Tom Edwick dives into the ethics of SARS-CoV-2 vaccine development.
As we move into month four of lockdown, life as we knew it seems little more than a distant memory. Life in this new covid era has thrown up a lot of fun experiences that I wouldn’t have had to deal with otherwise, like having to swerve suddenly and unexpectedly off the pavement, in a last ditch attempt to maintain a responsible distance from a stubborn oncoming pedestrian. Never before have I smiled at a cashier, only to realise that they probably couldn’t tell behind my facemask, leaving me with unreasonable anxiety that I came across as rude. My skin is rubbed raw from all this hand-washing, and I’ve nearly run out of new songs to sing while I do it.
Though lockdown has eased in many places, concerns of a second wave, and the recent news of potential airborne spread of coronavirus, makes a return to normality seem some way off yet. There is one thing that would expedite a transition back to ordinariness – a vaccine. Unfortunately, the road to a vaccine can be long and bumpy at the best of times, and in case you hadn’t noticed, we’re kind of in the middle of a pandemic.
So, why do we need a vaccine? Early on in the pandemic, there was talk of herd immunity as a potential response to the crisis. The logic went like this: if people catch the virus and survive, they will develop antibodies to SARS-CoV-2 and become immune. If enough people develop immunity – between 70 and 90 per cent of the population – the virus will eventually run out of people to infect, and die out. Here’s the kicker – not only did scientists discover early on that this strategy would be incredibly irresponsible and deadly, but a recent study from King’s College London suggests that acquired immunity is lost within months of infection.
If natural herd immunity isn’t possible, what do we do? We vaccinate. In simple terms, a vaccine is a harmless form of the virus, or part of it, that stimulates an immune response and allows the body to develop antibodies, and thus immunity. All those injections you got as a kid weren’t for nothing. So far, we have managed to fully eradicate two deadly diseases through vaccination, both caused by viruses: smallpox and rinderpest. Next on the chopping block are polio, and measles, mumps, and rubella (though anti-vax movements are making the latter a little difficult). The crux of all this is that a coronavirus vaccine is looking like our only clear way out of this mess. It’s true there are countries that have been extremely successful in countering COVID-19
with track and trace programmes, widespread testing, and just a better response generally than here in the UK. But we are a globalised society, reliant on international travel and commerce, and coronavirus continues to wreak havoc in developing nations. Until there’s a vaccine, there won’t be a complete return to life as it was, if that’s even what we want (though that’s a story for a different article).
Vaccine development usually takes a long time – 10 to 15 years, in fact. There are multiple stages: the exploratory phase (what are the technologies?), pre-clinical trials (testing on cell cultures and animals), clinical trials (testing on humans), regulation, manufacture, and quality control. Not only is the process time consuming, but researchers need to be 100 per cent sure there aren’t any serious side effects. It would kind of defeat the point of a vaccine if it caused more harm than good. There are scenarios where the patient has to make a decision based on the costs and benefits of the treatment. Chemotherapy is no walk in the park, but if someone’s chances of survival can be boosted, they may deem it worthwhile. In the end, it is the individual’s decision. Vaccines are different. They are deployed widely to the population as a preventative measure. Not just for the benefit of the individual, but for society as a whole – especially those who are immunocompromised, or allergic to a vaccine. The decision is collective. Therefore, vaccines need to be completely safe, and this just takes time.
The trouble with COVID-19 is that it is an emerging infectious disease thought to have jumped from a non-human animal host, and as such, is completely new to human populations. Unlike the flu or the common cold (which is also in the coronavirus family), we haven’t coexisted with SARS-CoV-2 for any period of time – and I’m talking evolutionary time here – and our immune systems have been completely caught off guard. As a result, the disease has been incredibly damaging. As of writing this article more than half a million people have died worldwide, and positive cases exceed 12 million. Therefore, the pressure to develop a vaccine quickly is immense, and the progress we have seen so far is unprecedented. The quickest vaccine ever developed was for mumps, which took four years. With coronavirus, there has been talk of pushing through a vaccine in 12-18 months. Inevitably this is going to involve jumping through some ethical hoops.
COVID-19 has thrown a pandemic-shaped spanner in many of the conventional ways of doing things, and vaccine development may be one of them. Typically, when vaccines make it to clinical trials they are tested on increasingly large groups of people as they progress. Patients are given the vaccine, but notably they are not given the disease – they have to wait until they catch it naturally. This is why the clinical phase can be so time consuming. To expedite this process for coronavirus, researchers have been discussing the implementation of ‘challenge trials’, where patients are deliberately infected with the disease. However, to make these properly controlled trials, not all patients will receive the vaccine – some will be given a placebo. For this reason, challenge trials are normally reserved for diseases that aren’t very serious, or for which we have effective treatments. COVID-19 ticks neither of those boxes. But with the death toll rising and uncertainty surrounding the disease, it may be time for a rethink.
Thankfully, there are people out there who are doing just that. In an article published in Science, lead author Seema Shah, a medical ethicist at Northwestern University, Illinois, proposes a rigorous ethical framework for if we want to go ahead with challenge trials. Besides answering the obvious question of whether a vaccine works, Shah and her colleagues suggest that these trials could also be useful for elucidating the unknown details of the disease. By investigating how COVID-19 progresses in patients from day one, we could further understand infection dynamics, virulence, and the factors that contribute to positive patient outcomes – all things that are difficult to monitor in the ICU. Another, cruelly ironic argument in favour of challenge trials is that the better we fight coronavirus (and the less that people are infected), the less opportunities we have to study it. These trials would allow continued study of SARS-CoV-2 in human hosts, before we have another outbreak.
The framework is not a ringing endorsement of challenge trials, which have a complicated history and numerous cases of questionable ethics, but more of a consideration of how we choose to go forward. There are a multitude of things to weigh-up. Will the trials be safe? Is the risk worth the reward? Will patients be fairly compensated? Should they be paid at all? And perhaps most importantly, is the vaccine going to be available to those who need it most? As a society we have a poor track record on exploiting disadvantaged and poor communities for medical advancement, and then pricing them out of, or restricting access to, the very advancements they helped create. We like to think of science and medicine as free of the baggage of politics and human conflict, but so often the very real issues of race, inequality, and vested interests mean that the spoils of innovation are not evenly distributed.
The development of a vaccine brings back the ever present question of how we value an individual life, and at what cost we choose to progress science and medicine. So, looking beyond the vaccine, the pandemic, and into the future, we need to make sure we all cast a more critical eye on how we develop, test, and distribute medicine so that it benefits everyone.
Written by Tom Edwick and edited by Tara Wagner-Gamble.
Tom’s thoughts…Honestly, it is a really tough call for whether we should do challenge trials. The potential for good is obvious – a vaccine would save countless lives. But we should be careful that we don’t end up exploiting people in the process. I think the simplest way to do this is to have the trials done on a voluntary, unpaid basis. This means that people in financial difficulty aren’t disproportionately represented in the trials, as often is the case. By removing payment from the system, you attract a wider sample of the population, and make sure that those involved aren’t ignoring the risks because they need the money. There is a lot of support for this approach too. An organisation of researchers, called 1 Day Sooner, are advocating for challenge trials, and at the time of writing have received volunteer pledges from nearly 33 thousand people. So, if we can do it safely and ethically, without exploitation, I’m all in.
Find me on… Twitter @EdwickTom
Tom (he/him) is a recent ecology graduate from the University of Edinburgh, and the host of EUSci’s Not Another Science Podcast.