The effects of incessant labours were beginning seriously to tell on Jenner’s health, when in 1810 he lost his eldest son from consumption, in his 21st year. This event preyed much on his mind, and left him in a state occasioning great anxiety to his friends. In the same year he lost his firm friend the Earl of Berkeley, and his beloved sister, Mrs. Black. Under these troubles he felt the more acutely the calumnious attacks to which he was constantly subjected. Dr. Parry of Bath, writing to him about this time, says—“For Heaven’s sake, think no more of these wasps, who hum and buzz about you, and whom your indifference and silence will freeze into utter oblivion. Let me again entreat you not to give them one moment’s consideration, _opus exegisti ære perennius_. The great business is accomplished, and the blessing is ready for those who choose to avail themselves of it; and with regard to those who reject it, the evil will be on their own heads.” In 1811 occurred the first well-authenticated case of smallpox in a boy vaccinated by Jenner, the Hon. Robert Grosvenor. The disease became severe and threatened death, when all at once the later stages were passed through rapidly, and a good recovery was made. Other vaccinated children in this family were exposed to the contagion, and did not suffer. There seemed every reason, as Jenner explained, to ascribe the failure of protection in the first case to a peculiarity of constitution which would probably have exposed the patient to a second attack of smallpox. In fact, Dr. Jenner had vaccinated the child when in weak health at a month old. Lady Grosvenor was timid, and prevailed on him, contrary to his usual practice, to make one puncture only; and the pustule that resulted was deranged in its progress by being rubbed by the nurse. Nevertheless the case created much alarm and excitement, and greatly exhilarated the anti-vaccinists. Jenner’s simple answer was to admit the fact, alleging that if ten, fifty, or a hundred such events should occur, they would be balanced a hundred times over by cases of second attacks of smallpox. “I have ever considered the variolous and the vaccine radically and essentially the same. As the inoculation of the former has been known to fail in instances so numerous, it would be very extraordinary if the latter should always be exempt from failure. It would tend to invalidate my early doctrine on this point.” A letter of Jenner to Dr. Baron on this subject, exhibits perhaps the utmost degree of irritation that he showed. “The Town is a fool—an idiot,” he remarks, “and will continue in this red-hot, hissing-hot state about this affair, till something else starts up to draw aside its attention. I am determined to lock up my brains and think no more _pro bono publico_.... It is my intention to collect all the cases I can of smallpox, after supposed security from that disease.”