The End of Antibiotics

It is hard to defend the castle when the enemy attacks in the dark.  No matter how often it is repaired, the barbican wall is subject to cracks and breaches for the enemy to crawl through.  The rivers and sewers are vital to life, but they are also avenues for invasion.  The enemy’s probing is patient, relentless.  There is no cleft so small, no fissure so narrow but that it admits its share of invaders.

The defenders patrol the corridors, but it is a hard job.  Legitimate citizens crowd the dark halls, moving about their own business.  The Guard must detect the enemy by touch, feeling their way through the throngs, searching for the feel of something foreign, something wrong.

The job would be nearly impossible were it not for the dogs.  With sharper senses they, too, patrol the halls.  When they find an enemy, their job is not to kill.  They simply lock on, howling madly to get the guard’s attention.  It is a suicidal mission:  The weapons of the guards kill enemy and dog with ferocious impartiality.

Within living memory, nearly every castle faced not too distant, inevitable defeat.  At best, good planning and husbanded resources could delay the day.  All but the very luckiest were doomed to be like sand castles, swamped by a sea of hungry barbarians, vanishing as if they had never been.

Then there came a day when the land acquired new weapons, smart weapons.  Or were they allies?  Whichever you called them, they were Magic.  They could not only find the enemy in the dark, they magically aimed themselves at the chinks in the enemy armor.

They joined the guards on their patrols through the narrow lanes of the inner city.  Unlike the dogs, once they encountered an enemy soldier they attacked and slew on their own.  Their magical weapons were powerful and no enemy armor could resist them.  After such an encounter, there  was no work for the guards to do but mop up the remains.

It ushered in a new age.  For a time, life in the castles was better than it had ever been.  A breach, even a full scale assault, was automatically met with a devastating counter-attack.  The barbarian hordes continued to sweep through the lands, but seen from the castle walls they now seemed smaller, less dangerous.

But nothing remains forever.  The indefatigable enemy tried new disguises, tested new armor.  In time, their efforts met with success.  Some of the castles’ allies seemed to become blinded, unable to detect the enemy lurking in the dark hallways.  Others found that their weapons had lost their magic and could no longer destroy the enemies they found.

Which brings us to today.  Now the feelings of invincibility are fading.  Every day brings the story of another castle fallen to yet another new tribe of the barbarians.  New treaties, new allies, and new weapons promise a return to the glory days, but each proves an illusory hope.  The future promises, instead, a return to the dark era where each new castle was raised, enjoyed a short life, then vanished in the flood.

Few of us remember clearly the days before 1935, when doctors had few medicines that really did much of any good.  About all doctors had to offer were a few pain killers, some tonics and bed rest.  Medical science had reached the stage where they could, with reasonable assurance, reduce fractures, sew up cuts and deliver babies.  They knew a fair amount about preventing some infections and some diseases, but once an infection or a disease set in, they were nearly as helpless as their patients.  In fact, they were just about as helpless as Galen or Hippocrates had been before them.

1935 saw the first of the new weapons, the sulpha drugs.  They were the first inkling that we were entering a new age:  The Age Of Antibiotics.  Prior to that age, for all of human history, the major killers were infectious diseases.  During that age, our age, the major killers have become the degenerative diseases, whose numbers include cancer.

For those of us raised in that Age, eventual triumph seemed almost inevitable.  The early days were punctuated with announcements of new antibiotics to treat this disease or that.  It was not too long ago that the world medical community confidently predicted the eradication of all infectious diseases.  Given that our time has also been marked by a nearly universal conversion to a new faith called Science, this prediction did not seem too farfetched.

But by the late 1940’s, the first cases of penicillin resistance in bacteria had been discovered.  It was reported as a minor oddity, nothing to be too worried about.  Even when more resistance to other antibiotics began to appear, it did not look too dangerous.  It was assumed that as each bacteria had to evolve its own resistance to each new drug, the drugs would always be ahead on the development curve.

It hasn’t happened that way.  Instead, we have discovered that bacteria have cute little methods of broadcasting resistance across entire bacterial species and even between species.  They can also accumulate resistances so that they can become multiply drug resistant.  The result has been that the time in which an antibody is effective before resistant strains begin to appear is becoming shorter and shorter.  Still worse, diseases have already appeared which are resistant to every known antibiotic.  If you get one of those, your doctors will be as helpless as their medieval predecessors.

So what follows?  It seems we are witnessing the end of the Age Of Antibiotics.  Do we simply revert back to a new Age of Infectious Diseases?  Are our doctors doomed to find their every weapon made impotent?  To find themselves as helpless as their ancestors?  Will we see the average lifetime fall back to wherever nutrition and hygiene can give us before the diseases get us?

Maybe.  But, then again, just maybe not.  There IS a glimmer of hope available, it just isn’t glowing where you might expect to look for it.

The obvious place to look is where the drug companies have poured so many millions.   I just cannot see conventional antibiotics getting any great life extension.  Their problem is that entire methodology is essentially a technological attempt to do what the immune system is designed to do.  To find a chemical substitute.  They are therefore vulnerable to what might be called better chemistry.  Their target’s speed of acquiring resistance is becoming faster than their time of development.  And that’s that.

So let’s look in another direction.

While all this has been going on, our species has also been experiencing another plague, HIV.  Because HIV attacks the immune system, and because it’s mutation rate is so high, it has been a real brute to understand, much less successfully combat.  This has had a quite extraordinary side effect:  It has forced the pace of our understanding of the human immune system ahead at least fifty years in the space of the last ten.

To go back to the original metaphor of the immune system, rather than looking for new weapons to defend our castle, let’s look at our own natural defenses, particularly that faithful watchdog and his kin.

The immune system is extremely specialized.  The system’s “guards” cannot recognize all of the possible invaders, which could be any of thousands of bacteria, viruses or fungi.  Instead it uses  watchdogs.  In this case, the watchdogs are the family of antibodies.  Their primary job is to identify the foreigners that might harm us.  Nothing more.

They function by being pre-programmed to search for a particular enemy protein group, an antigen.  Once they detect the antigen, the immune system can trigger a number of defensive processes.  A common one is to have the antibody simply bind itself to the invader and metaphorically call for help, as in the metaphor.  Help arrives in the form of a leukocyte, which recognizes the antibody on the invader and impartially engulfs and digests them both.

Thanks to the effort to understand how HIV cripples the immune system, we are finally beginning to really understand the complex responses that the immune system is capable of.  In the case of antibodies, we are beginning to understand how they are shaped to detect specific protein groups on the surfaces of foreigners.  We have even begun programming antibodies ourselves.

I believe that the next stage of the battle against disease, the successor to antibiotics, will be to use genetic engineering to USE the body’s immune system.

It might work like this:  First, we analyze the specific genotypes of the disease.  Then we  program that genotype onto cloned antibodies.  Then we inject them into the patient.  Then we simply let the immune system do the rest.

The irony here is wonderful.  Fifteen years ago, a very clever prognosticator might have seen that antibiotics were on their way out and recognized that there was no clear successor within decades of being ready.  The stage was set so that the failure of antibiotics would have been followed by, at best, faced a technology gap.  Even if we assume that the pace might have been forced, a lot of people would have died in the interim.

Instead, a new virus appeared that did the forcing for us.  Right now, it looks as if there might be a neat and precise handoff between the failing antibiotics and the genetically engineered immune response as our disease fighter.

If it happens, we will owe it all to two unpopular elements:  The HIV virus itself and the homosexuals, who were the first to get HIV in large numbers and were the ones who brought the political clout to bear to get the funding for the research.

Just think:  Jerry Falwell’s and Pat Robertson’s parishioners’ children may soon owe their lives to the Gays.

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