The century that transformed medicine

The century that transformed medicine

Homo sapiens, human beings, people with brains as talented and competent as ours, have walked the earth, often struggling to subsist, for at least 150,000 years—1500 centuries.  It’s only “recently” during the last 250 years—that our world was transformed.  We increased our ability to communicate, travel, and feed our people. We vastly expanded our numbers, warmed the planet, and began to deplete the resources that sustain us.  And we learned how to fight and cure many of the ailments that afflicted and shortened the lives of our grandparents and great grandparents.   My wife has two uncles who died in the 1930s from a strep throat, an infection that’s currently rapidly healed with a few doses of an antibiotic.  A family member had an asthma attack so severe she was almost intubated—placed on a breathing machine. Another was stung by a bee and developed anaphylactic shock.  Either would probably have died a century ago.

When I was an intern (in 1963) we treated people with new myocardial infarctions with “quiet and rest.”  One fateful night, as I entered a room to do an admission history and physical, the patient –a man who just had heart attack– was confused, pale, and dripping wet—sweating.  He barely had a blood pressure and was in cardio-genic shock.  I started an IV and infused the available drugs.  Nothing helped and he died.  Nowadays heart attack victims who don’t instantly die are rushed by ambulance to a nearby hospital where a cardiologist and team are waiting to catheterize their coronary arteries and to unblock and “stent” the occluded vessel. (Some of the improvements in care are not due to better drugs.)

When I entered medical school in 1958, the drug industry was in its infancy.   Europe and Japan were still recovering from the devastation wrought by the Second World War, antibiotic treatment of infection was relatively recent, and enthusiasm for the potential of new medications was high.  (We had learned a huge amount in the preceding hundred or so years.)  

Before 1700 humans didn’t know the world was full of tiny micro organisms.  They were invisible to man before the Dutch scientist Van Leeuwenhoek developed potent glass lenses, lined two up in a tube, and created a powerful microscope.  When he looked into a drop of water he visualized creatures whose existence, until that moment, was unknown. 

The source of contagious diseases was a mystery before the Frenchman, Pasteur, hypothesized that they were caused by various micro bugs.  (A few decades earlier the Hungarian Semmelweis had shown that child bed fever was brought about by doctors who went from the autopsy room to the delivery room without first washing their hands.)  The British surgeon, Joseph Lister, started performing surgery under antiseptic conditions in the late 1800s and others followed his lead.

The first antibiotic, sulfanilamide was created by scientists at the Bayer Company in Germany in 1935.  They were unable to patent their drug and it was produced in small factories throughout the world. 

In the 1920s, A Scot, Alexander Fleming, realized that fluid coming from a penicillium mold growing in one of his Petri dishes killed the bacteria in the container.  He tried to isolate the juice—which he called penicillin– but he was only able to collect a small amount.  A decade later a group of Brits led by Howard Florey and Norman Heatley got interested in the fluid and extracted enough to treat a few lab animals.  In May of 1940 “they infected eight mice with a fatal dose of streptococcus.  Four of the creatures were then injected with penicillin.  Hours later “the untreated mice were dead and the penicillin-treated mice were still alive…. Penicillin’s spectacular possibilities were obvious.”  More needed to be done, but Britain was at war and Florey’s research could not proceed.   That’s why he and Heatley brought some of the mould to the U.S.  They convinced scientists at the agricultural research lab in Peoria Illinois to help them search for a Penicillium mold that would produce more than a trickle of the magic juice.  One of the labs mycologists, Kenneth Raper, found the super mold growing on a cantaloupe in a nearby store.  It was “50 times more potent than anything previously tested, and it became the primogenitor for almost all of the world’s penicillin.”  The group then looked for companies that could produce the antibiotic in large amount, and Pfizer stepped up big time.  The chemical business was, at the time, fermenting large amounts of mold and using it to produce citric acid.  They now started producing penicillin in their huge deep tanks and were quite successful.  Eventually Pfizer produced most of the penicillin that went ashore with Allied forces on D-Day.  After the war Pfizer used deep-tank fermentation to manufacture a second antibiotic, streptomycin, and later a third antibiotic, Terramycin. 

            The penicillin experience woke up the scientific community and helped create a sense that it might be possible to create drugs that would cure or help many of the diseases of man.

In 1958, when I started medical school, aside from antibiotics doctors had (in retrospect) relatively few medications to work with.  We had aspirin, barbiturates, and a number of treatments that were largely the derivatives of plants, minerals and animals.  (like Colchicine, a drug used to treat gout (and a few other maladies) that was extracted from Colchicum autumnal…the meadow saffron.)  We worked with glass syringes and hypodermic needles made of steel.  After they were utilized, the needles were washed, sharpened, sterilized and reused. 

Chloral hydrate, the first synthetic hypnotic was introduced in 1869, in 1884 the profession learned that topical cocaine numbed our membranes and skin.

A number of vital replacement hormones became available in the first half of the 20th century: Thyroid pills 1915; cortisone in 1948 and hydrocortisone in 1953.  (Cortisone saved Jack Kennedy’s life.)  Insulin was extracted from animals in 1923; prior to that juvenile diabetes was a lethal disease. 

Wright’s 1959 book told of all the antibiotics that existed at the time, and there were quite a few.   In addition to sulfa (1930s) and penicillin (1940s) doctors could prescribe Terramycin (the first tetracycline), Chlorampenicol, streptomycin, erythromycin, neomycin, nystatin and a few antituberculosis drugs including isoniazid.  Antibiotics were already being “overused” and bacterial resistance was an emerging problem.

 Narcotics including Demerol and methadone (late 1930s) were available for pain control; and we could alter blood clotting with heparin and dicoumeral (similar today’s Coumadin.)  For diseases of the heart we had digitalis, quinidine, nitrates and not much more.  Excess fluids could be flushed by an injection of a mercury based diuretic, though there was a new promising diuretic called chlorothiazide. 

 During my more than 40 years as a practicing doc I witnessed medicine’s ability to diagnose and treat improve in a step wise manner. 

Conditions that would have killed or disabled a century ago are now handled routinely, and we live, on average, twice as long as our great grandparents.  Doctors replace knees and hips, clouded eye lenses, and damaged kidneys, livers, hearts and lungs.  They balloon open and stent narrowed arteries.  Tumors are removed and major surgery is often performed through tiny openings in the skin.  Our innards are visualized with CAT scans, MRI’s, and ultrasound machines.  Primary care physicians, through regular exams, problem solving, adjusting medications, and encouraging healthy “habits” have made a major contribution to the quality and quantity of our lives

Newer and better drugs were discovered and developed and, in at least five instances, they have “changed the game.” 

–Immunization banished small pox and has nearly eradicated polio

–Penicillin and antibiotics gave us the ability to fight many of the infections that once killed people in their prime. 

–Transplanted organs survive thanks to our ability to prevent rejection, and we are getting better at controlling  an overzealous immune systems.

–Drugs turned a once uniformly lethal infection–HIV– into a controllable, chronic disease.  

–CRISPR and other gene “editing” techniques have recently emerged, and they are on the verge of curing a number of mankind’s inherited “curses”.  Disorders like hemophilia.    

By Atul Gawande’s count we have isolated and named 60,000 conditions and diseases.  Doctors perform over 4000 “medical and surgical procedures and techniques”, and there are thousands of drugs doctors can prescribe.  Some of them are special, different, and really change medicine’s ability to cure or control illness.  Others are me-too drugs, and are minimally different from one another  Many of the medications we use are expensive.  A few—in the absence of great insurance– are unaffordable. 

As Gawande points out, sometimes doctors can’t fix or help some sick people because we don’t know how…. metastatic cancer and dementia top the “lack of knowledge” list.  But (Gawande again) too often “the knowledge exists but– we don’t deliver.”  The cost of medications can be a major contributor to our “ineptitude.”

The Troubled Health Dollar by Steve Fredman