The Spanish orphans who became living vaccine incubators

In this blog our Senior Research Fellow, Professor Ken Donaldson, looks at the history of transporting vaccines.

We are currently at the mercy of a pandemic and are awaiting ‘cavalry’ in the form of vaccines.  The first vaccine that has emerged from testing needs to be stored at -70 o and this highlights the necessity for safe and careful storage of vaccines. This is imperative since the success of vaccination relies entirely on the structural integrity of the vaccine. This is because it represents the target the immune system is being directed towards. If it isn’t a faithful copy of the whole or part of the microbe in question, or if it is degraded in any way, then the immune response it produces could be useless.  Fortunately, additional vaccines in the pipeline which appear equally effective do not need to be stored under such stringent conditions, making universal vaccination less challenging. We are fortunate indeed that, not only do we have the wherewithal to develop vaccines, but also simpler and somewhat more ethical methods of preserving them than in the past, as this blog will show!

Small Pox

Amongst infections of the past, few were as feared as smallpox. I have written a blog about smallpox previously and that provides a more extensive background to the disease than can be afforded here; you can access the blog here. Smallpox has been around since ancient times, becoming epidemic in Europe between the 5th and 7th centuries and killing millions of people right up to the 20th century. Caught from droplets released by coughs and sneezes and from the skin lesions (vesicles) it causes, it starts with a skin rash but affects all the main organ systems. The disease progresses to high fever, killing up to one half of those infected and blinding or severely scarring the skin of most of the survivors.

The discovery of variolation

It had no doubt been noted that those who caught a mild version of smallpox never caught the full-blown disease. Some cultures therefore took scrapings from the skin lesions and made these into a powder: This was delivered by sniffing into the lungs, conferring protection against future infection. In a variant of this approach, called variolation, scabs or pus from smallpox lesions were scratched into the skin, also generally producing resistance to disease. Although mild symptoms of fever and sometimes minor rash ensued from such inoculations, even a mild infection was enough to produce immunological memory and so patients were effectively immunised. There were, however, obviously risks of inducing full-blown smallpox itself from this procedure and this occurred quite commonly.

The discovery of vaccination

By the late 18th century it had been noted in the UK that infection with a very similar disease to smallpox, called cowpox and caught from cattle, could protect against smallpox. The fact that milkmaids, for whom cowpox was an occupational disease, had a beautiful complexion, never marked by smallpox like many women, was a clue that Dr Edward Jenner spotted. He went on to show that infecting with the live cowpox virus , called vaccination after vacca the Latin for cow, produced a mild rash and fever that resolved, leaving the recipient protected for ever against smallpox. Jenner thus showed that the close similarities between the cowpox and smallpox microbes meant that an immune response raised against cowpox was also effective against smallpox, ensuring that vaccination was a success. Jenner published on his theories and findings about vaccination and in 1798 he wrote a book about his experiences, following which vaccination gradually grew in popularity in the UK.

The Spanish response

By 1800, news of Jenner’s breakthrough in preventing such a terrible disease had reached Europe. Spain, whose many colonies had especially suffered the scourge of smallpox, sought to take advantage of this new technology. The ruling King Charles IV had experience of smallpox, since many members of the Bourbon royal family had been afflicted. The King read Jenner’s book, describing the benefits of vaccination with cowpox virus in preventing smallpox infection in 1799, and was immediately galvanised into action. He called a meeting and sought advice from the Royal Physician Dr Joseph Flores who drew up plans to send a team to the New World bringing vaccination to the Spanish colonies there.

The Spanish Royal Vaccine Expedition

The expedition was formally named the The Spanish Royal Vaccine Expedition but also the Balmis expedition on account of the Director, Dr Francisco Javier Balmis (1753-1819), whose drive was very important to the success of the expedition.   The corvette Maria Pita was chosen to carry the medical team and deliver the wherewithal to initiate smallpox vaccination in the Spanish colonies. The ship was headed by Captain Pedro del Barco y Espana, and contained members of the vaccination group: director (Balmis), deputy director, 3 assistant surgeons, 2 first aid practitioners and 4 nurses

The Maria Pita departs from A Coruna in 1803 on its smallpox vaccination expedition.  (Unknown author, Public domain, via Wikimedia Commons)

Transporting the cowpox vaccine

Of most interest to this article was the method employed to get a viable and useable vaccine at the end of the journey across the Atlantic. At this time there was no real knowledge of the nature of the harmful entity in smallpox but, as Jenner had shown, fresh pustules of cowpox were a source of vaccine. There were no fridges or freezers nor the least idea how to preserve a vaccine and so a remarkable approach was adopted whereby the infection was passed along a human chain of children during the long transatlantic journey. To achieve this, 22 orphaned Spanish children, between 3 and 9, were brought along in the care of  Isabel Zendal, who is considered by the World Health Organisation to be the first nurse in history to be sent on an international mission. Groups of two children were used at each stage and at the outset of the expedition 2 children were infected with cowpox from a cow.  After setting sail on 30 November 1803 these children soon developed infectious vesicles and on day 10 of their infection, doctors sampled the vesicles of the  ‘cowpox children’ and injected this into the arms of two unimmunized children who then developed cowpox. On day 10 of infection the vesicles on the arms of these next ‘cowpox children’ were used as source of material to transfer the infection to the arms of yet another two healthy children. In this way, on arrival in the New World, there were a number of children who had recovered from cowpox but, most importantly, two children who had fresh infection and had pustules from which vaccine could be prepared.

Monument in A Coruña in honor of the orphan children who took part of the expedition. The original uploader was Caronium at Galician Wikipedia. (Original text: Caronium), CC BY-SA 3.0 http://creativecommons.org/licenses/by-sa/3.0/, via Wikimedia Commons

On arrival in the New World the Maria Pinta took on a further 26 Mexican boys as the new vaccine carriers and then travelled around to many Spanish colonies and in all, almost 1.5 million vaccinations were achieved in the Canary Islands, Colombia, Ecuador, Peru, Mexico, the Philippines and China

The legacy of the expedition

This was a remarkable humanist undertaking on a truly international scale and one writer described it thus:-  ‘the expedition is a model of how an expensive, logistically complex international public health effort can translate advanced medical therapy into local cultural contexts.’ It is estimated that a quarter of a  million children were vaccinated and Jenner himself described the expedition thus “I cannot imagine that the annals of history will provide a more noble or extensive example of philanthropy than this one’.

 Although we may have qualms about the use of the orphan children in in the present day and careful of an ‘ends justifies the means’ argument, one writer observed that

 ‘forming a living transmission chain (through the orphans), may not be an acceptable vaccination method by our current hygienic and professional standards; yet it was a creative and effective way of carrying the vaccine at a time when refrigeration, sterile containment, and asepsis were nonexistent’.

The Balmis expedition was the first international vaccination campaign and it was a huge success that should be better publicised in order to try and counter the current irresponsible and dangerous anti-vax craze that is sweeping the world.

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