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.)

The complex legacy of Rosalind Franklin

As a woman in science, I have always admired Rosalind Franklin. Hers is such an archetypal story, one that fits well with the image of women in science being undervalued and underrepresented. I decided to read Rosalind Franklin: The Dark Lady of DNA by Brenda Maddox to see how much of what I knew about Franklin was myth and how much was reality.

Franklin, it seems, was a well-balanced woman, interested in fashion and dressing sharply as well as in mountaineering and outdoor pursuits. She was passionate about her work and loved her time in the lab, but found yearly vacations necessary. She had a knack for buying the perfect gift, especially for the young children in her life. Franklin came from an upper class Jewish family; she went to excellent schools and showed an early gift for math and science. After graduate school in Cambridge, she took a position as a researcher in the lab of Jacques Mering in Paris. She used X-ray crystallography to study the structure of coal, a project she chose for its usefulness to the war efforts. The environment in France suited her well. She developed confidence as a scientist; others in the group described her fastidiousness and her "golden hands". Although Franklin loved life in Paris, she returned to England for a position at King's College London. After agreeing to the position, the group head, (Sir) John Randall, informed her that she would be working on the structure of  "certain biological fibres...(called) desoxyribose nucleic acid". 

The Biophysics Department at King's was one of the first of its kind. The field of biophysics was sparked by the publication of What is Life? by Erwin Schrödinger in 1944. The book led physicists (like Randall at King's College) to decide that studying biology was a worthwhile pursuit. When Rosalind arrived at King's in 1951, it was a well-established department with a good number of female faculty. Despite this diversity, women were not allowed in the King's senior common room. From the moment she arrived, Rosalind did not feel comfortable. While normally affable and approachable, King's staff members described her as dark, moody, and awkward in conversation. Maddox suggests that class and religion (rather than gender, as suggested by other biographers of Franklin) were the root of the trouble for Franklin at King's. No matter the cause, the tension was not imagined or exaggerated, as evidence by the minor celebration at King's after Franklin's departure.

For Franklin, the conflict was highest with Maurice Wilkins; Maddox makes several suggestions as to what may have kept them from a successful collaboration. Without this icy relationship, Wilkins would surely have conferred with Franklin prior to sharing her data with Watson and Crick. While the book suggests that Wilkins' position as assistant head of the department gave him every right to the data, Wilkins should have spoken with Franklin before sharing her unpublished results as a matter of scientific courtesy.

Rosalind Franklin had a tense relationship with James Watson as well. Watson has become notorious for his traditional view of women (as well as his outdated views of race). For example, upon first meeting Wilkins, Watson noticed that Wilkins took a liking to his sister. Watson considered using his sister as a lure to secure his place in the work on DNA. Watson repeatedly called Franklin "Rosy", a habit that irritated Rosalind, who would only allow close family and friends to call her "Ros". Watson was genuinely afraid that Franklin might strike him due to her "hot anger" after he barged into her office without knocking. Rosalind's anger at this unwelcome entrance may have been an attempt to protect her territory. The week prior, Franklin had complained to a friend that the notebooks in her office had been read without her approval.

Franklin's photograph 51

In 1953, Franklin was planning a move to Birkbeck College. Before the move, she wanted to finish two papers for publication in Nature: one on the two forms of DNA and one on the helical structure of DNA based on her crystal data (her famous photograph 51). At the same time, Watson and Crick were building a model of the structure of DNA. Franklin found this approach to be premature. In fact, her Nature paper (published as the last of the three of papers in the April 1953 issue) had all the important features of the double helical structure that were present in the Watson and Crick paper. To me, her cautious approach to scientific pursuits was likely due to her training. For women, "science was taught... [as] an intellectual endeavor calling for neatness, thoroughness and repetition, rather than excitement and daring (p 33)." This careful approach was in stark contrast to the tactic taken by Watson and Crick. This cautiousness may have cost Franklin her place in history as much as her difficult relationship with Wilkins.

Google doodle celebrating Franklin's 93rd birthday

Interestingly, Franklin's relationship with James Watson improved after the 1953 Nature publications. However, Franklin was never aware of the importance of her data in the work done by Watson and Crick. Only after her death did Watson and Crick clarify how critical her crystal data were for their success.

Franklin died of ovarian cancer in 1958 at the age of 37. Many have speculated that her work with X-ray radiation led to her cancer. Franklin's early passing highlights the link between scientific discovery and personal sacrifice, which is also a theme for other famous women in science, like Marie Curie (whose story is beautifully told in Radioactive) and Marguerite Perey, who discovered Francium (this long read by her great niece tells her fascinating story). Interestingly, Maddox suggests that Franklin's early onset of cancer may have been due to a mutation in the BRCA gene, a mutation that is more prevalent among Ashkenazi Jews like Franklin. (I have previously explored the population genetics of BRCA gene mutations in my review of The Wandering Gene and The Indian Princess.)

Maddox's book does not make any judgement about Rosalind Franklin's legacy. Interestingly, her 2003 article in Nature suggests that much of what popular culture has taught us about Rosalind Franklin is inaccurate and is biased by the lens of feminism. There, she calls Franklin "the Sylvia Plath of molecular biology." Franklin's sister, Jennifer Glynn, has written several insightful essays about her sister's legacy. In "Remembering my sister Rosalind Franklin", she discusses Watson's portrayal of Franklin as an"obstructive belligerent bluestocking, churning out results secretively and without understanding " in the 1968 book The Double Helix. In 1975, Rosalind's friend Anne Sayre published Rosalind Franklin and DNA to serve as a counterpoint to Watson's book. Both Maddox and Glynn suggest that this book served to swing the pendulum to the extreme of the "wronged heroine" who was robbed of the Nobel Prize.

Franklin's legacy should be neither of these extremes. It is clear that life in science was difficult for women, who were "judged and criticized much more harshly than a man and got less acknowledgment for work well done. (Maddox, p. 288)" Franklin's training was also biased due to her gender; in fact, she had all the major elements of the structure of DNA before Watson and Crick even started to build their model. Because she was trained to be so thorough and was warned against daring, she was hesitant to publish her work until she was absolutely sure of the conclusions. Franklin's interactions with Wilkins, Watson, and Crick were affected by her gender, which closed doors of collaboration for her. In balance, it seems that Franklin would not likely have been nominated for the Nobel with Watson and Crick. However, had she lived, she may have received a Nobel for her work with tobacco mosaic virus; Aaron Klug (her trainee and beneficiary after she died) won in 1982 for work that he started with Franklin. Thus, while Rosalind Franklin's legacy as a wronged heroine may be in question, there is no doubt that she was a superb scientist and an immensely interesting person.

Photo credit Ben Hammersly via Twitter (@benhammersley)

The Fly Room: a new film about Thomas Hunt Morgan's genetics laboratory

I just discovered the website for the new movie The Fly Room. I could not be more excited to see this film as it combines two of my favorite things: science and cinema. The film is set in Thomas Hunt Morgan's genetics lab at Columbia University. From 1911-1928, Morgan's lab, nicknamed the Fly Room, pioneered the use of fruit flies as a model organism to understand genetics. The lab made several major contributions towards understanding mutations, heredity, and sex-linked traits. Morgan's Fly Room has a unique combination that make it a great subject for a film: an unusual lab space, memorable scientists, and cutting-edge science. (Sam Kean's The Violinist's Thumb does an excellent job of telling this fascinating story in a way that highlights all of these features.)

The lab space has been described as being not much bigger than a broom closet. Archival photos, such as the one above, show benches covered with old milk bottles filled with fruit flies and stuffed with gauze. The lab used bananas to feed the flies, which caused a characteristic fetid odor. It seemed like fruit flies were everywhere, an impression made worse by the small space. Of course, Morgan's habit of squishing non-mutant fruit flies on any available space helped contribute to the mess. The Space Revisited section of the website includes some great movies and details about the process of recreating the unique space for the movie.

The Fly Room at Columbia University - Restored to Its Original State from Imaginal Disc on Vimeo.

The lab also hosted an amazing array of characters. One of these scientists was Calvin Bridges, a handsome genius with an appetite for both science and women. Calvin Bridges was a brilliant scientist, but his philandering damaged his career (Morgan disapproved of his behavior and would not promote him) and cut short his life (Calvin died of syphilis at age 41). After his death, his lab mates burned his personal diaries to protect his reputation.



Alexis Gambis, the film's writer and director, became fascinated with the story of the Fly Room during his PhD in molecular biology at the Rockefeller University. Based on his interest in the story of Calvin Bridges, Gambis sought out Betsey Bridges, the late scientist's daughter. Exchanging stories with Betsey gave Gambis a new way to tell the story of the Morgan lab. The film uses Betsey's visit to the Fly Room as a young girl to explore the girl's relationship with her father as well as the science at the heart of the Morgan lab.

As evidenced by the recent films The Imitation Game and The Theory of Everything, casting scientists as characters in the story of science can create a useful narrative tool. While the focus of these films has been entertainment (indeed, all of these films have taken some degree of poetic license), they also serve as a tool to elucidate the scientific process and inform the public about the importance of basic research. The critical reception of The Fly Room has been very good. I am confident it will show in Boston soon, so I will be sure to update this post when I get to see the film.

More information:
Here is a great story on The Week: Exploring The Fly Room
You can follow The Fly Room on Twitter to see where it is showing next. 

Sources:
Sam Kean's The Violinist's Thumb
Cold Spring Harbor Laboratory library: Morgan's lab

Poisons and venoms - deadly consequences and therapeutic benefits

I picked up Poison - Sinister Species with Deadly Consequences by Mark Siddall from the new release shelf at my local branch of the Boston Public Library. It was a whim, but it paid off. Poison has many similarities to Amy Stewart's Wicked Bugs, including the small format and the detailed pen-and-ink scientific illustrations. The subject matter also has a good amount of overlap. Siddall, a curator for the American Natural History Museum, wrote the book in connection with an exhibit by the same name. The book was immensely readable with many fascinating vignettes, which makes me sad that I missed the exhibit (although the ANHM website suggests that it is traveling). If you want to get a sense of the style of the book, check out Siddall's piece in IFLScience.

Siddall explores a few of the many different ways that plants and animals can kill or at least send you writhing in pain. The most surprising fact of the book: platypodes are venomous! The male platypus has spurs on its hind limbs, which can deliver venom. The venom, produced only during mating season as a defense against competing males, is actually strong enough to cause mild paralysis in humans. Another incredible story concerned two vastly different organisms (pitohui birds and phyllobatid frogs) that produce the exact same toxin (batrachotoxin) despite being separated by more than 10,000 miles and millions of years of evolution. It seems that the birds and frogs both eat a particular species of flower beetle that produces this chemically unique toxin. Both species have evolved a tolerance to the poison in the beetle and can use the toxin to protect themselves from predators.

Reading the book reminded me of all the amazing things that scientists are learning about the therapeutic potential of these naturally occurring poisons. As a Scientific Editor, I read papers that examine the components of venoms from a variety of organisms. Venoms have evolved over millions of years, so they are essentially drugs designed by nature; one review article describes them as a "billion-year drug discovery program with unlimited resources" (Vetter et al., 2010). Because venoms come from such diverse species, they provide a large array of chemical and pharmacological novelty. Strikingly, venom toxins from different organisms often target common cellular pathways (e.g., ion channels, cell receptors) and use similar mechanisms to exert their effects.

Sample venomics work flow; Warrell et al., 2013

Venoms are comprised of a complicated mixture of proteins and peptides, thus, venoms can elicit complex physiological responses in the target organism. Generally speaking, venoms are classified as cardiotoxic or neurotoxic, as they can affect the heart or the nervous system, respectively. Toxins that show cardiotoxic properties can prevent blood clotting and lower blood pressure. Neurotoxic venoms show potential as pain relievers and as therapeutics in the treatment of neurological diseases. To identify drug candidates, scientists use venom extracts as a starting place (Harvey and Stöcklin, 2011). High-throughput screening techniques can be used to find venom components with an activity of interest. Then, chemists create synthetic analogues, which can be modified to enhance the pharmacological properties (e.g., binding affinity or specificity) and decrease possible side effects. Recent technological developments have improved the ability to screen and characterize the components of even small quantities of venom; this relatively new field, called venomics, is unlocking the therapeutic potential of venom compounds (Vetter  et al., 2010).

Tubocurarine was the first venom toxin to be used in a clinical setting; in 1942, it was introduced as a muscle relaxant. However, native South Americans were using a crude extract created from the bark of a climbing vine; the resulting curare served as an arrowhead poison for hunting animals. Similarly, the drug Captopril was developed from the active compound from pit viper venom, which was also originally used as an arrowhead poison. Because this compound can lower blood pressure, it is used to treat hypertension and heart failure.

Cone snail uses a harpoon to attack prey (from PBS.org)

Cone snails were once highly sought after for their beautifully patterned shells; the Glory of the Sea variety was worth thousands of dollars due to its rare and unusual shell. Recently, the value of the cone snail is due to its unique pharmacology. This predatory snail uses a harpoon-like appendage to attack its prey and inject a paralyzing neurotoxin. When scientists analyzed the components of cone snail venom, they found several compounds that were useful pain relievers. One of which, ziconotide was approved in 2004 under the trade name Prialt for the treatment of chronic pain. Prialt works by blocking calcium ion channels (membrane proteins that create channels for the selective passage of calcium) that are involved in the transmission of neuronal signals, thereby inhibiting the transmission of pain signals.

Many different venomous animals have evolved toxins that target ion channels, likely due to their conservation in many organisms. For example, sea anemone venom was the source for stichodactyla toxin, or ShK, which blocks potassium ion channels. One analog, ShK186, is currently in phase I clinical trials for the treatment of rheumatoid arthritis and multiple sclerosis. Interestingly, insects express only one type of sodium ion channel, which makes them very sensitive to ion channel inhibitors. Various species of spiders exploit this weakness by using venoms that target ion channels. Thus, these spider venoms could be sources for novel insecticides (Klint et al., 2012). Many of the ion channel inhibitors identified from venoms have also become useful tools for studying the cellular function of ion channels in the laboratory.

There are many more examples of useful therapeutics coming surprising sources. For instance, the saliva of the Gila monster was the source of Exenatide (trade name Byetta), which is used to control glucose for the treatment of type II diabetes. As screening technology and drug design methods continue to improve, scientists will be able to unlock the full economic and therapeutic potential of venom toxins.

Sources:

Review article: Venomics: a new paradigm for natural products-based drug discovery (open access)
Review article: Spider Venom peptides that target voltage-gated sodium channels: pharmacological tools and potential therapeutics leads (from a Toxicon Special Issue: Advancing in Basic and Translational Venomics)
Introduction: From venoms to drugs and Review article: From snake venom toxins to therapeutics: cardiovascular examples and (from a Toxicon Special Issue: From Venoms to Drugs) 
From Venoms to Drugs - blog
The Scientist: From Toxins to Therapeutics

What ever happened to Brontosaurus?

I have only recently realized that Brontosaurus is no longer a dinosaur. All of my son's books about dinosaurs had the longed-necked sauropod labeled as Apatosaurus, suggesting that something is very different from when I was a kid. Luckily, Brian Switek's book My Beloved Brontosaurus: on the road with old bones, new science, and our favorite dinosaurs explains what happened. Briefly: in 1877, Yale paleontologist O.C. Marsh discovered a partial skeleton of a young dinosaur that he named Apatosaurus; two years later when he found a similar skeleton, he called it Brontosaurus. In 1903, another paleontologist (Elmer Riggs) argued that the differences between the two skeletons were not great enough to warrant two different species. Because Apatosaurus was named first, it had priority for the scientific name. For some unknown reason, this development did not filter down to popular culture or even museums. According to Switek, the changes weren't made until the late eighties. Even after that, it was hard for people to adapt to the change. Switek compares the sadness we experienced at the loss of Brontosaurus with the news that Pluto was no longer a planet.

Brontosaurus stamp from 1989

Switek, a lifelong dinosaur freak, uses what he learned about dinosaurs as a child to illustrate how much our understanding of dinosaurs has changed. In the case of dinosaurs like Apatosaurus, everything we were taught was incorrect: they are no longer considered to be slow creatures, dragging their tails through a semi-aquatic environment. Another major change in our picture of dinosaurs is that they were not scaly like alligators; scientists now think that most, if not all, dinosaurs had feathers. As the connection between dinosaurs and birds is strengthened, scientists have started to consider that the prehistoric creatures may have even been brightly colored like birds. This is another case where the general public is likely to have a tough time adapting its image of Tyrannosaurus rex as a furry rather than a scaly lizard.

Young adult (left) and adult Triceratops skull

Switek also highlights some of the major unanswered questions about dinosaurs, including what sort of developmental changes dinosaurs went through. Interestingly, the well-known Triceratops shows how much dinosaurs may change in their lifetime. The skull on the left is consistent with what we think of as a Triceratops. The skull on the right is also a Triceratops (although for a while it was called a Torosaurus); the difference may simply be age. (Switek digs further into this story for Smithsonian.) Of course, the big question still is: what caused the extinction of the dinosaurs? The author treats this question fairly, discussing where scientists are landing on this issue (most agree that a very large meteor was to blame). Along the way, he also discusses how dinosaurs were not immune to the "slings and arrows of life". Many fossilized dinosaur remains have been diagnosed with pathogens of varying sorts, as well as cancer (as I learned in reading The Cancer Chronicles).

It is a great time to be a dinosaur lover. There have been some really amazing dinosaur finds in the past few years. For instance, for more than fifty years, the 8-foot-long set of arms shown on the right spurred the curiosity of many dinosaur fanatics; in October, researchers published their discovery of a full Deinocheirus skeleton, which was almost as weird as you might have imagined looking at those crazy arms (coverage by Ed Yong). The gigantic sauropod (and not so close relative of the Brontosaurus) called Dreadnaughtus was found in southern Argentina also made headlines due to its great size. Amazingly, this is not the end of the size spectrum for sauropods; size was clearly a huge advantage for these beasts.

The stories of these amazing creatures that dominated the Earth for millions of years are fascinating. Switek's book has inspired me to visit some of the great museums and dig sites in the states.

LabLit: books about scientists and the realities of life in the lab

While exploring the Internet, I recently found the LabLit List, a frequently updated list of books that have scientists as central characters. In contrast to science fiction, these books occur in realistic settings. Lab lit books include some science to contribute to the plot. Because most lab lit is written by non-scientists, the science is not always very detailed. However, there are a few novelists who trained as scientists, including Carl Djerassi, Ann Lingard, and Jennifer Rohn (Rohn's book The Honest Look is next on my reading list). The lab lit books that I have read really capture the intensity of life in the lab, showing both the camaraderie and the competitiveness. So if you left the lab, but still fondly remember your days as a lab rat, this is likely a good genre for you. Below, I have written short reviews of three representative lab lit books that I have enjoyed.


Antisense by Richard Marshall

Principal investigator Daniel Hayden is a neuroscientist studying the molecular basis of aggressive behavior in mice. The beginning of Antisense is firmly planted in the lab, but quickly veers into the personal life of Hayden. I enjoyed some of the science bon mots; for example, when explaining blotting techniques Marshall writes, "we ran out of things to blot before we could head east." By the middle of the book, I worried that the plot would be the common male midlife meltdown, but the story generally redeemed itself. The science was interesting, but not very detailed. I was frustrated when Hayden started making grand conclusions based on a single experiment, but soon realized that this was likely the author's way of showing the PI's changing mental state. Likewise, the title was a clever choice, which was appropriate for the science as well as the character's journey.


Intuition by Allegra Goodman


Allegra Goodman's 2006 novel Intuition is set in a high-stakes, ultra-competitive lab at a fictional cancer research institute in Boston's Longwood Medical Area. (Coincidentally, I was working at a similar institute when I read the book in 2007.) Intuition explores why the stakes are so high and what can happen when scientists succumb to the pressure. Goodman spent time in several labs to understand the lab environment. As a result, the book successfully captures many of the typical lab characters and accurately paints the daily life of a researcher. However, the science is not very detailed. Rather, the story focuses more on interpersonal dynamics in the lab and the possibly fraudulent data of one researcher. In light of some of the recent, high profile retractions (e.g., STAP stem cells) and the growing concerns about reproducibility in science, Intuition is increasingly relevant.


Life by Gwyneth Jones


Life tells the story of Anna Senoz, a mid-career scientist who makes an amazing discovery about the X and Y chromosomes: her sequencing data suggest that the Y chromosome is slowly being transferred to the X chromosome. Senoz studies the transferred Y story in secret, as she fears the implications and consequences of her results. The author chose the topic of sex chromosome balance as a way to discuss gender discrimination. (Here is a fascinating essay from Gwyneth Jones on her intentions for this novel.) Senoz suffers both major events (e.g., sexual assault) and minor slights (e.g., senior scientists referring to Senoz as a "good girl"), which affect Senoz's career and personality. The science in the book was well detailed, but did not feel realistic. Perhaps the book could have focused on an authentic scientific phenomenon, like intragenomic conflict in sex chromosomes (some discussion of the topic here). For me, this was the most successful of the many lab lit books I have read. However, it feels a bit more like science fiction than the other titles. Indeed, Life won the Philip K. Dick award in 2005. 

The Cancer Chronicles - George Johnson's personal exploration of cancer, its origins, and treatments

I have recently reviewed books about the discovery and treatment (The Philadelphia Chromosome) and the causes of cancer (Toms River). So the subject matter in George Johnson's The Cancer Chronicles is quite familiar to me. Johnson does have a unique angle – his wife was diagnosed with uterine cancer, which led him to use his expertise as a science writer to learn more about the disease. This perspective helps create a personal element to the book, but does not distract from the science.

Several of the stories were previously covered in other books that I have reviewed: Boveri's prescient hypothesis linking chromosomal aberrations with cancer (The Philadelphia Chromosome), Thomas Hunt Morgan's mutant fruit flies (The Violinist's Thumb), scrotal cancer in chimney sweeps (Toms River), and the Radium girls (The Poisoner's Handbook). Johnson covers new ground in the chapter called "Jurassic Cancer", which examines the other animals in which cancers have been found. In fact, most animals get cancer; the one exception is naked mole rats. Surprisingly, various types of malignancies have even been identified in dinosaur fossils. Another chapter examines how far back in human populations cancers have been described. Johnson writes, "There were signs of cancer in an Iron Age man in Switzerland and a fifth century Visigoth from Spain" (p 49). In both animals and humans, it is difficult to know the exact frequency of the disease, but it is clear that cancer is not strictly linked to industrialization or environmental factors. 

Hanahan and Weinberg, 2000.

Rather, it seems that cancer is inevitable. The landmark review "The Hallmarks of Cancer" (and its update in 2011) states that cancer is basically caused by the accumulation of several mutations. The review's author Robert Weinberg estimates that every second four million cells are replicating in a human body. Each time a cell replicates, there is a chance for error. While there are many error correction mechanisms, mistakes do get through. This genetic variability is the fodder for evolution by natural selection. It is also the source for cancer. Thus, it makes sense that cancer is generally seen throughout the animal kingdom and throughout time. Johnson concludes that it is comforting to know that cancer has always been with us.

Johnson also discusses cancer cell evolution, which is a topic of intense interest in scientific research. Cancer cells are constantly changing to evade the body's defense mechanisms. During treatment, some cancer cells can develop resistance to chemotherapeutics. Understanding how chemoresistant cancers can be treated is a major unanswered question. In the case of Gleevec/imatinib-resistant cancer, a single mutation is responsible for Gleevec-resistance, which allowed the development of a second drug (nilotinib) to kill cells with the imatinib-resistant mutation. Unfortunately, and as is to be expected with a complex disease such as cancer, most chemo-resistant cancers are not as clear cut. 

Overall, the book is quite easy to read and covers many important topics, albeit not at the depth of other, more focused books on the topic of cancer. I will definitely be adding The Emperor of All Maladies to my reading list to give this topic another perspective.


** Post script: Johnson's book was short-listed for the 2014 Royal Society Winton Prize for Science books.