Wonder Drugs

A Little History Of Science: Wonder Drugs

There may be five million trillion trillion bacteria on earth. That’s 5 × 1030 or 5 with thirty noughts after it – an astounding number. Bacteria can live almost anywhere on earth: in the soil, the oceans, deep underground on rocks, in Arctic ice, in the boiling water of geysers, on our skin and inside our bodies. Bacteria do all sorts of useful things – without them what would happen to all the rubbish they digest? We benefit from that digesting trick too. The bacteria that live in our guts help us break down the food we eat to release the proteins and vitamins. Some bacteria even turned out to make useful drugs, along with some other micro-organisms, the fungi.

Most of us have been prescribed some of these antibiotics. In the nineteenth century, scientists had discovered how harmful some bacteria are, causing disease and infecting wounds. Chapter 27 tells the story of how their ‘germ theory’ of disease became accepted.

Straight away, they began looking for drugs that could kill the invading bacteria without harming the cells of the body. It was a quest for ‘magic bullets’, said the German doctor Paul Ehrlich (1854–1915) He came up with a drug to treat syphilis, but it contained arsenic, which is poisonous, so it had to be used very carefully and had serious side effects.

In the mid-1930s, the German pharmacologist Gerhard Domagk (1895–1964) began to use the chemical element sulphur. (Pharmacology is the study of drugs.) He produced a compound called Prontosil, which was effective against several kinds of disease-causing bacteria. One of the first experimental patients was his daughter, whose hand had become infected with Streptococcus, a nasty bacterium that causes infections of the skin.

Doctors had said that the only way to try and save her from the life-threatening infection was to amputate her arm. Prontosil successfully cleared up the infection. It was also effective against scarlet fever and a fatal bacterial infection called puerperal fever, which killed women after they had given birth. Prontosil began to be widely used from 1936 and contributed to a dramatic fall in the number of these deaths. It and other sulphur-containing drugs were among the best drugs doctors could prescribe against certain bacteria. Domagk won a Nobel Prize in 1939 (though at the time the Nazis forbade Germans from accepting it).

The next Nobel Prize for the discovery of a drug came in 1945. Three men, the Scot Alexander Fleming (1881–1955), the Australian Howard Florey (1898–1968) and the German refugee Ernst Chain (1906–79), shared the prize for the discovery of penicillin, the first ‘antibiotic’ drug. An antibiotic is a substance produced by one micro-organism that can kill other micro- organisms. It harnesses for our benefit something that happens in the natural world all the time. Penicillin was purified from a natural source, the micro-organism Penicillium notatum, a mould or kind of fungus. You can see small rings of blue fungi growing on old, mouldy bread. If you like to eat mushrooms, you are of course eating another kind of fungus. There are thought to be 1.5 million species of fungi on our planet. They have complex life-cycles including a spore stage, which is similar to the seeds of plants. Today antibiotics can also be created in the laboratory rather than from a natural source, but it’s the same basic idea.

Penicillin’s story begins in the 1920s. Like all the best stories, there are several versions. One has it that in 1928 a spore of the mould drifted through an open window in Alexander Fleming’s laboratory at St Mary’s Hospital in London. What he noticed was that some of the bacteria he was growing on a Petri dish stopped growing where the spore had landed. He identified the spore as coming from Penicillium, did more work with it and published his results to share them with other bacteriologists. But he couldn’t see how to make enough of whatever the spore had produced to be of any use. So he left it as a curious, possibly promising, laboratory observation.

A decade later, Europe was plunged into the Second World War.

War always brings outbreaks of infectious diseases, among soldiers and civilians alike. So the pathologist Howard Florey, who had settled in England, was asked to look for effective drugs against infections. One of his associates, Ernst Chain, began reading everything he could find, including Fleming’s old paper. Next he tried extracting the active substance produced by the penicillin mould. In March 1940, their laboratory assistant, Norman Heatley (1911–2004), found a better way of obtaining this promising substance. Working in difficult wartime conditions, they had to make do with few resources, using bedpans and milk churns as containers for growing the solutions of mould. Nevertheless, they obtained some relatively pure penicillin. Tests on mice showed that it was very effective in controlling infections. Purifying the miraculous substance was extremely difficult: it took a tonne of a crude solution of penicillin to produce two grams of the drug. Their first patient was a policeman who had become infected after a scratch from a rose thorn. When given the drug, his condition improved briefly. They filtered his urine to recover the precious drug, but he died when the supply ran out.

Wartime Britain did not have the industrial resources to produce enough penicillin. So in July 1941, Florey and Heatley flew to the USA to encourage American pharmaceutical companies to take this on. Florey was an old-fashioned scientist. He believed that discoveries such as theirs were for everyone’s good and should not be patented. (Patents are a way of protecting inventors’ ideas and making sure that no one else can copy them.) The Americans had other ideas. Two companies in particular developed special methods of producing penicillin on a vast scale. To make back all the money they had invested in the research, they took out patents, which meant that no one else could use their methods to make the drug. By 1943, penicillin was available for military and some civilian use. It was shown to be effective against the Streptococcus bacterium, as well as some of the organisms that cause pneumonia, a lot of wound infections and some sexually transmitted infections.

Soon, enough was being made to ensure that those who could be treated would live, when otherwise many would have died, especially the soldiers fighting to end the war. While Florey and his team were busy with penicillin, Selman Waksman (1888–1973) was working on the antibiotic properties of bacteria. Waksman had come from Ukraine to the United States in 1910. He was fascinated by the micro-organisms that live in the soil, and had seen how some of these micro-organisms killed other bacteria in the soil. From the late 1930s, he tried to isolate compounds from these bacteria that could act as antibiotics. With his students, he isolated some effective substances, but they were too toxic to be used in humans. Then, in 1943, one of his students isolated Streptomyces, and the drug streptomycin was made from it. It proved effective and not too harmful to patients.

Amazingly, it worked against the bacterium that causes tuberculosis, that deadly disease that had killed more people than any other disease during much of the nineteenth century. Although it was less common in the West by the 1940s, it was still taking its toll every- where. Its victims were often young adults, leaving loved ones bereft, and children without their parents.

Penicillin and streptomycin were just the beginning of a whole range of antibiotics and other chemicals that cured infectious diseases. In the years after the Second World War, they made people very optimistic about the power of medicine to combat and even eradicate such disease. Fewer people in the West died from infections, and with the exception of new infections such as AIDS, this has continued. Without doubt, many young people in the twenty-first century can live healthier lives than their parents or grandparents.

But if the optimists of the 1960s had looked carefully at the story of an earlier ‘miracle drug’, they might have realised miracles are unlikely. That earlier drug was insulin, used to treat diabetes since the 1920s. Diabetes is a horrible affliction. If it is not treated, the body wastes away, its victims become painfully thin, are always thirsty, urinate frequently and eventually sink into a coma before dying. It mostly affected young people, who died within a couple of years. It is a complicated disease, but the special cells that produce insulin naturally in the pancreas – an organ near the stomach – stop doing their job. Insulin is a hormone, a chemical ‘messenger’, and it keeps the correct amount of sugar (glucose) in our blood.

While penicillin originated in a lucky chance, the story of insulin is one of painstaking research into how some parts of the body work. Researchers had already shown the role of the pancreas by removing it from dogs (or other animals) that then suffered a diabetes-like illness. Over the summer of 1921, at the University of Toronto, Canada, Professor J.J.R. Macleod (1876–1935) was away.

A young surgeon called Frederick Banting (1891–1941) and his medical student assistant Charles Best (1899–1978) conducted a series of simple experiments. With the help of a biochemist, James Collip (1892–1965), they managed to extract and purify insulin from the pancreases of dogs. When they gave the insulin to their experimental animals that had had their pancreases removed, they recovered from their diabetes.

Insulin was described as a ‘force of magical activity’. It could literally bring the victims of this kind of diabetes back from certain death. One of them was fourteen-year-old Leonard Thompson, the first person treated with insulin injections in 1922. Leonard was severely underweight and was confined to a hospital bed because he was so weak. The injections brought down his blood sugar towards normal levels, he gained weight, and was able to leave hospital with his syringe and insulin supply.

One year later, Banting and Professor Macleod were awarded the Nobel Prize, and shared the prize money with Best and Collip. Such speedy recognition showed how important everyone considered their work to be. Insulin was very important. It offered years of extra life to many young people who would otherwise have died.

What it didn’t offer was a normal life. Diabetics had to monitor their food, give themselves regular insulin injections, and frequently test their urine for sugar. This was much better than nothing. But a decade or two later, many of these early diabetics began to suffer from other health problems: kidney failure, heart disease, difficulties with their eyesight and painful ulcers on their legs that refused to heal. Insulin changed an acute fatal disease into a lifelong problem to be managed forever. The same problems also apply to the other kind of diabetes, which occurs mostly in overweight adults and is called Type II diabetes. It is now the most common form, and more and more people suffer from it. Modern diets contain too much sugar and refined foods, and obesity has become a global epidemic. Medical science has helped: pills can lower the blood sugar. But Type II diabetics face the same kind of problems in later life. Medicine is simply not as good as our own natural systems at regulating the level of sugar in our bodies.

Nature has shown us that we can’t rely on penicillin and other antibiotics. These drugs are still useful, but the bacteria that cause disease have adapted to them. Darwin’s discovery of natural selection applies throughout nature, and many bacteria have developed defences against the antibiotics that used to kill them. The Staphylococci and the tubercle bacillus (which causes tuberculosis) have shown themselves to be especially adaptable. Like all other living creatures, their own genes sometimes mutate, and the mutations that help them to survive are the ones that pass on to the next generation. Treating infections has now become a kind of cat-and- mouse game: developing new drugs to attack germs that evolve to resist almost anything we can throw at them. One recent problem is MRSA (methicillin-resistant Staphylococcus aureus). S. aureas is one of those bacteria that normally lives on our bodies, even if it may cause the usual slight infection after a scratch. Its antibiotic- resistant form is dangerous. It is commonly found in hospitals because so many antibiotics are used there, and the bacteria that do survive are often those that have developed resistance. And it is not just bacteria that fight back against our attempts to control disease.

Some of the parasites that cause malaria are resistant to almost all the drugs we have. We now know that bugs tend to develop their resistance when patients don’t finish taking the full course of their medicine, or when the wrong dose is given. It also happens when the drugs are misused: antibiotics are often given to patients inappropriately, for infections, colds or sore throats caused by viruses. (Antibiotics fight bacteria, and can do nothing against viruses.) If your dose of antibiotics is not enough to kill the disease-causing bacteria, the treatment can instead help resistant bacteria to survive. Those bacteria might in the future cause untreatable disease.

Despite all these problems, doctors have many more powerful and effective drugs than ever before. Some, like insulin, control rather than cure the disease, but all these modern medicines have given people in the ‘developed’ world the chance to live longer lives. In many countries in the ‘developing’ world, too, life expectancy has also risen. But there, serious problems remain: it is not always easy to see a doctor, get enough to eat, drink clean water, or live in a comfortable home. Since the early 1990s, the gap between rich and poor has widened in rich countries, and has widened too between the rich and the poor countries. This shouldn’t be.

Today it costs a lot of money to provide medical care. We use a lot of clever technology to diagnose illness and then treat it. Developing and testing new drugs now takes much more money than it did to produce penicillin. So we need to look after ourselves if we can. No matter how amazing the medicines, it is still true that ‘prevention is better than cure’.