## The Shock We Saw Coming?

The impact of a mortality shock is by definition hard to predict. We don't know with certainty if or when a shock might occur, or what effects it might have on mortality in the years that follow. However, something that might break this pattern is antimicrobial resistance (AMR), the property of certain pathogens — be they bacterial, viral or fungal — to evolve immunity to previously effective treatments. Although this is an area we've heard much about in recent times, it has actually been subject to rigorous examination for more than half a century. Resistance to penicillin was even warned of by its discoverer during his Nobel acceptance speech.

"The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant."

After penicillin's arrival in 1928, it might be comforting to imagine it took some years of careless use before resistance developed to clinically visible levels. Sadly this was not the case for that antibiotic or those that followed. According to science historian Robert Bud, the penicillin derivative methicillin, developed to counter resistance, was discovered in 1959, first used in UK treatments in 1960 and implicated in the first MRSA illnesses and fatalities in 1961 and 1962. Today conservative estimates of global annual mortality due to AMR are in excess of 700,000, about half of that currently attributed to diabetes. Carriers of resistant strains exist in every community, making this a truly global problem, although one that hits hardest in the developing world.

Decades of drug development did not eradicate the problem but merely attempted to outrun it. It is therefore unsurprising that new discoveries are increasingly rare. This is not simply due to the exhaustion of low-hanging fruit, but also due to the economics of the problem. At estimates well in excess of one billion US\$ and over ten years to develop a new agent, pharmaceutical companies prioritise investments with a long-term mass-market, such as statins, over acute treatments taken for days rather than decades. This investment preference is even more difficult to overcome when those same acute treatments carry the expected obsolescence conferred by antimicrobial resistance.

In 2014 the UK government commissioned a review on this topic, which in turn procured specific scenario modelling reports on economic impact from both the RAND Corporation and KPMG. These reports only examine a subset of pathogens, and they necessarily contain a number of arguable assumptions, so the model results carry significant uncertainty. However, while it is common for actuaries considering longevity risk to hypothesise the impact of "a cure for cancer", the headline mortality impact the review predicts is that in 2050 AMR will be a bigger cause of death globally than cancer is today. Indeed, the fear now being expressed at high levels is that AMR has the potential to be more than a "shock", but instead a longer-term step change in mortality and morbidity. The impacts are felt not just in direct treatment for microbial infections, but also in all manner of medical interventions dependent on antimicrobial prophylaxis, such as general surgery, chemotherapy and organ transplantation.

So, should those concerned with longevity risk anticipate a reversal in mortality improvements? That seems less than prudent, since the fightback is building on multiple fronts. A key mitigation is to minimise overuse of antibiotics so the search is underway for a rapid and accurate test for bacterial infection that is inexpensive enough for global use. Additional initiatives are ongoing to eliminate the use of human antibiotics as agricultural growth promoters, a common practice outside of the EU. On the pharmaceutical front, researchers are finding better ways to use existing treatments, whilst regulators are actively incentivising new developments. Further hope stems from research into novel treatments such as faecal transplantation, just one of a number of strategies where microbes are used to treat microbial disease. The sheer breadth of work ongoing is perhaps exemplified by the ironic discovery that aspects of this threatened return to the medical dark ages might be tackled by medicine from the very same era...

Assume we have a random variable, $$X$$, with expected value ... Read more