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Smallpox vaccine mystery persists

As any high school student will testify, the first, foremost and famous vaccine in history was the one first developed in 1798 by Edward Jenner against smallpox.

It is curious, then, and not a little ironic, that today no one knows what source virus Jenner used to create his life-saver.

Smallpox was once the lethal scourge of millions. Jenner’s creation started a public health battle that ended in 1980, when the virus (a few samples securely locked away in laboratories notwithstanding) was declared eradicated.

According to the standard, school-approved, story, Jenner’s insight came when he noticed that while every year lots of people fell ill to smallpox, milkmaids didn’t. He reasoned that this was because cows regularly contracted a disease called cowpox – a similar but mild illness that didn’t seem to affect people, but resulted in blistered udders.

By touching the cowpox blisters, Jenner wondered, were the milkmaids absorbing something that protected them from smallpox? Experiments began, and the world has been forever grateful since…

Certainly, as the war against smallpox continued over the ensuing decades cowpox was often used as the source of the virus for the vaccine. The cow disease was caused by a very weak close relative of the much more virulent human one. Introduced into the bloodstream, cowpox prompted the immune system to produce antibodies, which worked triumphantly against both viruses.

But was it the source virus used by Jenner himself? Is the classroom story correct in this (one might suggest critical) respect?

Simply running a genetic line back from the virus used today to produce smallpox vaccine would not, frustratingly, provide an answer. These days, the vaccine is derived from a virus known as vaccinia, which exists only in laboratories. No one knows where it came from.

This rather awkward admission arises because of very poor record-keeping a long time ago. Vaccinia has not been found anywhere outside of lab cultures. Genetically, it is a combination of cowpox and smallpox. It’s very effective as a vaccine source, but given its mixed heritage is almost certainly not a direct descendent of Jenner’s original culture.

Opening this 1902 vial of smallpox vaccine resulted in surprises.

Joe Esparza

Now, research reported in the New England Journal of Medicine throws a new possible source into the pot.

A letter from a team of researchers led by Livia Schrick of the Robert Koch Institute in Germany reports on the gene sequencing of a rare smallpox vaccine sample dating from 1902.

The scientists opened a vial of vaccine made in 1902 by a Philadelphia company, HK Mulford.

After amplifying and sequencing the genetic material recovered, the team found that the contents bore a 99.7% similarity not to cowpox but to another virus, horsepox.

Even more curiously, they also found that certain DNA components were missing at either end of the sequence created. These deletions are not present in the genomes for either cowpox or horsepox – but they are found in vaccinia.

Jenner, of course, lived in Britain, and the 1902 vaccine sample was made in the US, so Schrick and her colleagues in one sense move us no closer to identifying the absolute original source of the smallpox treatment.

However, they suggest, the data does at least add weight to the suggestion that the virus that in the end did most of the work in eradicating disease – vaccinia – derived from an equine and not a bovine ancestor.

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