"I will lift up mine eyes to the pills."
Malcolm Muggeridge describing the age of modern medicine in a 1962 newspaper column
For those living in industrialized nations Muggeridge's paean to the power of pills is no hyperbole. The 20th century has seen an almost complete transformation in our understanding and treatment of infectious disease. Successful medications have reconfigured our approach to most bacterial and fungal infections while effective vaccines have been developed against infections such as smallpox, measles, typhoid fever, rubella, diphtheria, tetanus, yellow fever, pertussis and polio.
In developing nations the story has been tragically different. Separated by poverty, geography, scarcity of antimicrobials and a lack of political will on the part of governments whose priorities may not be public health, individuals living in such areas have long been consigned to the health care margins. Nevertheless, the fact that these tools against infection exist and are still effective constitutes the health care miracle of the last 500 years.
Apart from smallpox vaccines, quinine and penicillin, few of these breakthroughs have been accidental discoveries, stumbled upon by chance. Instead, they are the result of dedicated scientific effort and vast amounts of money, time and human labour expended over decades.
Magic Bullets and Miracle Drugs
From German microbiologist Paul Ehrlich's seminal theory of the "magic bullet" as a metaphor for cures wrought by heavy metals (eventually used as a widespread treatment for parasitic and sexually-transmitted infections) to the discovery and eventual release of penicillin, the history of antimicrobial research is replete with victories won against almost insurmountable odds. Among Ehrlich's contributions was the first use of arsenic (Salvarsan) in for the treatment of syphilis and the first description of the body's immunological response to infectious organisms.
In 1928, British scientist Alexander Fleming pushed the frontiers even further when he observed the antibiotic effects of a mould that later became known as penicillin. The product of this seemingly humble fungus proved so effective in fighting infections formerly deemed fatal, that scientists dubbed it a "miracle drug". Fleming's discovery triggered a health care revolution unprecedented in the annals of medical science. From that one initial specimen flowered an entire family of penicillin-based antibiotics.
Later discoveries included streptomycins, tetracycline, quinolones, antifungals, antiparasitics and, more recently antivirals. These drugs collectively known as antimicrobials have saved the lives of millions, reduced illness, and allowed the development of complex surgical procedures previously considered too hazardous due to post-operative infection. At the same time antimicrobials have prevented disability such as deafness, blindness, and disfigurement from such diseases as leprosy and elephantiasis.
In 1927 German scientist Gerhard Domagk upped the ante with his research into sulfa compounds after he discovered a brilliant red dye, known as Prontosil red, cured mice injected with lethal doses of haemolytic streptococci. From mice, Domagk graduated to his own daughter whom he successfully relieved of a persistent streptococcal infection. Prontosil was eventually used to treat puerperal fever slashing the mortality rate from 20% to 4.7% in Germany. The Nobel Institute was so impressed by his discoveries that it belatedly awarded him the prize during a special 1947 ceremony in Sweden after the Second World War.
Progress followed hard on the heels of Domagk's ground-breaking research. In 1938 a British team led by A.J. Evans developed yet another sulfonamide sulfadiazine 693, later called sulfanilamide that also proved effective in treating streptococci including pneumococci. Winston Churchill - among many - can credit the drug with prolonging his life after falling ill with pneumonia at a critical juncture during the Second World War. In 1940, Russian émigré Selman Waksman isolated a fungus that eventually led to the development of the anti-tuberculosis drug streptomycin a discovery that garnered him the Nobel Prize. Many scientists believed that tuberculosis had finally been conquered with the development of isoniazid. Like other anti-TB medications however, the new drug easily encouraged resistance in the ever-resilient bacilli. In 1957, this dilemma was solved when a Lepetit research team headed by Piero Sensi discovered another anti-TB family of drugs later released under the name rifampicin. Used in combination with streptomycin and isoniazid in a strategic long-term therapy, this chemotherapeutic triad has successfully (that is, until recently) contained a dreaded disease once characterized as "galloping" consumption.
A Lull in the Action
After a flurry of discoveries between 1930 and 1970, the past 30 years have witnessed fewer discoveries in the fight against infectious killers. The 1970s brought acyclovir potent against herpes zoster (shingles), cold sores and genital herpes. This was the first time an antiviral successfully stymied pathogen replication without proving toxic to the host.
With the advent of HIV, the discovery and development of antiretrovirals has meant yet another leap forward in the fight against contagious diseases. The introduction of zidovudine (AZT) in 1985 was followed a decade later by the first protease inhibitor.
Nowadays, the cache of antimicrobial weapons targeting infectious disease has swollen to an impressive arsenal of more than 150 compounds. The cost, however, has been huge. Pharmaceutical companies routinely spend some US$ 500 million on research and development for every new compound that makes it to market. For every success, there are many failures. Every pathogen that develops resistance represents the dismantling of a legion of hopes, dreams and dollars.
Today drug resistance is already nibbling away at medications that took decades to develop. In clinical practice, microbial resistance has turned up during treatments with idoxuridine for herpes simplex, keratitis, acyclovir for mucocutaneous HSV infection, rimantidine for influenza and ganciclovir for CMV disease.
It's not a Breakthrough Unless it's Widely Available
Although antimicrobial drugs have saved the lives and eased the suffering of millions, health care benefits have not extended fully to those in the developing world. Extreme poverty, poor sanitation, malnutrition, inadequate drug access, poor health care delivery and ongoing conflicts represent major obstacles to healthy development.