 Serendipity is described in the dictionary as “the faculty of making
lucky or beneficial finds” and there could be no better example than
the unexpected emergence of the world’s most bitter substance,
nearly 50 years ago.
It all came about when chemists in an Edinburgh laboratory were studying
local anaesthetics. In particular, their quest was to find an alternative
to lignocaine (lidocaine), but one that had a much shorter after-effect.
One day, the research director entered my office and placed a small vial
containing a white
powder firmly on the desk. His first words were something like: “Do
you think you could find a market for this?”. The previous morning,
the room in which they had been working was permeated by an
intensely bitter taste. This was quickly traced to a compound that had
been spilled on a bench. The
research director told me that he had tasted a spot of the substance
and that the bitterness was still
evident.
The foregoing happened in a decade when Macfarlan Smith was making and
exporting substantial quantities of strychnine to Australia to eradicate
rabbits. The demand for this poison dropped steeply when myxomatosis
became prevalent and this, in turn, led to a shortage of brucine, a by-product
of strychnine manufacture. Brucine was in demand in the US, where is
was
used to
denature alcohol — to remove its “usefulness” as a
beverage by adding a bitter
substance or dye, or both. If alcohol was
denatured, no duty had to be paid on it so all alcohol for industrial
purposes (eg, antifreeze) was denatured.
Brucine was an important product for the company and so it was hoped that
the newly discovered bitter substance, called THS 58, might be a suitable
alternative. The next step was to ascertain if this was likely and accordingly
a visit to the Alcohol and Tobacco Tax Division of the US Treasury was
arranged in June 1959. An interesting feature of this trip was my voyage
(first class) from Greenock to Montreal on the Canadian Pacific liner Empress
of England, our chairman having considered this would be conducive to the
ensuing discussions. The crossing took exactly a week, the highlight being
the journey up the St Lawrence River to Quebec and on to dock in the centre
of Montreal. The journey continued by rail and air to Washington.
The discussions with the American authorities went well. They had earlier
examined a sample and confirmed it was much more bitter than anything
they had so far come across. Soon afterwards we received
notification that THS 58 had been accepted.
In the meantime a patent had been obtained for the substance and the
trade name Bitrex registered. But then a few months later came a setback.
Unexpectedly,
a red deposit (rust) was appearing in metal drums containing the denatured
alcohol. This was hurriedly investigated in Edinburgh and put down to
the presence of the chloride ion in the substance (denatonium benzyl
chloride).
Replacement of the chloride ion by the
protective benzoate ion (a rust inhibitor)
was successful — the bitterness remained — and the revised
product patented in due course.
From then on all went well and other countries gave approval of the
denaturant, including the UK
and Canada in the early days. Subsequently acceptance has spread more
widely and it is approved in more than 40 countries. Bitrex was recorded
in the
Guinness Book of Records as being the bitterest substance known. As far
as I know, there is no bitterness scale by which the degree of bitterness
can be measured, but comparisons can be made using the number of dilutions
required until the bitter taste is no longer detectable. In fact, in
a recent brochure, Macfarlan Smith claims that “Bitrex is so powerful
that a teaspoon of it added to an Olympic sized swimming pool can be
detected by a human being.”
Other uses
Most people dislike bitter tastes and it has been suggested that this
dislike evolved because it helped humans avoid accidentally consuming
poisons — many naturally
occurring bitter compounds are known to be toxic.
In the early days Bitrex was also used in the form of a paste to
discourage the biting of finger nails — older readers will probably
recall that pieces of aloes were commonly used for this purpose. A local
chemist had a degree of success with the product before it was taken
up by a national company. But pharmacy can have many interesting and
unexpected avenues and another use at this time was in a product named
Pigtail. The principal outlet for it was Denmark where tail biting in
pigs was prevalent.
Since then, Bitrex has been used as a safety additive for many household,
garden and personal care products — it renders such liquids much
less liable to be consumed by children. For example, it can be found
in floor cleaner, paint stripper, shampoo, perfume and slug bait. And
it is possible that there may be other uses for Bitrex so far not investigated.
This substance, which was discovered by accident, has proved to be of
great value as an aversive agent and its potency remains
unchallenged. On a personal note it has been of enthralling interest
over at least 26 years and provided a change from my involvement with
the sale of opiates worldwide and the procurement of adequate supplies
of opium — all of course strictly licit. |
The
Pharmaceutical Journal