SOME STORIES IN THE HISTORY OF MEDICINE
Lecture 1: Introduction and Beginning Germ Theory
Adam Blatner
(This six-lecture series is part of Senior University Georgetown’s Winter-Spring 2009 session.)
Lecture 2 History of the Recognition and Treatment of Infection ; Lecture 3 The Discovery of Anesthesia ; Lecture 4 The Early History of Immunology ; Lecture 5, Recognizing Nutritional Deficiencies ; Lecture 6, Hygiene: Sanitation, Hookworm, Dental Floss, & Summary
These talks will address several advances that emerged mainly between around 1790 through 1880—that is, mainly in the 19th century. That’s when your great-great-grandparents were alive, so it’s not all that very long ago!
I like history in general, and in the spirit of the microscope, about which we’ll speak a little later, let’s focus down on one level or facet at a time. In other lecture series I’ve spoken about the history of writing, the history of psychotherapy, and so forth. Being a physician, an M.D., I’m especially interested in the history of medicine, because for me it offers lessons for today about the complexity of events, how knowledge comes to be disseminated and used in culture. Slide 3
This is not a simple process! It involves such things as writing up what you have learned, clearly, getting the word out, getting it published, pushing the idea in many venues so it doesn’t just get lost on the dusty shelves, presenting, teaching. It involves continuing to experiment and strengthen the evidence. And so forth. Other variables will be noted as we tell some of these stories.
People get used to things, and they start to take them for granted—and our general level of health, our life expectancy, the idea that medicine nowadays seems to work for an increasing number of problems. Interestingly, the chances that you would actually be helped by going to the doctor rather than hurt more only changed around a century ago for the better.
Life before the breakthroughs to be mentioned, before immunizations, anesthetics, antiseptic and later antibiotic treatment, nutritional supplements, and levels of sanitation we now take as basic — well, people got sick a lot more, there were horrible epidemics, lots of kids died, people suffered more, what we now call post-traumatic stress disorder—PTSD— was sort of everyday struggle for life a century or two ago for large numbers of people. We tend to hear more about the leisured and protected classes in literature, but the point is that we should recognize more vividly how new this all is.
Also, bringing forward that potential of wonder and wow! in you is in my mind a core element in a liberal education, and serves to help you continue to feel young at heart.
In the mid-1970s a new concept, fractals, was brought into mathematics and science, and it has come to explain many things. It notes that many natural things like a coastline, the weather, the branching of trees, have sub-parts and the sub-parts have sub-sub-parts and if you examine it carefully, it seems to never end in the fine divisions that come. It’s occurred to me that history is also fractal in nature, which means that each event involves many other events—personal stories, backgrounds, cultural trends at the time, the development of parallel technology, and so forth. It’s fractal in the sense that you can keep examining the details and it opens up to a field of other questions and causes, and examining any of those open up to others, unendingly.
Slide 1. So here are some of the things we’ll be talking about. Slide 1 Schedule
The Beginnings of Germ Theory
A few people have imagined tiny somethings, and over the centuries, even that they might cause disease, be a factor in contagion. None of these ideas caught on widely, though, because the mainstream thinking was that disease was an imbalance in the system, and more specifically an imbalance of the four basic substances or humors in the body—blood, phlegm, black and yellow bile. So treatment involved bleeding, purging—that is, taking substances that caused vomiting and diarrhea, provoking salivation and sweating, exercise, and so forth.
Several approaches led to germ theory, including epidemiology—noticing which diseases happened how often and under which circumstances— and of course the idea of actually finding the agents of contagion, and that was interestingly not that easy;
Let’s start with the microscope, or even before that, the whole idea of lenses, and combining lenses. The optics hadn’t really been worked out, the mathematics, the degrees of curve in a lens.
Folks knew about curved glass magnifying: You can see that in a goldfish bowl. But if the curve is irregular or not just right, the effectiveness of magnification has to be wisely constructed.
I’m not about to go too much into the nature of the microscope—more interesting is how this tool opened up a whole world, and the implications of that world took more than two centuries to be appreciated!
Telescopes and microscopes both emerged around the same time, as an outgrowth of the sub-technology of lens-grinding, which also made possible more workable spectacles. The curve of the glass needs to be steady and regular, and it’s not just any old curve. All this emerged around the time of Galileo, in the early 17th century, around 1609. People were figuring out how to grind and polish lenses and the optics, the mathematics of assessing the curve of the lens.
By around 1660, a few scientists in Europe—and remember, science was just beginning—were exploring not only the heavens, but also the micro-world. One was Robert Hooke whose compound microscope—two different lenses that worked in combination— was able to see things expanded around 40-50 times. Slide 5 . Hooke was active in the newly founded Royal Society of Natural Philosophy or some such name... exploring these frontiers, and wrote about what he could see—like the legs of fleas!
Hooke wrote a book about these observations, and his drawings—titled Micrographia. He was curious about why cork floated and was able to see under his microscope that it was full of air, in little cells—and it was Hooke who coined the word “cell.” Interestingly, the idea that most of living tissue is composed of cells—both animal and vegetable— wouldn’t be appreciated for another almost 180 years.
More about him in a minute.
Slide 6. Here’s another view of Hooke’s microscope—it’s about 16 inches tall—because to the bottom left you can see an ordinary microscope slide—about 3/4 inch wide and 2½ inches long, and above that a little gizmo.
That’s a simple microscope, devised by Anton van Leeuwenhoek, who around that time was a draper in Holland and whose hobby was fooling with and inventing better microscopes. Slide 7
He made over 200 of them in his later years. Slide 8 These had one lens, really, a tiny globule of glass, finely ground so that it was clear and regular. When the curvature is very small, the magnification is correspondingly bigger—and van Leeuwenhoek’s were three to five times stronger than Hookes, allowing up to a magnification of 200 times—enough to see one-celled animals—L. Called them animalcules— and even as moving dots, bacteria.
Van L finally began to write about his observations, sending a goodly number of letters to the Royal Society, which at that point was somewhat unique as a forum for new discoveries. He never wrote a book, but rather a series of letters, with illustrations, etc. (Slide 9)
This was a time when lots of stuff was happening. Isaac Newton was talking about gravity. There was first Bubonic Plague in London, and then smallpox. Leeuwenhoek’s work was a few years later, around 1673. He observed a number of things over the next ten years in his letters, and some were controversial. First, note that L’s work didn’t get connected much to the idea that the little animacules he described might have anything to do with disease.
But he did open up the micro world, writing about one-celled animals in a drop of standing water, the scum of his teeth, the way the living, squiggling things died if he had just drunk hot coffee, even the number of little animalcules in semen—though he was most modest about that, presenting that in a separate letter. Van L. Was impressed with the sheer number of these tiny creatures: There are more of these in my mouth than men in the whole kingdom.
(Indeed, we’ll mention this again in the last lecture when I talk about dental plaque!) Slide 10.
To review: Microscopes opened up new scales of vision: Slide 11: Scale microsize:
Hooke was able to see around this small: This was the limit.
This is a logarithmic scale, meaning every unit of length refers not to a unit but a ten-fold diminution of size. So here’s where Leeuwenhoek’s microscopes opened up. Note that he had very good vision, and had also worked out ways of viewing specimens that he unfortunately kept secret, so it wasn’t easy to replicate his work.
Now an interesting anecdote—and important for our appreciation of history, because I not infrequently wonder what breakthroughs are happening today that aren’t yet widely appreciated— is that the Royal Society told Hooke to replicate Van L.s work and he couldn’t. He tried several times! (Fenster, mavericks...p70), but over a year of several trials, several types of specimens, and finally with a stronger microscope, Hooke did verify van L’s work. The politics of some wanting to reject—the van L was just this guy, with no particular qualifications. Some allies, some not enemies but doubters...
The 1700s – the 18th century, saw not only the American revolution, but also an advance in microscope technology—but not much.
And we’ll come back to it, but the thing was to actually identify the germs that caused disease. The mainstream didn’t believe yet in germs, or if they vaguely did, weren’t sure what they were or that they could be causative agents.
Another thing that was fairly new was a shift away from the humoral theory and toward something more specific. Anatomy was opening up, the prohibitions against dissection were lowered, and professors at medical school were beginning to correlate things like turning yellow in the skin and diseases of the liver or bile ducts. The idea that there were specific organs or certain tumors, or breaks in blood vessels, or locations of pus that correlated with certain specific symptoms was deeply exciting—this was in Europe— and Dr. Morgagni was a pioneer: Slide 14. The activity of performing an autopsy and comparing the signs and symptoms to what was found was a new and exciting technology, the in thing, and people began to travel internationally to the centers of learning in Europe in the latter part of the 18th and early 19th century.
This is very ironic, because the problem with autopsies is that while you learn things, unless you wash incredibly well, you carry on your hands and clothes the most god-awful infectious germs.
We’re getting to the story next time of Semmelweiss, contagion, infection, and antisepsis—laying the groundwork.
Another problem here is that the basic make-up of the human body at a more microscopic level was unknown, vague. Though Hooke described gross cells in cork, the idea that the body was composed of cells—which are a hundred times smaller—was not appreciated. Some pioneers in microscopy were exploring this, but their meaning was unclear. Perhaps cells just crystallized out, were products of spontaneous generation.
Spontaneous Generation
I mentioned the humors and their imbalance as one prevalent theory, and another was that folks had a very vague idea how tissues came to be, how life came to be. Ironically, we’re dealing with that now in contemporary science as people are wondering how life first came to arise out of the primordial soup!
Back in the 18th century, a common doctrine was spontaneous generation. If you let meat sit and rot, maggots came out of it. A few people did experiments that showed that this was really due to contamination, but it requires many experiments done on and off for decades—and even then folks were holding out even after around 1860, when the evidence was starting to pile up. More about that later. The point is that the idea of germs and how they worked wasn’t yet accepted.
Cells come from Cells
Another related point—and the thing is that these are related—it sometimes takes several breakthroughs or discoveries and their implications to be coordinated— is that life is made up of cells.
As an example, let me note that when I was growing up, I learned that cells contain a nucleus and cytoplasm, but what was in cytoplasm was as yet unclear. The electron microscope had only been invented a decade or so earlier, and gradually the parts within what I used to draw as a just dots began to be clarified. 15 intracelleular) – and it turns out that there are all sorts of intra-cellular structures.
As the microscopes and other research techniques expanded, we can begin to imagine something closer to the following, a composite drawing of the inside of a cell— an edge of a bacterial cell, and an edge of the nucleus, showing the thickness of protein molecules in the cell membrane, and cell structure. This is enlarged a million times.
The point here is that even in our own lifetime there has been accelerating knowledge, the pace of discovery speeding up tremendously. So let’s go back two hundred years again and appreciate the lack of knowledge that bacteria even existed, and if they did, that they could cause disease.
Pasteur1
The next character I’m going to discuss—and will be discussing him in different ways over several lectures, is Louis Pasteur, whose work gave us the idea of pasteurization. He was not a physician! He was a chemist! His non-MD status slowed down a little the acceptance of his ideas within medicine. He made a number of contributions: 17.
This is going to lead into next week’s talk.
General Comments
So at this point I’m going to make some more general comments on the history of medicine in order to set the stage for the series.
First, about germs and disease: Indeed, there were a few who made the connection and wrote about it a hundred years earlier. We should note here that history comes up with evidence that there were often others who talked about an idea—and no doubt countless others who might have thought a similar idea—but they didn’t write it up, didn’t get it published, didn’t stick around long enough to make a mark that would be recognized by others; so if it isn’t in writing, it’s as if you didn’t really do it, you just said you did. This is why we were taught in medical school—for medico-legal as well as other professional reasons—to write up legibly what we had found and what we did.
Second: Technology makes a difference. A modern example: In our lifetime you’ve heard that they now can re-attach a finger and even a hand. What’s required is a mixture of several technologies: microsurgery needles, (slide 18) instruments (19), sutures, and a significantly improved binocular (for depth) microscope. So until they figured out how to make such things they couldn’t really figure out how to use them. They could dream a little, but there’s a back-and-forth about history: Necessity may be the mother of invention, but sometimes—not infrequently, in fact—invention, or discovery, ends up waking people up to possibilities they hadn’t imagined! We’re seeing that a lot in the computer world, where, given a toy, the game is to find all the things you can do with that toy.
Back to Germ Theory, then.
One breakthrough in 1830 was the working out of a way to make lenses work better without so much distortion, and the father of the fellow whose name was later given to Listerine, Joseph Lister Senior, also a physician, invented a microscope that could do that, which advanced microscopy significantly.
The idea of really systematically developing microscopy further required the building up of a technology for fixing the tissues so they wouldn’t rot or dissolve as you were examining them, using various chemicals the way folks use formaldehyde for larger organs. (The problem with “get me the brain, Igor” in the Frankenstein movies is that brains rot very quickly, and even if you could transplant them, if you store them, the storage fluid kills everything, and fixes it.)
Once tissues are fixed, it required the microtome, 20 for cutting it into very thin slices so that the light can pass through it.
Another thing about germs and most tiny tissues: They’re transparent to light, rather than distinct. They need to be lit from the side, or stained with a chemical so that particles stand out. This, too makes it tricky to see. So that the early reports of germs often could not be seen by others using their version of the microscope. Again, this staining technology, and how to grow them—all that came into action after around 1870. That’s a whole ‘nother history that we won’t pursue, because as I said, threads go out from all directions, stories, what then, what before... and so forth.
I want to re-emphasize this point, because we are at a time when folks are claiming all sorts of things that are there—psychic phenomena, other dimensions, sub-atomic strings, dark energy— and there’s indirect evidence for such things—but then again what we may find goes beyond present theory and things aren’t the way the early theorists think they are. So much depends on the tools we use to figure it out.
Slide 21 I mentioned last year in a talk the proverbial blind men and the elephant and the angle I want to put on it is that even if the blind men weren’t fools and argue over which of them was right; even if they compiled their impressions and constructed a model of the elephant as felt from different parts; and they constructed a pretty accurate surface model; they still would have no knowledge of the insides of the elephant, nor of how those insides worked; nor how the elephant operated in its own ecological system. So there are levels upon levels of frames of reference to be brought to what we’re learning.
General Perspectives about Medicine
One lifetime is too brief: The field, the art of medicine, grows over millennia. Actually, what Hippocrates, said to be the father of medicine—and you’ve heard of the Hippocratic Oath—what he said near the beginning of his writings—back around 400 BC, said, translated into Latin, was Vita breva; ars longa.
I say this to bring you to a point of readiness for listening to the other lectures: We have been spoiled a bit by all the advances. There are so many things we do not know yet—and these are by no means trivial mysteries or fine points. At this point, life is a fatal disease and most don’t go out easy. There are innumerable frontiers. Imagine your doctor saying between each line she utters, “we’re not really sure yet,” or “there are aspects about this that are not yet known.” Perhaps phrases like, “Well, that’s still controversial.” Really, what they’re saying is “Maybe I’m mistaken.”
A problem, though, is that there are so many quacks out there who are very sure that they do know, and that if it weren’t for the God complex they project on the doctors, their brilliant insights would be accepted. I want to say to them: You need to make your case—it’s not for the mainstream to do it for you. And you need to use the kinds of hard evidence that can’t be faked or that isn’t a result of the placebo effect.
We can learn from the history of the emergence of germ theory:
Related to cells and the whole theme of germ theory is the idea that the evidence was ambiguous. We had inferences, suggestions, well before knowing what the mechanism was. First, bacteria are perhaps only a hundredth to a thousandth the size of a cell! (Both bacteria and cells all range in sizes quite a bit, just like tiny shrews and large elephants differ in size.)
Now it isn’t absolutely necessary that a mechanism be known if a discovery is to be accepted. For example, we have known that aspirin reduces inflammation by 1900, but the mechanism how that happens didn’t get developed until the discovery of the substances called prostaglandins in the 1970s, and how these chemicals—yes, first discovered in the prostrate gland of men—were subsequently found to be all over and worked as mediators of inflammation. Still, even without the explanation it was useful to have a chemical that worked.
Not so with germs, which led to an obvious discomfort, an inconvenience, a difficulty in fighting them, or protecting one’s patients against them. Therefore, if they didn’t exist or at least were not really what caused the problem, then it would be far easier to ignore all this precautionary behavior.
Modern surgery is made far more complex and expensive because of germ theory, so the evidence had to accumulate, and it did so, that severe problems arise when less than good sterile and antiseptic procedures are used.
Since the 1970s, there has been a resurgence of antibiotic resistant bacteria and a threat of complicating infections in wounds or places of vulnerability; worse, the best place to catch one these harder- (much harder!) To treat germs is of all places in the hospital. So hospital programs for infection control have become well over twice as careful—perhaps five or ten times as careful in all sorts of expensive equipment and time/labor intensive processes ways to avoid contamination.
For example, doctors ties—of all things—the mark of professionalism—well, there’s increasing evidence of problems of visiting several patients in a row with that carrying stuff—minute amounts, but still more than nothing. Often there’s a nurse in charge of infection control and the political pressure for getting docs to wash enough before going into or after coming out of seeing a patient are heavy, not easy. Psychologically, I explain this by a common phenomenon: If you mean well, it’s hard to realize how toxic, how destructive your good intentions can be! Heavy denial.
Well, that’s already after a century and a quarter of germ theory! Imagine how hard it was to convince doctors that they are participating in making their patients worse! Unthinkable!
One of my interests is the way a technology opens up all sorts of discoveries that hadn’t been anticipated. The microscope opened up worlds for exploration, but it took literally centuries before sufficient people began to recognize that microscopic-sized creatures could actually be involved in disease. I mean, everyone knew that disease was caused by an imbalance of the humors, so new theories about what caused disease were unclear.
Well, that imbalance of the humors was not so absolute: People vaguely new that there was contagion, though they couldn’t yet explain it. It was somewhat clear about the Black Plague, Smallpox, the Great Pox—that is, the syphilis epidemics that were common in Europe in the centuries after Columbus—and attenated, got milder, more subtle, in the 18th century, but still destroyed the minds and bodies of countless creative people in the 19th century and well into the 20th centuries
So the stories of germ theory, contagion, and surgical antisepsis overlap.