Armand Leroi's Mutants: where the Mutter Museum meets Geek Love

Mutants: On Genetic Variety and the Human Body by Armand Marie Leroi explores the genetic and developmental reasons for variations in the human form. I thought this book would be a good follow up from Inheritance, which focuses on rare genetic disorders that often have a relatively minor physical abnormality, such as eyes that are widely space (hypertelorism). Based on the cover and title, I expected the book to be a bit of a carnivalesque spectacle– part Mutter Museum, part Geek Love. In fact, the text treated these "mutants" respectfully and with due scientific diligence. The focus was generally on the developmental pathways that were altered in the mutations observed, but there was some exploration of the toll these mutations took on their bearer.

The book begins with the historical observations of mutants and the explanations for why these mutations arose. In the beginning, "monsters" were thought to be caused by the wrath of God. Eventually, scientists began to understand the developmental causes for these variations. In a chapter called "A Perfect Join", Leroi writes about conjoined twins, specifically how they form. Interestingly, conjoined twins are more likely to have a condition called situs inversus, where the internal organs are inverted on the left-right axis. In fact, the rare singleton birth with this condition has been useful in teaching us why our organs are oriented the way they are. Situs inversus is one symptom of Kartagener's syndrome, which is caused by a mutation in one of the proteins (dynein's outer arm) that control the movement of cilia (tiny projections on the surface of many different cell types). The other symptoms are chronic bronchitis (cilia are important for clearing the lung and nasal passages) and sterility in males (the same proteins are required for the movement of sperm). I always find it amazing how a small mutation in one protein can have such profound consequences. My favorite lines from the book describe how scientists study gene function: "It is actually quite hard to prove that a gene...does what one supposes. One way...is to eliminate the gene and watch what happens. This is rather like removing a car part...to see why it's there. Sometimes only a rear-view mirror falls off, but sometimes the car dies."

A funny story arises in the explanation of the Hox genes, which essentially control the pattern of embryonic development such that Hox1 makes a head, Hox2 makes a torso, etc. Mutations in Hox genes can lead to abnormal body plans, even changes in the number of vertebrae and ribs. About one in every ten adults has an extra pair of ribs, an abnormality that was first observed in a woman, leading the doctors on the case to conclude that it was evidence of the truth of Adam and Eve. In reality, the physiological variation occurs at equal rates in men and women.

The chapter on skin color explores the mutations that lead to albinism, piebaldism, and even red hair. Dozens of different mutations in MC1R (melanocortin 1 receptor), a protein that helps control pigmentation, have been described in red heads. (Because my house has three different types of red heads, I really fell into an Internet rabbit hole on this subject. I think I will write something more about this later.) The genetics of skin color are also complex and have been difficult to study due to the complicated social issues surrounding the subject. Leroi tells the story of a white woman living in Apartheid-era South Africa. Following a diagnosis with Cushing's disease, her adrenal glands were removed, which led to hyperpigmentation due to an abundance of the hormone melanotrophin. As her skin darkened, her social status and living conditions quickly changed. To me, the story highlights the problem with thinking that we can biologically define race. (A Troublesome Inheritance was released recently and covers this very topic, so watch this space for my review.)

Leroi also discusses the genetic basis for aging; in the simplest terms, aging is due to the "inability of natural selection to act against the mutations that cause disease in the very old." This hypothesis explains why dominant mutations like Huntington's can fix in the population. An experiment in fruit flies explored what would happen if only aged flies were reproducing; the effect should be an increase in genetic changes that promote longevity and fertility at an advanced age. After ten generations, the longevity of these flies increased by 30%; after fifty generations, life expectancy doubled. The flies were generally hardier, but the increased life expectancy came at a cost: the fruit flies were less active in their youth as they needed to preserve themselves to ensure survival and mating. This experiment supports the idea that aging comes at the expense of vitality in youth.

Overall, Mutants was quite readable; it had a nice balance of the science behind the mutations and the descriptions of the lives of the people who were affected with these mutations. I should note that the book was released in 2003, so some of the science is a bit out of date. For me, a good read is one that teaches me new science and spurs me to read and write more. Mutants definitely fits the bill in that regard. 

Dr. Mütter's Marvels can tide you over as you await the return of The Knick

I am anxiously awaiting the return of The Knick, Steven Soderbergh's original series on Cinemax (Season 2 is scheduled to premiere in fall 2015). Set in the fictional Knickerbocker Hospital in New York City at the turn of the twentieth century, the show focuses on Dr. John Thackery (played by Clive Owens), a doctor who pushes the boundaries of medical techniques (with some mixed results). This fascinating and dark series is unique in its setting (although it does remind me a bit of Deborah Blum's The Poisoner's Handbook) and content. The episodes often highlight the limits of surgery at the time. (Slate did a nice piece on the historical accuracy of the show.)

The Knick also includes appearances from several historical characters, including Typhoid Mary and Dr. Henry Cotton. (Interestingly, Cotton also makes an appearance in the HBO show Boardwalk Empire, which occurs a few decades later.) Cotton thought that insanity was due to infection and prescribed the removal of various organs and teeth for his patients. The doctor took his approach to the extreme by removing all of the teeth from both of his children to ensure their sanity. Ironically, both children committed suicide. (Two great articles about Cotton's unique cure: Neuroskeptic and Oddly Historical.)

The Knick is one of those shows that you think about long after it is over. It also made me curious about medical history in that time period. When I found the book Dr. Mütter's Marvels: A True Tale of Intrigue and Innovation at the Dawn of Modern Medicine by Cristin O'Keefe Aptowicz, I knew I had to read it. The book details the development of medicine in the mid-1800s. The focus of the book is Thomas Dent Mütter (nee Mutter, 1811-1859), a plastic surgeon "who took on the realities of nineteenth century medicine: performing complex surgeries on patients that were wide awake, in an unsterilized environment, lit by candle, lamp, or daylight." Mütter was integral in the founding of Jefferson Medical College in Philadelphia; he played an important role in innovating the practice of surgery, the care of patients, and the teaching of medicine. While short-lived, Thomas Mütter had a lasting effect in the lives of many of his students, many of whom went on to make their own historical contributions in medicine.

Mütter became a doctor at the leading edge of a surgical revolution. At the start of his career, neither anesthesia nor aseptic technique was in practice. Imagine a time when patients were at least partially conscious for a surgery. Surgeries occurred in large operating theaters where the seats closest to the action were in the highest demand. In addition to medicinal wine, alcohol, laudanum and opium were sometimes available for patient use. Surgeons were assisted by nurses as well as several burly men, who held the patient down during surgery. There were, of course, stories of patients who broke free, attacking the doctor and running out of the room, "leaving a trail of their own blood behind them". Operating rooms were a gruesome place and surgery was only performed for the most difficult cases. When the procedure was over, the patients were immediately sent home in a carriage, with no recovery time and no after care. At Jefferson Medical College, Mütter insisted that recovery rooms be built to improve outcomes for patients. Dr. Mütter had a revolutionary approach to patient care, investing time with his patients both before and after the operation; his bedside manner was likely driven by his own experiences as a patient, having suffered many years of ill health due to gout. The success of Mütter's methods was reflected in the relatively low mortality rates for Jefferson Medical College.

The Ether Dome at MGH

The book details the fascinating history of the development of anesthesia, which is peppered with nitrous-addicted doctors and unfortunately-time side effects. As early as the 1830s, nitrous oxide and sulphuric ether were in recreational use (at "laughing gas parties and ether frolics") and were even found in use in sideshows, where promoters ballyhooed their strange and amazing properties. In 1844, a dentist named Horace Wells stumbled upon one of these sideshows and realized the therapeutic potential of these compounds. Unfortunately for Wells, his first public display of the use of nitrous was a disaster when his patient shouted in pain during a tooth extraction. Wells' reputation was tarnished by a side effect of nitrous oxide, which can cause agitation in patients even though they feel no pain. In October 1846, the first successful public demonstration of the use of ether was performed at the Ether Dome at Massachusetts General Hospital in Boston. (For a more complete story on this, check out the Radiolab episode: Ether Dome or this great story on Slate.) Word of the success of ether spread quickly; soon after, Mütter was using ether in his surgeries in Philadelphia. Many in the old school were reluctant to use the gas. They had some medical reasoning on their side: there were a large number of deaths caused by variations in the quality and composition of the ether used as well as lack of knowledge about exact dosages. However, they also used scripture to bolster their belief: pain was something that should be endured (especially by women, of course). Interestingly, surgeons were also hesitant to adopt anesthesia as they felt that not having a conscious patient removed an important element of their surgical procedures, which they likened to "removing one of their senses."

The introduction of anesthesia was a critical development in medical history. However, patients continued to die at astonishing rates. This was generally due to the lack of antiseptic procedures. Some doctors (including Mütter) saw a connection between clean hands and surgical areas and positive patient outcomes. Germ theory was proposed as early as the mid-16th century, but without proof of microorganisms, alternative theories took hold as well. In addition, the idea that a gentleman could be dirty or spread disease was unthinkable. In the late 1840s, puerperal fever was a common infection among new mothers, as doctors with unwashed hands would spread the infection from one patient to the next**. Several papers that examined the spread of puerperal fever helped convince many doctors that aseptic techniques were important in patient survival. However, aseptic surgical technique was not in common practice for another few decades.

Dr. Mütter's Marvels has many interesting details about the history of the teaching of medicine. In addition, the book chronicles the development of the practice of obstetrics and gynecology, fields that were plagued by unscientific notions about women. There are also some really great stories about Mütter's practice as a plastic surgeon and the amazing surgical procedures he performed to transform "monsters" into humans. Finally, the book discusses Dr. Mütter's unique collection of medical specimens, which he collected throughout his life for use in his lectures. As his death neared, he was sure to find a home for his collection, which is now housed at the Mütter Museum. Thomas Dent Mütter lived a relatively short life, but he left a significant legacy in this museum as well as in the history of medicine.


** Footnote: Women had an average of eight births at the time; one in every four births resulted in the death of a child, one in two hundred in the death of the mother. One strange fact: the first time a woman could feel the baby moving (the quickening) was the cut off for when the fetus was considered a rational soul. Thus, abortion before this time, which varies from 15-20 weeks, was not illegal. One in thirty pregnancies were terminated with an array of readily available abortifacient drugs and mild poisons. (This fascinating history of abortifacients gives additional details.)