ear Reader,

I have subjected the characters of WHEN HE WAS WICKED to more than their fair share of medical misfortune. Researching the conditions of both John and Michael was complicated; I had to make sure that their disease processes made scientific sense, while at the same time revealing only what was known by medical science in 1824 England.

John died of a ruptured cerebral aneurysm. Cerebral aneurysms are congenital weak spots in the walls of blood vessels within the brain. They may lie dormant for many years or they may rapidly enlarge and then rupture, leading to bleeding in the brain, which can be followed by unconsciousness, coma, and death. Headaches brought on by ruptured cerebral aneurysms are sudden and explosive but can be preceded by a lingering headache for some time prior to the actual rupture.

Nothing could have been done to save him; even today approximately one-half of ruptured cerebral aneurysms lead to death.

During the 19th century, the only way to make a definitive diagnosis of a ruptured cerebral aneurysm was at autopsy. It is extremely unlikely, however, that an earl would have undergone a postmortem dissection; therefore, John’s death would have remained a mystery to those who loved him. All Francesca would ever know was that her husband had a headache, lay down, and died.

The turning point in the treatment of cerebral aneurysms came with the widespread use of angiography in the 1950s. This technique, which consists of the injection of radiopaque dye into the vessels feeding the brain to give an X-ray picture of the vascular anatomy, was developed by Egas Moniz in Portugal in 1927. An interesting historical footnote: Moniz won the Nobel Prize for Medicine in 1949, but not for his work in the ground-breaking and life-saving field of angiography. Rather, he was honored for his discovery of the frontal lobotomy as a treatment for psychiatric illness.

As for malaria, it is an ancient disease. Throughout recorded history, it has been observed that exposure to warm, moist, humid air is associated with periodic fevers, weakness, anemia, kidney failure, coma, and death. The name of the disease comes from the Italian for “bad air,” and reflects the belief of our ancestors that the air itself was to blame. In When He Was Wicked, Michael cites “putrid air” as the source of his illness.

Today we understand that malaria is in fact a parasitic disease. The hot, swampy conditions themselves are not to blame, but rather serve as breeding grounds for mosquitoes of the genus Anopheles, the vector of the infection. During an insect bite, female Anopheles mosquitoes unwittingly inject microscopic organisms into the hapless human host. These organisms are single-celled parasites of the genus Plasmodium. There are four species of Plasmodium that can infect people: falciparum, vivax, ovale, and malariae. Once in the bloodstream, these microorganisms are swept into the liver, where they multiply at a furious pace; within a week, tens of thousands of parasites are released back into the bloodstream, where they infect red blood cells and feed upon the oxygen-carrying hemoglobin inside. Every two or three days, through a synchronized process that is poorly understood, the offspring of these parasites erupt from the red cells, leading to high fevers and violent chills. In the case of falciparum malaria, the infected cells can become sticky, and glom onto the inside of blood vessels in the kidney and brain, leading to renal failure and coma—and death, if treatment is delayed.

Michael was fortunate. Although he did not know it, he suffered from vivax malaria, which can persist in patients’ livers for decades but rarely kills its victims. The exhaustion and fevers caused by vivax malaria, however, are severe.

At the end of the book, both Michael and Francesca worry that a higher frequency of attacks might indicate that he was losing his battle with the disease. In truth, with vivax malaria, this would not have mattered. There is little rhyme or reason to when a vivax patient might suffer an episode of malarial fevers (except in the case of immunosuppression, such as cancer, pregnancy, or AIDS). In fact, some patients experience a complete cessation of fevers and remain healthy for the rest of their lives. I’d like to think that Michael was one of the lucky ones, but even if not, there is no reason to think that he did not live to a ripe old age. Furthermore, since malaria is strictly a blood borne disease, he could not have transmitted it to members of his family.

The cause of malaria would not be understood for decades after WHEN HE WAS WICKED took place, but the fundamentals of treatment were already known: A cure could be achieved by consuming the bark of the tropical cin-chona tree. This was usually mixed with water, yielding “quinine water.” Quinine was first sold commercially in France in 1820, but its use was fairly widespread for some time prior.

Malaria has been mostly eradicated from the developed world, in large part because of mosquito control efforts. However, it remains a leading cause of death and disability among people who live in the developing world. Between 1 million and 3 million people die of falciparum malaria every year. That averages one death every thirty seconds. Most of the dead are in sub-Saharan Africa, and most are children under five years of age.

A portion of the proceeds of this book will be donated to malarial drug development research.

Sincerely,