Catherine then sought to have inoculations throughout her empire stating: "My objective was, through my example, to save from death the multitude of my subjects who, not knowing the value of this technique, and frightened of it, were left in danger." By 1800, approximately 2 million inoculations were administered in the Russian Empire.In China, the Qing dynasty had extensive protocols to protect Manchus from Pekings endemic smallpox. U.S. Presidents George Washington, Andrew Jackson, and Abraham Lincoln all contracted and recovered from the disease. Washington became infected with smallpox on a visit to Barbados in 1751. Jackson developed the illness after being taken prisoner by the British during the American Revolution, and though he recovered, his brother Robert did not. Lincoln contracted the disease during his presidency, possibly from his son Tad, and was quarantined shortly after giving the Gettysburg address in 1863.Famous theologian Jonathan Edwards died of smallpox in 1758 following an inoculation.Soviet leader Joseph Stalin fell ill with smallpox at the age of seven. His face was badly scarred by the disease. He later had photographs retouched to make his pockmarks less apparent.Hungarian poet Ferenc Kölcsey, who wrote the Hungarian national anthem, lost his right eye to smallpox. Tradition and religion
In the face of the devastation of smallpox, various smallpox gods and goddesses have been worshipped throughout parts of the Old World, for example in China and India. In China, the smallpox goddess was referred to as Tou-Shen Niang-Niang (Chinese: 痘疹娘娘).
The chlorine group at the 6-position of the heterocyclic ring is more reactive than the chlorine at the 2-position, hence it can be selectively replaced by an amino group, which was then converted to an amide using nitrous acid. Finally, the remaining chlorine was replaced by the amino group of aciclovir using ammonia in methanol. This synthesis and other methods for preparing the compound have been reviewed. History
Aciclovir was seen as the start of a new era in antiviral therapy, as it is extremely selective and low in cytotoxicity. Since discovery in mid 1970s, it has been used as an effective drug for the treatment of infections caused by most known species of the herpesvirus family, including herpes simplex and varicella zoster viruses. Nucleosides isolated from a Caribbean sponge, Cryptotethya crypta, were the basis for the synthesis of aciclovir. It was codiscovered by Howard Schaeffer following his work with Robert Vince, S. Bittner and S. Gurwara on the adenosine analog acycloadenosine which showed promising antiviral activity. Later, Schaeffer joined Burroughs Wellcome and continued the development of aciclovir with pharmacologist Gertrude B. Elion. A U.S. patent on aciclovir listing Schaeffer as inventor was issued in 1979. Vince later invented abacavir, an nRTI drug for HIV patients. Elion was awarded the 1988 Nobel Prize in Medicine, partly for the development of aciclovir. A related prodrug form, valaciclovir came into medical use in 1995.