Anti-inoculation Bomb Throwers Fizzle Out
Despite quarantine efforts, almost half of Boston is infected with small pox. Red flags fly from doors where the deadly disease has struck. Reverend Cotton Mather is been campaigning for small pox inoculations. He submits his own son, Samuel, to the experiment along with 248 volunteers. Many people think he is simply spreading the disease further. James Franklin, the elder brother of Ben Franklin and publisher of the New England Courant, is vigorously opposing inoculation. The people are in a panic. Tempers flare and someone has lobbed a grenade into Cotton Mather's home. It rolls under Mather's chair. The fuse fizzles and dies. It is a dud. At the end of the epidemic, 844 Bostonians are laid to rest. Samuel Mather lives. Out of the inoculated, only 6 die, but very few have learned this lesson... not even Benjamin Franklin who will watch his son, William, die of small pox a few years later. In 1759, Benjamin Franklin will have a pamphlet printed to promote the inoculation of children.     
The Modern Russian Empire Begins
The Great Northern War has ended better than expected for Russia. With the recent treaty, Tsar Peter the 1st (otherwise known as Peter the Great) gives up claim to most of Finland except around the capital of Saint Petersburg and he picks up Estonia, Livonia, Ingria. He also pays 2 million thalers to Sweden to call it even. Russia has been expanding the equivalent of a Netherlands every year. (There is even a Russian village in Alaska.) This treaty marks the transition point for Russia into an Empire that will live on until 1917. Emperor Peter the Great has managed to drag Russia into the modern era, and he is making the rest of Europe nervous. They have enough trouble managing with a Holy Roman Emperor. Most of them don't want a second Emperor to deal with.  
The Popes Are Reforming the Church Slowly
Pope Innocent the 13th bans the practice of nepotism... that is... handing off cushy jobs or land grants to relatives. He also reduces spending. He will hold the office for a few years and when he dies he will be succeeded by a man of few words... The Servant of God, Pope Benedict the 13th. He will abolish the lottery in Rome, and force a reduction in the lavish lifestyles in Rome. Benedict will also lift the ban on smoking.  
This Year in Wikipedia
Year 1721, Wikipedia.
- Cotton Mather - Wikipedia (2015). Retrieved on 16 October 2015. “At the extreme, in November 1721, someone hurled a lighted grenade into Mather's home.”
- James Franklin (printer) - Wikipedia (2015). Retrieved on 16 October 2015. “James began publishing the Courant in Boston in 1721 with wife, Ann, and brother, Benjamin, working alongside him. While at the Courant, James gathered a group, referred to by some as 'The Hell-Fire Club', for assistance, and introduced 'yellow journalism' to Boston. The Courant was considered controversial, and James was imprisoned for four weeks in 1722 for writing 'scandalous libel'. The paper was suppressed in 1727 and they left Boston in the same year.”
- Farmer, Laurence (August 1957). "When Cotton Mather Fought The Smallpox". American Heritage 8 (5). http://www.americanheritage.com/content/when-cotton-mather-fought-smallpox. Retrieved 30 January 2016. "During the next weeks and months it took on terrible dimensions. When it had finally run its course more than half of the small community’s ten thousand inhabitants had contracted the disease, more than eight hundred persons had succumbed to it. As if this were not enough, the town’s ordeal was heightened by a medical controversy which split the community wide open and shook it to its foundations. Bloodshed often appeared imminent. At one juncture it was avoided only by the misfiring of a grenade.".
- (2004) "Chapter V. The Rejected Blessing", Grandfather's Chair: Part II.. Retrieved on 30 January 2016. “Accordingly Samuel was inoculated; and so was Mr. Walter, a son-in-law of Cotton Mather. Doctor Boyleston, likewise, inoculated many persons; and while hundreds died who had caught the contagion from the garments of the sick, almost all were preserved who followed the wise physician's advice.”
- Benjamin Franklin, Smallpox Pamphleteer. History of Vaccines (March 19, 2010). Retrieved on 30 January 2016. “As you may have learned from our Smallpox Timeline, Franklin lost his four-year-old son to smallpox in 1736. He became an advocate of inoculation, arguing that although it was not without risk, it was far safer than natural infection.”
- Smallpox — Timelines. History of Vaccines (2016). Retrieved on 30 January 2016. “Smallpox raged through Boston in 1721, ending in 844 deaths. During this epidemic, physician Zabdiel Boylston, at Cotton Mather's urging, variolated 248 people, thereby introducing variolation to the Americas. Of those variolated, six died. The case fatality for variolation was about 3%, and the disease case fatality was 14%. About 900 people left town for fear of catching the disease.”
- Alex Shrugged notes: Assuming estimates of the population of Boston at the time are correct (about 10,000) and that half the population contracted the disease then a death rate of 844 out of 5000 is 16.9%. The citation I have from "History of Vaccines" says 14% so I assume my rough estimate is wrong. I am going with the citation.
- Revolution of Peter the Great, The. questia.com. Harvard University Press (2003). Retrieved on 1 February 2016. “Peter the Great remains the single most important figure in all of Russian history, a status that makes him, given Russia's importance in the modern world, one of the most important figures in all of modern history.”
- Treaty of Nystad - Wikipedia (2016). Retrieved on 1 February 2016. “In Nystad, King Frederick I of Sweden formally recognized the transfer of Estonia, Livonia, Ingria, and Southeast Finland (Kexholmslän and part of Karelia) to Russia in exchange for two million silver thaler, while Russia returned the bulk of Finland to Swedish rule.”
- Catherine the Great - Wikipedia (2016). Retrieved on 1 February 2016. “Yekaterina Alexeyevna or Catherine II, also known as Catherine the Great 2 May [O.S. 21 April] 1729 – 17 November [O.S. 6 November] 1796), was the most renowned and the longest-ruling female leader of Russia, reigning from 1762 until her death in 1796 at the age of 67. She was born in Stettin, Pomerania, Prussia as Sophie Friederike Auguste von Anhalt-Zerbst-Dornburg, and came to power following a coup d'état when her husband, Peter III, was assassinated. Russia was revitalized under her reign, growing larger and stronger than ever and becoming recognized as one of the great powers of Europe.”
- Pope Benedict XIII - Wikipedia (2016). Retrieved on 1 February 2016. “Pope Benedict XIII repealed the world wide smoking bans that had been set by Pope Urban VII back in 1590 and the one imposed by Pope Urban VIII.”
- Pope Innocent XIII - Wikipedia (2016). Retrieved on 1 February 2016. “Pope Innocent XIII was reform-oriented, and he imposed new standards of frugality, abolishing excessive spending. He took steps to finally end the practice of nepotism by issuing a decree which forbade his successors from granting land, offices or income to any relatives - something opposed by many cardinals who hoped that they might become pope and benefit their families.”