Chemical Warfare

Elusive Potion

For myriad maladies:

The quest for a cure 

            For thousands of years, mankind has sought substances that would cure diseases, including those that are infectious. Some were quite effective. The Egyptians left records of a poultice they used for treating wounds. It consisted of grease from animal fat, honey, and bits of linen. Honey has antimicrobial properties, and the fat helped keep bandages from adhering to the wound. Linen was a “sponge” to remove some of the dead tissue and pus from the area.  

            The sap of the balsam tree, which grows in the Middle East, was found to have anti-infectious properties. Applied to wounds, it can help prevent infection and promote wound healing. It is the root of the word “balm.”

            There were many others. By far, though, the most popular and enduring was a potion attributed to a Hellenistic king, Mithridates VI, who ruled the area of Pontus on the south Black Sea around the year 120 BCE. He was looking for something to help treat poisonous snake bites, and he created a potion containing lots of herbs and somewhat toxic plants, including opium, cinnamon, myrrh, and castor. It also included the flesh of venomous reptiles. Some ingredients, like hemlock, were dangerous, but they were used in diluted form, much in keeping with the Greek theory that “if it doesn’t kill me, it makes me stronger.” After experimentation on prisoners, he took what seemed to work and blended it into a concoction initially called mithridatium, named after its inventor. It later became known as theriac, from the Latin “theriaca,” or antidote to poison. (From the Latin therapia, we get the word “therapy”).

            Amazingly, theriac sometimes seemed to work. Distinguishing actual therapeutic benefits from the placebo effect is difficult, especially several hundred years after the fact. Who knows which of its many ingredients was effective, as it took the “shotgun” approach: throw a bunch of stuff against the wall and hope that some of it will stick.  

            The Greeks, of course, were very influential. (It is often said that the success of Rome was founded on Greek philosophy). The reputation of theriac spread far and wide. And just like a story that goes around and changes slightly with each telling until it is altered substantially, so did the formulation of theriac change by location and time. Some recipes called for as many as 100 ingredients, some half that. Making it was a big deal, with whole communities involved in a festival atmosphere. Theriac was the absolute go-to drug for nearly 2,000 years. Today, very few people have ever heard of it.

            Even theriac, though, was ineffective against the ravages of many infectious diseases that battered humanity over the ages: smallpox, bubonic plague, influenza, malaria, typhoid, typhus, dysentery, tuberculosis, and many others were unaffected by this complex concoction. Much more was needed.

            The first bona fide drug used to treat a specific infectious disease has an amazing history. Its story is one of exploration, treachery, science, and exploitation. Drugs today can be developed, tested, and marketed in a few years. This one took centuries. But it was the first formulated pharmaceutical that was specific and effective for a severe infectious disease. Its name was quinine, and the disease was malaria.

            
             The Quechua people were inhabitants of the highlands of the Andes in Peru, parts of Bolivia, and extending up into Ecuador. Theirs was an agrarian culture; they lived close to the land. An herbal remedy they were devoted to was the bark of a tree that populated the forested area where they lived, one they called Quina Quina. (The name comes to us from the Spanish, who probably put their mark on it. To the Quechua, it meant “holy bark”). For a long time, they used the tree bark to treat quite a few maladies, primarily the chills we experience when beginning a fever. It helped reduce the fever and shorten the time of illness.  

            The Spanish entered the area we now call Peru in the early 1530s and established settlements there. The disease we know as malaria did not exist in the Americas before the presence of the Europeans, but it became prevalent shortly after their arrival. Certainly, there were severe local infections, but the introduction of infectious organisms from Europe and Africa created a whole new array of maladies. The Quechua people used their tree bark remedy to help with the infections.

            Most likely, some Spanish settlers were introduced to the holy bark tree, but it took the cure of a ruling-class woman to popularize it in Europe. The viceroy's wife in Peru was a Spanish countess named Anna del Cinchon. While in Peru, she came down with a case of what might have been malaria. The local Indians suggested she bathe in a pond near her home beneath a Quina Quina tree and drink some bitter water from the tree bark. Her fevers ended in a few days, and she was cured. Whether this story is true or merely apocryphal, it carried weight. The tree was named after her. The scientific name of the tree assigned by Carl Linnaeus is Cinchona.

            It became apparent to the Spanish that this local tree bark effectively reduced malaria symptoms. Some of the bark was brought back to Europe and tried there. Jesuit missionaries did most of the first transport and application, so the colloquial term became “Jesuit bark.” Later it came to be called quinine. It found some usefulness in southern Europe, Spain, and Italy in the early days, but there were problems. There are around two dozen species of cinchona trees, and they don’t all produce the same amount of active ingredient. Different growth conditions, such as soil, rain levels, and elevation, can alter the tree’s underlying chemistry. Fraud and deception were inevitable with how it was brought back by sailors and tradesmen seeking profit. Also, the active ingredient is an alkaloid, which doesn’t dissolve very well in water. Mixing in a bit of alcohol in the right amounts helps. So, some batches worked quite satisfactorily with malaria patients, others not as well, and some not at all. Add to that the problem of accurately identifying a genuine malaria case without laboratory equipment and confusion reigned.  

            The big “breakthrough” for quinine, if that’s the right word, came in England in the 1670s. King Charles II suffered tremendously from what was most likely malaria. Court physicians tried in vain to alleviate his symptoms. In near desperation, the king called upon a Mr. Robert Talbor, who was said to have a “miraculous cure for the ague,” as malaria was called at that time. Talbor’s secret recipe worked almost miraculously, and the king recovered his health. A little later, in 1679, the son of the king of France, Louis XIV, contracted the disease. Talbor cured him too. It was later revealed that Talbor’s formula was rose leaves, lemon juice, ground-up cinchona, and wine. The alcohol in the wine helped dissolve the active ingredient. With the cure of these two high-ranking individuals, the cinchona bark gained respectability and was widely recognized.

            The reputation of the bark grew. Here, for the first time in history, was a substance that, when taken orally, could cure or reduce the symptoms of a severe infectious disease. While valuable in treating individual cases, quinine assumed an immense role in world affairs. The Industrial Revolution demanded a supply of natural resources, many of which came from malaria-infested areas. Quinine helped ensure that the workers in these areas were more productive. Infected individuals and their employers were willing to pay large sums for the antidote. Scientists of the time were interested in studying the tree and its bark, and it was planted in different areas of the world. The cinchona bark became more valuable than gold, and it literally grew on trees.

            Quinine is an alkaloid that works in several ways, but its activity against the Plasmodium species that cause malaria was fortuitous. Malaria didn’t exist in the New World when the Quechua people started using their tree bark. They used the bark to control fever and the chills accompanying it. For them, it was non-specific, just like we might take an aspirin tablet to reduce a fever. (Aspirin is also derived from a chemical found in the bark of a tree. Salicin, from which aspirin is derived, is found in the bark of the white willow tree). But it just so happens that quinine interferes with the malarial parasite’s ability to digest hemoglobin. Even though the bugs sit in the middle of a red blood cell filled with the stuff, they essentially starve to death. It works best on Plasmodium falciparum, the most virulent species of malaria. But it is not 100% effective, depending on the malarial species and stage of the disease. Still, its introduction to medicine was monumental: an oral medication that could effectively treat an infectious disease.

            Quinine is still helpful today. The World Health Organization lists it as the number one choice for treating severe malaria in adults, and all types of malaria in young children and pregnant women. Also, quinine water, the “tonic” in the British beverage gin and tonic, is still going strong.