brain cells due to that unfortunate similarity of the brain protein with flu protein. Finnish scientists have contributed to the overall body of work on this. Most interestingly, Chinese scientists noted an increase in narcolepsy cases in China after their 2009 H1N1 pandemic – even though Pandermrix prophylaxis wasn’t employed there.
What I’d have dearly liked Belluz to highlight is the fact that continued, tenacious, rigorous scientific work on vaccines, not bogged down by irrational fears, has suggested ways in which the brain protein in these rare individuals may be protected or the vaccine made safer by omission of specific compoments – thereby saving them from the unwanted side-effects of the Pandemrix vaccine while providing the full benefit of protection from the H1N1 influenza. We don’t need to “cheerlead” for vaccines; we can cheerlead for science.