CHEMISTRY: THE BEST MEDICINE A drug introduced in 1981, isolated from a soil fungus, revolutionized the transplantation of human organs. What drug was that? Cyclosporin. Early transplants were plagued by organ rejection. The recipient''s immune system considered the organ a foreign intruder and mobilized its forces for battle. Doctors realized that if transplants were ever to be successful, the body''s immune system would have to be held in check. By the time Dr. Christiaan Barnard performed the world''s first heart transplant in 1967, drugs that curbed immune activity were available, but they left a lot to be desired. The medications managed to keep the immune system from rejecting the organ, but the extent of immune suppression was such that it left the patient susceptible to all sorts of infections.
In fact, Louis Washkansky, the first recipient of a transplanted heart, died of pneumonia he contracted because of suppressed immunity. But the problem of rejection was essentially solved when cyclosporin came onto the scene in 1981. The discovery of the first truly effective anti-rejection drug was somewhat serendipitous, and dates back to the early 1970s. In those days, pharmaceutical companies searched high and low for novel antibiotics, investigating whatever fungus they could get their hands on. After all, antibiotics isolated from fungi, such as penicillin and streptomycin, had already proven their worth. Hoping to find some novel antibiotic-producing fungus, pharmaceutical companies routinely asked their employees to bring back soil samples from their travels. The Sandoz company lucked out. A soil sample collected in Norway yielded a strain of fungus that produced a compound composed of a ring of amino acids, eventually named cyclosporine.
It looked like a good candidate for antibiotic activity. Unfortunately, it turned out not to have any such properties. Eventually, though, disappointment turned to elation when cyclosporine was found to have a marked immunosuppressive effect! Administering the drug presented a problem, however, since it was almost completely insoluble in water. When taken orally, it never made it into the bloodstream. But researchers discovered that dissolving the drug in olive oil did the trick. In 1978, the first kidney and bone marrow transplants in which cyclosporine successfully prevented rejection were performed in England. Today, hearts, kidneys, livers and bone marrow are routinely transplanted, thanks in large part to cyclosporine. There is a footnote to the cyclosporine story, and a rather significant one.
After a transplant, monitoring the use of all drugs taken by patients is critical because some medications can interfere with the action of cyclosporine. St. John''s wort, for example, an herbal remedy available without a prescription, can negate the effect of cyclosporine and result in rejection. This interaction came to light when a heart transplant patient''s body rejected the donated organ even though an appropriate amount of cyclosporine had been administered. Unknown to his physicians, he had been taking St. John''s wort purchased at a health food store to ward off his depression. He almost warded off his new heart. Around 1000 BC, a Chinese monk introduced the idea of blowing a substance up the nose of people to protect them from smallpox.
What was this substance? A powder made from the scabs of pustules on the skin of people who had survived smallpox. The eradication of this horrific disease, which is thought to have first appeared around 10,000 bc, is one of the greatest triumphs of medicine. The last recorded case of smallpox occurred in Somalia in 1977, more than thirty years ago. How did this triumph come about? Simple: vaccination! The name associated with the introduction of the smallpox vaccine is Dr. Edward Jenner, an English country physician who acted on the observation that milkmaids who had come down with a disease known as cowpox never contracted smallpox. Jenner injected young James Phipps with material taken from a milkmaid''s cowpox pustule and then exposed him to smallpox. (Obviously, there were no ethics committees at the time to approve research.) The boy didn''t get the disease, and the era of vaccination, the term deriving from the Latin for cow , was on its way.
Although Jenner usually gets the credit for introducing the smallpox vaccine, it was twenty years earlier that Benjamin Jesty, a farmer, inoculated his wife with the cowpox virus and showed that it protected her from the disease. Unfortunately, he didn''t have enough oomph to influence the medical community. Even more amazing is that a technique known as variolation had been introduced by a Chinese monk almost two thousand years earlier. After the death of the son of a high-ranking Chinese official, the monk sought a way to cure the scourge of smallpox. He hit upon the idea of blowing the dust made from ground-up pustules taken from the skin of smallpox victims up the nose of healthy people. In all likelihood this was predicated on the observation that people who had survived smallpox became immune to the disease. Lady Wortley Montague learned of this technique when her husband had a political posting in Turkey. She brought it to the attention of the British royal family and suggested that variolation could be tested on condemned prisoners.
Indeed, four such men were treated, and months later were exposed to smallpox. All four survived. This was enough to convince the royal family to undergo variolation. The French thought the English were crazy. In fact, Voltaire opined that "the English are fools, they give their children smallpox to prevent their catching it." They weren''t fools. In smallpox survivors the virus becomes weakened and can offer protection to others, with only a small risk of causing the actual disease. The death rate from smallpox was usually somewhere between 20 per cent and 40 per cent, but the death rate from variolation was only about 1 per cent.
It is interesting to note that this ancient technique saved many from contracting smallpox long before it was replaced by Jenner''s more effective vaccination. "It may be that the world''s oldest medicine is the earth itself." To what does that statement refer? The ingestion of clay to absorb toxic substances. Terra sigillata, which literally means "earth that has been stamped with a seal," was originally dug up each year only on August 6, on the Greek island of Lemnos. It was mixed with the blood of a sacrificial goat, shaped into lozenges and dried. The famous Greek physician Galen recommended it as an antidote to poisons way back in the second century ad. Kings and popes commonly ate terra sigillata with their meals. Clays really do have the ability to bind various substances, and they even exhibit a property known as "cation exchange.
" This means they can absorb positively charged ions such as those of mercury and lead, which are highly toxic. Indeed, terra sigillata used to be an antidote to poisoning by mercuric chloride. A story from the sixteenth century speaks of a condemned German criminal who, in a bid to avoid execution, proposed an experiment to the court. He would act as a human guinea pig and take a potentially lethal amount of mercuric chloride, followed by terra sigillata in wine. If he survived, he would be released. Although he went through a torturous experience, the man did survive and was indeed freed! Today, refined clays, as in Kaopectate, are used to treat diarrhea caused by bacterial toxins in the gut. The clay can absorb the toxins and relieve the condition. Both George Bush Sr.
and his wife, Barbara, were diagnosed with Graves'' disease. This initiated the testing of the water in the White House for what substance? Iodine. Graves'' disease is a form of hyperthyroidism, a condition in which the thyroid gland produces too much thyroid hormone. As a result, metabolism speeds up, leading to weight loss, insomnia, muscle weakness, tremors, sweating, frequent loose stools, palpitations, bulging eyes and a feeling of edginess. Thyroid hormone contains iodine, and it''s conceivable that too high an intake of iodine can cause it to be overproduced. But the usual cause of Graves'' is an autoimmune reaction in which antibodies in the blood stimulate the overproduction of thyroid hormones. Since the odds of a husband and wife both developing this type of autoimmune reaction at roughly the same time are about three million to one, the White House water was tested for iodine. No excess was found, so it seems that George and Barbara were that unlucky couple in three million who simultaneously came down with Graves'' disease due to an autoimmune reaction.
Other possibilities, such as a pituitary tumour, were ruled out. Autoimmune reactions can be triggered by a viral or bacterial infection, so the first couple may have shared some infectious agent. The president and first lady received plenty of good-natured advice from the public about what to do, including eating broccoli, which is known to contain goitrogens, compounds that interfere with thyroid function. While this makes some theoretical sense, a grotesque amount of broccoli would have to be consumed for any effect on the thyroid to be noted. In any case, this was one bit of advice the president, having publicly expressed his distaste for the vegetable, was not likely to take. After those remarks, growers dumped truckloads of broccoli in front of the White House in protest, so he certainly would have had enough availa.