[ed. note: Michael Jorrin, who I call Doc Gumshoe, is a longtime medical writer (not a doctor) who writes for us about medicine and health a couple times a month. He has agreed to our trading and disclosure restrictions, but does not generally write directly about investment ideas. His ideas, thoughts and words are his own, and you can see all his past pieces here.]

Since the Doc Gumshoe piece in October 2013, it has only gotten worse, or at least, a lot more worrisome.   Just at the end of February, the World Health Organization issued yet another dire warning about “superbugs” – pathogens which appear to be resistant to all known antibiotics.

Is this a major threat to you, the denizens of Gumshoeland, most of whom reside in North America?   Doc Gumshoe tries to steer a careful course between sounding alarms when alarms need to be sounded and his native optimism, for which he was regularly chided by his clear-eyed mother.   In this case, I tend to agree with WHO.   The situation is serious, and likely to get worse unless there are aggressive initiatives, few signs of which appear to be on the horizon.

Whether these superbugs are a menace to non-hospitalized people in okay health as they are going about their daily activities is the question to which most of us would like a reliable answer.   But here’s a statistic as provided by the Centers for Disease Control: infections due to resistant pathogens have been the cause of death for 23,000 Americans in the last year for which data are available, and the number is predicted to hold steady or increase slightly.   Considering the numbers that die of heart disease and cancer – about 600,000 of each disease – the 23,000 that will die from superbugs may seem like a relatively minor menace.   However, for the sake of comparison, it’s estimated that 38,000 Americans will die in automobile accidents this year, and we as a nation do not view car crash mortality as a minor menace.

And, by the way, that 23,000 is likely to be an underestimate.   In attributing causes of death, the CDC eliminates any deaths that could be attributed to other causes.   If the patient had a resistant infection that led to pneumonia, but died of heart failure, the cause of death is heart failure.   No matter that if the patient had not become infected with pneumonia, he/she would not have succumbed to heart failure.

Multidrug-resistant (MDR) pathogens in the Enterobacter class, including E. coli, have increasingly been identified in children with a range of diseases, especially urinary tract infections.   A study published this February (Meropol S. J Pediatric Infec Dis 2017) investigated 107,610 discharge records from 48 pediatric hospitals, and found that a small but rapidly increasing percentage of these infections were caused by MDR bacteria.   In January 2007, just 0.2% of those infections were due to MDR bacteria, but the proportion increased to 1.5% by March 2015, an increase of 750%.   These pediatric infections did not lead to an increase in fatalities, but they did cause significant increases in the time children remained hospitalized.

About three-quarters of these MDR infections were acquired in the community.   The authors of the study observed that this fact was an additional cause for concern.   It is understood that in spite of stringent precautions, hospital-acquired (nosocomial) infections are a threat.   But the presence of MDR pathogens in the community means, in the words of the authors, that “they will spread – we can catch them anywhere.”   They urged more controlled use of drugs such as third and fourth generation cephalosporins and carbapenems.

The particular development that has most recently pushed the superbugs into the spotlight is that some of the antimicrobials that have been considered to be drugs of last resort for treatment of resistant infections have just in the past few years been found to be ineffective against some resistant pathogens.   The drugs in question are carbapenems and a member of the polymyxin group called colistin.   Resistance to carbapenems is still somewhat rare, but carbapenem- resistant Enterobacter species have been found in 44 states in the US.

Colistin is a seldom-used drug in humans because it is associated with severe kidney damage, but it has been held in reserve for use in severe infections with pathogens that resist all other available agents.   Obviously, clinicians would not routinely use a drug that might cause kidney damage if there were a more benign antibiotic available.   For example, a pathogen that causes severe lower respiratory and urinary tract infections, Klebsiella pneumoniae, causes life-threatening infections particularly in hospitalized patients.   Klebsiella is routinely treated with drugs in classes such as fluoroquinolones and third- and fourth-generation cephalosporins.   If those don’t work, the next option would likely be a carbapenem.   But some resistance to carbapenems began to be noted in 2008.   Colistin would then be the drug of last resort.   However, the first patient with a colistin-resistant pathogen was identified in the US in 2016.   After colistin, there are no other options.

How did this come to be?

With regard to colistin, the likely culprit is China, where pig farmers annually feed about 12,000 tons to their pigs to accelerate their growth.   Bacteria resistant to colistin were found in 2015, and at present more than 20% of pigs in China are colonized with this drug-resistant bacterial strain.   Of more concern is the report that about 1% of hospitalized humans have that drug-resistant strain.   And of greater concern still is the mechanism through which these pathogens become resistant.   The gene that conveys resistance is not part of the bacteria’s own DNA, but is part of a plasmid, which is a DNA ring independent of the bacterial DNA and can transfer genetic material between different cells.   In other words, resistance in one bacterial species can be transferred to another.

Chinese pig farmers are by no means the only culprits in the spread of antibiotic resistance.   It’s estimated that somewhere around 80% of all the antibiotics used in the US are fed to animals.   There has been a lot of squabbling about this issue between the livestock and poultry industries and organizations focused on human health.   The former claim that putting antibiotics in the feed means that their animals will be healthier and safer to eat, and will pass fewer diseases along to humans.   But the health authorities push in the other direction.   It’s one thing to keep disease at bay among the pigs and chickens.   It’s entirely another thing to pump them full of antibiotics so as to bring them to market more quickly.   And those antibiotics are also present in the pork chops and chicken cutlets that we eat, as well as in the animal waste.   Tiny amounts, no doubt, but capable of engendering microbial resistance.   How does this happen?

Why do microbes develop resistance to antibiotics?

The short answer is, to survive!   Micro-organisms, like all organisms, evolve in nature.   Every organism is constantly under threat from other organisms, and every species of organism constantly undergoes mutations, some of which are beneficial, and some of which turn out to be the opposite of beneficial.   So a beneficial mutation tends to spread, while a mutation that increases risk tends to die out.   The same thing is true for micro-organisms, which exist in a highly competitive environment.   Microbes have evolved fighting antibiotics, probably for billions of years.

“But how could this be?” you say – antibiotics have only been in existence since about the middle of the 20^th century.

Technically, that’s true, if we think of antibiotics as drugs developed by scientists with the express purpose of combating infection.   But antibiotics exist in nature, and many of the antibiotics used clinically are derived from natural, living organisms, which for their own survival, prey on micro-organisms in their environment.   Some of the microbes that survived these hostile organisms did so because they possessed mutations that incapacitated their enemies, those organisms that we might think of as “natural” antibiotics.   The ones that had the mutations survived and reproduced, while the ones without the mutations failed to reproduce.

How does resistance to antibiotics spread among micro-organisms?

It’s really kindergarten Darwin.   A population of organisms is threatened by a deadly agent, which we call an antibiotic.   Some, but not all, of the organisms perish.   Some survive because they happened to dodge the antibiotic, but others survive because they possess a characteristic that makes the antibiotic less effective against them – perhaps not total immunity, but something that permits them to fight against the antibiotic.   (Later on, we’ll look at some specific mechanisms through which microbes resist antibiotics.)

Let’s say that prior to being exposed to the antibiotic, a fairly small proportion of the micro-organisms had this protective mutation – maybe 5%.   Exposure to the antibiotic kills off half of the entire microbe population right away.   But the surviving half includes most of the ones possessing the protective mutation – i.e., antibiotic resistance – so those now constitute about 10% of the remaining microbe population.   So in the next generation of microbes about 10% will have inherited resistance.    Continuous exposure to the antibiotic kills off the unprotected microbes, sparing the resistant microbes, until most of the microbial population is resistant to that antibiotic.

It’s not as simple as that, of course.   In most cases, antibiotic resistance is far from total.   It confers a survival advantage, which is transmitted to succeeding generations.   But it’s not a bullet-proof vest.   Many antibiotics, at sufficient concentrations, will kill – or at least stop the proliferation of – resistant pathogens.   So this brings us to one of the truly vexatious aspects of treating infections, which is that resistance to antimicrobials is often the result of stopping treatment too soon or treating at insufficient doses.   An objective of treating infections, beyond getting rid of the infection itself, is eliminating the infection-causing pathogens, so that the patient is not left with a population of resistant pathogens that may come back and cause a really difficult-to-treat infection.   As infectious disease docs say, “Dead bugs don’t multiply.”

A typical scenario that leads to antibiotic resistance

Clarence is nine years old.   He seems to catch cold every month or so, to the extreme vexation of his dear mother, Minerva.   These don’t seem to be bad colds – he just sniffles and gets a runny nose, so Minerva doesn’t keep him home from school, because it would be a major inconvenience, since she has to go to work.   But the third cold of the school year is a bit worse, so Clarence stays home from school, and after a couple of days, Minerva decides to take him to the doctor.   The doctor tells her that what Clarence has is almost certainly a common virus, and Clarence will be fine in a couple of days, but if he’s not, bring him back, because we want to be sure he doesn’t develop a more serious infection.   But Minerva, having taken Clarence to the doctor, wants to walk out of the office with something – a prescription for some medicine of some kind.   So the doctor, against his better judgment, writes a prescription for a common antibiotic.   He figures that there’s always a possibility that Clarence might develop a bacterial infection that could lead to something nasty, like an ear infection.

The instructions on the package say that the pills should be taken daily for ten days.   But after two days, Clarence feels just fine.   His cold has gone away!   He doesn’t want to take his daily pill, and his mother doesn’t want to engage in a battle of the wills to make him do it, and besides she doesn’t think he needs it.

But about a month later, Clarence develops another cold.   This time, Minerva knows just what to do.   She still has several of those antibiotic pills left in the medicine cabinet, and she gives Clarence a pill right away, and gives him another one the next day.   And the pills work great!   Clarence is cured of his cold in two or three days.

What his mother doesn’t know is that the pills did nothing to cure Clarence’s cold, since it was indeed caused by a common virus, which was totally unaffected by the antibiotic.   Like most colds, it went away on its own.   What the pills did, however, was to create an environment in Clarence’s upper respiratory system that fostered the growth of pathogens resistant to that class of antibiotics.   All of us are colonized by micro-organisms that have the potential to cause troublesome infections.   Mostly they are kept in check by competition from other microbes.   But it doesn’t take much to upset the balance.   Many antibiotics are indiscriminate in their effects.   They don’t know which are the good guys and which are the bad guys – they attack them all.   The ones that are most likely to survive are the ones that possess those protective mutations that fight back against the antibiotics, and those resistant survivors are the ones that reproduce and become the dominant microbial species.

So now Clarence’s pharynx is populated by a resistant strain of a particular pathogen called Staphylococcus aureus.   Clarence is basically a healthy lad, and the Staph aureus in his mucous membranes don’t do him much harm.   But now there’s a visit from his grandmother, Eunice, who adores him.   Eunice is getting on and has had her share of health problems over the years.   The next time Clarence comes home from school with a cold, Eunice catches cold.   But Eunice’s cold gets worse.   She becomes very congested.   She develops bronchitis, which progresses to a lower respiratory infection.   She is, quite legitimately, prescribed an antibiotic.   But, guess what, the antibiotic doesn’t work!   That’s because Clarence not only passed his rhinovirus to his grandmother, he also transmitted his resistant strain of Staph aureus to the old lady, who is a bit frail to start with.

Not to turn this into a tragedy, we’re going to say that Eunice was admitted to the hospital, her sputum was cultured, a methicillin-resistant Staph aureus (MRSA) was identified, she was treated with one of several antibiotics that deal effectively with the little buggers, and she recovered.   But it doesn’t always turn out that way.   Eunice might easily have been one of the 23,000 people in the US who will likely perish this year as a result of an antibiotic-resistant infection.

What this little story tells us is that there are at least a couple of different ways a resistant pathogen can infect us.   We can foster and harbor resistant pathogens in our own bodies, and we can also be infected by resistant pathogens out there in the community.

Which pathogens are most likely to become resistant?

The answer is, those pathogens that are most likely to be exposed to antibiotics.   That’s pretty obvious.   But which pathogens are those?   Not the rare ones, the ones carried by rare reptiles in the jungle or the ones that reproduce only in unusual situations.   For example, tetanus is the result of a toxin produced by a bacterium called Clostridium tetani.   This particular bacterium is present in soil, and is especially prevalent in animal feces.  To cause a tetanus infection, the bug has to penetrate into the bloodstream.   A nice way to get tetanus was to step on a nail in a street where horses had deposited their usual dung droppings.   Clostridium tetani is susceptible to penicillins, macrolides such as erythromycin, and many other common drugs.   I do not know of any instances of antibiotic resistance with this particularly nasty pathogen.

The bacteria most likely to become resistant are the ones that commonly colonize us humans.   It’s not nice to think about, but we are hosts to untold numbers of microbes that can, under the right circumstances (right for them, but not for us!) cause serious and even deadly diseases.   Among the pathogens that commonly live in or on our bodies are ones such as Staphylococcus aureus, which can cause skin and soft tissue infections as well as respiratory infections; Escherichia coli, which can cause a wide range of infections including necrotizing fasciitis, the infection reported in the media as due to “flesh-eating bacteria;” also Streptococcus pneumonia  and a number of others.

Normally, the populations of these potentially dangerous pathogens have to compete with the immense numbers of harmless and even beneficial microbes with which they share their room and board.   It’s the competition between all the microbes that keeps the numbers of any single species in check.

Because they essentially live with and on us, they are exposed to whatever antibiotics we’re exposed to.   The susceptible Staph aureus that dwelt in Clarence’s system all got killed off by the antibiotic that his doctor prescribed, leaving only the resistant pathogens, which he then passed on to his grandmother.   And it needs to be understood that the antibiotic does not induce resistance – what happens is that the presence of the antibiotic selects for resistance.   Giraffes got their long necks not because the fruit that they were plucking off the trees made their necks grow longer, but because the longer-necked individuals in the herd had a survival advantage.   The microbes with properties that disable their enemies have a survival advantage over the ones that don’t possess those properties.   We can call those properties antibiotic resistance.

Some pathogens, however, come pre-armed with the mechanisms that result in resistance.

The “Iraquibacter”

A bacterial strain that has recently triggered alarms in the infectious community is Acinetobacter baumanii, which didn’t get a lot of attention until military personnel in Iraq and Afghanistan began to be infected with this particular pathogen.   A. baumanii  infected many soldiers who had been injured by explosive devices.   Their open wounds came into contact with the pathogen, which can survive for fairly long periods on exposed surfaces.   When the infected soldiers were admitted to hospitals, the pathogen spread in those sites.   A. baumanii  has been identified as the cause of nearly 20% of cases of pneumonia in patients who require the assistance of a ventilator in some hospitals.   It happens to be related to Staph aureus, Klebsiella, and Pseudomonas aeruginosa.   (This last pathogen is also a particular danger to hospitalized patients who require intubation.)   All of these bugs are good at developing the mutations that combat antibiotics, and A. baumanii excels at that game, which is to say that it comes on board all ready and able to do battle against the antibiotics that may be deployed.

A particularly menacing characteristic of this bacterium is that is possesses not just one, but several distinct mechanisms of antimicrobial resistance.   These include:

• Beta-lactamase:   By far the most common antibiotics are the cell-wall antibiotics, which, as the name implies, attack the bacterial wall.   These include all of the penicillin-related antibiotics, known as beta-lactams, including amoxicillin, ampicillin, and methicillin, but also the cephalosporins, which are the largest class of antibiotics, as well as vancomycin and daptomycin.   A. baumannii has been shown to produce at least one beta-lactamase, which is an enzyme responsible for cleaving the four-atom lactam ring typical of beta-lactam antibiotics, thereby destroying the antibiotic.

• Biofilm formation:   A. baumanii has the ability to form a biofilm, which reduces its sensitivity to antibiotics and permits it to survive on artificial surfaces for an extended period.   Thus, it can survive in the hospital environment unless aggressive cleaning is carried out.

• Efflux pumps:   Some pathogens develop the capacity to pump the antibiotic out of the cell, so that the antibiotic does not attain the concentration necessary to kill the pathogen.   A. baumanii possesses not one but two efflux pumps.   Efflux pumping is the means through which pathogens inactivate several antibiotics that target protein synthesis, such as the tetracyclines and the macrolides, a group of drugs including erythromycin and its relatives.

A. baumanii was initially treated with carbapenems, but when resistance to carbapenems began to emerge, colistin was the next – and last! – drug in line.   Thus, when resistance to colistin began to emerge, shock waves went through the infectious disease community.   What was left?   The answers were not encouraging.

Before we leave the subject, let’s look at some other mechanisms of resistance.

• Inhibiting bacterial synthesis of folic acid:    The sulfonamides (“sulfa drugs”) target bacterial synthesis of folic acid, which the bacteria require to survive – except that some bacteria develop a form of resistance which entails not needing to synthesize their own folic acid, but scavenging it from other sources.

• Attacking DNA gyrase:   The fluoroquinolones (ciprofloxacin and others) attack DNA gyrase, which twists the single DNA strands into the familiar double helix.   However, some bacteria develop mutations in their DNA gyrase, rendering them resistant to fluoroquinolones.

Antibiotic resistance presents a major problem both to the medical community and to the pharmaceutical industry.   The medical community is pressed to try to exercise maximum care in prescribing antibiotics so as to try to limit the spread of antibiotic resistance.   The pharmaceutical industry is challenged to come up with new antibiotics that will effectively treat the emerging resistant microbes.

Possible responses by the medical community

Doctors by nature and training tilt towards intervention – do something rather than nothing.   In the case of Clarence, there were at least a couple of errors.   Clarence’s doctor should not have given in to Clarence’s mother and prescribed an antibiotic.   Clarence had a cold, almost certainly caused by a virus, which would not be in the least affected by an antibiotic such as the one the doctor prescribed.   If Clarence developed a bacterial infection, that would be when to start treatment with an antibiotic, not before.   And, having prescribed the antibiotic, the doctor should have been emphatic with Minerva that Clarence had to complete the entire course of antibiotics – take all the pills.   Finally, Minerva should not have kept the unused antibiotics in the medicine cabinet.

The ideal procedure in treating an infection is something like this: first, precisely identify the pathogen; then, hit the pathogen with an agent that precisely eradicates the entire population of that particular pathogen, quickly, and without affecting any of the other micro-organisms in the patient’s system, and, of course, without causing the patient any adverse effects.   Ideally, there are data showing that the pathogenic population has been wiped out in a certain time period, so after that time period, treatment with the antibiotic can stop.   This is called definitive treatment.

Needless to say, it seldom happens that way.   Antibiotics generally are active against a group of pathogens, not just one single pathogen.   And they almost always kill off not only the pathogens that are causing the infection, but a lot of harmless and even beneficial micro-organisms.

However, equally important is the element of time.   It is not always possible to identify the source of an infection quickly.  Microbiologists can narrow the search, using a variety of techniques, but it takes time.   Some microbes grow fairly quickly in a culture, but others may take a week or even longer, and some may not grow at all.   In the meantime, the patient is getting sicker.

That’s when empiric treatment comes in.   The physician basically makes an educated guess, based on symptoms, and also of knowledge of what pathogens are prevalent in the community at that time.   Or, if the infection has taken place in a hospital setting, the hospital will have kept extremely careful track of which microbes are the current likely culprits.

Based on whatever information is available at the time when it becomes clear that the patient requires treatment, the physician will chose an antibiotic.   Empiric treatment frequently means that the choice will be a broad-spectrum antibiotic, i.e., one that is effective against a wide range of pathogens.   But, of course, it is precisely those antibiotics that most lead to increasing resistance in the microbial population.

So, the bottom line is that empiric treatment is frequently inevitable, because there isn’t enough information to develop an effective narrowly-targeted treatment plan quickly enough.   But empiric treatment also – and inevitably – leads to resistance.

What should the pharmaceutical companies be doing?

Business leaders are always telling us that every problem is really a challenge and an opportunity, and we would all like to think that they are right.   But let’s take a look at the particular challenges to drug development posed by the spread of resistance to antibiotics.

Here’s a scenario: a pharma outfit identifies a particular fungus in a tropical forest that seems to do a really good job in inhibiting the formation of cell walls in surrounding soil bacteria, which kills the bacteria.   After some crafty lab work, they are able to manufacture the active molecule, and they test it in Petri dishes, and then in animals, and finally in humans, and run it through a series of clinical trials, and at last get it approved by the FDA.   They finally bring it to the market as a new, highly effective antibiotic that treats a number of infections, including infections with many common resistant pathogens.

One would think that would be a perfect example of the problem – resistant pathogens, confronted and turned into an opportunity.

Let’s suppose that this new antibiotic was effective against lower respiratory infections, including Pseudomonas aeruginosa, a nasty pathogen that’s particularly dangerous in hospitalized patients.   Why wouldn’t doctors routinely use this new drug in all such patients?  

The answer might well be that even though the clinicians know about this drug, and are aware that patients may develop a resistant infection, they prefer to use a more common antibiotic, and to hold back the new drug until they are pretty sure they really need to use it.   Why?   Because drugs that are highly effective against certain resistant microbes are rare, and some clinicians and hospitals don’t want to expose a lot of pathogens to these new drugs, lest the pathogens also become resistant to the new drugs.   They want to reserve the new drugs as the ultimate weapons – the drugs of last resort

This, of course, is precisely contrary to what the pharmaceutical company wants.   They would like their new antibiotic to be widely used, so as to recoup the enormous investment they made in research and development.   They’ll accept the risk that if their new drug is widely used, resistant pathogens are likely to emerge.   They may figure that they’ll keep on developing new antibiotics, so when their new antibiotic loses some of its effectiveness due to pathogenic resistance, they’ll have something else.

So there’s some inherent conflict between the infectious disease treatment community and the pharmaceutical industry.   ID folks are quite clear that the relatively small number of drugs that are highly effective against certain resistant pathogens should be reserved until it has been determined that indeed it’s that specific resistant pathogen that’s causing the infection.

That means that a pharmaceutical company could, conceivably, invest billions on bringing a terrific new antibiotic to market, and then discover that the medical establishment is using it so sparingly that the pharma outfit is not recovering its investment.

In fact, reluctance on the part of clinicians to use – “overuse,” they might call it – the most effective antibiotics is clearly a disincentive to pharma outfits to invest the necessary dollars to develop such antibiotics.   They figure that their R & D dollars might be better spent on some other treatment areas.

Some specific results of this situation:

• FDA approvals of new antibiotics have declined by 90% since the 1990s.

• Pfizer terminated research into new antibiotics in 2011.   This doesn’t mean that Pfizer is out of the antibiotics business.   Late last year Pfizer plunked down $1.5 billion for AstraZeneca’s antibiotics portfolio, which includes a couple of advanced cephalosporins – ceftaroline fosamil, marketed as Zinforo by AZ and as Teflaro by Allergan, which treats some resistant Staph aureus infections, and another beta-lactamase inhibitor, a drug combination of avibactam and ceftazidine marketed as Avycaz.

• Several Big Pharmas have conducted no antibiotic research at all in the 21^st century.   These include Bristol-Myers Squibb, Eli Lilly, and Sanofi.

• The London School of Economics conducted a study that concluded that a pharmaceutical company that launched a new antibiotic would suffer a net loss of about $50 million.

All of this indicates a major slowing of antibiotic research, but not quite a grinding halt.   Many pharmaceutical companies have had antibiotics in the pipeline for several years and have already invested huge sums in their development up to now, so they aren’t unwilling to throw some more money into the hopper in an effort to recoup at least some of their investment.   And several of the newly-launched antibiotics have scored sales in the two to three hundred million dollar range in their first year on the market – not enough to offset their R & D costs in one fell swoop, but a promising start.

What’s to be done?

Even though new antibiotic approvals have slowed to a trickle, research on antibiotics continues.   More than 12,000 antibiotic clinical trials are under way, although most of them are trials in existing antibiotics.   But smaller biotechs are doing lots of preliminary research, probably in hopes that if they happen on something promising, they will get funding from another source, such as Big Pharma, or – better yet! – be bought out.

It has been proposed by a number of prominent individuals and organizations, including the Infections Disease Society of America (IDSA) that the time may have come for government to get involved in a push for new antibiotics.   One suggestion has been that government should offer a major prize to a pharma outfit that comes up with an effective antibiotic that treats those crucial resistant pathogens.   This prize would have to be very major indeed to persuade a pharmaceutical outfit to risk a billion or more on the chance that they might score a big hit.

However, a small step in that direction has already been taken by NIH, which offers substantial prizes for the discovery of diagnostic procedures that might rapidly identify whether a patient is infected with a resistant bug.   Such tests would not only make it more likely that infected patients would get treated with the right antibiotic, but also that only patients reliably identified as infected with resistant pathogen would get those super antibiotics that kill superbugs.

Initiatives such as those won’t solve the whole problem.   What do we do when a newly-developed antibiotic is copied by a lab and then routinely given to a majority of newborns in India?   Or fed to livestock to speed growth and get animals to market sooner?   Or prescribed by harried physicians to every kid with sniffles who is brought to the consulting room by an anxious mother?

I certainly do not know the answer to those and many other questions on this difficult issue.   I do know that medical researchers are not taking their foot off the gas pedal, and, as I said above, there’s lots of activity on the biotech front (which I will investigate for another piece).   In the meantime – and here my inherent optimistic nature asserts itself – it’s clear that we, particularly in the more developed world, are much better able to ward off infectious diseases than our parents’ generation, and much, much, much better off in that regard than  generations before.   If we look out for ourselves, we should be okay.

* * * * * * * *

The next item on Doc Gumshoe’s agenda is to have his other knee – his left knee, this time – swapped for a nice new one made of titanium.   The right knee swap took place two years ago, in April 2015, and I described the whole procedure and the ensuing rehab torture ordeal in a piece on May 4^th of that year.   In the two years since that experience it has become clear that my new right knee is now my good knee and the left knee is in need of replacement.   That in itself speaks for the success of the procedure.   I’ll keep you posted!