Humans have always faced disease outbreaks, sometimes spreading widely as pandemics. Dealing with these, reducing their frequency and reducing harm when they occur is an important reason why we now live longer than our ancestors. We have become very good at managing risk and harm as human society has progressed. A reduction in inequality and evidence-based health policies have been central to this success. Understanding how we got to this point and the forces that are pulling us back is vital to maintaining this progress.
The world around and within us
Infectious disease outbreaks happen. They once defined much of life, removing half the population in childhood and sometimes coming in waves that killed up to a third of entire populations. These historic outbreaks and life-shortening endemic diseases were mostly caused by bacteria, spread through poor hygiene and living conditions. Since we (re-)invented underground sewers, and (re-)understood the importance of clean drinking water and a good diet, mortality has greatly declined. We now live, on average, much longer. The development of modern antibiotics brought another huge step forward – most deaths during the Spanish Flu, before modern antibiotics were invented, were likely due to secondary bacterial infections.
Viruses also kill people directly and have devastated populations that had been relatively isolated for thousands of years. Measles and smallpox came close to wiping out whole populations, such as those of Oceania or the Americas, at the beginning of the European colonial era. But now, with perhaps the exception of HIV (and respiratory viruses in the very frail elderly), the risk to most of us is low. Vaccination has further reduced this risk, but the vast bulk of reduced mortality in wealthy nations occurred well before they became available for most vaccine-preventable diseases. This fact was once taught routinely in medical schools when evidence-based medicine was a primary driver of policy.
Humans have evolved to live with bacteria and viruses, both friendly and harmful. Our ancestors have been dealing with them in different variants for hundreds of millions of years. We even contain descendants of simple bacteria within our cells – our mitochondria – containing their own genome. They and our far, far distant ancestors found a happy symbiosis where we protect them, and they provide energy for us.
We also harbour billions of ‘foreign’ cells within our body – most of the cells we carry are not human, but have a completely different genome. They are bacteria living in our guts, on our skin and even within our blood. They are not an enemy – without some of them we would die. They help us break food into forms we can absorb, they produce or modify essential nutrients and they protect us from bacteria that would kill us if left unchecked. They produce chemicals that allow our brains to think critically and face the outside world with humour. Our bodies are a whole ecosystem in themselves, an unbelievably complex and beautiful symphony of life that sustains our being and gives a home and face to our spirit.
The natural idea behind vaccines
In modern medicine, we fiddle with the edges of this complexity like drunk elephants in a jeweller’s shop. We see obvious problems and throw a chemical at them, hoping that by killing certain bacteria or changing some chemical pathway we can do more good than harm. Often, we can, which is why medicines such as antibiotics often solve immediate problems. They also cause side-effects, such as by killing bacteria that were protecting us, but when used wisely they are clearly a good thing. This is not surprising, as most modern medicines are derived from a natural template that was protecting some other organism. However, they nearly always work by supporting own defences in dealing with a threat, rather than working alone.
Vaccines are more holistic. They rely on training our own innate defences – the immune system that has developed since multicellular organisms emerged. Certain cells specialise to protect the others, sometimes sacrificing themselves in the process like worker bees or soldier ants. If we are infected by hostile bacteria or a virus, our immune systems are good at remembering what worked and reproducing that when the same or similar pathogen infects us. By injecting a protein or other part of a potential pathogen, or even a dead or harmless equivalent, we can give our bodies the chance to develop that defensive immune response without running the risk of severe illness or death. An intrinsically good idea.
Vaccination can also come unstuck. This is partly because biology is too complex to be easily fooled by a fake pathogen. We usually have to add chemicals (‘adjuvants’, such as aluminum salts) to the vaccine to make it over-stimulate the immune system and get a better response. We also often add preservatives so that we can keep them longer at room temperatures, and so vaccinate more people at lower cost. Some of these chemicals are theoretically harmful, with different effects in different people, and this will vary with the quantity and frequency they are given. This is a large driver of concerns regarding vaccination, but unfortunately not a large driver for research. We don’t have a clear idea of the risk or who is most vulnerable.
So, the normal issues concerning medicines apply. You would not want to vaccinate someone against a really mild illness if there was a significant risk of causing a worse illness in the process. Similarly, you would not want to keep pushing cumulative doses of adjuvants into people by adding vaccines for ever less serious diseases, if the potential risks increased with the more doses you gave. There would be a balancing point. This is an area we have little data on, as there is little financial incentive to get it – it won’t sell vaccines. The driving business imperative of vaccine manufacturers is to sell the product, not to protect people.
mRNA vaccines are easier
A more recent approach to stimulating a protective immune response is to inject the body with modified mRNA. RNA is a genetic material occurring naturally in our cells. It is a copy of part of our genome, and is used as a template to make a protein. In its use as a vaccine, RNA is modified to make it last much longer (replacing uracil with pseudo-uracil). This means the cell will produce more protein. Packaged in lipid nanoparticles – tiny packets that can enter any cell in the body – it is incorporated into cells throughout the body after injection. This is uneven – studies suggest that most remains at the injection site and draining lymph nodes. The lipid nanoparticles, and therefore the mRNA, also accumulates in higher concentration in certain organs, particularly the ovaries, testes, adrenal glands, spleen and liver.
The aim of mRNA vaccination is to make the body’s own cells produce the foreign protein. These cells are mimicking the pathogen. The immune system then targets them as if they were dangerous, killing them and causing local inflammation. We don’t yet know the long term consequences of causing inflammation and cell death in the ovaries of young girls, or the results of stimulating inflammation and probable cell death in a foetus in a pregnant woman. However, having given these injections to a lot of children and pregnant women, we should understand this better in the future. We only have evidence of inducing foetal abnormalities in rats. Harm could also arise if the cells are programed to produce an intrinsically toxic protein, such as SARS-CoV-2 spike protein in Covid mRNA vaccination (as can also happen through a severe infection by the virus itself).
Much of our own genome is thought to be bits of viral genome that have been accidentally incorporated by our ancestors over millions of years. So, theoretically, this could also happen with injected RNA. This has been shown in laboratory conditions, but time will tell how frequently it happens in humans.
mRNA vaccines are easier and quicker to make, and are therefore potentially very profitable to pharmaceutical companies. This is their big advantage. Quick solutions with high profit margins drive innovation, because innovation is mostly paid for by people who want to make far more money than they invested. Though theoretically risky to health due to their mode of action, this is only a problem from a commercial viewpoint if the costs to the company of addressing the harm outweigh profit, or create a bad reputation that ruins the market. This is why immunity from liability, and sponsorship of the media, are important for vaccine manufacturers.
Pharmaceutical companies sponsor media like CNN and are a crucial source of advertising revenue. In return, they hope that journalists minimise criticism and investigative reporting. Withdrawal of Pharma advertising and sponsorship could kill many media companies. Pfizer has also paid the highest fine for healthcare fraud in history, Merck failed to provide safety data on a product that killed tens of thousands of people, and Johnson & Johnson and Purdue Pharma were implicated in stimulating the U.S. opioid crisis that continues to kill tens of thousands of people every year. Yet, most people probably see these companies as intrinsically ‘good’. We are frequently told by the media that they are helping us.
Resilience and health
For any of these types of vaccines to work, they need an adequately functioning immune system, as their whole purpose is to stimulate a useful and remembered response. Immune responses can be impaired by chronic illnesses such as diabetes mellitus or gross obesity. They also require essential nutrients, such as certain vitamins and minerals, that enable the immune system’s cells to function effectively. Without these, natural immunity won’t work. Even antibiotics may be far less effective if the immune system is not working well. If we temporarily obliterate someone’s immune system to treat some cancers such as leukemia, he or she can die of quite common, usually mild, infections.
Impairment of immune systems can mean a virus that most healthy young adults would barely notice, such as the SARS-CoV-2 virus that causes COVID-19, may kill a frail, elderly diabetic person –especially if that person is living indoors, getting little sun (essential for producing vitamin D) and is fed a diet like mashed potato and gravy.
The key to combatting infectious disease is therefore maintaining resilience against infection. How we promote or restrict resilience strongly influences the need for, and benefits and harms of, medical interventions. This underpinned all pre-2020 public health orthodoxy. Resilience is obviously not achieved by living in a sea of bacteria-killing chemicals that have broad effects on the complex endogenous community of organisms that is us. But it is supported by drinking, eating and living in ways that keep our immune systems responsive and primed but limit exposure to organisms that directly harm us.
The problem with building resilience against infection is that it requires few commodities and is hard to monetise. The entire Covid debacle illustrates this well. For instance, while evidence early in the outbreak clearly associated mortality with low vitamin D, an extreme reluctance persisted in normalising vitamin D levels as prophylaxis. So much so that an article in Nature in 2023 found that up to a third of deaths might have been avoided if such a basic, cheap and orthodox measure had been undertaken.
We hear of total Covid mortality in the media quite regularly, but not, strangely, ‘low vitamin D mortality’ or ‘metabolic syndrome mortality’, which most Covid deaths probably were. If a starving child dies of a cold, he died of starvation. If a malnourished elderly care home resident dies of Covid because her diet and lifestyle prevented her from mounting a competent immune response, we were told she died of Covid. There is a reason why elderly people in Japan died far less from Covid than those in the United States, and it wasn’t masks (which, however pointless, were worn by both).
Pandemic preparedness – learning from COVID-19
This leads us to the issue of how to prepare for pandemics, and why we follow an alternative route. It is clear, and important to note, that major natural pandemics are now rare and of decreasing risk. We have not had a major event of this type since the Spanish Flu, before the advent of modern antibiotics which would now treat the secondary infections from which most mortality occurred. We had influenza ‘pandemics’ in the late 1950s and 1960s, but they did not even interrupt Woodstock. Terrible outbreaks such as the cholera epidemic in what was then East Pakistan in the early 1970s reflected a breakdown in sanitation coupled with starvation. The West African Ebola outbreak in 2014 killed less than 12,000 people –the equivalent of fewer than four days of tuberculosis.
COVID-19 intervened in 2020, but as it probably arose from laboratory manipulation (gain of function research), we cannot count it among natural outbreaks. Preventing gain-of-function outbreaks would obviously involve addressing the cause – fairly reckless research and (perhaps inevitable) lab leaks – rather than spending tens of billions of dollars on mass surveillance. We don’t actually need such research; we had been fine for almost a century without it.
However, as a respiratory virus targeting predominantly frail, elderly, immune-suppressed people, Covid tells us much about how to prepare for natural outbreaks. The logical approach, given the above history of natural pandemics and the evidence from COVID-19, would be to reduce the people’s vulnerability to virus infection. We can do this by ensuring people have well-functioning immune systems through good diet, ensuring good levels of micronutrients and reducing metabolic diseases, building personal resilience.
We cannot force diets and outdoor exercise on people, but we can educate people and make these more accessible. Doing this in aged care facilities during Covid would have been more effective than simply putting ‘Do Not Resuscitate’ labels on their charts. We could encourage the use of gyms and playgrounds, rather than closing them. Another advantage of the resilience approach is that it has broad benefits far beyond pandemics; reducing diabetes mellitus, cardiovascular diseases and even cancer deaths, and helps us all cope with normal, day to day infections. It also reduces the sales of pharmaceuticals, which is both an advantage (if you are buying them) and a problem (if you are selling them).
Less effective approaches to pandemics
The alternate approach would be to invest very large sums of money in very early detection of outbreaks and potential outbreaks, then ‘locking people down’ (a term used for prisons) and providing a rapidly produced vaccine. Problems with this approach include the near impossibility of detecting naturally occurring outbreaks of airborne viruses early enough to prevent them becoming widely established, even with intensive surveillance (as there are eight billion people and a lot of places on Earth).
A further issue is the impossibility of thoroughly testing such a vaccine for medium and long term adverse effects. Other problems include the inevitability of harming economies through ‘lockdowns’, the problem of confining ordinary people as if they were criminals, and the inevitability of economic harm that disproportionately affects lower income people. While not an issue for large pharmaceutical corporations who would obviously gain, most people are likely to end up worse off.
As noted earlier, locking down people will also further reduce their immune competence, making them more vulnerable to actually dying. People got fatter, and vitamin D levels also dropped, during the home confinements of the Covid outbreak.
The surveil-lockdown-vaccine approach is also really expensive. The WHO and the World Bank are estimating over $31.1 billion a year just for the basics, without the actual surge financing and vaccine production when an outbreak occurs. This is almost 10 times the current total WHO budget.
Weighing priorities
So, we have these two alternate approaches. One is better for health and economies in general, but probably an overall negative in financial terms for pharmaceutical companies and their investors. So, leaving ethics aside, the logical choice for those driving the current pandemic preparedness agenda is probably the latter. The WHO, the large public private partnerships (e.g. Gavi, CEPI), health regulatory agencies, research institutions and even medical societies are quite dependent on funding from Pharma and Pharma investors. The pharmaceutical companies and their investors are not suicidal – they are not going to push a pandemic strategy that will not only minimise vaccine sales but also reduce their assured long-term incomes from chronic metabolic diseases that support an increasingly important part of their product portfolio. Their job is to enrich their investors and themselves, not to support people and institutions that harm their profits.
There was a time when the momentum was very much on the resilience side. WHO was set up in this way, more or less. Countries contributed money and oversaw policy whilst WHO staff prioritised the diseases that killed the most people and had reasonable remedies. Now, funders decide over 75% of WHO’s direct programmes (WHO does what the funder says with the funder’s money) and up to a quarter of its budget is from private sources. Gavi and CEPI are solely about getting vaccines to market. The balance has tipped back to the benefit of the private investors and a few major country funders with strong pharmaceutical sectors. The priority of living longer is subsumed by the priority of profit. In the circumstances, this is logical and expected.
The great dilemma
This all brings us to a dilemma. We need to decide whether these conflicts of interest matter; whether healthcare should primarily be directed to improve wellbeing and life expectancy or directed to maximise the extraction of money from the general population to be concentrated in fewer hands. Covid showed how wealth concentration can be achieved through a virus that barely affects most people. It is a very repeatable paradigm, and taxpayers in the U.K. and elsewhere have been working hard to fund the 100-day vaccine programme that can really turbocharge further impoverishment.
If we consider that enhancing the financial wellbeing of a relative few with public money, whilst reducing the overall life expectancy of the many, is a good enough cause, then we should continue down that road. The WHO’s new pandemic agreements are geared to this, and the World Bank, World Economic Forum and similar entities in the finance world consider it a solid approach. There are also good historical precedents. Feudal and colonialist systems can be quite stable and modern technology may make them more so.
However, if we consider that ideas of equality, well-being of all (at least those who so choose) and individual sovereignty (a complicated concept but fundamental to pre-2020 human rights norms) are important, then we do have a path that is far cheaper and broader in its benefits, but much harder to implement. At present it does not feature in the dozens of pages of text in the two pandemic agreements being promoted by WHO. In fairness, they don’t really have that as an aim. Diverting tens of billions of dollars to surveillance efforts whilst reducing resilience demonstrates that health and wellbeing is not WHO’s primary intent in this case.
So, rather than arguing over fine print in these pandemic agreements, we first must make an obvious and fundamental decision. Is the intent of all this to live longer, more equitably and more healthily? Or is it to grow the pharmaceutical sector of wealthy countries? We cannot do both, and we are currently set up to support Pharma. It will take a lot of unravelling and rethink on conflict-of-interest rules to make this a public health programme. It probably comes down to who makes decisions, and whether they want an egalitarian society or a more traditional feudalistic and colonialist approach. This is the real question to be addressed in Geneva.
Dr. David Bell is a clinical and public health physician with a PhD in population health and background in internal medicine, modelling and epidemiology of infectious disease. Previously, he was Director of the Global Health Technologies at Intellectual Ventures Global Good Fund in the USA, Programme Head for Malaria and Acute Febrile Disease at FIND in Geneva, and coordinating malaria diagnostics strategy with the World Health Organisation. He is a Senior Scholar at the Brownstone Institute.
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