Wednesday, May 19, 2021

Vaccine heroes and Empress Catherine the Great of Russia

On desktops click to enlarge

Margaret Heckler (née O'Shaughnessy was US Ambassador to Ireland 1986-1989; Heckler played a crucial role in obtaining a $120m grant for the International Fund for Ireland, an economic development organisation: 1931-2018) was President Reagan's secretary of health and human services in 1984 when she predicted that there would be a vaccine for HIV/AIDS within 2 years, and 37 years later there still isn't one. In an interview in 2006 Heckler said that Dr Anthony Fauci (1940-) "was so dedicated that he never took time out for lunch. He simply came to my meeting in his white coat and went right back to the Clinical Center. That was the spirit. Now, he was extraordinarily devoted and conscientious about it."

I end this piece with a comment from Dr Fauci on Covid-19.  

Vaccines are rare and in 2016 the US Centers for Disease Control (CDC) listed 26 diseases that can be countered with a vaccine. Nine are for particular groups or travel, including smallpox which was eradicated by 1979. 

Only 43 significant first vaccines to counter a disease have been produced in the Western World in 1796-2020 (see below).  

On October 12, 1768, Thomas Dimsdale, (1712-1800), an English physician, arrived in St Petersburg to give a smallpox vaccine to Empress Catherine the Great of Russia (1729-1796) who was a former Prussian princess. The method of vaccination was called variolation (from the variola virus that caused smallpox) or inoculation. Dimsdale made small cuts in the monarch's arms, and with a cloth, he rubbed pus from a 6-year old infected boy into the cuts. After 4 days the empress got a dose of mild fever and following another 10 days, she felt well and ordered Dimsdale to give the vaccine to her heir, Grand Duke Pavel Petrovich. The doctor got the title Baron of the Russian Empire and a large gift of money, and he returned to Russia in 1781 to vaccinate Konstantin and Alexander, Pavel Petrovich’s sons.

Catherine often corresponded with Voltaire, the nom de plume of François-Marie Arouet (1694-1778), but they never met. She wrote that “the mountain had given birth to a mouse” and called her contemporary anti-vaxxers (people opposed to vaccines) “truly blockheads, ignorant or just wicked.”

The satirist had become obsessed with Russia and had written a book about Peter the Great (1672-1725). In 1717 a week after Czar Peter was welcomed to Paris by the 7-year-old King of France, Louis XV, Voltaire was imprisoned in the Bastille for mocking the French royal family. A year later he had become Voltaire.

Catherine had married Peter the Great's grandson Czar Peter III (1728-1762) and was suspected of his murder in an army coup. Voltaire praised Catherine for her commitment to modern medicine and she responded that the best medicine for her while recovering from the inoculation, was the laughter that came from reading Voltaire's 'Candide' (1759). The happy ending of the book in Turkey dovetailed with the Czarina's imperial policy as she had gone to war against the Ottoman Empire in 1768; she promised to conquer Constantinople on Voltaire's behalf, so that he, too, might retire in Turkey, just like Candide.

The Russo-Turkish War of 1768–1774 was a major conflict that saw Russia triumph over the Ottoman Empire.

The term 'small pockes' (pocke meaning sac) dates from the 16th century, so-called to distinguish it from the 'great pockes" — an archaic name for syphilis.

Smallpox was a scourge of humanity from antiquity until it was declared eradicated in 1979 by the World Health Organisation (WHO). For example traces of smallpox pustules (bumps on the skin that contain fluid or pus) were found on the head of the 3,000-year-old mummy of the Pharaoh Ramses V and it may have originated in Egypt or India. It is believed that the disease was introduced to Europe sometime between the 5th and 7th centuries and it often triggered epidemics during the Middle Ages. Europeans introduced it to the Americas, which had a devastating effect as the natives had zero immunity to it.

A Bangladeshi child with smallpox 1973
The US Centers for Disease Control say smallpox was a terrible disease. People who survived usually had scars, which were sometimes severe. It could also result in blindness. "Before smallpox was eradicated, it was mainly spread by direct and fairly prolonged face-to-face contact between people. Smallpox patients became contagious once the first sores appeared in their mouth and throat."

Between 1% to 2% of those variolated died as compared to 30% who died when they contracted the disease naturally.

Even in the late 1800s, the case-fatality rate in infants was up to 80% in London and 98% in Berlin.

The writer and poet Lady Mary Wortley Montagu (1689-1762) learned about variolation in Constantinople in 1717 when she was the wife of the British ambassador there. She had survived the disease herself and had her children inoculated. Back in London in 1721, her advocacy of variolation was viewed with scepticism.

However, Caroline, princess of Wales (1683-1737), wished to have her children inoculated. It went ahead after an experiment with prisoners and abandoned children, under the supervision of Sir Hans Sloane (1660-1735), the Royal Physician who was Anglo-Irish.

Inoculation was risky and in 1782 and 1783, two young sons of King George III (1738-1820) died after the procedure.

Edward Jenner vaccinating 8-year old James Phipps, May 1796

Genesis of the modern vaccine — word derived from Latin for cow: vacca

In 1914 Sir Francis Darwin (1848-1925), son of the famous English naturalist, geologist and biologist, in a memorial lecture on Sir Francis Galton, a noted polymath, said that " science, the credit goes to the man who convinces the world, not to the man to whom the idea first occurs."

It was known among some English farmers in the 18th-century that cowpox (also called vaccinia), a mild disease of cows, when transferred to otherwise healthy humans produced immunity to smallpox.

Benjamin Jesty (c. 1737–1816), a Dorset farmer, was one of the pioneers of vaccination using cowpox material. He had contracted cowpox himself and had acquired immunity to smallpox.

According to the Lancet, the British medical journal, "During 1774, in the face of a smallpox epidemic, he vaccinated his wife and two young sons with cowpox lymph taken from lesions on the udder of an infected cow. Jesty devised and undertook his vaccination method 22 years before Edward Jenner, who is usually credited as the originator of the same practice."

In 1805 a panel of experts in London confirmed that Robert Jesty, Jesty's eldest son, had still immunity to smallpox acquired in 1774.

Edward Jenner (1749-1823) is said to have heard a dairymaid say when he was in his teens “I shall never have smallpox for I have had cowpox. I shall never have an ugly pockmarked face.” He later practised as a physician in Berkeley, Gloucestershire, England, and he also maintained an interest in the natural sciences.

In May 1796, Jenner met a young dairymaid, Sarah Nelms, who had fresh cowpox lesions on her hands and arms and using matter from Nelms' lesions, he vaccinated (a word coined by Jenner), an 8-year-old boy, James Phipps, who was the son of his gardener. The boy developed a mild fever and he recovered after 10 days. In July 1796, Jenner inoculated the boy again, but this time with smallpox material. James showed that he was immune to it.

The House of Commons granted Dr Jenner the sum of £10,000 in 1802 and 5 years later the Parliament awarded him £20,000 more. The sum of £30,000 in 1807 was worth £2.8m in 2020.

Jenner gave the adult James Phipps and his family a free lease on a cottage in Berkeley.

Britain banned variolation in 1840, and in 1853 vaccination of children against smallpox became compulsory in England and Wales. In Scotland and Ireland, the ratio of deaths among children under 5 years still remained at 75% of the total smallpox deaths, until compulsory vaccination was introduced by law in 1863.

In November of that year shortly after President Lincoln (1809-1865) delivered his Gettysburg Address on the site of a Pennsylvania battlefield, the president almost died when he became ill with symptoms of smallpox.

1802 "The Cow Pock—or—the Wonderful Effects of the New Inoculation" plays on the fears of vaccines.
© The British Museum

Vaccine heroes

From Jenner to Covid-19 in more than two centuries 43 significant vaccines in the Western World have first been developed to counter a disease (for example in the 183 years until smallpox was eradicated variations of vaccines were used ). See here and here.

Louis Pasteur (1822-1895) of France was likely the greatest scientist of the 19th century. His work on food safety and medicine were stunning achievements as were vaccines for anthrax and rabies. It has been claimed that "The discovery of the chicken cholera vaccine ...revolutionized work in infectious diseases and can be considered the birth of immunology."

I wrote last year on Maurice Hilleman (1919-2005), who was a prolific developer of vaccines:

Pandemics: Forgotten vaccine hero saved millions of lives

Jonas Salk (1914-1995) and Albert Bruce Sabin (1906-1993) separately developed vaccines for polio. These gifts to humanity were launched respectively in 1952 and 1962.

I remember in primary school taking the Sabin vaccine including a cube of sugar! It was an oral vaccine (administered in drops or on a sugar cube). It eclipsed Salk's vaccine across the world as the latter was by injection.

The Covid-19 vaccines are the culmination of years of research.

The Pfizer-BioNTech and Moderna vaccines use Messenger RNA (mRNA) which gets our cells to make a protein — or even just a piece of a protein — that triggers an immune response inside our bodies.

The Sinovac, Oxford-AstraZeneca and Johnson and Johnson vaccines are called Viral Vector vaccines which use a modified version of a different virus (the vector) to deliver important instructions to our cells.

None of the vaccines use the live virus that causes Covid-19 nor do they interfere with the human genetic DNA (deoxyribonucleic acid).

Pfizer, the American pharmaceutical firm, has said that the production of its vaccine requires 280 inputs from suppliers in 19 countries.

Katalin Karikó and Drew Weissman getting vaccinated in December 2020

The 66-year old Katalin Karikó, a Hungarian-born biochemist who emigrated to the US in 1985, has, at last, got recognition for her decades of work on the development of mRNA. At the University of Pennsylvania, she had temporary positions and problems with funding. A member of the staff agreed to file for a patent when she told him that her discovery could halt his receding hairline!

Dr Karikó told The New York Times that her annual earnings were never more than $60,000. Compare that with Andrew Cuomo, New York governor, who will receive more than $5m from his book about leadership during the Covid-19 pandemic!!

The scientist collaborated with Prof Drew Weissman from 2005 and there is speculation that they may be awarded a Nobel Prize.

Dr Karikó is now a vice president at BioNTech, the German biotech firm that is Pfizer's vaccine partner.

Dr Özlem Türeci and Dr Ugur Sahin who are wife and husband founded BioNTech

Sahin's family moved from Turkey to Germany when he was 4 years old while Türeci was born in Germany.

Prof Sarah Gilbert of the Jenner Institute at the University of Oxford, led the team that developed the Oxford-AstraZeneca vaccine:

Innovation in modern times involves teams and we the beneficiaries of the vaccines that have been produced in record time should appreciate the stunning contribution of the relative few to the Earth's population of over 7bn.

Let us hope that sometime in 2021 or 2022 all countries will have access to sufficient vaccinations. However, vaccine hesitancy may prevent the vanquishing of the virus.

“We need to have some humility here,” Dr Anthony Fauci, the adviser to President Biden, has said on herd immunity. “We really don’t know what the real number is. I think the real range is somewhere between 70 to 90%. But, I’m not going to say 90,” he added.