My wife and I were discussing the orthodontic treatment lots of kids go through to get their teeth straightened out. This is mainly done for cosmetic reasons with some clinical value added as well. Despite the thousands of dollars charged, the treatment provided using braces is rather crude as it involves tying your teeth up with metal wires/rods/screws and pulling and pushing them to get them moved to the correct location in your mouth. There are new techniques like InvisAlign that costs even more but are functionally the same. I'd say latest cancer treatment drugs fit the other end of the sophistication spectrum. Though perceived as a single disease by most of the world population, cancer being a family of diseases with a rich sociopolitical, medicinal history warrants a book of this kind.
He starts all the way from Egyptian Physician Imhotep (circa 2625 BC) who described breast cancer precisely with the conclusion that there is no cure for it. As the chapters progress, he discusses Hippocrates' (400 BC) ideas of four fluids (blood, black bile, yellow bile and phlegm) that need to be in good balance for the human body to function properly, Greek physician Galen's (160 AD) thoughts about black bile being the cause of cancer, subsequently Vesalius disputing this idea of black bile in 1540, and then rolling on to Dr. Halsted's radical surgery ideas that became the accepted norm at the turn of the 20th century. Major contributors to the forward movement of the research such as Sidney Farber, the NY socialite Mary Lasker, the Jimmy Fund, Emil Frei & Emil Freireich's (who in the 1960s created the strategy to cure acute Lymphoblastic Leukemia using toxic drugs leading to the idea of chemotherapy), Henry Kaplan (who came up with radiation therapy for Hodgkin's Lymphoma) start making appearances in the middle of the book though the narration is not strictly chronological in order. As time progresses many of the ideas (like radical mastectomy) get questioned leading to combination therapy (e.g. small lumpectomy and chemo combination to address breast cancer), idea of universal cure gets more and more elusive, each president since Nixon promise a lot of money and 10 year target to cure cancer that all fall flat, links to various carcinogen and cancer (e.g. cigarettes, asbestos) gets established. Reconciliation of the three different theories that were thought to be the cause of cancer (retro viruses, chemical carcinogens and genes) and their conflation slowly leads to the realization that cancer needs to be handled from prevention, early detection as well as fine-tuned treatment perspectives together. I liked the big picture that evolves through the underlying meta story illustrating how science progresses in fits and starts while tackling large problems (unlike in Hollywood movies where one problem gets a clear solution developed by one person).
What is most exciting is the rounds of development over the last two decades where the pathology is understood in lot more detail. This effectively leads to the understanding as to how cells at a mutated gene level called oncogenes accumulating the combination of mutations that leads to endless reproduction (as if the acceleration pedal of a car is pressed all the way down), tumor suppressor genes disabled (equivalent to brakes that will prevent runaway accidents in a car disabled) and maintenance genes that are supposed to clean up errors failing, leads to cancer. Exquisitely designed drugs like Herceptin & Gleevac start to address exact cause of specific tumors. Since such targeted solution for specific cancer type works perfectly (HPV vaccine, Judah Folkman's Angiogenesis drugs are all examples), there is often an immediate euphoria saying there has been a breakthrough and “cancer cure” is around the corner. But invariably the enthusiasm gets deflated quickly when the cancer morphs and relapses and/or the developed solution fails to work for any other cancer type.
With the Human Genome project completed around year 2000 giving us the complete map of the normal human genome, now comparing normal genome to the cancer cells to see which gene had what mutation has been a big development leading to the idea of creating the Cancer Genome Atlas that is still ongoing. This is probably thousand times more complicated/difficult compared to the complexity of the human genome project itself. But the increases in computing capacity, knowledge gained so far and other such factors should make this plausible. While getting this clearer picture help the researchers understand what needs to be done, actual work seems daunting due to the explosive combinations that need to be explored to list all the possible mutations for all the different types of cancers with mutations continuing endlessly adding more complexity to the scope of this endeavor. But the current understanding developed by Vogelstein about thirteen different pathways in which cancer can manifest due to multiple gene mutations described in this nice Nature review paper at least places an upper bound on the size of the problem. This whole field is overwhelmingly dominated by the research teams in US, though there is work/trials that go on in Europe and Japan to a much smaller extent. There is even a story about a South African physician who has been presenting some stunning results related to breast cancer treatment using high does chemo & bone marrow transplant in the 90's that all turned out to be fake that is quite disheartening to read.
Correctly solving cancer in many ways resembles solving some issues in the telecommunication world in a much shorter timescale. Just to give an example, for the past six months our team has been struggling to address a customer issue on the other side of the world where occasionally packets (i.e. information being transmitted) get corrupted (like cells becoming cancerous) that can crash the system (people dying). Simply replacing the whole software/hardware to solve this issue is equivalent to sledgehammer approaches of killing all the new cells being formed via Chemotherapy or radical surgery without precisely understanding the root cause of the issue. Since we don't see the packet corruption in our lab testing, our engineers have been patiently sending the customer software patches (equivalent to drugs) and analyzing the logs that we receive back (test results). We are getting close but haven't resolved the issue fully. When we actually find the root cause which is often a combination of factors, it will be equivalent to identifying the set of specific mutations causing a particular type of cancer. Changing a few lines of code in one or more places out of the millions of lines of code in use on the customer equipment should then very precisely fix the issue. Understanding the exact root cause and sending in a perfect fix could give you great satisfaction. Since no lives are being lost and since this get completed over a period of few months rather than a few decades, such debug efforts are uninteresting to the people outside our world. I can also point out all the ways in which these processes are not equal/comparable. But the excitement and satisfaction derived is no less and so I can fully relate & to some extent understand the process of cancer research.
The US television channel PBS had done a six hour documentary (by the famous documentarian Ken Burns) covering the book's material. I saw that too. Since this book is 500 pages long with a lot of material to digest, I took few months to read it and so watching the documentary helped refresh my mind. If you are not going to read the book, I will highly recommend the documentary. But reading the book should provide lot more details that can't be gleaned from the documentary alone. One complaint I had about the book is how the author had glossed over the exponential raise in the cost of cancer treatment. Particularly in the US, where cancer research and treatment is easily in the leading edge, cost is simply sky rocketing since the cost of treatment/drugs is determined solely by the pharma industry without any government imposed price controls. The PBS documentary covers this aspect a little better and also dives into immunotherapy (drugs like Yarvoy making the rounds now) in lot more detail than the book.
While I can understand readers thinking this book is a bit too dense in content for easy reading, I am glad such works are being created. It deserves the Pulitzer Prize it has received. :-)
-sundar.
