In the wake of the tragedy of World War II, a cure for TB was hailed as a timely miracle. Selman Waksman was catapulted into the limelight and revered as the latest medical hero and disease fighter. He toured the world and his face appeared on the cover of Time magazine. But amidst all of the publicity no mention was made of Albert Schatz. Then in 1950—a year that Waksman describes in his 1954 autobiography, My Life with the Microbes, as the darkest of his whole life—Schatz sued for royalties as a co-discoverer of streptomycin.[33]
This was not the first time, nor would it be the last, that the head of a laboratory would receive the recognition for the work done by an assistant under their aegis. In this case it was the diligent PhD student Schatz who had brought Streptomyces griseus to his professor’s attention. In more recent times, Waksman has been accused of highlighting his own role to reporters while not acknowledging Schatz’s part in the discovery. However, Albert Schatz and Selman Waksman jointly signed the patent for streptomycin.
Supposedly, it was rumours that Waksman was secretly providing information to a pharmaceutical company and receiving large royalties from the patent of streptomycin in return that was the catalyst for Schatz taking legal action. Waksman reluctantly agreed to settle and Schatz was declared co-discoverer and awarded a small share of the royalties. With his much larger share Waksman established a Foundation for Microbiology and gave a small percentage to the other laboratory workers at Rutgers.
In 1952 when Waksman was awarded the Nobel Prize for Physiology or Medicine the Nobel Committee emphasised that his contribution to the advancement of medicine was paramount, even though he was neither a physiologist nor a physician, and that they as physicians regarded him as ‘one of the greatest benefactors of mankind’.[34] It is said that at that time the committee had not heard of Albert Schatz.
Totally overshadowed after the discovery, Albert Schatz did receive his doctorate from Rutgers in 1945 and then spent his life working in various universities. During his academic life he published several books and more than 700 scientific papers. In 1994, Dr Schatz was awarded the Rutgers University Medal, the university’s highest honour. It was for his work on streptomycin, a public acknowledgment of his discovery of a cure for TB. Albert Schatz passed away in 2005, 30 years after Selman Waksman had died suddenly from a cerebral haemorrhage on 16 August 1973.
Selman Waksman’s tombstone at Wood Hole, Massachusetts, is inscribed with the words ‘Out of the earth shall come thy salvation’.35 The research carried out by Selman Waksman, Albert Schatz and their colleagues to produce streptomycin has indeed brought salvation to millions of people. It is still a mainstay of TB therapy and is effective against a number of bacteria, including some that are resistant to other antibiotics. Because resistant tubercle bacilli emerge during treatment, showing how determined they are to survive, antibiotics are usually used in combination with one or more drugs. Among these is isoniazid (INH), which kills the organisms and renders them non-infectious. The introduction of INH in the 1950s brought about the closure of separate TB hospitals.[36]
ANTIBIOTICS AND TUBERCULOSIS TODAY
The success of the antibiotic drugs penicillin and streptomycin has spawned a huge pharmaceutical industry that in turn has led to the ‘commercialisation’ of cures. Gone are the days of scientists experimenting in home laboratories and sharing their discoveries with the world at large. Sophisticated private laboratories have been set up almost in competition with those in universities and other non-profit institutions, and although new experimental drugs are being developed, mass-producing them is the domain of multinational drug companies. The first entirely synthetic antibiotic, an effective treatment for typhoid fever, was developed by the drug company Parke-Davis in 1949.
The fight against bacteria is ongoing. Many are becoming resistant to the drugs we use to attack them, including penicillin. The percentage of pneumococcal strains that are drug-resistant is on the rise and, in our chemotherapeutic era, thousands of hospital patients die every year because of drug-resistant bacterial infections. Five decades ago with the advent of streptomycin it was thought that by the year 2000 tuberculosis would have been eradicated and perhaps even be extinct. In 1965 Waksman published a book on the discovery of streptomycin, the title of which, The Conquest of Tuberculosis, reflects the belief at the time that TB would be defeated.[37] TB, however, is making an impressive comeback. New strains of the tuberculosis bacteria that are resistant to previously effective treatments surfaced in the 1980s and have become increasingly prevalent in poor and developing countries. The return of tuberculosis and the threat it poses is highlighted every year on 24 March, World Tuberculosis Day, which commemorates Robert Koch’s discovery in 1882 of Mycobacterium tuberculosis.
A number of factors have contributed to the spread of TB in recent decades. In some countries, funds previously used to control the disease have been diverted to treat other public health problems, including HIV/AIDS. The emergence of this modern incurable disease which attacks the body’s immune system has had a profound effect in two ways on the reemergence of TB. People with a damaged immune system are 30 times more vulnerable to tuberculosis and, conversely, TB can accelerate HIV in a person who has both diseases.[38] Increased poverty, homelessness, travel and migration have also contributed to the spread of TB. Also, the efficacy of current TB therapies is limited because people with TB need a daily cocktail of drugs for up to six months which means keeping up with long-duration therapies is difficult.
The frightening statistics speak for themselves. In Britain in 1955 tuberculosis cases numbered around 50,000 but had dropped significantly to around 5500 by 1987 due to the availability of antibiotics. However, at the beginning of the new millennium there were over 7000 confirmed cases. Tuberculosis infects around 8 million people annually and kills 2 million of those infected. Virtually all TB deaths are in the developing world, where the victims are mainly young adults. Half of all new cases are in six Asian countries: Bangladesh, China, India, Indonesia, Pakistan and the Philippines; and a staggering 29 per cent of all TB cases occur in Africa where AIDS is also rampant.
In 1993 the World Health Organization, alarmed by the re-emergence of TB with multi-drug-resistant strains, declared a ‘global health emergency’ and introduced a program called DOTs.[39] The acronym, standing for ‘directly observed treatment, short-course’, refers to the direct observation by trained personnel of TB sufferers taking their medications. Since 1995, some 183 countries have adopted DOTs and 22 million TB patients have been treated under the program.
In 2006 at an extraordinary conference convened in South Africa alarm bells rang when the WHO revealed that they were not winning the war against the new strains of TB. Of the 9 million cases of tuberculosis reported in 2005, 180,000 could be classified as ‘extreme drug-resistant’ and the WHO reclassified TB, along with HIV/AIDS and malaria, as a ‘priority disease’.
The crusade to find better weapons to defeat TB has been taken up by the Stop TB Partnership which is comprised of more than 400 entities, including international organisations, individual countries, donors from the public and private sectors, governmental and non-governmental organisations and individuals. In January 2006, at the World Economic Forum in Davos, Switzerland, the WHO Stop TB Partnership announced a new US$56 billion strategy, ‘The Global Plan to Stop TB 2006–2015’. The aim is to stop the spread and reverse the incidence of TB, which now kills 1.7 million people each year, by 2015, by implementing effective TB care around the world and by assessing current research needs for the development of new drugs, vaccines and diagnostics. If fully implemented, the global plan will treat 50 million people for TB, halve TB prevalence and death rates and save 14 million lives.
As the saga continues, the best approach to preventing and combatting TB is still considered to be through continuing vaccination programs, but the search for new treatments has been taken up by various entities including public–private partnerships, government-funded researchers, industry and philanthro
pies. In partnership with Stellenbosch University in South Africa, the drug company GlaxoSmithKline is involved in a program to help identify ‘biomarkers’ in people who may respond to specific treatments.[40] Biomarkers can be used to predict whether or not patients will respond quickly to treatment or if TB is likely to recur. This kind of research certainly reflects the Koch tradition.
Despite the cumulative work of all those who have waged war on tuberculosis and the extraordinary scientific discoveries made by Robert Koch, Albert Calmette and Camille Guérin, and Selman Waksman and Albert Schatz, the curable White Plague remains invincible. It continues the struggle for its own survival while taking a toll of 5000 lives a day. It is estimated that every second someone in the world becomes infected with TB and one person dies every 15 seconds. There may yet be many challenges ahead before tuberculosis is finally vanquished.
POSTSCRIPT
There is no statute of limitations on the amount of time it can take to thank someone for saving your life. Fifty years after the discovery of streptomycin, on 21 March 1996, Senator Bob Dole, who was then a US presidential candidate, sent a letter to Albert Schatz written on United States Senate letterhead. ‘During my recovery after World War II,’ wrote Dole, ‘streptomycin defeated an infection that threatened my life.’
In 1997, a year after Albert Schatz received the letter from Bob Dole he was contacted by a German-born woman, Inge Auerbacher, who 50 years after the event had read an article about Schatz being the co-discoverer of streptomycin and the controversy surrounding the events of that time. During World War II, Inge had been a prisoner at the Terezin concentration camp in Czechoslovakia where she contracted tuberculosis. After the war, as a refugee she emigrated to the United States where she was cured with the new, life-saving drug. Inge, like so many others wanted to express her gratitude to Albert Schatz. The two became friends and the product of that friendship is a book they co-authored, Finding Dr. Schatz, the story of a scientist who changed the world and a woman who lived because of him.
Until the end of his life Albert Schatz took quiet pleasure in the fact that he was still receiving letters from people all over the world who thanked him for saving their lives.
CHAPTER 4
OF RATS AND FLEAS
SOLVING THE RIDDLE OF THE BLACK DEATH
How many valiant men, how many fair ladies, breakfast with their kinfolk and the same night supped with their ancestors in the next world! The condition of the people was pitiable to behold.[1] Giovanni Boccaccio
Bubonic plague has an infamous place in history. No other disease can lay claim to its apocalyptic persona. A ferocious killer that can lay dormant for centuries, its horrific symptoms and pervasive, destructive consequences meant that the plague was feared far more than its nearest rival, smallpox. Bubonic plague was a scourge of epic proportions that arose sporadically and raced through mediaeval Europe and Asia, leaving countless millions dead in its wake. The great plague that devastated Europe in the fourteenth century was the most deadly of all and was aptly named the ‘Great Mortality’, the ‘Great Pestilence’ and the ‘Black Death’.
In 1894, when plague broke out in Hong Kong, two research teams set off on a race to find a cause. The leaders of those teams, the eminent Japanese researcher Shibasaburo Kitasato and the unorthodox French bacteriologist Alexandre Yersin, were opposites in personality and in their scientific approach, and to this day controversy over the discovery of the micro-organism that causes plague persists. Without a cause there could be no cure and the development of a preventive vaccine for bubonic plague by the bacteriologist, Waldemar Haffkine, in a makeshift laboratory in India in 1896 is another dramatic story in the life of the plague.
***
To appreciate the enormity of the contribution made by these three scientists it is necessary to become familiar with the horror of the rapacious Black Death itself. Since ancient times plagues have decimated societies. An account in the Hebrew bible of a plague that struck the Philistines around the eleventh century BC describes symptoms which are consistent with bubonic plague, in particular large buboes, inflamed and painful swellings in the groin, armpits or neck. Also indicative, was that this plague followed an excessive number of rat deaths; throughout history there has been a link between rat plague and bubonic plague. The reason for this was not established until the early 1900s when it was proven that plague was carried by rodent fleas.
In 430BC the Greek historian Thucydides wrote about a disease that struck Greece during the Peloponnesian War. In Athens alone, one-third of the population died, including Pericles, Athens’ leader during its golden age.[2] With advances in science it is now possible for scientists to give a retrospective diagnosis. Cases have been made for the Greek plague being smallpox, typhus, measles and bubonic plague. A recent study of the DNA found in the dental pulp of plague victims from that time has led some scientists to conclude the disease was typhoid while others dispute this, suggesting that the DNA tests were flawed.
In the first century AD a plague broke out in Libya, Egypt and Syria and a Greek anatomist recorded the symptoms—acute fever, pain, agitation and delirium—in addition to the typical buboes behind the knees and around the elbows, again suggesting bubonic plague. There is no debate, however, about a plague that began in 540AD in Pelusium in Egypt. It was bubonic plague and by 542AD it had reached Constantinople, modern-day Istanbul. Ships from Egypt bringing massive amounts of grain to the bustling city also carried a cargo of contagion, rats and fleas, which soon infested the massive public granaries.
Called the Plague of Justinian, it is the first recorded pandemic in history. At its peak in Constantinople, 5000 people died daily and ultimately almost half of the city’s inhabitants were wiped out. The pandemic was catastrophic, killing up to a quarter of the population of the eastern Mediterranean.[3] In 588AD a second major wave of plague spread through the Mediterranean into what is now France. The death toll has been estimated at a staggering 25 million people.
It was eight centuries later that the Great Mortality swept through Asia and Europe, this time killing approximately one-third of the entire population and changing the course of history. It is almost impossible to conceive of death on this gargantuan scale. The Black Death began its killing spree in Constantinople in 1334 and spread inexorably through Europe and beyond for the next twenty years. It arrived in Alexandria, Cyprus and Sicily in the autumn of 1347 and by winter was rampaging through mainland Italy.
Giovanni Boccaccio’s book, The Decameron, is a fictional work which opens with a description of the outbreak of plague in Florence in 1348.[4] Boccaccio describes how the first sign of having caught the plague was developing lumps in the groin or armpits. Following this, livid black spots appeared on the arms, thighs and other parts of the victim’s body. He noted that people usually died within three days of the onset of symptoms.
An observation that the disease lay dormant for a while before infected people became symptomatic led the governors of Venice to pass a decree in 1348 that ships sailing into the harbour be isolated to allow time for the Black Death to reveal itself. A period of 30 days, trentina in Italian, was initially mandated but was later extended to 40 days, quarantine. This is the origin of the English word ‘quarantine’.[5] By 1423 a dedicated quarantine station had been established on an island near Venice in an attempt to prevent the disease re-entering the city.
In 1348 the Black Death reached France and Germany, hit London in September and then spread rapidly through Scotland, Wales and Ireland. It is estimated that 1.5 million of England’s 4 million people died. The plague was relentless, an invader like no other. Even the northern countries of Scandinavia were not immune. The plague found its way to Norway and then embarked on a journey through Eastern Europe. By 1351 bubonic plague had galloped across Europe and entered Russia.
THE NATURE OF THE PLAGUE
It is now known that there are three human forms of the disease commonly known as bubonic plague—bubonic, septicaemic and pneum
onic plague.[6] Even though the first sign of having contracted plague is usually flu-like symptoms with all three forms, they do differ symptomatically and in the route of infection. This could account for the different descriptions of plague in historical accounts. The bubonic form is spread by fleas which deposit bacteria into a victim’s lymphatic system when they bite. The bacilli then travel to the nearest lymph node, which becomes inflamed. After an incubation period of three to seven days the initial symptoms become evident: chills, fever, diarrhoea, headaches and painful swelling in infected lymph nodes where the bacteria replicate in high numbers in the buboes. Death can occur in less than a week after infection. Historically, 60 per cent of all people who were infected with plague had the bubonic type and the mortality rate ranged between 30 and 70 per cent.
Pneumonic plague, which is extremely contagious, is the most virulent but least common type of plague and in approximately 95 per cent of cases is fatal if untreated. It is not transmitted by fleas but is a secondary infection from the bubonic form spread from human to human. The bacilli are present in the water droplets from coughs or sneezes and they can also be present on clothing. The incubation period for pneumonic plague is usually between two and four days, but can be as little as a few hours. Symptoms include headache, weakness and coughing up blood from the respiratory tract. When the bacilli reach the lungs, victims develop severe pneumonia and death follows rapidly within one to six days.
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