Book Review: Stiff by Mary Roach

While browsing the community public library aisles came across this book called Stiff: The Curious Lives of Human Cadavers. I had heard about it ~10 years back and so it piqued my curiosity. It easily turned out to be the most morbid book I have ever read! The author Mary Roach being a journalist, book had an easy to read feel to it. It is not hard to comprehend but packs quite a few interesting facts/angles in its 300 pages. 

She starts off the first chapter with an onsite reporting of a CME (Continuing Medical Education) type seminar where plastic surgeons practice their face lifting skills on cadavers. This makes perfect sense since physicians that are training to be surgeons in their residency often learn the trade on the job by assisting board certified surgeons operating on real patients that doesn't leave much room for error. They initially start off with closing sutures and move up stage by stage to doing the surgery themselves under more experienced surgeon's supervision. You can immediately see the value in getting trained on cadavers where you can make all the mistakes you want to acquire the knowledge/skills you need. But the morbidity streak starts on the first chapter itself as she gets into the details of how the training is provided not on full cadavers but just using human heads that have been separated from their bodies and the details of the separation process. Still a gentle start. Next chapter dives into body snatching and other tales from the dawn of human dissection. Since dissection wasn't an allowed practice by the church and there were weird promulgated laws that defined the confines of where/when such research can take place, there were a lot of black market trading/work that went on. Body snatching from graves was a very profitable business for grave diggers themselves in those days!

Next four chapters were the most educational as they dive into so many types of research that won't be possible but for the help provided by cadavers. As the author writes in the acknowledgements section, researchers working on cadavers don't want to be on the spotlight since their work is often and very easily misunderstood and their research funding is invariably very vulnerable to negative publicity it tends to attract. But we need to salute the kind of work that gets done in these areas in one of a kind places. Take the vaguely named Anthropological Research Facility that is part of the University of Tennessee Medical Center outside Knoxville. I heard about this facility on the radio just couple of months back. They study the decaying process of cadavers under varying conditions and publish detailed reports. These conditions include dry, wet, humid, buried, underwater, shallow/deep graves, car trunks, inside concrete, mud, plastic wraps and every other scenarios criminals all over the world might have thought of! Without these studies forensic analysis of murder victims can never be as accurate as it is these days to help nab the culprits. An ORNL (Oak Ridge National Lab) team is working with them to develop an electronic nose that can smell the body and tell you when the person died. Findings like barring extreme temperatures, corpses lose 1.5 degree Fahrenheit per hour until they reach the temperature of the air around them, if the unique volatile fatty acids/compounds of human decay are not found in the soil, the body had been moved and so forth can not be added to our forensic science knowledge base without this work. 

Next chapter talks about cadavers being used in automobile crash tests to first assess what level of force inflicts which type of injury on human beings. While we never hear about this research on the media or car advertisements, the crash test dummies that are often shown in safety test videos come later. Those dummies measure how much force was in play in various crash conditions to be compared to what a human being can withstand based on previously completed cadaver tests! Following chapter talks about what data you can gather from dead bodies found in plane crashes. If a bomb had been exploded from a plane toilet, you'd see burn marks on the fronts of the people sitting right behind the toilet. On the otherhand, if you see burn marks on the back of floating bodies in the sea, it might be from burning fuel that caused the mark after death as dead victims will usually be lying face down on water. 

There is a chapter on tests done to assess the impact of bullets/bombs on victims. This is again very sensitive as relatives like to hear that their dead relative's body was used for organ donation rather than being used for shooting practice. So, even though gathered information could be quite useful, wherever possible researchers use gelatin like substitutes that is also easy for studying exit wounds as the artificial substance is clear (i.e. no need to do surgery to understand what happend inside) and can be reused. One chapter that touches upon embalming was also detailed enough to give a good view of the process the schools put their students through to prepare them for this trade.

Subsequent chapters, while providing the needed comprehensive completeness of the subject, go into weird and gruesome areas of animal research, cannibalism and the so called religious research related to crucifixion. If you read the book and happened to be queasy, you can skip chapters 7 to 10 to save yourself some trouble. Last chapter gets back into alternatives for burial/cremation discussing water reduction and composting of human bodies that are more eco friendly! If you have seen the Body Works exhibit that is making the rounds around the world, the plastination treatment used to produce those exhibits are also covered. If case if you are interested this YouTube video has a quick primer. :-)

Perhaps since the material might be off putting to lot of readers, the author intentionally finds/maintains a sense of humor throughout the book. Though it wasn't disrespectful in anyway, it still felt a bit a odd. But one can understand it from a defense mechanism point of view for the treatment of this subject. 

One heck of an unusual, peculiar, unorthodox book!

It reinforced my conviction that when I die, donating all my useful organs and allowing my body to be used for medical research is the right thing to do.  I already have it recorded in my Last Will and Testament. Do you? 

-sundar.

Book Review: The Billion Dollar Molecule by Barry Werth

I have been meaning to read books related to biology since I am not deeply in touch with that field on a daily basis. So, after checking with a good friend in the biomedical industry for suggestions, ordered three books. Finished reading the first one called "The Billion-Dollar Molecule: One Company's Quest for the Perfect Drug" by Barry Werth. It is a 20 year old book that tells the story of the formation of a new company called Vertex Pharmaceuticals, created in 1989 as a scrappy upstart trying to compete against the industry Goliaths like Merck. Since the book came out in 1994 itself, it covers only the first 4 years of the company. Within that time frame, it already did IPO and had become a multimillion dollar entity. 

Main character in the narration is Joshua Boger who is an ex-Merck employee that is the founder, President and Chief Scientific Officer for this new pharma start up. Usually big pharma companies used to keep analyzing soil samples, plants, insects and other existing entities one by one in a hit or miss approach to see if any of them can be identified to have useful molecules that could treat diseases. Boger's apparent path breaking idea is to skip that brute force approach and design a needed molecule from scratch. He calls it structure based design. While there is no guarantee that this will promptly result in useful drugs quickly, his assessment was that drugs created using this model will have lot less side effects since they are built to address a specific need rather than picked out from a more complex product and distilled down to form a drug that may still have lot of residual effects that can manifest into undesirable side effects. Other reason is designing drugs in this fashion could cost a lot less (and so will be suitable for a scrappy start up). Though the idea makes sense in theory, constructing the molecule this way is not easy since you may not even know exactly what is it that you want to begin with. 

The team takes up an experimental drug called FK-506 that belongs to a Japanese company. While the drug's efficacy in immunosuppresant therapy appeared good, it was also found to be highly toxic in several animal study. So, Vertex took it up to improve the drug by redesigning the needed molecule retaining the needed therapeutic effects sans toxicity. Initially for more than a year company tries to to understand the molecular structure of FK-506 to determine how it works as an immunosuppresant drug. As the race goes on, towards the end the Vertex team fails in it attempt as a competing academic discloses the structure and the mechanism as to how it works. Vertex with a few last minute somersaults manages to get its paper also published on the Nature journal to claim co-credit and victory. Around the same time they also start working with the British drug maker Burroughs Welcome to develop a protease inhibitor to address HIV & AIDS and eventually develop a compound called VX-478 that performs better than competing one from Merck. While these research efforts are in progress in their labs (in Massachusetts), Boger runs around Wall Street to get funding for the start up, makes deals with companies in Japan, Europe to get more money, share credit for research, line companies up as collaborators who will manufacture the drug when the Vertex research bears fruit. While the outside world may normally think that serious research work is done in calm, quiet environment with people dedicated to science, book talks about instances where this company scientist and other academics rush to meet Nature & Science journal deadlines to get a paper out with a date stamp to claim credit for their discoveries, push prestigious journals like Nature to re-examine their decision to reject a paper and eventually accept it, how in conferences scientists jockey for positions/credit and so forth.  

The author probably understands the science involved very well and so describes the work glossing over a lot of the details or doesn't understands the details and so is not able to explain them well. Being an outsider, I didn't find the science described well to understand it properly. There are more than a dozen second line characters that appear in the book. Many are described as geniuses but what they they do is not clearly described. To me, other than Boger, many of the characters overlapped each other due to the fuzzy nature of the narration and so I had a hard time remembering each one's important contribution or role. Since the book is ~430 pages long, each time I crossed about 100 pages, I tried to see what was effectively communicated in the previous section. Other than the general notion that a small start up is trying to create drugs, not much else stands out. When I cross another 100 pages and don't seem to have learned anything new, I start wondering how did the last 100 pages get filled up!

Perhaps since I have lived through the dotcom boom and bust, reading this book now doesn't seem to give any extremely new insight as the overall story unfolds very similar to what happens in tech startups. If I had read it in the mid-90's it might have appeared eye opening. Just two decades late, I guess! In the end Vertex (VRTX) seems to have done well. While its IPO in the early 90's was at $12 with its initial market cap hovering around 60 million dollars, its stock is at $127 now fetching with it a market cap of 31 billion dollars! Saw reports that it is the undisputed leader now for drugs to treat Cystic Fibrosis. 

While there are often books, movies, and documentaries about how some little start up managed to hang on by its nails then grew to become a huge multi billion dollar behemoth, I find stories in the opposite end of the spectrum more interesting. There was a documentary I saw a while back called Startup.com. During the dotcom boom era the documentary producer got permission to record developments as a small tech company called GovWorks.com started building its service, working with several local municipal governments in the US. Their business model is to develop a web portal to collect local property tax, income and other taxes, parking fines, speeding tickets, etc., deliver it as a contracted service to the local government and public and take a cut from the money collected for the service provided. It was a novel idea at that time. Even now there is no single portal you can use to pay for local government services as each municipal office maintains its own portal. The documentary maker's goal was to record how this idea becomes a company, does IPO and makes everyone involved a multimillionaire. But as the dotcom bust occurred, this company wasn't able to get enough local governments to sign up for their services and as the funding starts to dry up, the two friends who originally start the company become enemies. The one who became the CEO, calls the other guy who becomes the CTO, not good enough to keep leading the company. The CTO sues the company, heating things up. Finally the whole company craters and is shutdown! While the story might be depressing, that is what happens to most of the new startups. While success stories are needed to keep motivating people to take the jump, failure stories are also needed for us to learn the lessons. I hardly see them being told in the media of any kind!

Picked up Genome by Matt Ridley next. Will see how it fares.

-sundar.