Not to be sneezed at: How we found the cause of hay fever

The recent good weather in the UK has seen barbecues dusted off and people taking to the garden. Cue sneezes and runny eyes and noses. Yes, with the nice weather comes hay fever. Hay fever or allergic rhinitis affects somewhere between 26% and 30% of people in the UK. Symptoms include sneezing, swelling to the conjunctivae and eyelids, runny nose (rhinorrhea) and a blocked nose. Sometimes it can result in hospital admissions and death.

We all know that pollen is the cause behind hay fever. Pollen in the air is inhaled and trapped by hairs in the membrane of the nostrils. There the body responses to proteins on the surface of the pollen. These proteins are called allergens. Different types of pollen have different allergens. A type of white blood cell called a B cell produce an antbody called immunoglobulin E or IgE specific to a particular allergen. The IgE then binds to a type of cell called mast cells. These are found in some of the most sensitive parts of the body, including the skin, blood vessels, and respiratory system. Mast cells contain 500 to 1500 granules containing a mix of chemicals including histamine. This binding causes mast cells to release their histamine. It is histamine which causes the symptoms of hay fever by binding to histamine receptors throughout the body. Antihistamines work by binding to these receptors instead of histamine and blocking them.

But two centuries ago hay fever was a mystery. It took a couple of doctors with sneezing and blocked noses to research the problem to link it to pollen. This musing is their story.

The first description of what we would call hay fever came in 1819 in a study presented to the Medical and Chirurgical Society called ‘Case of a Periodical Affection of the Eyes and Chest’. The case was a patient called ‘JB’, a man “of a spare and rather delicate habit”. The patient was 46 and had suffered from cattarh (blockage of the sinus and a general feeling of heaviness and tiredness) every June since the age of eight. Numerous treatments including bleeding, cold baths, opium and vomiting were tried to no avail. What makes this study even more interesting is that ‘JB’ was the author, John Bostock, a Liverpool-born doctor who was not afraid to experiment on himself.

View fullsize

John Bostock

Bostock tried to broaden his research by looking for more sufferers, He found 28. In 1828 he published his work and called the condition, “catarrhus aestivus” or “summer catarrh”. After Bostock published an idea spread amongst the public that the smell of hay was to blame. This led to the colloquial term “hay fever”. Bostock didn’t agree and felt that the heat of summer was to blame. He rented a clifftop house near Ramsgate, Kent for three consecutive summers which helped. In 1827 The Times reported that the Duke of Devonshire was "afflicted with what is vulgarly called the Hay-fever, which annually drives him from London to some sea-port". In 1837 a few days before King William IV died the same paper reported that the king had "been subject to an attack of hay fever from which he has generally suffered for several weeks".

View fullsize

Charles Harrison Blackley

In 1859 another doctor, Charles Harrison Blackley, sniffed a bouquet of bluegrass and sneezed. He was convinced that pollen was to blame and methodically set out to prove it. He experimented on himself and seven other subjects. He first applied pollen to the nose and noted how it produced the symptoms of hay fever. He then covered microscope slides with glycerine and left them in the sunshine under a little roof for 24 hours before removing them and studying them under a microscope. He was then able to count the number of pollen granules in the air. In noted the prevalence of grass pollen in June, the time when symptoms were at their worse. To prove that wind could carry pollen great distances he then put similar slides up in kites to altitudes of 500 to 1500 feet. He discovered the slides there caught an even greater number of granules than at the lower level. In 1873 he published his work, Experimental Researches on the Causes and Nature of Catarrhus aestivus.

Fast forward to 1906. An Austrian paediatrician, Clemens von Pirquet, notices that if patients vaccinated against smallpox with horse serum are given a second dose they react quickly and severely. He correctly deduces that the body ‘remembers’ certain substances and produces antibodies against them. He calls this ‘allergy’. In the 1950s mast cells are discovered. In 1967 IgE is identified. The mechanism of allergic rhinitis and other allergies is finally understood. With this came new lifesaving treatment such as the EpiPen.

For a lot of us hay fever is an annual nuisance. But as we reach for the antihistamines and tissues we should thank a couple of 19th century sufferers who happened to turn their symptoms into a life’s work and, as a result, make hay fever that bit easier for us.

Thanks for reading

- Jamie

Medical school medieval style

Quacks who Quaff · Episode 01: The history of warfarin, the first medical schools and the 2013 Salice Salentino Riserva

We discuss the first Medical schools (and review wine) in the first episode of the Quacks Who Quaff podcast.

View fullsize

Philosophia et septem artes liberales, the seven liberal arts. From the Hortus deliciarum of Herrad of Landsberg (12th century)

View fullsize

It’s tempting to see medieval doctors as a group of quacks and inadequates stuck between the Dark Ages and the enlightened Renaissance. Certainly, it was a dangerous time to be alive and sick. In the twelfth century the majority of people lived in rural servitude and received no education. Average life expectancy was 30-35 years with 1 in 5 children dying at birth. Healthcare policy, such as it was, was based on Christian teachings; that it was everyone’s duty to care for the sick and poor. To that end medieval hospitals more resembled modern day hospices providing basic care for the destitute and dying with nowhere else to go. Education and literacy were largely the preserve of the clergy and it was in monasteries where most hospitals could be found. The Saxons built the first hospital in England in 937 C. E, and many more followed after the Norman Conquest in 1066, including St. Bartholomew's of London, built in 1123 C.E. The sick were cared for by a mix of practitioners including physicians, surgeons, barber-surgeons and apothecaries. Of these only physicians would have received formal training. The vast majority of people providing healthcare were practising a mix of folklore and superstition.

However, it was in the early medieval period that the first medical schools were formed and the first ever medical students went to university. In this musing I’m looking at what medical education was like in the Middle Ages at the most prestigious university of the age as well as the common theories behind disease and cure.

The Schola Medica Salernitana was founded in the 9th century in the Southern Italian city of Salerno. In 1050 one of its teachers Gariopontus wrote the Passionarius, one of the earliest written records of Western Medicine as we would recognise it. Gariopontus drew on the teachings of Galen (c. 129-199 CE) and latinised Greek terms. In doing so he formed the basis of several modern medical terms such as cauterise. Another early writing mentioned a student: “ut ferrum magnes, juvenes sic attrahit Agnes” (Agnes attracts the boys like iron to a magnet”). This shows that the first medical school in the world had female students.

The medical school published a number of treatises such as work by a woman called Trotula on childbirth and uterine prolapse and work on the management of cranial and abdominal wounds. In head wounds it was recommended to feel for and then surgical remove pieces of damaged skull. In abdominal trauma students were advised to try to put any protruding intestine back inside the abdomen. If the intestine was cold it was to be warmed by wrapping the intestines of a freshly killed animal over it beforehand with the wound being left open before a drain was inserted.

Anatomy remained based on the work of Galen. Doctors were encouraged to dissect pigs as their anatomy was felt to be the most closely related to humans. However, the teachers were more innovative when it came to disseminating knowledge, in verse form often with a spice of humour. 362 of these verses were printed for the first time in 1480 and would increase to 3520 verses in a later edition. By 1224 the Holy Roman Emperor Frederick II made it obligatory that anyone hoping to practice Medicine in the kingdom of Naples should seek approval from the masters of Salerno medical school.

But Salerno medical school did not teach any other subjects and so did not evolve into a studium generale or university as they began to spring up. By the fourteenth century the most prestigious medical school in Europe was the University of Bologna, founded in 1088, the oldest university in the world. In the United Kingdom medical training began at the University of Oxford in the 12th century but was haphazard and based on apprenticeship. The first formal UK medical school would not be established until 1726 in Edinburgh.

The University of Bologna was run along democratic lines, with students choosing their own professors and electing a rector who had precedence over everyone, including cardinals, at official functions.

The Medicine course lasted 4 years and consisted of forty six lectures. Each lecture focused on one particular medical text as written by Hippocrates (c. 460-370 BCE), Galen, and Avicenna (c. 980-1037 CE). Students would also read texts by these authors and analyse them using the methods of the French philosopher Peter Abelard to draw conclusions. His work Sic et Non had actually been written as guide for debating contrasting religious text, not scientific work. This reflected how religion and philosophy dominated the training of medical students. The university was attached to a cathedral and students were required to be admitted to the clergy prior to starting their studies. Further to studying Medicine students were also required to study the seven classical liberal arts: Grammar, Rhetoric, Logic, Geometry, Arithmetic, Music and Astronomy.

At the time knowledge of physiology and disease focused on the four humors: phlegm, blood, black bile, and yellow bile. Imbalance of one was what caused disease, for example too much phlegm caused lung disease and the body had to cough it up. This was a theory largely unchanged since its inception by the ancient Egyptians. This is why blood letting and purging were often the basis of medieval medicine. The state of imbalance was called dyskrasia while the perfect state of equilibrium was called eukrasia. Disease was also linked to extremes of temperature and personality. For example, patients who were prone to anger or passion were at risk of overheating and becoming unwell. Patients would also be at risk if they went to hot or cold places and so doctors were taught to advise maintaining a moderate personalty and avoiding extreme temperatures.

Diet was taught as important to prevent disease. During blood letting doctors were taught to strengthen the patient’s heart through a diet of rose syrup, bugloss or borage juice, the bone of a stag’s heart, or sugar mixed with precious stones such as emerald. Other foods such as lettuce and wine were taught as measures to help balance the humors.

Pharmacy was similarly guided by ancient principles. The Doctrine of Signatures dated back to the days of Galen and was adopted by Christian philosophers and medics. The idea being that in causing disease God would also provide the cure and make that intended cure apparent through design in nature. For example, eyebright flowers were said to resemble the human eye, while skullcap seeds were said to resemble the human skull. This was interpreted as God’s design that eyebright was to be used as a cure for eye disease and skullcap seeds for headaches.

God, the planets and polluted air or miasma were all blamed as the causes of disease. When the Black Death struck Italy in 1347 a contemporary account by the scholar Giovanni Villani blamed “the conjunction of Saturn and Jupiter and Mars in the sign of Aquarius” while the official Gabriel de Mussis noted “the illness was more dangerous during an eclipse, because then its effect was enhanced”. Gentile da Foligno, a physician and professor at the University of Bologna, blamed a tremor felt before the plague hit opening up underground pools of stagnant air and water. Doctors therefore were taught to purify either the body through poultices of mallow, nettles, mercury, and other herbs or the air by breathing through a posy of flowers, herbs and spices. De Mussis mentioned that “doctors attending the sick were advised to stand near an open window, keep their nose in something aromatic, or hold a sponge soaked in vinegar in their mouth.” During the Black Death a vengeful God was often blamed. The flagellants were a group of religious zealots who would march and whip themselves as an act of penance to try and appease God. There’s a sense here of being close but not quite. Of understanding that balance is important for the body, that environmental factors can cause disease and that there was something unseen spreading disease. Close but not yet there. The Middle Ages isn’t known as a time of enlightenment. That would come with the Renaissance. But it was not a barren wasteland. It was a time of small yet important steps.

It was in the Middle Ages that laws against human dissection were relaxed and knowledge of human anatomy began to improve. An eminent surgeon of the time Guy de Chauliac would lobby for surgeons to require university training and so started to create equivalence with physicians. Physicians began to use more observations to help them diagnose disease, in particular urine as seen in the Fasciculus Medicinae, published in 1491, then the pinnacle of medical knowledge at the time (this book also contained Wound Man as discussed in a previous musing). The scholarly approach encouraged at medical school led to methodical documentation from several physicians; is is through these writings that we know so much about the Black Death and other medieval illness. An English physician Gilbertus Angelicus (1180-1250) teaching at the Montpellier school of Medicine would be one of the first to recognise that diseases such as leprosy and smallpox were contagious.

Perhaps most importantly, it was in this period that the first medical schools and universities were established. These particular small steps would begin the role of doctor as a scholar and start to legislate the standards required of a physician. This would be an vital first step without which future advances could never have been possible.

Thanks for reading

- Jamie

The world’s first forensic scientist

Our setting is a rural Chinese village. A man is found stabbed and hacked to death. Local investigators perform a series of experiments with an animal carcass looking at the type of wounds caused by different shaped blades and determine that the man had been killed with a sickle. The magistrate calls all of the owners of a sickle together. The ten or so suspects all deny murder. The sickles are examined, all are clean with nothing to give away being a murder weapon. Most in the village believe the crime won’t be solved. The magistrate then orders all of the suspects to stand in a field and place their sickle on the ground before stepping back. They all stand and wait in the hot afternoon sun. It’s an unusual sight. At first nothing happens. Eventually a metallic green fly lands on one of the sickles. It’s joined by another. And another. And another. The sickle’s owner starts to look very nervous as more and more flies land on his sickle and ignore everyone else’s. The magistrate smiles. He knows that the murderer would clean his weapon. But there would be tiny fragments of blood, bone and flesh invisible to the human eye but not beyond a fly’s sense of smell. The owner of the sickle breaks down and confesses. He’s arrested and taken away.

I think it’s safe to say that we love forensic science dramas. They’re all of a type: low lit metallic labs, ultraviolet lights, an array of brilliant yet troubled scientists and detectives dredging the depths of human depravity. Forensic science is the cornerstone of our criminal justice system, a vital weapon in fighting crime. Yet the tale of the flies and the sickle didn’t take place in 2019. It didn’t even take place this century. It was 1235 CE.

This account, the first recorded example of what we would now call forensic entomology, was recorded in Collected Cases of Injustice Rectified a Chinese book written in 1247 by Song Ci, the world’s first forensic scientist. This is his story.

View fullsize

Song Ci from a Chinese Stamp (From China Post)

Song Ci was born in 1186 in southeast China. He was born in a period of China’s history called the Song dynasty (960-1279 CE). This period saw a number of political and administrative reforms including developing the justice system to create the post of sheriff. Sheriffs were employed to investigate crime, determine the cause of death and to interrogate and prosecute subjects. With this developed a framework to investigate crime.

The son of a bureaucrat he was educated into a life of scholarship. First training as a physician he found his way into the word of justice and was appointed judge of prisons four times during his lifetime.

View fullsize

Bust of Shen Kuo (From Lapham’s Quarterly)

This was a time of polymaths. Song Ci was inspired by the work of Shen Kuo (1031-1095) a man who excelled in many different areas of philosophy, science and mathematics. Shen Kuo argued for autopsy and dissected the bodies of criminals in the process proving centuries held theories about human anatomy wrong. In the UK such a practice would not be supported in legislation for another seven centuries.

Song Ci built on Shen Kuo’s work, observing the practice of magistrates and complying recommendations based on good practice. This would form his book Collected Cases of Injustice Rectified; in all fifty-three chapters in five volumes. The first volume contained an imperial decree on the inspection of bodies and injuries. The second volume was designed as instruction in post-mortem examination. The remaining volumes helped identify cause of death and the treatment of certain injuries.

Of note the book outlines the responsibilities of the official as well as what would be considered now routine practices such as the importance of accurate notes and the need to present during the post-mortem (including not being put off by bad smells). There are procedures for medical examination and specific advice on questioning suspects and interviewing family members.

Forensically, the richest part of the text is within the section titled "Difficult Cases". This explains how an official could piece together evidence when the cause of death appears to be something else such as strangulation masked as suicidal hanging or intentional drowning made to look accidental. A pharmacopoeia is also provided to make obscure injuries appear. There is a detailed description of determining time of death by the rate of decomposition and whether the corpse has been moved.

Whilst forensic science has obviously progressed since the work of Song Ci what is striking is how the foundations of good forensic work have not changed. He wrote about determining self-inflicted wounds and suicide based on the direction of wounds or the disposition of the body. He recommended noting tiny details such as looking underneath fingernails or in various orifices for clues of foul-play. Standard procedure today.

Song Ci died in 1249 with little heraldry. However, in modern times there has been an increased appreciation of his work. Just think how few 13th century scientific publications could have been as relevant as his after nearly a millennium.

There is an Asian maxim that “China is the ocean that salts all the rivers that flow into it”. All of us try to contribute in some way to the river of life. Any practitioner or appreciator of forensics must recognise the tremendous contribution Song Ci and his contemporaries made to progress the flow of justice.

Thanks for reading

- Jamie

Those who cannot remember the past: how we forgot the first great plague and how we're failing to remember lessons with Ebola

“Those who cannot remember the past are condemned to repeat it”

George Santayana

To look at the History of Medicine is to realise how often diseases recur and, sadly, how humans repeat the same mistakes. It is easy to look back with the benefit of hindsight and with modern medical knowledge but we must remember how we remain as fallible as our forebears.

Our first introduction to the History of Medicine is often through learning about the Black Death at school. The story is very familiar; between 1347 and 1351 plague swept the whole of Europe killing between a third and two-thirds of the continent. At the time it was felt the end of the world was coming as a disease never before seen took up to 200 million lives. However, this was actually the second time plague had hit Europe. Nearly a thousand years earlier the first plague pandemic had devastated parts of Europe and the Mediterranean. Half the population of Europe were affected. This was Justinian’s plague, named for the Holy Roman Emperor whose reign the disease helped to define. Yet despite the carnage Europe forgot and had no preparation when plague returned.

Between 2014 and 2016 nearly 30,000 people were hit by the Ebola outbreak in West Africa. Our systems were found lacking as the disease struck in a way never before seen. We said we would learn from our mistakes. Never again.

Yet the current Ebola epidemic in the Democratic Republic of the Congo (DRC) is proving that even today it is hard to remember the lessons of the past and how disease will find any hole in our memory. This is the story of Justinian’s plague, the lessons we failed to learn then and now as we struggle with Ebola.

Justinian’s Plague

View fullsize

Justinian I. Contemporary portrait in the Basilica of San Vitale, Ravenna . From Wikipedia.

It’s 542 CE in Constantinople (now Istanbul). A century earlier the Western provinces of the Roman Empire collapsed. The Eastern empire continues in what will be called the Eastern Roman or Byzantine Empire. Constantinople is the capital city, then as now, a melting pot between Europe and Asia. Since 527 CE this Empire has been ruled by Justian I, an absolute monarch determined to return to the glory years of conquest.

The Empire has already expanded to cover swathes of Northern Africa. Justinian’s focus is now on reclaiming Italy. The Empire is confident and proud, a jewel in an otherwise divided Europe now in the Dark Ages.

View fullsize

The Eastern Roman Empire at the succession of Justinian I (purple) in 527 CE and the lands conquered by the end of his reign in 565 CE (yellow). From US Military Academy.

View fullsize

Procopius of Caesarea (Creative Commons)

The main contemporary chronicler of the plague of Justinian, Procopius of Caesarea (500-565 CE)  identified the plague as arriving in Egypt on the Nile’s north and east shores. From there it spread to Alexandria in the north of Egypt and east to Palestine. The Nile was a major route of trade from the great lakes of Africa to the south. We now know that black rats on board trade ships brought the plague initially from China and India via Africa and the Nile to Justinian’s Empire.

Procopius noted that there had been a particularly long period of cold weather in Southern Italy causing famine and migration throughout the Empire. Perfect conditions to help a disease spread.

In his book Secret History Procopius detailed the symptoms of this new plague: delusions, nightmares, fevers and swellings in the groin, armpits, and behind their ears. For most came an agonising death. Procopius was of no doubt that this was God’s vengeance against Justinian, a man he claimed was supernatural and demonic.

Justinian’s war in Italy helped spread disease but so did peace in the areas he’d conquered. The established trade routes in Northern Africa and Eastern Europe, with Constantinople in the centre, formed a network of contagion. Plague swept throughout the Mediterranean. Constantinople was under siege for four months during which time Procopius alleged 10,000 people died a day in the city. Modern historians believe this figure to be closer to a still incredible 5,000 a day. Corpses littered the city streets. In scenes prescient of the Black Death, mass plague pits were dug with bodies thrown in and piled on top of each other. Other victims were disposed of at sea. Justinian was struck down but survived. Others in Constantinople were not so lucky, in just four months up to 40% of its citizens died.

The plague’s legacy

The plague continued to weaken the Empire, making it harder to defend. Like the medieval kings after him Justinian I struggled to maintain the status quo and tried to impose the same levels of taxation and expansion. He died in 565 CE. His obsession with empire building has led to his legacy as the ‘last Roman’. By the end of the sixth century much of the land in Italy Justinian had conquered had been lost but the Empire had pushed east into Persia. Far from Constantinople the plague continued in the countryside. The plague finally vanished in 750 CE by which point up to 50 million people had died, 25% of the population of the Empire.

Procopius’s description of the Justinian plague sounds like a lot like bubonic plague. This suspicion was confirmed in recent research.

View fullsize

Yersinia pestis bacteria, Creative Commons

At a two separate graves in Bavaria bacterial DNA was extracted from the remains of Justinian plague victims. The DNA matched that of Yersinia pestis the bacterium which causes bubonic plague. The DNA was analysed and found to be most closely related with Y. pestis still endemic to this day in Central Asia. This suggests the route from infection via trade from Asia to Europe.

After 750 CE plague vanished from Europe. New conquerors came and went with the end of the Dark Ages and the rise of the Middle Ages. Europeans forgot about plague. In 1347 they would get a very nasty reminder.

It’s very easy now in our halcyon era of medical advances to feel somewhat smug. Yes, an interesting story but wouldn’t happen now. Medieval scholars didn’t have germ theory. Or a way of easy accessing Procopius’s work. Things are different now.

We’d study Justinian’s plague with its high mortality. We’d identify the cause. We’d work backwards and spot how the trade link with Asia was the route of infection. We’d work to identify potential outbreaks in their early stages in Asia. By the time the second plague epidemic was just starting we’d notice it. There would be warnings to spot disease in travelers and protocols for dealing with mass casualties and disposal of bodies. We’d initiate rapid treatment and vaccination if possible. We’d be OK.

Ebola shows how hard this supposedly simple process remains.

Ebola: A Modern Plague

View fullsize

The Ebola virus (Creative Commons)

Ebola Viral Disease is a type of viral haemorrhagic fever first identified in 1976 during an outbreak in what is now South Sudan and the DRC. Caused a spaghetti-like virus known as a filovirus this disease causes severe dehydration through vomiting and diarrhoea before internal and external bleeding can develop. Named for the Ebola River where it was first identified it spreads by direct human contact with a mortality rate varying from 25% to 90%. An epidemic has been ongoing in DRC since August 2018. We are in our fourth decade of knowing about Ebola. And five years ago we were given the biggest warning yet about its danger.

Up until 2014 the largest outbreak of Ebola had affected 315 people. Other outbreaks were much smaller. Ebola seemed to burn brightly but with only a few embers. In 2014 it became a forest fire.

View fullsize

A healthcare worker during the Ebola outbreak of 2014-16 (From CNN.com)

The West Africa Epidemic of 2014-16 hit Guinea, Sierra Leone and Liberia. The disease showed its potential in our age of global travel as the first cases appeared in America and Europe. In all there were 28,160 reported cases. 11,308 people died. Ebola caught the world napping. What had been a rare disease of Africa was potentially a threat to us all. Suspicion of foreign healthcare workers and miscommunication about the causes of Ebola were blamed for helping to further the disease. Yet there was hope as promising experimental vaccines were put into production.

As the forest fire finally died down there was a chance to reflect. There were many publications, including from Médecins sans frontières, about the lessons learnt from Ebola and how not to repeat the lessons from the past. These were all along similar themes: the importance of trained frontline staff, rapid identification of the disease, engaging and informing local communities, employing simple yet effective methods to provide disease spread and the use of the new vaccine to protect contacts and contacts of contacts. There was lots of criticism about the speed of the World Health Organisation response but also a feeling that with new tools and lessons learnt things would be different next time.

When Ebola surfaced again last year in the DRC there was initial hope that lessons were learnt. Over 100,000 people have been vaccinated; a new weapon. However, the disease continues a year on with over 1000 cases and over 800 fatalities and fresh concern that this outbreak is far from over.

There remains delays in identifying patients with Ebola; not surprising as the early symptoms mimic more common diseases such as malaria. As a result patients are not isolated quickly enough and may infect others before their test results are back. Also the talk of engaging communities is falling flat. In a region torn apart by decades of civil unrest there is widespread mistrust of authorities with blame falling on the Ebola units themselves for causing death. It is estimated that 30% of patients are staying at home and being a potent vector for disease rather than coming forward. There has also been violence against healthcare workers and hospitals as a result of this fear. Reassuringly, where local communities and healthcare has come together Ebola has been stopped but this is not the norm and behavioural scientists are being used to help connect with locals. Despite the lessons learnt Ebola is continuing to be a difficult adversary.

It is easy in the West to feel we are immune from misinformation and fear. Yet look at the current measles epidemic in New York State. Look at the anti-vaccination movement, labelled a “public health timebomb” by Simon Stevens, the chief executive of NHS England last week. We are no more immune than anyone else to irrationality. Nor too proud to learn the lessons of the past; the ‘ring’ style of vaccinating contacts against Ebola is the same as used during the successful campaign to eradicate smallpox over four decades ago.

Medical advances have come on in ways no-one in the Middle Ages could have foreseen. We have never had more ways to share our knowledge of disease or so many ways to prevent suffering. Yet people remain the same. And that’s the tricky part. Let’s not forget that bit.

Thanks for reading

- Jamie

There is nothing new under the sun: the current New York measles epidemic and lessons from the first 'anti-vaxxers'

View fullsize

An 1807 cartoon showing ‘The Vaccination Monster’

What has been will be again,
    what has been done will be done again;
    there is nothing new under the sun.

Ecclesiastes 1:9

Quacks who Quaff · Episode 04: Medicine vs poison, first anti-vaxxers & The Liberator: Blood & Chocolate

We discuss the first anti-vaxxers (and review wine) in the fourth episode of the Quacks Who Quaff podcast.

The State of New York is currently in the midst of an epidemic. Measles, once eradicated from the USA has returned with a vengeance. Thanks to a rise in unvaccinated children fueled by the ‘anti-vaxxer’ movement 156 children in Rockwood County have been infected by measles; 82.8% of these had never had even one MMR vaccine. With measles now rampant in the boroughs of Brooklyn and Queens the state government has taken an unusual step. In New York in the USA, the home of liberty and personal choice, no unvaccinated under-18 year old is now able to set foot in a public space. Parents of unvaccinated children who break this ban will face fines or jail.

In a previous blog I wrote about the fight against smallpox first using variolation (which sometimes caused infection) and then the invention of the world’s first vaccine. This musing is about how vaccination was made compulsory in the United Kingdom, the subsequent fight against it through a public campaign and how that movement raised its head again in the last few decades. This is the story of the first ‘anti-vaxxer’ movement and how the arguments regarding vaccination show there isn’t really anything new under the sun.

Early opposition to vaccination

Following Edward Jenner’s work into using cowpox to offer immunity against smallpox in 1796 the Royal Jennerian Society was established in 1803 to continue his research.

Even in these early days there was opposition to the vaccine. John Birch, the ‘surgeon extraordinary’ to the Prince of Wales pamphleteered against Jenner’s work with arguments one might expect to see circulating today on social media:

View fullsize

A section of John Birch’s pamphlet from https://vaxopedia.org/2017/10/07/who-was-john-birch/

He of course did not mention how he was making a lot of money through inoculating patients against smallpox (a practice that vaccination would replace) or using novel treatments such as electrocution.

View fullsize

Wood painting caricature from 1808 showing Edward Jenner confronting opponents to his vaccine (note the dead at their feet) (Creative Commons)

Despite Birch’s efforts by 1840 the efficacy of Jenner’s vaccine was widely accepted. Decades before germ theory was established and viruses were identified we finally had a powerful weapon against a deadly disease. Between 1837 and 1840 a smallpox epidemic killed 6,400 people in London alone. Parliament was persuaded to legislate. The 1840 Vaccination Act made the unpredictable variolation illegal and made provision for free, optional smallpox vaccination.

At the time healthcare in the UK was largely unchanged since Tudor times. Parish based charity had been the core of support for the sick and poor until workhouses were made the centre of welfare provision in 1834. With the workhouse came a stigma that illness and poverty were avoidable and to be punished. Government was dominated by two parties, the Whigs and the Tories both of whom were non-interventionist and the universal healthcare provided by the NHS was over a century away. Consider this laissez-faire backdrop with punitive welfare. The fact free vaccination was provided is remarkable and I think reflects the giddy optimism at a future without ‘the speckled monster’ of smallpox.

The Anti-Vaccination Leagues

The Vaccination Act of 1853 went further. Now vaccination against smallpox was compulsory for all children born after 1st August 1853 within the first three months of their life with fines for parents who failed to comply. By the 1860s two-thirds of babies in the UK had been vaccinated.

There was immediate opposition to the 1853 Act with violent protests across the country. This was the state’s first steps into the health of private citizens. The response seems to have been motivated in much the same way as the modern day opposition in the US to vaccination and universal healthcare in general: that health is a matter of private civil liberty and that vaccination caused undue distress and risk. In England and Wales in particular although the penalties were rarely enacted their presence alone seems to have been motivation for opposition. The Anti-Vaccination League in London was established in 1853 to allow dissenting voices to coalesce.

The Vaccination Act of 1867 extended the age by which a child had to be vaccinated to 14 with cumulative fines to non-compliance. That same year saw the formation of the Anti-Compulsory Vaccination League. They published the National Anti-Compulsory Vaccination Reporter newsletter in which they listed their concerns, the first three being:

I. It is the bounden duty of parliament to protect all the rights of man.

II. By the vaccination acts, which trample upon the right of parents to protect their children from disease, parliament has reversed its function.

III. As parliament, instead of guarding the liberty of the subject, has invaded this liberty by rendering good health a crime, punishable by fine or imprisonment, inflicted on dutiful parents, parliament is deserving of public condemnation.

Further newsletters were formed over the following decades: the Anti-Vaccinator (founded 1869), the National Anti-Compulsory Vaccination Reporter (1874), and the Vaccination Inquirer (1879). All of these continued to place political pressure against compulsory vaccination. Much like today the main body of arguments focused on personal choice and the testimony of parents alleging that their child was injured or killed by vaccination. In Leicester in 1885 an anti-vaccination demonstration attracted 100,000 people. A staggering number when the city’s population in total at the time was around 190,000.

A royal commission was called to advise on further vaccination policy. After deliberation for seven years listening to evidence across the spectrum of opinion in 1896 they published their findings. Smallpox vaccination was safe and effective. However, it advised against continuing compulsory vaccination. Following the 1898 Vaccination Act parents who did not want their child to be vaccinated could ‘conscientiously object’ and be exempt. There was no further appetite for Parliament to intervene in the rights of parents. Even the fledgling socialist Labour Party, no enemy of government intervention, made non-compulsory vaccination one of its policies.

Whilst the two World Wars saw a change in public opinion towards a greater role in society for government, culminating in the creation of the National Health Service in 1948, vaccination remains voluntary in the United Kingdom. The first half of the 20th century saw the advent of vaccines against several deadly diseases such as polio, measles, diphtheria and tetanus. In 1966 an ambitious worldwide vaccination programme led by the World Health Organisation saw smallpox become the first disease to be eradicated by mankind in 1980. There were dreams of polio and measles going the same way. It was not to be.

Anti-vaccination re-emerges

Herd immunity is a key component for any vaccination programme to be effective. Not everyone can be vaccinated and so they rely on being surround by vaccinated people to prevent transmission. The level of vaccination in a population required for herd immunity varies between diseases. The accepted standard to prevent measles transmission is 90-95%.

On 28th February 1998 an article was published in the Lancet which claimed that the Measles, Mumps and Rubella (MMR) vaccine was linked to the development of development and digestive problems in children. Its lead author was Dr Andrew Wakefield, a gastroenterologist.

View fullsize

The infamous Lancet paper linking the MMR vaccine to developmental and digestive disorders

The paper saw national panic about the safety of vaccination. The Prime Minister Tony Blair refused to answer whether his newborn son Leo had been vaccinated.

Except just like John Birch nearly two centuries before him Andrew Wakefield had held a lot back from the public and his fellow authors. He was funded by a legal firm seeking to prosecute the companies who produce vaccines. This firm led him to the parents who formed the basis of his ‘research’. The link between children developing developmental and digestive problems was made by the parents of twelve children recalling that their child first showed their symptoms following the MMR vaccine. Their testimony and recall alone were enough for Wakefield to form a link between vaccination and autism. From a research sense his findings were no more useful than those the Victorian pamphlets used. But the damage was done. The paper was retracted in 2010. Andrew Wakefield was struck off as were some of his co-authors who did not practice due diligence. Sadly, this has only helped Wakefield’s ‘legend’ as he tours America spreading his message tapping in to the general ‘anti-truth’ populist movement. Tragically unsurprisingly, often in his wake comes measles.

Earlier this year the largest study to date investigating the links between MMR and autism was published. 657,461 children in Denmark were followed up over several years (compare that to Wakefield’s research where he interviewed the parents of 12 children). No link between the vaccine and autism was shown. In fact, no large high level research has ever backed up Wakefield’s claim.

There are financial and political forces at work here. Anti-vaccination is worth big money. The National Vaccination Information Center in the US had an annual income of $1.2 billion in 2017. And the people they target are economically and politically powerful. Recent research in America shows that parents who refuse vaccinations for their children are more likely to be white, educated and of higher income. They prize purity and liberty above all, emotional reasoning over logic. They vote. And their world view is prevalent in certain circles.

Tweet by Donald Trump 28th March 2014

In the UK in 2018 the rate of MMR vaccination was 91.8%, worryingly close to no longer being effective for herd immunity. There have been debates in the UK about re-introducing compulsory vaccination. In France certain childhood vaccinations are now compulsory. Social media companies are under pressure to silence the groups anti-vaxxers use to spread their message and recruit. The state is once again prepared to step into personal liberty when it comes to vaccines.

In 1901 52% of childhood deaths in England and Wales were due to infectious diseases. By 2000 it was 7.4%. In 1901 40.6% of all deaths were children. By 2000 it was 0.9%. No-one would want that progress to reverse. But history does have a habit of repeating itself if we let it. The debates continue to be the same: the rights of parents and the individual versus those of the state and public health necessity. This is a debate we have to get right. History tells us what will happen if we don’t. After all, there is nothing new under the sun.

Thanks for reading

- Jamie

Sweating Sickness: England’s Forgotten Plague

Quacks who Quaff · Episode 02: History of opium, sweating sickness & 2012 Domaine du Vieux Lazaret Châteauneuf-du-Pape

We discuss the sweating sickness (and review wine) in the second episode of the Quacks Who Quaff podcast.

The history of medicine is littered with diseases which impacted on the course of humanity. The Black Death. Smallpox. Influenza. HIV/AIDS. Each one has left its own mark on our collective consciousness. And yet there is an often-overlooked addition to this list: sweating sickness. This disease tore its way through Tudor England, killing within hours, before disappearing as quickly and mysteriously as it arrived. In its wake it left its mark, a nation changed. The identity of this disease remains a matter for conjecture to this day. This is the story of England’s forgotten plague.

Background to an outbreak

It’s summer 1485. An epic contest for the throne of England is reaching its bloody climax. In a few weeks on August 22nd at the Battle of Bosworth Henry Tudor will wrest the crown from King Richard III and conclude the Wars of the Roses. Away from the fighting people start dying. As contemporary physicians described:

“A newe Kynde of sickness came through the whole region, which was so sore, so peynfull, and sharp, that the lyke was never harde of to any mannes rememberance before that tyme. “

These words take on added impact when you remember the writer would have experienced patients with bubonic plague. What was this disease “the like was never heard of”? Sudor Anglicus, later known as the English sweating sickness, struck quickly. The French physician Thomas le Forestier described victims feeling apprehensive and generally unwell before violent sweating, shaking and headaches began. Up to half of patients died, usually within 24 hours. Those who lived longer than this tended to survive. However, survival did not seem to offer immunity and patients could be struck multiple times. 15,000 died in London alone. We don’t have an exact figure for its mortality but it is commonly estimated at 30-50%.

Outbreaks continued beyond 1485 and the reign of Henry VII and into that of his grandson Edward VI in five further epidemics; 1508, 1517, 1528, and 1551, each time in summer/autumn. The disease remained limited to England apart from 1528/29 when it also spread to mainland Europe.

View fullsize

John Keys

The principle chronicler of the sweat was the English doctor John Keys (often Latinised to John Caius/Johannes Caius) in his 1552 work ‘A Boke or Counseill Against the Disease Commonly Called the Sweate, or Sweatyng Sicknesse.’ This is how know so much about how the disease presented and progressed.

Key’s noted that the patients most at risk of the disease were:

“either men of wealth, ease or welfare, or of the poorer sort, such as were idle persons, good ale drinkers and tavern haunters.”

Both Cardinal Wolsely and Anne Boleyn contracted the disease but survived. Wolsely survived two attacks. Anne’s brother-in-law William Carey wasn’t so lucky and died of the sweat. The disease’s predilection for the young and wealthy led to it being dubbed the ‘Stop Gallant’ by the poorer classes.

Key’s was the physician to Edward VI, Mary I and Elizabeth I. As he was born in 1510 his work on the first epidemics of sweating sickness was based on prior reports of the illness; it could therefore be said he had performed a kind of literature review. Unlike le Forestier his lack of first hand experience and the fact he focused mostly on noble deaths has led to criticism. However, Keys was clear that the sweat was different to plague and other conditions. This goes with le Forestier and other physicians at the time.

The impact of the sweat permeated Tudor culture. Even in 1604 William Shakespeare was concerned enough about sweating sickness to write in his play ‘Measure by Measure’:

“Thus, what with the war, what with the sweat, what with the gallows, and what with poverty…”

How the sweat changed history

Henry Tudor was an ambitious man with a fairly loose claim to the throne of England: his mother, Lady Margaret Beaufort, was a great-granddaughter of John of Gaunt, Duke of Lancaster, fourth son of Edward III, and his third wife Katherine Swynford. Katherine was Gaunt’s mistress for 25 years before they married and had 4 children already before she gave birth to John Beaufort, Henry’s great-grandfather. If this sounds complicated it is. Henry was not a strong claimant and his chances had been further weakened by an Act of Parliament in 1407 by Henry IV, John of Gaunt’s first son, which recognised his half-siblings but ruled them and their descendants ineligible for the throne.

View fullsize

Henry Tudor’s ancestry from http://www.livimichael.co.uk/succession-the-players

Henry needed alliances if he was going to get anywhere. He attempted to take the crown in 1483 but the campaign was a disaster. He was running out of time and needed to kill Richard III in battle if he was going to be king. He accepted the help of King Charles VIII of France who provided Henry with 2000 mercenaries from France, Germany and Switzerland. This force crossed the English Channel on 7th August 1485. In was in this army that the sweat first appeared. There is debate about whether this was before or after the Battle of Bosworth but Lord Stanley, a key ally of Richard III and a contributor of 30% of the king’s army, used fear of sweating sickness as a reason to not join the royal forces in battle. It’s therefore possible that sweating sickness was seen before Bosworth and helped shape the course of English history.

View fullsize

Arthur Tudor (1486-1502)

Sweating sickness may have had a further impact on the Tudors and their role in our history. Henry VII’s first son, Arthur the Prince of Wales died in 1502 aged 15. Sweating sickness has been suggested as the cause of his sudden death. His death saw Henry VII’s second son, also called Henry, become first in line to the throne which he took in 1509 as King Henry VIII.

What was the sweat?

Unlike other plagues the identity of sweating sickness remains a mystery to this day. The periodicity of the epidemics suggests an environmental or meteorological trigger and possibly an insect or rodent vector.

A similar disease struck Northern France in 1718 in an outbreak known as ‘the Picardy sweat’. 196 local epidemics followed until the disease disappeared in 1861 with its identity also a mystery. Interestingly, the region of France where the Picardy sweat arose is near where Henry Tudor’s group of French, German and Swiss solders amassed prior to the Battle of Bosworth.

Several diseases have been proposed as the true identity of the sweat. Typhus (not as virulent), influenza and ergotism (don’t match the recorded symptoms) have been suggested and dropped. In 1997 it was suggested that a hantavirus could have been responsible. Hantaviruses are spread by inhalation of rodent droppings and cause similar symptoms to sweating sickness before killing with bleeding and complications to the heart and lungs. Although rare they have been identified in wild rodents in Britain. If we remember how the sweat seemed to strike following summer when rodent numbers would be at their highest and add in the poor sanitation of Tudor times then hantavirus is a strong candidate.

We’ll likely never know the true identity of sweating sickness unless it re-emerges. If that’s the case based on the terror it inspired to Tudor England we should be glad to keep it a mystery.

Thanks for reading.

- Jamie

The Most Famous Case Report Ever

Case reports are nothing new. We’ve all told colleagues about interesting cases we’ve seen. I’ve presented a couple at RCEM. They tend to focus on the weird and wonderful, cases with surprising twists and turns but with actual limited learning. That’s why case reports are at the bottom of the table when it comes to levels of evidence. However, one in particular could be said to have marked a turning point in modern medical practice.

The Morbidity and Mortality Weekly Report (MMWR) has been published weekly by the Centre for Disease Control and Prevention (CDC) since 1950. Each week they release public health information, possible exposures, outbreaks and other health risks for health workers to be aware of. One case report in particular stands out out of all of their back catalogue. It was written by various doctors from the University of California, Los Angeles and Cedars-Mt Sinai Hospital, Los Angeles. It was published on June 5th 1981:

View fullsize

The MMWR June 5th 1981

Reported by MS Gottlieb, MD, HM Schanker, MD, PT Fan, MD, A Saxon, MD, JD Weisman, DO, Div of Clinical Immunology-Allergy, Dept of Medicine, UCLA School of Medicine; I Pozalski, MD, Cedars-Mt. Sinai Hospital, Los Angeles; Field Services Div, Epidemiology Program Office, CDC.

Pneumocystis Pneumonia (PCP) is a rare form of pneumonia caused by the yeast like fungus Pneumocystis jiroveci. The fungus can live in the lungs of healthy people without causing any problems so to see it in 5 otherwise healthy young (the oldest was 36) people was odd.

Less than a month later the MMWR published further cases of PCP as well as Kaposi sarcoma in 26 previously well homosexual men in Los Angeles and New York since 1978. Kaposi sarcoma is very rare form of cancer previously seen usually in older men of Jewish/Mediterranean descent. Again it was virtually unheard of it in young men. It was suspected that something was affecting their immune systems preventing them from fighting off infections and malignancy.

View fullsize

At the time there were many theories as to what was causing the immune systems of patients to shut down. It was felt that it was linked to the ‘gay lifestyle’ in some way leading to the stigmatising description in the media of GRID (Gay-related immunodeficiency) first used in 1982. By 1983 the disease was linked also to injecting drug users, haemophiliacs who’d received blood products and Haitians. This led to another stigmatising phrase ‘the 4H club’ (Homosexuals, Heroin addicts, Haemophiliacs and Haitians).

In 1982 however, the CDC had actually given it a proper name: ‘Acquired Immune Deficiency Syndome’ or ‘AIDS’.

The fact it was being transmitted to blood product recipients suggested the cause had to be viral as only a virus could pass the filtration process. In 1983 two rival teams, one American and one French, both announced they had found the virus causing AIDS with ongoing debate as to who got there first. Each team gave it a different name. In 1985 a third one was chosen: ‘Human Immunodeficiency Virus’ or ‘HIV’. By that time the virus had spread not just in America but in Canada, South America, Australia, China, the Middle East and Europe. Since 1981 worldwide more than 70 million people have been infected with the HIV virus and about 35 million people have died of AIDS. 

The MMWR of 5th June 1981 is now recognised both as the beginning of the HIV/AIDS pandemic and as the first publication of HIV/AIDS. Although only a case report it shows the value of these publications at the front line. Only by recording and publishing the ‘weird and wonderful’ can we start to share practice, appreciate patterns and spot emergent diseases.

Thanks for reading

- Jamie

Mass Hysteria & Moral Panic: The Dancing Plagues and #Momo

“The only thing we have to fear is fear itself” - President Franklin Roosevelt

Human beings are social animals with conventions and norms. Yet sometimes we act in ways that defy logic or reason. Very often the inspiration for this is fear. In this week’s blog I’ve looked at the ‘Dancing Plagues’ of the Middle Ages and the ‘Momo Challenge’ of last month and how they illustrate the power of fear over people. In a previous blog I wrote about the importance of being accurate with psychiatric diagnosis and so I’m also going to use them as examples of the difference between mass hysteria and moral panic.

In 1374 in Aachen along the River Rhine in what is now Germany locals suddenly started dancing. They didn’t stop. They couldn’t stop. Justus Hecker, an 18th century physician researched the phenomenon and described it as:

“They formed circles hand in hand, and appearing to have lost all control over their senses, continued dancing, regardless of the bystanders, for hours together, in wild delirium, until at length they fell to the ground in a state of exhaustion. They then complained of extreme oppression, and groaned as if in the agonies of death, until they were swathed in cloths bound tightly round their waists, upon which they again recovered, and remained free from complaint until the next attack.”

The dancing spread to Liege, Utrecht, Tongres and other towns in the Netherlands and Belgium, up and down the Rhine river. It was known as St. John’s Dance or St. Vitus’ Dance as these saints were blamed for causing the ‘disease’.

In July 1518, this time in Strasbourg, a woman known as Frau Troffea started dancing and carried on for 4 to 6 days. By the end of the week 34 people had joined her and at the end of month 400 people were dancing. It didn’t stop. It seemed contagious. Local authorities initially thought that the people just needed to get the dancing out of their systems and so organised musicians to encourage dancing. It didn’t work. Dozens collapsed and died out of exhaustion.

The ‘Dancing Plagues’ continued to occur randomly throughout medieval Europe. It’s still a mystery why so many people acted in such a bizarre way. Possession was blamed but exorcisms had no effect. Doctors at the time wondered if the stars or even spider bites were to blame. Various different theories have since been put forward such as encephalitis which can cause delirium and hallucinations or poisoning of grain by the ergot fungus. None completely explain all the symptoms. There may have been an element of religious demonstration but that doesn’t explain how the dancing seemed contagious.

It may be that ‘Dancing Mania’ was due to mass hysteria.

Mass hysteria is a "conversion disorder," in which a person has physiological symptoms affecting the nervous system in the absence of a physical cause of illness, and which may appear in reaction to psychological distress.

It has been suggested that mass hysteria has 5 principles:

1. "it is an outbreak of abnormal illness behavior that cannot be explained by physical disease"

2. "it affects people who would not normally behave in this fashion"

3. "it excludes symptoms deliberately provoked in groups gathered for that purpose," such as when someone intentionally gathers a group of people and convinces them that they are collectively experiencing a psychological or physiological symptom

4. "it excludes collective manifestations used to obtain a state of satisfaction unavailable singly, such as fads, crazes, and riots"

5. "the link between the [individuals experiencing collective obsessional behavior] must not be coincidental," meaning, for instance, that they are all part of the same close-knit community

In 1374 Europe was still recovering from the Black Death of 1347-1351. The people of Strasbourg in 1518 had suffered a famine. At a time where disease and famine were the preserve of God’s wrath perhaps the stress of potential apocalypse manifested itself in a a plague of dancing.

If you think that mass hysteria is confined to the dark pre-Renaissance ages you’d be very wrong. In 1999 26 school children in Belgium fell ill after drinking cans of Coca Cola. After this was reported in the news more students in other schools also fell ill. Coca Cola withdrew nearly 30 million cans from the market as about 100 people eventually complained of feeling unwell after drinking their product. Except when they were examined nothing organically wrong could be found and the students had drunk cans from different factories.

Professor Simon Wessely, the former president of the Royal College of Psychiatrists, has written a lot about mass hysteria and is clear: mass hysteria does not make a person insane. The patient thinks they are unwell and communicate that illness. This brings us to moral panic and #Momo.

If you’ve been anywhere near social media the past month chances are you heard about Momo or ‘The Momo Challenge’. These were posts, shared widely, warning about a character called Momo who has started appearing in online videos aimed at children threatening them and encouraging them to perform acts of violence against themselves and others. It led to widespread discussion and warnings from authorities:

View fullsize

Except it wasn’t real. There is no evidence of Momo or any character infiltrating videos of Pepper Pig and inspiring children to hurt themselves. This obsession over an imaginary character was been traced to a solitary post in America warning about Momo. Over the following month there was an exponential growth of interest into this imaginary threat. Charities warned that the fear mongering would actually do more harm than good.

Guardian graphic. Source: Google trends. Numbers represent search interest

Professor Wessely defines moral panic as the “phenomenon of masses of people becoming distressed about a perceived — usually unreal or exaggerated — threat portrayed in catastrophising terms by the media“. Like mass hysteria there’s a threat. Unlike mass hysteria people don’t believe themselves to be unwell. The sociologist Stanley Cohen described four stages of moral panic in response to a perceived threat:

1. The threat is then depicted in a simple and recognizable symbol/form by the media

2. The portrayal of this symbol rouses public concern

3. There is a response from authorities and policy makers

4. The moral panic over the issue results in social changes within the community

Look at these four steps and then the graph above. #Momo illustrates moral panic perfectly. It also brilliantly illustrates how misinformation and as a result panic can be spread by social media. Moral panic is the result of fears the ‘threat’ poses to our way of life. It is therefore a powerful tool by the far right. Watch how Donald Trump and his supporters spread inaccurate information about illegal immigrants to push their border wall agenda.

The world is a scary place and as a species we instinctively fear the unknown especially when our way of life or our lives themselves are believed to be at risk. The panic at Oxford Street, London last December where gun shots were reported is believed to be due to a ‘perfect storm’ of fear over terrorism and violence. People panicked when a fight broke out. Next thing hundreds of shoppers were running and their imagination took over. What’s worse is when that fear is used to ostracise whole groups of people. The Witch Trials of Salem, on which both mass hysteria and moral panic have been blamed, is a classic example of this. For all the drama caused what the #Momo phenomenon also shows is a potential solution to fear: knowledge and a measured response.

Thanks for reading

- Jamie

Flogging, Bellows, Barrels, Smoke Up the Bum and Abraham Lincoln - Early CPR

Last week saw the start of induction of our new third year students starting the clinical phase of their time at university. I was on CPR duty for much of it. CPR as we know it was developed in 1960. For the centuries before that there were many different techniques attempted to revive a patient without a pulse. It’s fair to say these were, ahem, interesting.

Flogging

View fullsize

In the early Middle Ages a patient would be flogged or flagellated sometimes with nettles to try and revive them. It was presumed that the shock would awake the patient rather than any consideration of their circulation.

Bellows

View fullsize

In an early example of artificial ventilation bellows began to be used in the 1500s to blow air down the patient’s throat and into their lungs. However, simple air manoeuvres were not used. Bellows were popular for about 300 years until in 1829, the French physician Leroy d’Etiolles demonstrated through his work on barotrauma that over distension of the lungs could kill an animal so they went out of fashion.

Fumigation

View fullsize

Fast forward to the 1700s and fumigation comes into use. The physician would light a pipe of tobacco and use the above contraption to literally blow tobacco smoke up the patient’s rectum. It was believed that the smoke’s effects would revive the patient through the irritant effects of the tobacco smoke.

Barrel Method

View fullsize

Resuscitation would then go back the lungs and a technique to force air in and out of the chest. This led to the barrel method where the barrel was used to force inspiration and expiration. You can kind of see what they were trying to do here with a mechanical intervention.

Russian Snow Method

View fullsize

Meanwhile in Russia in the early 19th century the snow method came into fashion. The idea being to slow the metabolism of the patient and hope that circulation would return at a later date.

The Assassination of Abraham Lincoln

View fullsize

Whilst at Ford’s Theatre on 14th April 1865 US President Abraham Lincoln was shot by John Wilkes Booth in the back of the head. Charles Leal, a young military surgeon, and another doctor Charles Sabin Taft attempted to revive Lincoln with a three stage approach:

Method “A” “... As the President made no move to revive then, I thought of another way of death, apnea, and I assumed my preferred position for him with artificial respiration to revive …” “… I knelt on the floor on the President, with one knee on each side of the pelvis and in front of him. I leaned forward, opened my mouth and inserted two fingers of his right hand as far as possible .. . and then I opened the larynx and I did a free passage for air to enter the lungs … “

Method “B”: “… I put an assistant in each of his arms to manipulate in order to expand the chest and then slowly pushed his arms down the side of the body as I pressed the diaphragm above: These methods caused the vacuum and air is forced out of their lungs … “

Method “C”: “… Also with the thumb and fingers of my right hand pressure intermittent sliding pressure below the ribs stimulated the apex of the heart …”

Lincoln did become more responsive but it was clear his wounds were fatal and he died the next day. The three stages above are almost recognisable to the ‘ABC’ method we’re taught today. The doctors took steps to protect Lincoln’s airway, there was some consideration to force ventilation and an attempt at pressing the heart. It’s still not CPR as we would know it.

It took the US Military adopting mouth-to-mouth resuscitation and CPR as well as public campaigns helped by the arrival of Resusci Anne (more on her here) for CPR to become a key part of both medicine and health education.

It’s very easy to laugh at these previous techniques and sometimes hard to see the logic behind them. However, we don’t know which staples of Medicine we use today will be deemed irrelevant or even wrong. For example, we no longer perform gastric lavage and even collar and blocks are being debated as sometimes doing more than good. Maybe in the future medics will view us as incredulously as we do at someone blowing tobacco smoke up the rectum of a moribund patient. Maybe.

Thanks for reading.

- Jamie

Smallpox: the Giants' Shoulders Edward Jenner Stood on to Overcome 'The Speckled Monster'

Convergent evolution is a key principle in Biology. Basically, it means that nature will find the same ‘solutions’ for organisms filling similar environmental niches. So in different species with no close relation but who encounter similar environments (say sharks and dolphins) you’ll see similar features (both have fins). The same is true in the history of science. Very few discoveries are actually made in solitude; more often there were several people working on the same problem but often only one gets the fame. For Charles Darwin see Alfred Russel Wallace. For Sir Isaac Newton see Robert Hooke.

Quacks who Quaff · Episode 03: Onesimus & variolation, serendipitous reptiles & the Cono Sur 20 Barrels Pinot Noir

We discuss the unsung heroes in the fight against smallpox and variolation (and review wine) in the third episode of the Quacks Who Quaff podcast.

When it comes to vaccination and the conquest of smallpox, one of the most deadly diseases to ever afflict mankind, one name always comes to mind: Edward Jenner. We all know the story: an English country doctor in the 18th century observed how milkmaids who contracted cowpox from their cattle were immune to the far more serious smallpox. On 14th May 1796 he deliberately infected the eight-year-old boy James Phipps with cowpox. The boy develops a mild fever. Later Jenner exposes Phipps to pus from a smallpox blister. The boy is unaffected by smallpox. A legend is born. Vaccination becomes the mainstay of the fight against smallpox. In the 20th century a worldwide campaign results in smallpox being the first disease to be eradicated.

Of course, as we all know, things are rarely this straightforward and there are many less famous individuals who all contributed to the successful fight against smallpox.

View fullsize

Dr Jenner performing his first vaccination on James Phipps, a boy of age 8. May 14th, 1796. Painting by Ernest Board (early 20th century).

Smallpox, the ‘speckled monster’, has a mortality rate of 30% and is caused by a highly contagious airborne virus. It long affected mankind; smallpox scars have been seen in Egyptian mummiesfrom the 3rd Century BCE. Occurring in outbreaks it is estimated to have killed up to 500 million peoplein the 20th century alone. Throughout history it was no respecter of status or geography, killing monarchs and playing a role in the downfall of indigenous peoples around the world. Superstition followed smallpox with the disease even being worshipped as a god around the world.

Doctors in the West had no answer to it. But in other parts of the world solutions were found. With colonisation and exploration the West started to hear about them. More than seventy years before Jenner’s work two people on either side of the Atlantic were inspired by custom from Africa and Asia. 

Left: Shitala, the North Indian goddess of pustules and sores

Right: Sopona, the god of smallpox in the Yoruba region of Nigeria

View fullsize

Lady Mary Wortley Montagu

In 1721 in London Lady Mary Wortley Montagu the wife of the Ambassador to Turkey who had lost her brother to smallpox having survived the disease herself is keen to protect her daughter. Whilst in Turkey she learned of the local practice of ‘variolation’ or inoculation against smallpox. Pus from the pustules of patients with mild smallpox is collected and scratched into the skin of an uninfected person. This was a version of a process dating back to circa 1000 AD in China where pustule material was blown up the nose of a patient. Mary was impressed and her son was inoculated in Turkey in 1715. 

Six years later in London her daughter was similarly inoculated in the presence of doctors of the royal court, the first such procedure in Britain. She campaigns for the practice to be spread.

View fullsize

Cotton Mather

Also in 1721, an outbreak of smallpox is ravaging Boston, Massachusetts. An influential minister Cotton Mather is told by one of his African slaves, Onesimus, about a procedure similar to inoculation. According to Onesimus as a younger man a cut was made into his skin and smallpox pustules were rubbed into the wound. He told Mather that this had made him immune to smallpox. Mather hears of the same practice in China and Turkey and is intrigued. He finds a doctor, Zabdiel Boylston, and the two start performing the first inoculations in America.

Lady Wortley Montagu and Cotton Mather never met, they lived on opposite sides of the Atlantic and yet learnt of the same practice. Convergent medical advances in practice.

Inoculation is not without risk however and Prince Octavius, son of King George III dies in 1783 following inoculation. People inoculated with smallpox are also potentially contagious. An alternative is sought.

In 1768 an English physician John Fewster identified that cowpox offered immunity against smallpox and begins offering the practice of immunisation. In 1774 Benjamin Festy, a dairy farmer in Yetminster, Dorset, also aware of the immunity offered by cowpox,, has his wife and children infected with the disease. He tests the procedure by then exposing his son to smallpox. His son is fine. The process is called vaccination after the Latin word for cow. However, neither men publish their work. In France in 1780 politician Jacques Antoine Rabaut-Pommier opens a hospital and offers vaccination against smallpox. It is said that he told an English doctor called Dr Pugh about the practice. The English physician promised to tell his friend, also a doctor, about vaccination. His friend’s name? Edward Jenner.

It is Jenner who publishes his work and pushes for vaccination as a preventative measure against smallpox. It is his vaccine which is used as the UK Parliament through a succession of Acts starting in 1840 makes variolation illegal and provides free vaccination against smallpox. In a precursor of the ignorance of the ‘anti-vaxxer’ movement there is some public hysteria but vaccination proves safe and effective (as it still is).

View fullsize

Cartoon by British satirist James Gillray from 1802 showing vaccination hysteria

Arguably, without Jenner’s work such an effective campaign would have been held back. As the American financier Bernard Baruch put it, “Millions saw the apple fall, but Newton was the one who asked why.” However, Newton himself felt that “if I have seen further it is because I have stood on the shoulders of giants.” History in the West has a habit of focusing on rich white men at the exclusion of others, especially women and slaves. Any appreciation of Jenner’s work must also include those giants whose shoulders he stood by acknowledging the contribution of people like Lady Wortley Montagu and Onesimus and of Fewster and Festy - the Wallaces to his Darwin.

Thanks for reading

- Jamie

How 'The Unknown Woman of the Seine' became 'Resusci Anne'

She’s been called “the most kissed face in the world.” I think it’s fair to say that most of us will encounter Resusci Anne/Resus Anne/Rescue Anne/CPR Anne at some point of our lives. The mannequin itself dates from the 1960s when it was first produced by Laerdal Medical. However, as often with medical history, the story of Anne goes back further than that.

Paris in the 1880s showing the beginnings of the Eiffel Tower

It’s Paris in the late 1880s; a busy, bustling city where, much like London, there was what we would now consider a morbid curiosity with death and it was not uncommon for people to vanish. The body of a young woman, presumed to be no more than 16 years old, is pulled out of the River Seine. As is customary her body is displayed in the mortuary window on a marble slab (a popular attraction at the time) in the hope a family will come forward. They don’t.

Her body shows no sign of disease or trauma. Suicide is suspected. But something else intrigues the pathologist. Her face upon which is a calm, knowing half smile quite unlike anything you’d expect from a person drowning. The pathologist was so taken by her he ordered a plaster cast to be made of her face.

View fullsize

Copies of the plaster cast became widespread as both a decoration and artistic inspiration. Parallels were drawn with Ophelia, the character in William Shakespeare’s ‘Hamlet’ who drowns after falling out of a willow tree. The French philosopher Albert Camus compared her enigmatic smile to the Mona Lisa.

In Richard Le Gallienne’s 1899 novella, ‘The Worshipper of the Image’, the protagonist Antony falls in love with the death mask. The Russian born poet Vladimir Nabokov wrote a whole 1934 poem titled “L’Inconnue de la Seine” in which he imagined her final days:

Urging on this life’s denouement,
loving nothing upon this earth,
I keep staring at the white mask
of your lifeless face.

In 1926 the death mask was included in a catalogue of death masks and was titled, ‘L'Inconnue de la Seine’ (The Unknown Woman of the Seine) and her legend was complete.

Fast forward to 1955 and the Norwegian toy manufacturer Asmund Laerdal saves his son Tore from near drowning in a river. Shortly after he is approached to design a mannequin to help teach cardio-pulmonary resuscitation. He decides that a female mannequin would be less scary for students and wants her to have as natural a face as possible.   Remembering a plaster cast of L’Inconnue he decides to replicate her face. L’Inconnue is reborn as ‘Resusci Anne’. The rest is history.

As Laerdal themselves put it: "Like Leonardo da Vinci's Mona Lisa, and John Everett Millais' Ophelia, the girl from the Seine represents an ideal of beauty and innocence." An anonymous victim of drowning now responsible for teaching cardio-pulmonary resuscitation around the world having briefly been the focus of gothic romantic obsession. It’s unlikely she could ever have imagined this legacy in her short life.

Thanks for reading

- Jamie

The Story behind Gray's Anatomy (the real one)

Choosing the Twitter name @mcdreeamie might have been mostly because I work at NUH DREEAM but I’d be lying if I didn’t know about the TV show ‘Grey’s Anatomy’ and watched the odd episode. However, this blog is about the real Gray’s Anatomy, the book. So please only read on if you’re interested in the book and not Meredith or Derek.

I was bought a copy of Gray’s Anatomy as a present from my uncle once my place in medical school was guaranteed and it has made a eye-catching addition to my book shelf ever since. For this blog I thought I’d look a bit into Gray and how the book came about.

View fullsize

Henry Gray

Henry Gray was born in 1827 in Belgravia, London. That’s pretty much all we know about his early life until he started at St. George’s University, also in London, in 1842. He’s thought to have lied about his age in order to enrol.

Back then in order to be a medical student one would also have to a practising member of the Church of England and show proof. To become a staff surgeon at St. George's Hospital, Gray would first have to pass the Apothecaries exam, then an exam to obtain membership in the Royal College of Surgeons, and later a difficult exam to become a Fellow of the Royal College.  He was described as good looking and a bit dandyish and hard working. He was interested in anatomy and dissection from the very beginning.

Gray benefited, along with his peers, from a recent change in the law: The Anatomy Act of 1832. This gave freer licence to medical students and teachers to practice human dissection. Whereas before restrictions had led to a dark business in grave robbing and corpse selling now everyone wanting to practice dissection had to be registered with the Home Secretary. London, the rest of England and Wales, Scotland and Ireland each had an inspector of anatomy who would keep a list of all bodies being dissected and report to the Home Secretary. Bodies could be dissected or claimed from prisons or workhouses if no one next of kin came for them. This meant Gray would have been able to practice anatomy in the open and within the law.

When he was 21 he won prizes in surgery. He became a member of the Pathological Society of London and a member of the Royal College of Surgeons. In 1852 , still in his twenties, he was made a governor of the hospital.

View fullsize

Self portrait of Henry Vandyke Carter

By 1853 he had met Henry Vandyke Carter, a medical student with a talent for drawing. Gray entered and won the Astley Cooper Prize (100 pounds - about £13000 now) for his work “The structure and use of the human spleen.” His 350 page book contained over 50 illustrations by Carter although no credit was given and payment was incomplete.

In 1855 Gray approached the shy Carter again this time regarding the possibility of a textbook for medical students. Carter was more careful this time and only began work when promised £10 (£1000 now) a month for 15 months to produce drawings. To put that into perspective I’ve found one freelance book illustrator online who changes £320 a day! By summer 1858 the first copies were ready for printing for the students arriving later that year.

View fullsize

Gray's markings on the first edition's title page, downplaying Carter's contributions and his titles

Called Anatomy: Descriptive and Surgical Gray sought to boost his name whilst diminishing that of Carter and his contribution. Carter, presumably very fed up of Gray by this point, went to India to practice and never received a penny of royalties.

Early reviews were a bit mixed. The British Medical Journal called it “far superior to all other treatise on anatomy, … a book which must take its place as THE manual of Anatomy Descriptive and Surgical.” The Medical Times and Gazette, however, found it “ not wanted…low and unscientific in tone…compiled, for the most part, in a manner inconsistent with the professions of honesty which we find in the preface… . A more unphilosophical amalgam of anatomic details and crude surgery we never met with.”

The second edition was released in 1861. That same year Gray’s nephew Charles became ill with smallpox. Gray treated Charles back to health. However, despite having received an early form of smallpox vaccination, Gray himself contracted the disease. He developed confluent smallpox, a more serious form where the lesions meet to form one whole sheet. On 13th June 1861, when he was due to be interviewed for a new post at St. George’s, he died aged just 34. As a smallpox patient all of his possessions, including his writings, were burnt. Carter stayed in India for 30 years before returning to England in 1888. He died of tuberculosis in 1897.

Gray’s Anatomy has never been out of print. In 2004 a Student edition was also released. Gray’s is published through Elsevier with online materials as well.

Henry Gray was clearly a precocious talent, albeit one with a thirst for fame. St. George’s continue to honour one of their most renowned alumni with their anatomy society. Whilst there have been rumblings of plagiarism he has clearly achieved the recognition he craved uniting nearly two centuries of students and practitioners who have used Gray’s.

Thanks for reading

- Jamie

The Wound Man: From Textbook to Emblem and Hollywood

If you think you’re having a bad day just remember The Wound Man. Stabbed, bludgeoned and shot yet still standing tall it’s safe to say that his image has been on a journey over more than half a millennium to becoming truly iconic. This journey has taken him from the pages of a medieval textbook to Hollywood via James Bond and the Royal College of Emergency Medicine.

Gunpowder made its way to Europe during the 14th century, probably along the Silk Road trade route with Asia. This meant that as well as the traditional war wounds from blades and arrows doctors were also seeing the effects of cannon and shrapnel. Doctors needed some form of reference to help with the myriad new forms of trauma they might encounter.

Along came Johannes de Ketham/von Kirchheim, a German physician living and working in 15th century Italy. In 1491 he published Fasciculus Medicinae (the little bundle of Medicine) in Venice; basically the Oxford Handbook of Medicine of its time complying medical knowledge as it was. Written in Latin, the original edition consisted of six illustrations with accompanying text. The world’s first ‘Wound Man’ was one of these illustrations. The illustrations and sections were as follows (diagrams are from the 1495 edition):

View fullsize

Urine and blood letting

• Urine section: the ‘little bundle’ starts immediately with a section on how a physician could use the colour and smell of a patient’s urine to diagnose their condition

• Bloodletting/phlebotomy section: a full male figure showing arteries and veins and where the patient could be bled

• Zodiac figure’: another full male figure annotated with when blood can be taken from certain areas of the body depending on the time of year

View fullsize

‘Zodiac Man’

View fullsize

Obstetrics and Gynaecology

• Gynaecology and obstetrics: including a pregnant anatomical female figure, and texts related to sexuality, generation, and disorders particular to women

• ‘Wound Man’: this section illustrated various specific injuries and how to treat them

View fullsize

The original ‘Wound Man’

View fullsize

‘Disease Man’

• ‘Disease Man’: labelled with various diseases and illnesses

The Fasciculus Medicinae was published again in 1495, 1500, 1509, 1513 and 1522 by which time its information was outdated and it was replaced as a prominent textbook. However, the concept of the ‘Wound Man’ continued with new injuries matching the advancements of military technology.

Possibly the most famous example of a ‘Wound Man’ was included in Feldbuch der Wundarznei (Fieldbook of Surgery), written by the Austrian field surgeon Hans von Gersdorff in 1531.

‘Wound Men’ continued to be used in textbooks until the 17th century, their forms changing with the artistic fashions of the day.

View fullsize

‘Wound Man’ from Feldbuch der Wundarznei (Fieldbook of Surgery), written by Hans von Gersdorff in 1531

The iconography of the ‘Wound Man’ led to its inclusion in the official blazon for the Royal College of Emergency Medicine, adopted on January 24, 1997. Used on the dexter side, it was chosen to show the injured patient in contrast to the healthy man on the sinister side. He represents how emergency medics are trained to treat patients with all kinds of injuries and injury mechanisms as well as the sheer variety seen in trauma patients.

‘Wound Men’ have been potent icons in fiction as well. ‘The Wound Man’ was a potential title for Ian Fleming’s James Bond novel ‘Dr No’, published in 1958, rejected partly because of the possibility people would mispronounce it as ‘wound up’ rather than a wounded man. In the 1981 novel Red Dragon by Thomas Harris the serial killer Hannibal Lector murders a patient and displays them with multiple injuries similar to a ‘Wound Man’ illustration in one of his books. This was also included in NBC’s television series Hannibal.

It’s safe to say that Medicine is full of symbols. ‘Wound Men’ are one of the most enduring as symbols of education, traumatic injury and an example of Medicine’s roots over the centuries.

Thanks for reading

- Jamie

How Saline Earned its Salt

The other day in Resus as I was putting up a bag of fluids for a patient I wondered how long it was we’d been using what seems an incredibly simple but important intervention for our patients. “Putting up a bag of fluids” is a core part of the resuscitation of an unwell patient to the extent it just rolls off the tongue.

Turns out the history of IV saline goes back to Victorian Britain and the cholera pandemics. The Industrial Revolution brought unprecedented numbers of people to the cities, especially London where the population trebled between 1815 and 1860. In many places sewage disposal was not much changed from Tudor days and so struggled to cope. By and large the response was simply to tip the waste into cesspits or into the nearest river hence ‘The Great Stink’ of 1858 which brought the city of London and even Parliament to a standstill.

These conditions were perfect for cholera, a disease brought to Britain from the Indian subcontinent in 1832. A secretory diarrhoea spread via the faeco-oral route it ‘enjoyed’ 5 pandemics between 1817 and 1896. Cholera presents with ‘rice water’ diarrhoea (up to a litre an hour) with a mortality rate up to 70% in untreated patients largely due to extreme dehydration.

Cholera challenged medics at the time and inspired some great work such as that of John Snow on Broad Street in 1854 who rejected the miasmic theory of spread and instead proposed there was a causative agent and that contaminated water was the source. In the same year the causative agent was identified by Filippo Pacini in Italy and was first grown in culture in 1884 by Robert Koch working in Egypt and India. Fluid replacement with intravenous fluid was another such innovation.

By 1832 the work of Dr W B O’Shaughnessy had concluded that the blood of cholera patients had lost most of its water as well as its saline contents and the Lancet recommended “the injection into the veins of tepid water, holding a solution of the normal salts of the blood.” That same year Thomas Latta, a physician working in Leith, Scotland attempted to treat a patient with cholera doing just this.

He first tried treating patients with fluids inserted rectally but found that not only did it not work it actually seemed to make their vomiting and diarrhoea worse. So then he tried intravenous injection. He wrote describing how over half an hour he injected 6 pints (3.4 litres) of fluid in the basilic vein of an elderly lady with cholera: “soon the sharpened features, and sunken eye, and fallen jaw, pale and cold, bearing the manifest imprint of death’s signet, began to glow with returning animation; the pulse returned to the wrist…” Sadly he left the patient in the hands of the house surgeon who did not repeat the treatment as the patient deteriorated again and so she died 5 hours later.

That same year Dr Robert Christison wrote to the Dutch government advising them on this new treatment. He described 37 cases treated with intravenous fluids of whom 12 survived. He mentioned certain risks including air embolus, phlebitis and the potential risks of introducing so much fluid to a patient but generally recommended the treatment. Looking back there were probably other risks too such as secondary infections from unsterile injections they wouldn’t have been aware of.

In these early days there was no standardisation of what the fluid should contain with some physicians using egg whites with their fluid and some adding albumin. It wasn’t until Dr Sydney Ringer’s work in the 1880s that an optimum physiological solution was found. The dangers of potential fluid overload were identified quite early on as well with S.K. Mujumbar of Port Blair, India writing in 1916 of the need to identify cholera patients who actually need fluids so as not to cause “an extra amount of work on the already weakened and embarrassed heart”.

0.9% Saline has since become a staple of modern medicine and is included on the World Health Organisation’s list of essential medicines last published in 2017.

Further pandemics of cholera occurred in 1899-1923 and 1961-1975 by which time advances in public health medicine meant Western Europe was unaffected. The last outbreak in the USA took place in 1910-1911. Cholera remains endemic in many countries in Africa and has continued to re-surface whenever sanitation is affected such as in Haiti following Hurricane Matthew. Diarrhoeal disease is the second highest cause of mortality and leading cause of malnutrition in the under-fives worldwide. The WHO describes diarrhoea as “preventable and treatable”. Re-hydration whether orally or intravenously remains the mainstay of treatment.

So whenever we are putting up a bag of fluid for a patient we are continuing a tradition first started by Thomas Latta injecting 6 pints of fluid into the basilic vein of his patient in Leith.

Thanks for reading

- Jamie