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 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 the wealthy 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.
The Natural Idea Behind Vaccines
In modern medicine, we fiddle with the edges of this complexity like drunk elephants in a jeweler’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 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 protects some other organism. However, they nearly always work by supporting our own defenses in dealing with a threat, rather than working alone.Vaccines are more holistic. They rely on training our own innate defenses; the immune system that has developed since multicellular organisms emerged. Certain cells specialize to protect the others—sometimes sacrificing themselves in the process like worker bees or soldier ants. If we are infected by a hostile bacteria or 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 overstimulate 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 (clearly also, of itself, a good thing). Some of these chemicals are theoretically harmful, with different effects on 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.
mRNA Vaccines Are Easier
A more recent approach to stimulating a protective immune response is to inject the body with modified RNA. 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 accumulate in higher concentration in certain organs, particularly the ovaries, testes, adrenal glands, spleen, and liver.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 the 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.
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, they 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 potatoes and gravy.
The key to combating 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.
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 not 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 less than 4 days of tuberculosis.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 people’s vulnerability to virus infection. We can do this by ensuring people have well-functioning immune systems through a good diet, ensuring good levels of micronutrients, and reducing metabolic diseases. Building personal resilience.
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. A problem with this approach includes the near impossibility of detecting naturally occurring outbreaks of airborne viruses early enough to prevent them from becoming widely established, even with intensive surveillance (as there are 8 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 that would obviously gain, most people are likely to end up worse off.
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. The other supports Pharma income. 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 minimize 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.
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 well-being and life expectancy, or directed to maximize 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 UK and elsewhere have been working hard to fund the 100-day vaccine program that can really turbocharge further impoverishment.If we consider that enhancing the financial well-being 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, the 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, 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 the WHO. In fairness, they don’t really have the same aim. A sensible degree of surveillance certainly makes sense, but diverting tens of billions of dollars to such an effort whilst reducing resilience demonstrates that health and well-being are not the WHO’s primary intent in this case.
So, rather than arguing over the 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 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 unraveling, and rethink on conflict-of-interest rules, to make this a public health program. 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.