Variolation: Immunity to Smallpox



Lady Mary Wortley Montagu (1689–1762)

Small pox was one of the most common infectious diseases that killed thousands in recurring epidemics. It can be traced as far back as ancient Egypt and in various outbreaks it regularly killed off large numbers of people. By the 17th Century it had recurred in many societies. Thomas Sydenham believed that small pox was best understood as a disease of passage: once you got it and survived there was no chance of getting it again. We are startled at his equanimity because there were such high mortality rates. Apparently in the 17th seventeenth and throughout the eighteenth centuries, about 60% of the population got small pox and 20% died of it: death was a much greater spectre in daily life than it is today. One of the disadvantages of living in cities was that infectious diseases spread more quickly in them, and one of the advantages was that if you survived them your immunity increased. In the Americas and Australia after the arrival of Europeans, mainly small pox, but other diseases such as measles killed many millions of indigenous people who had had no previous contact and hence little immunity to the diseases. In some cases 90% of a particular population died.

Lady Mary Wortley Montagu was the wife of the British ambassador to the Ottoman Empire and saw how the Turks inoculated people to cause a mild form of smallpox and produce immunity to the disease. The procedure was called “variolation” and was performed by rubbing powdered small pox scabs on a superficial scratch, or injecting fluid from a small pox pustule. This method had ancient roots. Lady Wortley-Montagu contracted smallpox in 1715 and bore its scars. She had her son Edward variolated in Turkey and then when she returned to England and a smallpox epidemic started in 1721 she asked her doctor, Charles Maitland, to variolate her young daughter. Maitland tested the procedure by variolating six prisoners and infecting them with this mild version of smallpox. None of them later contracted small pox. We must assume that they were in one way or another exposed to it.

Variolation was taken up by royal families across Europe but it did not spread to the general public. Lady Mary is one of the very few women mentioned in most medical histories. But despite the introduction of variolation, there was still very little understanding of the nature of infectious diseases.  Variolation was not an entirely safe procedure because one did contract a mild version of small pox: about one in every hundred people who were variolated died of the disease – a much lower percentage than the 20% who died of small pox.


The Story of Scurvy Part 3


Almroth Wright (1861-1947)

In the early 20th Century there was still not a good understanding of deficiency diseases. Very  prominent researchers were still looking for more fundamental cures for scurvy than citrus juice. Almroth Wright, an important figure in immunology, and the founder and chief of the laboratory where penicillin was discovered, became well-known because of his discovery of a vaccine for typhus. His views were so prominent that he was widely considered to be an authority on many diseases including scurvy.  The supplement of the eleventh edition of the Encyclopedia Britannica published in 1911 continued to declare the uncertainty surrounding the causes of scurvy and even advocated several more “elemental” cures including those of Wright. Here is an extract from the Britannica entry for scurvy

The precise etiology is obscure, and the modern tendency is to suspect an unknown micro-organism; on the other hand, even among the more chemical school of pathologists, it is disputed whether the cause (or conditio sine qua non) is the absence of certain constituents in the food, or the presence of some actual poison. Sir Almroth Wright in 1895 published his conclusions that scurvy was due to an acid intoxication.    Wright has proposed giving what he terms anti-scorbutic elements (Rochelle salt, calcium chloride or lactate of sodium) instead of raw materials such as lime juice and vegetables, as being more convenient to carry on voyages.(Encyclopedia Britannica, 1911, Pg. 517.)

Of course this solution was just as useless as those of the 18th century.


 Theodor Frolich 1870-1947              Axel Holst 1860- 1931

It took more than a century for the idea of deficiency diseases to be established. In the late nineteenth and early twentieth century human and animal studies showed that diets that were deficient of particular nutrients could cause diseases like beriberi. The word vitamin derives from “vital amine” and even though vitamins were not all amines, the word has stuck. Vitamin C was first isolated by two Norwegian doctors Axel Holst and Theodor Frolich using deprivation studies on guinea pigs – one of several animals including humans that do not manufacture their own vitamin C. Their publication in 1907 was ignored for many years because deficiency diseases were just at the cusp of being recognized. The Nobel prize for Vitamin C was instead awarded in 1930 to Albert Szent Gyorgi who synthesized ascorbic acid (the scientific term for Vitamin C.)

The parallel to scurvy in our modern age is the disease of space sickness. The illness comes on unexpectedly with rapid heartbeat, chills, nausea and vomiting. It can recur at unforeseen intervals during a long space trip, cause dehydration and weight loss, and make it impossible to work. It can be life threatening if vomiting occurs when wearing a space suit. Training on a plane called “the vomit comet” helps potential astronauts prepare for the experience of space sickness, but there is no way to predict who will suffer or how much. Some astronauts have reported feelings of nausea for their entire time in space while others get over space sickness after several days.  So far no prescribed drug prevents the condition or cures it. Returning to earth almost always makes it better although there have been cases of irreversible neurovestibular damage to the sense of balance. There have been many formal studies of the condition without results. Informally however, it seems that marijuana reduces the symptoms and helps astronauts to regain their earth legs once they land, but it has, so far, not been part of any of the formal studies.



Scurvy: Why it Took So Long

If the 17th century is seen as the Age of the Scientific Revolution, the 18th marked the Age of Discovery. The ships of many nations were now travelling across the world for commerce, colonization and piracy. They were fitted with cannons to protect them against their enemies and to allow them to attack rich foreign ships laden with treasure. The cannons required a large complement of men in addition to the crew that sailed the ship. Often the ships would be at sea for months at a time without touching land and the provisioning for the very large crew was difficult. Hard Tack, fresh water and occasional bits of stew was the basic ration for most regular seamen. Scurvy was the result and without treatment it led to a horrible death.

The primary lesions of scurvy relate to bleeding and swelling and inflammation of soft tissues and bone. Wounds don’t heal because you can’t make collagen. Bleeding occurs into the skin around the roots of all your hairs, which later fall out. Swollen gums bleed, the jaw bone softens, and eventually your teeth fall out. Hemorrhagic spots develop in your eyelid linings. There’s painful bleeding into your joints, and into the surface membrane of bones, causing crippling pain, and eventually spontaneous breakage of bones. Eventually you’re coughing up blood and possibly asphyxiating. Bleeding develops in the intestines, leading to black, and then bloody, horrifically foul smelling stools. Anemia, weakness. Emotional liability. Bleeding into the sack around your heart so your heart can’t fill with blood and pump. Bleeding around the brain, compressing it, causing headache, vomiting, eventually coma and death as your brainstem is crushed as your swollen brain pushes itself down into the spinal canal. Perhaps your spirit hovers overhead to watch your body committed to the deep.

The situation did not improve between the first publication of Lind’s Treatise and its third and final edition in 1772. Deaths due to scurvy and other diseases far exceeded the number of battlefield deaths during the Seven Years War (1756-1763). Once more the pressure for a cure increased, and sea trials continued without any clear success.

James CookJames Cook (1728-1779)

It was during this period that Captain James Cook organized his first expedition to circumnavigate the world in 1778. He demanded and received every contemporary support for the control of scurvy: ample supplies of Lind’s concentrated juice, large stores of fresh and preserved fruits and vegetables, and a careful selection of crew. (We know that on some of the other voyages, crew members were often selected from the poorest and least healthy parts of the population and at time forcibly brought on board ship.) Cook stopped as frequently as he could to “refresh” the ship and provide the men with fresh food and water. The result was the first truly successful voyage of discovery in health terms: no one died of scurvy, although the disease did occur when there were particularly long stretches away from shore. Cook made his reputation and received the Copley medal from The Royal Society for his success in staving off the disease (Bown, 2003:166). The Copley medal was then, and remains, a prestigious award for outstanding achievements in research in any branch of science.

James Pringle

John Pringle (1707-1782)

Cook’s success was followed by intense scientific wrangling. Rivalrous explanations of Cook’s success were led by Sir John Pringle (1707-82), the then head of the Royal Society. Pringle reviewed the surgeon’s records, and with a strong bias concluded that “sweet-wort” (unfermented beer) was the most effective preventive of scurvy. This turned out to be a major obstacle to the Navy’s acceptance of other solutions, and became the treatment of choice for a number of years, though it was of little value (Carpenter, 1986:17).

The scientific research establishment from Pringle’s time to the early 20th century hindered rather than helped the prevention of scurvy. Researchers and scientists, as well as clinical practitioners transferred successful solutions from one problem area to another: if sweet-wort helps with one problem of digestion, we should try it for scurvy, which appears also to be the same kind of problem. These physicians and scientists were often so committed to their settled explanations and frameworks that they continued to press for wrong-headed solutions in the face of massive evidence to the contrary. The greater their authority, the more resistant they seemed to be to new ideas. Often their intransigence was positively harmful.

Pringle was himself, not only President of the Royal Society, but a Copley medalist. He associated scurvy with rotten foods and believed in giving sailors foods such as sweet-wort. This unfermented beer was supposed to ferment in the stomach and correct the problem. Pringle was not alone in putting obstacles in the way of a scientific solution to the problem of scurvy. Later, other figures such as Sir Robert Christison (1797-1882) President, British Medical Association and physician to Queen Victoria, Jean-Antoine Villemin (1827-92) of the French Academy of Medicine, William A. Hammond (1828–1900) U.S. Surgeon General, and even Lord Lister (1827–1912) advocated dramatically false or misleading views about scurvy (Carpenter, 1986). This was largely because they did not understand the nature of a deficiency disease like scurvy.


Sir Gilbert Blane (1749-1834)

In the face of the medical establishment, progress could still be made on the policy front. Gilbert Blane, a physician from an upper class family, joined the navy in 1781 as Physician to the Fleet. From this position he had privileged access to the Admiral. After a short time he wrote that scurvy “may be infallibly prevented or cured by fresh vegetables and fruit, particularly oranges, lemons or limes” (Carpenter, 1986:92). His early letters to the Admiralty did not overcome the obstacle raised by the superior scientific authority of Pringle. However, he persevered, and in 1793 he instituted a test on one ship with the help of a friendly Admiral. Each man received two-thirds of an ounce of lemon juice mixed into the daily ration of grog. The ship took 23 weeks to reach India without touching land. Several men showed some symptoms of scurvy, but those soon disappeared after an increased dose of lemon juice. By the time the ship reached Madras, no one was affected by the disease.

In 1795, soon after Blane became a Commissioner on the Board of the Sick and Wounded Sailors, the Board recommended a daily allowance of three quarters of an ounce of lemon juice as part of the daily ration. After this date, the incidence of scurvy dropped very quickly. Just as the poor health of sailors due to scurvy was thought by some historians to be a factor in the British loss during the American Revolution, their good health after the elimination of scurvy was considered to be a major factor in the British maritime victories during the Napoleonic Wars (Porter, 2002).

The puzzle about the application of controlled trial results to policy has a very simple solution. It is quite clear with a close reading of Lind’s text. After he describes his clinical trial Lind declares the efficacy of oranges and lemons in the treatment of scurvy but,

As oranges and lemons are liable to spoil, and cannot be procured at every port, nor at all seasons in equal plenty and it may be inconvenient to take on board such large quantities as are necessary in ships for their preservation from this and other diseases the next thing to be proposed is the method of preserving their virtues entire for years in a convenient and small bulk. It is done in the following easy manner. [Lind, 1753 #67, Pg. 156.]

And our heart stops as Lind goes on to describe in great detail a process of heating the juice in a glazed earthen basin to almost boiling to allow the water to evaporate and produce a thick syrup (called  a “rob”) that can be reconstituted at sea. In this way the “virtues of twelve dozen of lemons or oranges may be put into a quart-bottle, and preserved for several years.” [Lind, 1753 #67, Pg. 157.]

We now know that boiling citrus juice for many hours severely reduces the amount of Vitamin C in the resulting syrup, and the reconstituted juice significantly dilutes whatever is left. It would not, and indeed did not prevent scurvy. But this “rob” rather than fresh oranges and lemons was Lind’s clear recommendation in his book. Moreover there is good evidence that the rob was used repeatedly with little good effect.

We can conclude that even though Lind believed fresh orange juice was a cure for scurvy, Lind was justified in believing that fresh orange juice was a cure for scurvy because of the trial. And it was true that fresh orange juice was a cure for scurvy. However we cannot conclude that Lind knew that fresh orange juice was the cure for scurvy because he also believed that the potency of the cure would be maintained if he boiled the juice down to a syrup or “rob.” (This is a real life example of a famous philosophical counterexample to the justified true belief model of knowledge that was first presented by Edmund Gettier in the Journal Analysis in 1963.)

Throughout the rest of his life Lind did not understand the outcome of his experiment. In later years when he became an academic physician and the successful head of the first sailors’ hospital at Haslam, he continued to try a whole range of other cures for scurvy with no success.

As patients we have learned to our dismay that there are many other cases where the conclusions of controlled trials turn out to be either ineffective or positively harmful, often because some aspects of the effect of a trial are not properly understood. This is not necessarily due to negligence, but to an inherent limitation of such trials in particular and to the justified true belief model of knowledge in general. Lind’s failure to see the importance of freshness in the juice is but the first example of this limitation and it accompanies the very first trial.

Of course there can be other parts of trials that are not in fact controlled and can have serious impact on the meaning of the results. One of my patient colleagues was asked to bring the patient’s perspective to the design of a particular controlled drug trial of an anti-depressant. The trial made sure that patients were not taking any prescription drugs that might interfere with the drug being studied. My colleague asked if they made sure that the patients had not also used herbal remedies like St. Johns wort that might have an effect (as many people have done for millennia.) In the trial they had ignored the effects of all herbal remedies and only excluded other prescription drugs. If my colleague was right, they could no longer claim that the results came only from the intervention that they had made. Often it is not clear what must be controlled in the various arms of a trial. We know, for example, that many drugs prescribed for older people or pregnant women are not tested on them, with occasionally disastrous consequences.

There is a growing struggle with some opposition from pharmaceutical companies to understand more vigilantly the limits of the results of controlled trials and also to monitor patients more thoroughly after they take new medications because of the risk of hitherto unknown side effects on their particular cohort. This kind of uncertainty about how to apply the results of trials to individual patients is a useful conclusion. We must be especially vigilant in prescribing drugs for the growing number of patients who will be long term users of drugs to control the effects of chronic diseases.

Outbreaks of scurvy recurred in the 19th century. For example there were outbreaks in France where scientifically developed infant formula was substituted for mother’s milk and in the Royal Navy itself when the fresh citrus juice was replaced with an adulterated version of lime juice.


The Story of Scurvy: The Controlled Trial

James Lind Black and White

James Lind (1716-1794)

If the 17th century is seen as the Age of the Scientific Revolution, the 18th marked the Age of Discovery. The ships of many nations were now travelling across the world for commerce, colonization and piracy. They were fitted with cannons to protect them against their enemies and to allow them to attack rich foreign ships laden with treasure. The cannons required a large complement of men in addition to the crew that sailed the ship. Often the ships would be at sea for months at a time without touching land and the provisioning for the very large crew was difficult. Hard Tack, fresh water and occasional bits of stew was the basic ration for most regular seamen. Scurvy was the result and without treatment it led to a horrible death.

The primary lesions of scurvy relate to bleeding and swelling and inflammation of soft tissues and bone. Wounds don’t heal because you can’t make collagen. Bleeding occurs into the skin around the roots of all your hairs, which later fall out. Swollen gums bleed, the jaw bone softens, and eventually your teeth fall out. Hemorrhagic spots develop in your eyelid linings. There’s painful bleeding into your joints, and into the surface membrane of bones, causing crippling pain, and eventually spontaneous breakage of bones. Eventually you’re coughing up blood and possibly asphyxiating. Bleeding develops in the intestines, leading to black, and then bloody, horrifically foul smelling stools. Anemia, weakness. Emotional liability. Bleeding into the sack around your heart so your heart can’t fill with blood and pump. Bleeding around the brain, compressing it, causing headache, vomiting, eventually coma and death as your brainstem is crushed as your swollen brain pushes itself down into the spinal canal. Perhaps your spirit hovers overhead to watch your body committed to the deep. (Anderson, 2000 )


George Anson, First Baron Anson (1697-1762) (by Joshua Reynolds)

Thousands of common seamen died of scurvy during long voyages of exploration, colonization and especially during the naval wars of the 17th and 18th centuries. In a particularly famous case, in 1740 George Anson led a flotilla of six warships with more than 1900 men on a trip around the horn of South America to capture Lima Peru from the Spanish. He ended up travelling around the world, gaining enormous riches, but only 188 original crew members returned. Most of the deaths were due to scurvy. Anson, now rich and famous, published a best-selling account of his trip. His expedition intensified the rush to find a cure for scurvy.

James Lind (1716-1794)

The traditional story of how the cure was finally discovered is largely about James Lind, an Eighteenth Century naval surgeon who performed the first recorded controlled trial. Today, controlled clinical trials have become the gold standard of evidence based medicine: subjects are randomly allocated to one or other of different arms of the study and the results are analyzed to determine which of the treatments are effective.

In 1747 while Lind was a surgeon on the HMS Salisbury there was a second outbreak of scurvy. He selected twelve sailors suffering from the disease and divided them into six groups of two. All were given a similar diet of “water gruel sweetened with sugar in the morning; fresh mutton broth often times for dinner, at other times boiled biscuit with sugar etc and for supper barley and raisins, rice and currants sago and wine or the like.”[Lind, 1753 #67, Pg. 145.] He then used the following treatments (here quoted in full but reformatted with modern bullet points to differentiate the six groups, leaving the original spelling but clarifying some terms in square brackets):

  • Two of these were ordered each a quart of [hard apple] cider a-day.
  • Two others took twenty-five “gutts” [drops] of elixir vitriol [dilute sulfuric acid], three times a-day, upon an empty stomach; using a gargle strongly acidulated with it for their mouths.
  • Two others took two spoonfuls of vinegar three times a-day upon an empty stomach; haveing their gruels and their other food well acidulated with it, as also the gargle for their mouth.
  • Two of the worst patients, with the tendons of the ham rigid, (a symptom none of the rest had), were put under a course of sea-water. Of this they drank half a pint every day, and sometimes more or less as it operated, by way of gentle physic [laxative].
  • Two others had each two oranges and one lemon given them every day. These they ate with greediness, at different times, upon an empty stomach. They continued but six days under this course, having consumed the quantity that could be spared.
  • The two remaining patients, took the bigness of a nutmeg three times a-day, of an “electuary” [medicinal paste] recommended by an hospital surgeon, made of garlic, mustard seed, rad. Raphan[dried radish root], balsam of Peru [resin from the balsam tree] and gum myrrh; using for common drink barley-water well acidulated with tamarinds; by a decoction of which, with the addition of cremor tartar [potassium hydrogen tartrate], they were gently purged three or four times during the course. [Lind, 1753 #67, Pp. 145-146.]


The trial offered clear results. The two sailors given oranges and lemons, even though it was for only six days were much improved; one of them was “appointed nurse to the rest of the sick”[Lind, 1753 #67, Pg. 146.].  The results are indeed utterly clear, the conclusion overwhelming.

Lind says that the citrus fruit provided to the sick seamen was all “that could be spared.” The fruit was from the supply kept for officers. Some ships, like George Anson’s returned from long voyages with their officers alive and most seamen dead because the provisions for officers contained foods that saved them, but these, because they were scarce, were not shared with the crew even as they became ill. The size of the crew could not allow it and there was no understanding of the disease that would warrant it. It should also be noted that large numbers of crew members were needed not only to help with navigation but to man the cannons that gave these warships their advantage in battle and the health condition of many of crew members was poor to begin with.

From the patient’s point of view we wonder what happened to the two patients who were given orange and lemons for six days. When they went off these rations, did the scurvy return? We are pretty sure that all the other subjects died. Did the two also die?

Lind published a description of his experiment in A Treatise of the Scurvy in 1753. The book was very successful, translated into other languages and widely distributed.  But despite their knowledge of Lind’s discovery, the British Navy only introduced fresh citrus juice to the sailor’s diet in 1795. The cost of this delay was enormous: far more sailors died of scurvy than in battle. During the Seven Years War of 1756 to 1763 the level of death was horrific: of the 184,893 men who were in the navy, 133,708 died “of diseases and missing” and only 1,512 were “killed in engagements and by accidents” (The Annual Register, or a View of the History, Politics, and Literature, For the Year 1763, 1790, Pg. 50.) In addition some historians have argued that Britain’s failed naval blockade during the American revolutionary War, largely due to scurvy, was a major factor in the success of the American Revolution. (Carpenter).

The delay in the implementation of Lind’s results has been extensively used to illustrate and bemoan the time gap between research results and their application. It has become a standard example in the literature, with different emphases on the various lessons and conclusions to be drawn from it. Herbert Spencer, the 19th century father of Social Darwinism, a proto-libertarian, and sometime beloved of George Eliot, claimed that the story of scurvy demonstrated the ineffectiveness of government and its bureaucracies (Spencer, 1887). More recent medical historians declare that the delay was because, “Surprisingly, the Navy took no notice of Lind’s results” (Coleman, 1985:94). More recently, still others, like Jonathan Lomas, a Canadian with an interest in knowledge transfer, assert that this was an early example of continuing resistance of practitioners to apply the results of scientific research – a classic case of poor knowledge transfer (Lomas, 2002).

Although it was one among many, Lind’s book was a best seller for its time. It was widely circulated, translated into other languages and printed in three editions over the next 15 years. It made Lind’s reputation. When the Navy built an enormous hospital at Haslar devoted to treating sailors, Lind became its first director, despite the failure of his solution to be effectively implemented. He held this post quite honorably and continued to experiment with the sailors who came there until he retired, whereupon he was succeeded by his son.

Pierre Simon Laplace (1749-1827)


Perhaps the most extreme and secular view of mechanical materialism was espoused by LaPlace in the century late 18th century. By that time, the modern understanding of Boyle’s view of the body had spread to many physicians, but not the general public, much as quantum physics is understood by physicists, but not by many laymen today. The outdated physics and mathematics of that time continues to influence our current thinking in much the way Galen’s humoral theory remained deeply embedded in medicine. A good example of such an outdated idea that remains influential today is LaPlace’s Demon. Pierre Simon LaPlace wrote in 1814:

We may regard the present state of the universe as the effect of its past and the cause of its future. An intellect which at a certain moment would know all forces that set nature in motion, and all positions of all items of which nature is composed, if this intellect were also vast enough to submit these data to analysis, it would embrace in a single formula the movements of the greatest bodies of the universe and those of the tiniest atom; for such an intellect nothing would be uncertain and the future just like the past would be present before its eyes. Aphilosophical Essay on the Probabolities (note :  Laplace, Pierre Simon, A Philosophical Essay on Probabilities, translated into English from the original French 6th ed. by Truscott,F.W. and Emory,F.L., Dover Publications (New York, 1951) p.4)

This is the clearest and most deeply accepted account of mechanistic determinism that we have. Of course there can be no such being as Laplace describes. We do not expect to ever have such a formula because physics has passed that point. The new quantum mechanics concluded that there are many phenomena that are complex and by their very nature unpredictable. Yet many of us still believe foolishly, that the world is deterministic and hence that there can be no free will.

Although we now recognize that LaPlace’s notion of a completely deterministic universe is not possible, it is still deeply embedded in our thinking. Much as we continue to take hot chicken soup to combat the common cold we continue to consider that a deterministic and mechanistic account of all our actions remains feasible. This is to take away from us any immediate responsibility for our own actions including our health.

If our chemical mechanical body is controlled entirely by forces beyond our individual control then we must wait for their interventions to set us straight. This view gives our bodies over to the medical scientists who are the only ones who truly understand the laws that govern them and hence how to repair them.  The development of this view accompanied the rise of modern scientific medicine, It had its height in the first part of the 20th Century and although it remains a strong tendency today, the patient`s partnership in all aspects of healthcare is growing.


John Hunter and Scientific Surgery

John Hunter 1728-1793

John Hunter was one of the founders of scientific surgery. He studied human anatomy with his elder brother William, developed his skills as an army surgeon during the Seven Years War, and later opened a museum of specimens and an anatomy school in his house in London. Because of the better understanding of anatomy that emerged from the increase in human dissection of the 17th century, there were many surgical advances including improved instruments and much faster procedures. But there was still no true anaesthetic and little understanding of antiseptic measures. And so surgery remained dangerous, painful and often fatal.

The rapid urbanization meant that more almshouses were established to serve the old, the sick and the dying. Some were the forerunners of hospitals that became established in the next century. But for the most part people entering the poorhouses as sick indigent patients, died there. A very small number of free clinics served the poor and many patients looked far afield for help.

Boyle and the Philosopher’s Stone

Toward the end of his life Robert Boyle withdrew from society and no longer received guests. He said that he wanted to “recruit his spirits, range his papers”, and prepare some important chemical investigations which he proposed to leave “as a kind of hermetic legacy to the studious disciples of that art”, but he never made public what these were. In 1689 he petitioned to repeal an act passed during the reign of Henry IV which prohibited the alchemical transformation of other metals into gold. The relevant part of the act states “That none from henceforth should use to multiply gold or silver, or use the craft of multiplication; and if any the same do, they should now incur the pain of felony.” A letter from Boyle to Christopher Kirkby on 29 April, 1689 underscores his arguments.

I still am, of opinion that the act of Henry IV has been, and whilst it still remains in force, will be, a great discouragement to the industry of skillful men which is very happily improved in this inquisitive age. And therefore, that the repealing of a law, so darkly and ambiguously penned, will much conduce to the public good, and be in particular advantageous to the counties of Cornwall and Devonshire where tin so much abounds.



Gilbert Burnet (1643-1715)

Boyle with the help of his friend and spiritual advisor, Gilbert Burnet, the influential Bishop of Salisbury, succeeded in getting a new act passed in August of that year. It required that any gold and silver produced using these new processes be deposited in the royal mint in the Tower of London.


Isaac Newton 1642-1727

When he died in 1692, Boyle left for John Locke a recipe for the transmutation of gold along with a reddish brown powdery substance that was necessary for the process. Sir Isaac Newton received a version of the recipe but apparently not the red earth. An exchange of correspondence between them remains, in which Newton begins by telling Locke that he too knows of Boyle’s recipe. He then writes again explaining how he learned about Locke’s possession of it and requests a sample of the red earth and further details of the alchemical process. The correspondence ends with a note in which Newton declares that he has not succeeded in his alchemical quest and is skeptical of its possibility.

Many of these bits of information have been available from soon after Boyle died in 1692 and were published in his collected works in 1714. A great deal of his alchemical work was omitted from the published works; but some was kept unpublished and some actually discarded, presumably so as not to tarnish his scientific reputation. The correspondence from Newton to Locke emerged later from other sources. Over the last fifteen years or so with the careful examination of previously unexamined existing papers, the addition of yet more information and changing perceptions of the 17th century context, the view of Boyle has transformed. In earlier accounts, his religious, alchemical and medical interests were subordinated to his strong scientific empiricism, and he was portrayed as an earnest scientist with a high degree of skepticism about alchemy. More recently, as more of his papers have been examined, Boyle’s religiosity, his deep interest in alchemy and his role in medical research have been explored in greater detail with the result that his religious scruples, his connection to the alchemical tradition and to its application to medicine, are seen by some as at least as important in understanding his work as his direct dedication to what we now consider to be experimental science. What emerges for us is Boyle’s role using his enormous resources to pursue all approaches available to him to achieve his own health. He combined the mechanical view of the body espoused by Descartes, with the chemical account developed by Paracelsus. This chemical-mechanical account of the human body became dominant scientifically in the next century and became clinically central by the 19th century.



Robert Hooke

Robert Hooke (1635-1703) 

There are no contemporary portraits of Robert Hooke. This is a recent attempt to make a portrait of him from descriptions of the time

It was during the early 1650’s that Thomas Willis began to study the nature of fevers with Robert Hooke as his technician. Willis’ ideas about fevers combine some aspects of van Helmont’s notion of fermentation with a mechanical theory of the nature of circulation. Willis disagreed with Helmont’s account of an archeus as the cause of fever. Instead he provided a mechanical explanation: the accelerated fermentation of the blood causes it to heat up excessively, creating more pressure in the blood vessels and also speeding up the pulse.

A similar mix of views and approaches is evident in Willis’ conclusions after dissecting and examining many animal and human brains and nervous systems. Like Aristotle he distinguishes the animal from the rational soul. His anatomical work revealed the strong similarities between the brains of humans and many animals and so he concluded that the animal soul is seated in the brain and allows us and the animals to have sensations, to feel pleasure and pain and to have desires and passions. He distinguishes the animal soul from the human rational soul, which is immaterial and immortal. Willis’ religious views can thus be preserved.

Health, for Willis, involved maintaining the appropriate level and type of fermentation in the different parts of the body in order to allow it to function smoothly. This could be aided by the use of iatrochemical remedies such as his “steel syrup” which he made using his own secret recipe and sold to his patients.

Willis introduced Boyle to Robert Hooke who had shown remarkable mechanical skills as his assistant. Boyle hired Hooke as a “mechanick” and this clear relationship between virtuoso and assistant is in stark contrast to the ambiguous relationship he had with Starkey. Hooke, who, like Willis, had begun his student days as a servitor saw himself as “belonging to Boyle.” He lived in Boyle’s house and received an income from him until the early 1660s. In the early period Hooke was responsible for building the air pump which the two used to conduct Boyle’s most famous and successful series of experiments on the springiness of air. The air pump, like other significant technological innovations had a considerable cost, but it also opened up entirely new areas of experimentation. Boyle and Hooke used the device to perform the 43 experiments that included fresh evidence for the possible existence of a vacuum and various experiments that showed that fire would not burn and animals could not survive without air. (Killing small birds by depriving them of air was a favourite demonstration.)  This work resulted in Boyle’s first major scientific publication in 1660, New Experiments Physio-Mechanicall, Touching the Spring of the Air and its Effects.  In the later second edition he first articulated the basis for what has come to be known as Boyle’s law (under conditions of constant temperature and quantity, there is an inverse relationship between the volume and pressure for an ideal gas.)

Although the formal roles of Hooke and Boyle were clear, there has been some question about the extent of contribution of each to the process, with an increasing appreciation of Hooke’s work emerging in recent years. The period of his close collaboration with Boyle continued until Hooke moved to London in 1662 to take up his role as the unpaid curator of experiments at the Royal Society. It is very likely that Boyle continued to support him even after this move, as he did Henry Oldenberg, who had been appointed a secretary of the Royal Society in 1660. When Hooke was eventually funded by the Royal Society it was in order to pursue the History of Trades project. However he was so involved in collecting and demonstrating experimental effects, designing and constructing technological innovations in telescopes, microscopes and watches that he devoted almost no time to the History of Trades which eventually and inevitably died a slow death. But Hooke did make a preliminary list of the various artists, craftsmen, and tradesmen who were to be included:

Surveyors, miners, potters, tobacco pipe makers, glaziers, glass grinders, looking glass makers, spectacle makers, optick glass makers, makers of counterfeit pearls and precious stones, bugle makers, lamp blowers, colour makers, colour grinders, glass painters, enamellers, varnishers, colour sellers, painters, limners, picture drawers, makers of bowling stones or marbles, brick makers, tile makers, lime burners, plasterers, furnace makers, china potters, crucible makers, masons, stone cutters, sculptors, architects, crystal cutters, engravers in stones, jewelers, locksmiths, gun smiths, edge-tool makers, grinders and forgers, armourers, needle makers, tool makers, spring makers, cross-bow makers, plumbers, type founders, printers, copper smiths and founders, clock makers, methamatick instrument makers, smelters and refiners, sugar planters, tobacco planters, flax makers, lace makers, weavers, malters, millers, brewers, bakers, vintners, distillers.

It is not hard to see why it was not possible to collect all the information about the history of trades in a way that would capture every aspect of the procedures used by the wide variety of skilled craftsmen, professionals and tradesmen. Much of the “how to” knowledge is practice based rather than reducible to recipes. At the core of many “trades” was a long term apprenticeship which involved repeating the various procedures until they could be performed without error. The idea of transmitting this kind of knowledge in a written “history of trades” is not really practicable. So, for example, even today, no one learns surgery except by practicing procedures under close supervision until they are perfectly performed. There is no text book of surgery that can substitute for such practice. Nor can there be. The same is true for other “trades” from cooking to jewelry making.

When some years later, Hooke engaged in a lengthy, very public and quite nasty conflict with Isaac Newton over the origin of some of Newton’s ideas about the path of a falling body, he never for a moment raised the issue of the extent of his contribution to Boyle’s work, where he was recompensed for his subordinate role (as a mechanic). Despite Hooke’s later estrangement from Boyle, who had become more closely associated with Newton, the dying Boyle bequeathed him his best telescope and microscope.

In 1660, after Charles II became King, Boyle and eleven others founded the Royal Society. In 1662 it received a Royal Charter but no money. Boyle’s financial support in its early days was an important contribution to its survival and success. The initial membership of 143 men included not only serious scientists, but also fashionable and influential gentlemen. Over 40 of them were trained in the law; more than 30 were members of parliament. Many with only a passing interest in science came on Thursdays to witness Hooke’s demonstrations. The Royal Society played a critical role in the rise of the new science. Given the distinction that Bacon made between fact and law, members of the Royal Society came to play a vital role as especially reliable observers who could testify as to the veracity of the matters of fact displayed to them.

But not everyone was admitted to the Royal Society. Thomas Hobbes, for example, was excluded, largely because of his skepticism about the role of experiment in gaining knowledge. During this period, Hobbes’ reputation rested as much on his mathematical and scientific activity as on his political philosophy. He had contact with most of the central figures of the period including Bacon, Descartes, Harvey and Boyle. His disagreements with Boyle about the air pump experiments are well described in Leviathan and the Air Pump by Steven Shapin.  Like Descartes, Hobbes did not believe in the possibility of a vacuum, and he argued that the air pump experiments did not constitute valid evidence against his views. The air pump could not be shown to eliminate all air from the glass container. Moreover it might still leak. But his major difference with Boyle was that knowledge could not be derived from experimentation, but rather from the deduction from evidently true first principles. Hobbes came to Euclidean geometry late in life. He found that as he studied the theorems he could deduce significant facts about the world without resort to experiment at all. If one could get the correct fundamental basic principles about a subject, then one could deduce from them indubitable facts about the world. This was a very high standard for knowledge: one that Boyle’s experiments did not meet. For him, these experiments were demonstrations of particular effects done with imperfect instruments, for the edification of gentlemen. They did not result in any real increase in understanding of the world. Nor did he accept the authority of Boyle’s peers in the Royal Society as expert witnesses testifying to the supposed knowledge gained. If the world is truly a mechanism, it can be understood mathematically and causal connections can be deduced quickly, following from a comprehensive mechanical theoretical frame.

Hobbes was a practiced controversialist. He knew everyone and fought with many of them. His attacks on Boyle were preceded by an earlier dispute with Descartes who accused him of starting the fight only to advance his own reputation. In that case Hobbes had presented an argument for materialism and against Descartes’ claim that mind and body were distinct substances. Hobbes materialism was widely identified with atheism which was, at that time, a fear that had a stronger emotive connotation than did the threat of communism in the mid- 20th century.

John Locke and others

(c) Government Art Collection; Supplied by The Public Catalogue Foundation

(c) Government Art Collection; Supplied by The Public Catalogue Foundation

John Locke (1632-1704)

John Locke met Boyle in 1660. He came from a middle class family, went to Westminster School a bit later than Wren and Hooke and entered Christ Church, the most prominent college in Oxford in 1652. His first year was interrupted by his asthma, an illness severe enough to force him to recuperate in the country for several months that year and later at various times in his life. The university was then under the control of Puritans with mandatory attendance at two sermons a day as part of the educational process. This left him with a distrust of sectarianism and a belief in a kind of Christianity with less dogma and certainty about which approach was the right one. He graduated in 1656 and went on to get a Masters degree and take on several academic posts in Oxford. He appears to have been unsure of which path to take, but decided not to become a cleric despite his deep religious feelings. In the late 1650s he began to read medical texts, eventually becoming an academic physician. He developed a growing interest in the new science and met Boyle himself in 1660. He was never a prominent member of the Oxford study group, but his notebooks indicate that he read Boyle’s writings as they appeared and also much of Descartes with a special interest in physics.

Locke was a compulsive record keeper and much of what is known about his life is from notebooks and account books that he kept throughout his life. We know what he spent to furnish his college rooms and how much it cost him to live from term to term. Much of his collaboration with others was to help with record keeping and writing. Locke was actively involved in several of Boyle’s many efforts. One was to record the weather on a daily basis for many years in order to contribute to Boyle’s attempts to connect weather patterns and epidemics. Another was an unsuccessful attempt to measure differences in barometric pressure at the top and bottom of a mine in Somerset while recuperating from one of his many bouts of asthma. Locke also collected and categorized thousands of plants from the Oxfordshire countryside. Some of Boyle’s manuscripts were written in Locke’s hand. Though not an active participant in Boyle’s research on respiration he stayed abreast of it and wrote an unpublished paper Respirationis Usus on the topic.

Locke had training and experience in laboratory chemistry. In 1663 he attended a series of lectures in chemistry by Peter Stahl one of the chemists Boyle brought to Oxford. In 1666 he started an alchemical laboratory with David Thomas a medical colleague. Like Boyle, they attempted to make the alkahest as described by van Helmont. He jokingly wrote to Boyle that the laboratory could transmute gold from scholars’ pockets into his hands.

Anthoney Ashley Cooper

Anthony Ashley Cooper (1621-1683)

In 1666 Locke’s life changed when he met and became physician to Anthony Ashley Cooper (1621-1683) who came to Oxford hoping to find some relief from chronic pain by taking medicinal waters. Ashley, who later became the first Earl of Shaftesbury, was a well-known and wealthy politician who led the opposition to Charles II. He invited Locke to come to London to join his household. His responsibilities were various and gradually came to include everything from medical treatment to political advice. In a famous incident Locke along with Thomas Sydenham inserted a silver pipe into Ashley’s abdominal cavity to drain an abscess. This tube pipe remained in place for the rest of Ashley’s life and relieved him of the chronic pain he had suffered for a number of years. He was a grateful patient who became well known as “Tapski” because of the tube.


Thomas Sydenham (1624-1689)

Sydenham and Locke became closer colleagues when Locke accompanied him in on his medical rounds between 1667 and 1671. Sydenham’s views were an important influence on how Locke came to understand health, and also on his philosophical views. Locke acknowledges his importance in the epistle to the reader that begins the Essay Concerning the Human Understanding. It proclaims Locke’s modest hopes in a time when others are far more able than he:

The commonwealth of learning is not at this time without master-builders, whose mighty designs, in advancing the sciences, will leave lasting monuments to the admiration of posterity: but everyone must not hope to be a Boyle or a Sydenham; and in an age that produces such masters as the great Huygenius and the incomparable Mr. Newton, with some others of that strain, it is ambition enough to be employed as an under-labourer in clearing the ground a little, and removing some of the rubbish that lies in the way to knowledge.  


Sydenham was trained as a Galenic physician but increasingly became focused on clinical care. His close observation of patients led him to develop strong insights into diseases. He practiced at all levels of society and it seems that much of this practice was to observe clinical cases and record them for later use. He was famously among the first to consider diseases as natural kinds, as if they were species, each with its own natural course. This allowed him to observe and record the process of numerous diseases so that they could be distinguished from each other and treated independently. Each disease had distinguishing characteristics and ran a natural course from infection through a course of illness to healing or death. As a practicing physician he appears to have taken remedies where he could find them and to have tried a wide variety of cures. His recipes for medications include material from the empirics, the galenics, and the iatrochemistry of the newer paracelsians . There is a good example of this in the regimen he provides in one of his cures for asthma.

Take away ten ounces of blood from the right arm, and next day give the common purging potion, which must be repeated twice more, once every third day. On the intermediate days of purging let the following medicines be used: Take of the seeds of anise, finely powdered two drams; Locatellus’s balsam enough to bring it into a mass for pills and make six pills of a dram, three of which are to be taken every morning and at five in the afternoon, drinking four ounces of the bitter decoction without purgatives, warm after them. If the disorder does not go off, let the whole process be repeated. (Works of Sydenham, on acute and chronic diseases page 463 )


Sydenham is widely seen to be in the tradition of Hippocrates because of his close observations and record keeping of clinical cases. He brought to his observations a skepticism about the unquestioning acceptance of received methods and an openness to new clinical interventions from any source to see if they worked. He became a strong advocate of opium as a painkiller and was an early proponent for the use of Peruvian bark (from which quinine was made) to fight the ague (usually malaria). This cure has its roots in prehistoric America, and like many herbal cures was passed down through hundreds of generations in an oral tradition. It is interesting that, though Sydenham was just one of several early adopters of this material, Locke sees this as one of Sydenham’s greatest accomplishments. No doubt he himself benefited from quinine. Sydenham’s star began to rise only in the 18th century, when the quality of his clinical work became well recognized.

Arthur Coga

Arthur Coga (First patient to have a blood transfusion from a sheep)

As we have seen, much of the experimentation in 17th Century England was done with animals, but in 1667 the first transfusion into a human was performed. The patient was Arthur Coga, who had studied at Cambridge, and was said to be a bachelor of divinity. He was indigent, and “looked upon as a very freakish and extravagant man.” His pay was 20 Shillings. In a letter to Robert Boyle, he is described: “Mr. Coga was about thirty-two years of age; that he spoke Latin well, when he was in company, which he liked, but that his brain was sometimes a little too warm.” The experiment was performed on November 23rd, 1667 for the Royal Society, in the presence of many “spectators of quality, and four or five physicians.” Coga wrote a description of his own case in Latin, and when asked why he had not the blood of some other creature, instead of that of a sheep, transfused into him, answered, “Sanguis ovis symbolicam quandam facultatem habet cum sanguine Christi, quia Christus est agnus Dei” “The blood of a sheep symbolizes the blood of Christ, since Christ is the lamb of God” (Birch’s “History of the Royal Society,” vol. ii., pp. 214-16).


John Wilkins


John Wilkins (1614-1672)

In 1655, after he returned to England, Robert Boyle moved to Oxford and joined the scientific group begun by John Wilkins at Wadham College. Although Wilkins was Oliver Cromwell’s brother-in-law, he gathered around him a circle of new scientists with a wide range of political and religious backgrounds. Once in Oxford Boyle dramatically increased his level of activity. He found rooms outside the college, established laboratory space, hired assistants and amanuenses and began several streams of experimental work including a continuation of his alchemical work on metals and his studies of blood and digestion. He also started the series of experiments on “the springiness of air” that would make his reputation as a leading scientific figure. He appears to have connected all his work to health so that even his experiments on air were relevant to his interest in respiration and to provide some understanding of why blood changed colour once it passed through the lungs.

Boyle had already begun to correspond with Thomas Willis, the Helmontian physician with whom Petty had also worked on dissection. It was natural that when Boyle arrived in Oxford Willis became one of Boyle’s many collaborators. Willis had begun his studies at Oxford as a servitor – a student who paid his way by being a servant, most often to other students. He joined the Oxford group in 1648 and spent four years working with Petty. Together they performed autopsies and continued to dissect large numbers of living animals. Petty was a confirmed mechanist who believed that the body was a machine and the best way to understand it was to take it apart. Willis used his alchemical training to reduce blood and other bodily fluids to their more basic Paracelsian components. Under Cromwell his medical practice languished because of his Royalist Anglican sympathies and he was forced to apply his chemical skills as a “pisse-prophet”, a diagnostician of urine samples including tasting them for sweetness. (His practice expanded substantially after the restoration of Charles II to the throne and eventually he became one of the wealthiest practitioners in Oxfordshire. Much of this was due to his secret recipes for drugs that were expensive and apparently effective as well. His influence followed him when he moved to London in 1667 at the request of Archbishop Sheldon. )