Wednesday, 15 June 2011

Creosote for a tickly cough.

If you look amongst the potions and remedies in any pharmacy, you’ll find a preparation for cough that contains guaifenesin.  Quite often this chemical is mixed with other dubiously-effective drugs as cough mixtures, in the hope that at least one component will do some good.  However, a recent meta-analysis suggests we have very little evidence that these products have any consistent effect in either reducing cough, or loosening phlegm. The history of guaifenesin and its grandfather, guaiacum, stretch back over half a millennium, and it’s quite surprising how many conditions this placebo has been thought to cure.  Let's start at the begining with syphilis.

The origins of syphilis have long been the subject of debate. Recent genetic analyses support the theory that Columbus brought syphilis back from the Caribbean in 1493. By 1509, the Spanish had also brought back the supposed cure, based on the folk remedy of the local people of San Domingo: the resin of from one of the more interesting indigenous trees (Guaiacum). Extracts of this resin entered European pharmacological lore and quickly replaced the previous poison for syphilis (mercury). Indeed, it wasn’t until the mid to late 19th century (over 400 years) that physicians began to doubt the efficacy of this remedy. Because syphilis could be confused with many other skin conditions at the time, the supposed efficacy of guaiacum probably stemmed from its placebo effect in self-resolving, non-syphilitic conditions:

"Yet those who most strongly believed in its efficacy were constrained to admit occasional failures; and on the other hand, we can now see that many conditions which guaiacum was supposed to cure probably did not belong to the venereal class, so that the drug acquired a celebrity it did not deserve"
-Philips (1874) [A materia medica]

Arthritis and gout
Around the same time that guaiacum was used for treating syphilis, we find references to the supposed efficacy of this extract on rheumatic conditions.  This additional use probably occurred to physicians because, if left to run rampant, syphilis can attack the bones, producing arthritis-like symptoms.  Since the advent of antibiotics, we don’t see this very often today. It is understandable then, that being unclear on the differences between conditions, 16th century physicians may have treated syphilitic arthritis, other arthritic conditions and gout all with guaiacum. Indeed, the rich playboys of the age might well have sexual and gastronomic appetites that led them to have syphilis and gout at the same time. King Charles V (1500-1558) was said to have taken guaiacum for his gout, putting its use in both syphilis and gout within the scope of half a century or less.   The use of guaiacum in arthritis, gout and poorly-defined rheumatisms persisted beyond the late 19th century and into the 20th century when it was finally debunked.

Wood creosote (not coal-tar creosote)
Creosote was first isolated from Beech wood by Baron Carl Ludwig Reichenbach in the 1830’s and found to have properties that helped skin wounds heal.  Indeed, Reichenbach's kreosote is an allusion to the flesh healing properties it was thought to possess. It was used extensively through the 19th Century as an antiseptic (it probably helped wounds heal by cleansing them of micro-organisms, preventing infection).  Later, as chemistry improved it became clear that wood creosote is, in fact, mostly (70% or more) guaiacol, which turned out to be the same main constituent of the crude extract of guaiacum that had been used for centuries. Chemistry was beginning to solve the mysteries of nature, and the use of magical Caribbean trees started to decline.

Tuberculosis (TB)
Continental physicians tinkered with raw creosote for as a treatment of TB from the 1830’s onwards, but this practice fell in and out of fashion over the next 50 years.  Interest in the UK was reinvigorated in the late 19th century by Coghill, who recommended using injected, purified guaiacol, suggesting that it kills the germs responsible for TB.  This supposed antiseptic property of guaiacol ensured its use in treating TB for several decades.  At the dawn of the second world war, Hale White’s Materia Medica finally concluded:

“These drugs [various salts of guaiacol] have been used for the same purposes as creosote in the treatment of pthisis [tuberculosis] and as intestinal antiseptics.  They are equally useless.”

While it was becoming clear that guaiacol is useless for treating TB, it remained in use as an “expectorant”. It seems likely that physicians clung to the idea that guaiacol was useful in treating TB, even if it didn’t kill the infective organisms themselves.  Perhaps they just couldn’t give up on a drug with such a long history.  Medicine is a culture, after all, not a set of rules that everybody follows. Canadian-based Eldon Boyd experimented with guaiacol and the recent synthetic modification – glycerol guaiacolate (later renamed guaifenesin) - on animals during the 1940s. His data showed that both drugs were effective in increasing secretions into the airways in laboratory animals, when high enough doses were given.  Guaifenesin took off from there.