ignorance, part three

During the American Civil War, in 1863, Confederate General Thomas J. "Stonewall" Jackson was shot by accident by his own sentries as his party was returning from a reconnaissance. He was hit twice in one arm, and once in one hand. Though his wounds were not immediately life-threatening, he slipped into shock. Days later, after the arm had been amputated, he died of pneumonia.

This historical incident tells more than you might guess about the state of medicine at the time. He was one of the most gifted and effective commanders the South had, was immediately cared for by his own army, and received the best medical care available. The pneumonia tells a story about the unaccepted germ theory of disease, which had only just been stated clearly in published literature. Surgeons in those armies probably didn't have time to read this. The amputation was likely the result of fear of sepsis in the wounds.

The surprise for me was connected with that mention of shock. At the time, shock was taken to be a psychological reaction to serious wounds. The name still reflects this. The idea that it was simply due to low blood pressure from loss of blood lay in the future.

(Jackson had enough peculiar beliefs to justify psychological speculation. For example, he thought his one arm was longer than the other, and often held it up to equalize the flow of blood.)

How could anyone miss a simple thing like blood pressure? They had no way to measure this.

(Blood pressure is not unique in this respect. While it was possible to measure fever temperature, this was scarcely practical -- it took 20 minutes to get a reading. Sir T. C. Allbutt didn't invent a clinical thermometer which gave a reading in 5 minutes until 1866.)

The first sphygmomanometer was invented in 1881. A more usable version was available in 1896. Dr. Harvey Cushing, a pioneer neurosurgeon, promoted the use of this in 1901. (He was also a pioneer in aseptic surgery.) Measuring blood pressure only became standard practice some years into the 20th century. After World War I, this could be expected.

(During that war, there was no telling what medical treatment might be, for either soldiers or civilians. As the war ground to a halt, a pandemic called the Spanish Flu began. This is estimated to have killed some 50 to 100 million people, 3% to 6% of the world population.)

A second problem turns up if you ask what Jackson's doctors could have done about low blood pressure. (Don't bother to ask about blood plasma or IV saline solution.) Different blood types were unknown before 1901, so most attempts at transfusion were fatal because there was no type-matching. Even after the ABO blood groups were identified, transfusion sometimes killed patients because of hemolytic transfusion reactions. The Rh factor responsible was only discovered in 1939. Rarer blood types were found even later. At present we know of about 30 systems of antigens.

So, the absolute minimum requirements for (mostly) safe transfusions were not met until World War II. Testing for viruses was scarcely considered at that time. This became a major problem in the AIDS pandemic during the 1980s. (One clue about the source of the disease was the way epidemiology paralleled the less publicized epidemiology of hepatitis B, which was then known to be spread by a virus in contaminated blood, and also by sexual transmission.) This is one reason Lewis Thomas called medicine "The Youngest Science". Testing for gamma retroviruses in the blood supply is only the latest chapter in this saga.

Incidentally, although this is not commonly described, hepadnaviruses like hepatitis B are DNA viruses which replicate via an RNA intermediate formed by reverse transcription. The dividing lines between DNA viruses, RNA viruses and retroviruses are not cleanly drawn. This yields one possible explanation for inconsistent results in diseases where reverse transcription is detected, but no retrovirus is found. Hepadnaviruses need not insert their genes in the nuclei of host cells. It is possible they originated by recombination with endemic retroviruses.

There could be other classes of viruses using reverse transcription this way. As current controversy shows, recombination takes place frequently, and there is little special about research laboratories in this regard. Most wild animals have endemic, persistent viral infections which would cause laboratory animals to be culled. Ticks, and a variety of other blood suckers, transfer significant quantities of blood between animals, even those of different species. (Ask anyone with Lyme disease.) Ticks also transfer bacteria, as in Bartonellosis, or parasites, as in Babesiosis.

For an understanding of scale, think of a virion as a rowboat. On that scale a common bacterium would resemble an aircraft carrier. A parasite capable of carrying bacteria in its gut would be like an island with a large port -- say, the island nation of Bahrain. In the other direction, a piece of DNA like common retrotransposons would be like one oar in the rowboat. If islands are being transferred between species frequently, what are the chances of picking up an oar from a rowboat? Once this DNA is present, what are the chances of recombination? With billions of natural experiments in progress, what are the odds of a virus winning such a lottery?

Oh, one more little thing, about one quarter of the world's population, mostly in south and east Asia, have been infected with hepatitis B at some time. Given recombination of coinfecting viruses this offers an endless supply of novel infections for researchers to study. Typical lags between first indications of a new viral pathogen and real understanding run about 20 years. At present, over 80% of those infected with hepatitis C retain the virus in their liver, and only about half of those with confirmed cases of hepatitis C infection can be cured if treated properly.

A personal note: one great-grandmother of mine could remember the civil war. She lived into my lifetime, (though I don't remember her directly, and do not endorse her politics.) Together our lives cover the entire sweep of medical history from the paleolithic age in which "Stonewall" Jackson died to the present. Don't try to tell me the story is over.


Interesting anciendaze (and the history) - this strange slow world of virals and understanding. Can only hope it speeds up like other areas of medical breakthrough now.

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