Nanomedicine, Volume I: Basic Capabilities

© 1999 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999 Renaissance and Pre-Modern Medicine

While internal medicine languished through the Middle Ages, the surgeons of the Renaissance gained wide experience during the many religious wars of the period. They had many new problems to face, including the treatment of wounds caused by firearms. The French had employed gunpowder at the siege of Puiguillaume in 1338, and cannon were used by the English at the Battle of Crecy in 1346. Gunshot wounds at that time were caused by large missiles of low velocity that caused ragged wounds and carried pieces of clothing into the tissues. These wounds were severe and very liable to become septic. The universal belief among contemporary surgeons was that gunpowder itself was venomous. To neutralize the effect of this venom, the general practice was to cauterize the wound by injecting boiling oil.

The first man to break away from this old doctrine was Ambroise Pare (1510-90). Pare came to Paris in 1532 as an apprentice to a barber-surgeon and then moved to the great Hotel Dieu as resident surgeon. In that immense medieval hospital, the only one in Paris at the time, he gained great experience, and in 1536 he began his career as a military surgeon. As described in his book The Apologie and Treatise, he recounts how, during his first campaign as a greenhorn military surgeon in Turin in 1537, he had run out of boiling oil, the established treatment for gunpowder wounds, just after French troops had captured the castle of Villaine. So in place of boiling oil, he applied:

"...a digestive of yolk of eggs, oil of roses, and turpentine. In the night I could not sleep in quiet, fearing some default in not cauterizing, that I should find those to whom I had not used the burning oil dead impoisoned; which made me rise very early to visit them, where beyond my expectation I found those to whom I had applied my digestive medicine, to feel little pain, and their wounds without inflammation or tumour, having rested reasonable well in the night; the other to whom was used the said burning oil, I found them feverish with great pain and tumour about the edges of their wounds. And then I resolved with myself never so cruelly to burn poor men wounded with gunshot."

Pare also went on to show that bleeding after amputations should be arrested, not by the terrible method of the indiscriminate use of the red-hot cautery, but by simple tying of the blood vessels. His most famous phrase, so reminiscent of the old Hippocratic school of thought, was: "I dressed the wound, and God healed him."

In 1633 appeared the earliest book on first-aid for the injured, by one Stephen Bradwell, although the proffered advice sounds impractical and a bit odd to modern ears. For example, the treatment for the "Biting of a Madde Dogge" is to throw the patient into water. "In doing this, if he cannot swim, after he hath swallowed a good quantity of water, take him out again. But if he be skilful in swimming, hold him under the water a little while till he have taken in some pretty quantity." This procedure may not be wholly irrational -- standard 20th century first aid for dog bites includes a thorough cleansing of the wound with water.

Venesection remained a popular 17th century universal remedy. As described by the surgeon Richard Wiseman (1622-1676), "a gentleman of about thirty years of age coming out of Hertfordshire through Tottenham and riding upon the causeway near an inn, one emptying a chamber pot out of the window as he was passing by, his horse started and rushed violently between a signpost and a tree which supported part of the sign. The poor gentleman was beaten off his horse and lay stunned upon the ground." A barber-surgeon was hastily summoned but nothing much was done for the injured man until Wiseman arrived, whereupon:

"I found the gentleman lying upon the ground, the people and chirurgeon gazing upon him. I felt his pulse much oppressed, the right brow bruised and inquired whether they had bled him blood. The chirurgeon replied that he had opened a vein in his arm but it would not bleed. I replied, we must make him bleed through it by splitting his veins. Turning his head on one side, I saw the jugular vein on the bruised side turgid and opened it. He bled freely. After I had taken about twelve ounces, the blood ran down from his arm which had been opened before and would not bleed. We bled him till he came to life, and then he raved and struggled with us."

The patient's injuries were dressed and he was subjected to further bleedings, but evidently made a good recovery.

Even by the 18th century, the traditional surgeon's day-to-day business eschewed high-risk operations like amputations; rather, it was a round of minor procedures such as venesection, lancing boils, dressing skin abrasions, pulling teeth, managing whitlows, trussing ruptures, and treating skin ulcers. The fatality rates of these procedures were low, for surgeons understood their limits, and the repertoire of operations they attempted was small, because of the well-known risks of trauma, blood loss, and sepsis. Internal disorders were treated not by the knife but by medicines and management, since major internal surgery was unthinkable before anesthetics and antiseptic procedures. Improvements did occur in certain operations such as lithotomy. William Cheselden (1688-1752), a great British surgeon of the 18th century, perfected a technique which enabled him to remove a stone in the bladder in one minute (his record time was 54 seconds), thus reducing mortality from about 50% to under 10%. Cheselden's results were not bettered until almost the end of the 19th century.

In the 17th century, internal medical treatment was frequently overdone on those affluent enough to afford it. Critics often denounced physicians as meddlesome, capriciously practicing an often dangerous polypharmacy -- a blunderbuss approach. The deathbed of Charles II (1630-1685) of England was a conspicuous case of such medical overkill; after the king had suffered a stroke, his doctors moved in, and Sir Raymond Crawfurd (1865-1938) recreated the scene:

"Sixteen ounces of blood were removed from a vein in his right arm with immediate good effect. As was the approved practice at this time, the King was allowed to remain in the chair in which the convulsions seized him. His teeth were held forcibly open to prevent him biting his tongue. The regimen was, as Roger North pithily describes it, first to get him to wake, and then to keep him from sleeping. Urgent messages had been dispatched to the King's numerous personal physicians, who quickly came flocking to his assistance; they were summoned regardless of distinctions of creed and politics, and they came. They ordered cupping-glasses to be applied to his shoulders forthwith, and deep scarification to be carried out, by which they succeeded in removing another eight ounces of blood. A strong antimonial emetic was administered, but as the King could be got to swallow only a small portion of it, they determined to render assistance doubly sure by a full dose of Sulphate of Zinc. Strong purgatives were given, and supplemented by a succession of clysters. The hair was shorn close, and pungent blistering agents were applied all over his head. And as though this were not enough, the red-hot cautery was requisitioned as well."

One of the dozen attending physicians noted with pride that "nothing was left untried"; the King graciously apologized for being "an unconscionable time a-dying."

Meanwhile, the common citizen experienced poor health exacerbated by the many new dangers attending the Industrial Revolution. In 1775, Percivall Pott (1714-1788) pointed out that boy chimneysweeps developed scrotal cancer, due to soot irritation. In his Condition of the Working Classes in England (1844), Friedrich Engels (1820-1895), a Manchester factory owner as well as Karl Marx's collaborator, described workers who were "pale, lank, narrow-chested, hollow-eyed ghosts," cooped up in houses that were mere "kennels to sleep and die in." In 1832, the Leeds physician Charles Turner Thackrah (1795-1833) published The Effects of Arts, Trades, and Professions on Health and Longevity, documenting the diseases and disabilities of various occupations. Apart from factory workers, among those most exposed to harmful substances were cornmillers, maltsters, coffee-roasters, snuff-makers, rag-pickers, papermakers and feather-dressers. Tailors were so subject to anal fistulas that they set up their own "fistula clubs." Thackrah's overall verdict was bleak: "Not 10% of the inhabitants of large towns enjoy full health."

The single worst malady cultivated in populous cities was tuberculosis (TB), a disease characterized by fever, night sweats, and hemoptysis (coughing up blood), called "consumption" because victims were almost literally consumed. By 1800 TB was proclaimed the most common disease, and in 1815 Thomas Young (1773-1829) surmised that tuberculosis brought a premature death to one in four in the general population. Autopsies conducted in the chief Paris hospitals recorded TB as the cause of death in some 40% of cases. In the continental U.S. as late as 1890, the corresponding percentage was about 13%, and tuberculosis was still the leading cause of death (Table 1.2), though the data are partially suspect because cases of lung cancer were sometimes reported as "consumption".2226

One important 18th century improvement in internal medicine which decisively saved many lives was the introduction of inoculation and vaccination against smallpox. Smallpox, "the speckled monster," had become virulent throughout Europe and in bad years accounted for about 10% of all deaths; Queen Mary of England (1662-1694), Louis XV of France (1710-1774), and Queen Anne's son and sole surviving direct heir (d. 1700) died of it. Doctors had long been aware of the immunizing properties of an attack, and smallpox inoculation seems to have been known and practiced for centuries at a folk level throughout Arabia, North Africa, Persia, and India. Reports of a more elaborate Chinese method, involving the insertion of a suitable infected swab of cotton inside the patient's nostril, reached London in 1700. But it was a report from Mary Wortley Montagu (1689-1762), wife of the British consul in Constantinople, that Turkish women held smallpox parties at which they routinely performed inoculations with the aim to induce a mild dose so as to confer lifelong protection without pockmarking, that hastened acceptance in the rural medical community. The usual method was to transfer the infection by introducing matter from a smallpox pustule into a slight wound made in the patient's skin. Occasionally the patient developed a severe case of smallpox from such treatment, and some died. But usually the symptoms were slight -- a few score of pox only -- and immunity proved equivalent to that resulting from contracting the disease naturally.

Edward Jenner (1749-1823), an English country doctor who performed such inoculations, noticed that cowpox, a cattle disease occasionally contracted by humans, particularly dairy maids, also conferred immunity against smallpox. Suspecting that it might be possible to produce this immunity by arm-to-arm inoculation from the cowpox pustule, and surmising it would be safer than inoculation from smallpox pustules directly, since in humans cowpox was benign, Jenner tried the experiment, and it worked. In 1798 he published his discovery in An Inquiry into the Causes and Effects of the Variolae Vaccinae. By 1799 over 5000 individuals had been vaccinated in England and abroad the practice was taken up remarkably swiftly, being made compulsory in Sweden and supported by Napoleon, who had his army vaccinated. For the first time in history, organized medicine began to contribute to human population growth in a statistically significant fashion.

The Napoleonic Wars spurred new attempts to treat battle-wounded soldiers in a more timely manner. Traditionally, the wounded were left on the field unattended until the end of battle, but Napoleon's chief surgeon Dominique Jean Larrey (1766-1842) introduced the use of rudimentary carts called ambulances volantes (little more than horsedrawn rickshaws) as the first "ambulances" to evacuate and transport wounded soldiers from the field to nearby aid stations, even while the battle raged on. In 1792, Larrey organized the first air evacuation, by hot air balloon.

The use of ambulances didn't catch on until the late 1800s; until then, anyone injured in the streets of Paris, London, New York or Boston depended on the kindness of strangers or a nearby business shop for a place to rest until a doctor could be summoned.2287 The first "modern" ambulance appeared in the city of Cincinnati in 1865, but the first true city ambulance system was developed in association with Bellevue Hospital in New York City in 1866, receiving 1500 requests for transport in its first three years of service.2294 These horse-drawn ambulances, usually provided by local mortuaries, carried a driver and a surgeon, who was on board mainly to pronounce a patient's death at the scene or upon arrival at the hospital, since little could be done for the seriously injured.2287 The surgeon kept meticulous notes on the ride, recording the time of the call, transport and arrival times, and any other details that "a coroner's jury might possibly require".2294

The period also saw the development of many simple diagnostic tools that are taken for granted today. For example, a French physician, Rene Theophile Hyacinthe Laennec (1781-1826), in his Treatise On Mediate Auscultation (1819), described pathological lesions found in the chest at autopsy and showed how they correlated with disease detected in living patients, establishing for the first time the modern concept of clinicopathological correlation, the cornerstone of modern diagnosis. Laennec also developed an instrument that he named a "stethoscope" to assist him in his examination of patients, especially female patients, against whose chests the direct placing of a male ear was socially taboo. The original device was a straight wooden tube; by mid-century rubber tubing was introduced to create a flexible monaural stethoscope, and in 1852 an American physician, George P. Cammann (1804-1863), devised our familiar two-ear instrument.

The clinical thermometer is of like vintage. Galileo (1564-1642) invented the first thermometer in the late 16th century, but it was not applied to medicine. Early medical thermometers in the 18th century were a foot long and difficult to use at the bedside, and were reportedly carried under the arm "as one might carry a gun." The short clinical thermometer was devised by Sir Clifford Allbutt (1836-1925) in the 1860s, and was widely used during the American Civil War (1861-1865). The classical work in temperature diagnostics was Carl Wunderlich's (1815-1877) The Temperature in Diseases, published in 1868, which presented data on nearly 25,000 patients and analyzed temperature variations in 32 diseases, showing that temperature readings could differentiate fevers. Other devices emerged later to measure pulse and blood pressure. In 1854, Karl Vierordt (1818-1884) created the sphygmograph, a pulse recorder usable for routine monitoring on humans. Blood pressure was measured using the familiar inflatable band wrapped around the upper arm, called the sphygmomanometer, whose basic design was established in 1896 by Scipione Riva-Rocci (1863-1937). The hypodermic syringe was invented in 1853.

Biochemistry also began to play an increasing diagnostic function. In the 18th century, Matthew Dobson (d. 1784) developed tests for diabetes. In 1827, Richard Bright (1789-1858) showed show the kidney complaint subsequently called Bright's disease could be diagnosed by a single, simple chemical test. Chemical analysis was crucial to Alfred Becquerel's (1814-1862) urinalysis studies in 1841, establishing the average amounts of water, urea, uric acid, lactic acid, albumin, and inorganic salts secreted over 24 hours, and correlating these with various disease conditions. In 1859, Alfred Garrod (1819-1907) devised a simple chemical test pathognomonic for gout.


Last updated on 5 February 2003