Monday, September 2, 2019

My Book Choice of The Year - by Lily


The 2011 Pulitzer Winner in general non-fiction, The Emperor of All Maladies: A Biography of Cancer, by Siddhartha Mukherjee, is my book of the year. It is a book that I wish I had read 30 years ago before I decided to major in Biology research, only if the book were written that long ago…. It is a book that I have recommended to many of my friends since I finished reading it. It is a book that connected many dots in my mind and made me appreciate the importance of understanding history.

Cancer has been in existence for over 4600 years. The first reported case was by an Egyptian physician Imhotep in 3000 - 2500 B.C.  But understanding cancer has come a long way. It parallels our understanding of nature’s principles, physics, chemistry, biology, from anatomy to cells to genes. In 1908, German scientist-physician Paul Ehrlich, Nobel prize winner for his work in immunology and antibacterial work, pointed out that the cancer cells would be nearly impossible to target by chemicals the way chemicals selectively kill bacteria, because the similarity of cancer cells to the normal human cell. His idea was that to target abnormal cells one would need to decipher the biology of normal cells. I can’t help admiring the salience of his point given how little people knew about cells 100 years ago. Studying cancer has been like the blind men and the elephant. It is easy to think, by analogy to many other diseases, that cancer is a single cause disease. There were three camps claiming different theories as the causes of cancer. Virologist Peyton Rous claimed that viruses caused cancer based on his work of RSV (Rous sarcoma virus) inducing malignant tumors in animal models. Epidemiologists, like Richard Doll and Austin Hill, believed that exogenous chemicals caused cancer because of the link between chimney sweeper and scrotum cancer and their work on smoking and lung cancer.  Theodor Boveri’s successors believed that genetic changes inside the cell caused cancer. At the end, all three aspects turned out to be true. It is not until we start to understand the genes expressed in cancer cells and how their changes affect cellular behaviors, did we begin to start understanding cancer. This makes cancer such a beast to manage and treat.

The advances of science and medicine has been intertwined, at times with close interaction and other times isolated from each other. Cancer therapies started from physicians’ understanding of the disease and trial-and-error experiments. Before the era of rigorous clinical trials, which was not properly put in place with regulations until 1980s, physicians tried surgical procedures and chemicals directly on patients (often without proper control). The two dominant therapies were surgical removal for solid tumor and radiation/chemotherapy. With surgical removal, people didn’t understand why the tumors came back from other places, so they pushed hard to remove as much surrounding tissues as possible to the extent of disfiguring people. With radiation and chemotherapy, physicians didn’t understand why the same drug would be effective for some but completely useless for others, so they pushed hard for higher doses to the extent that the side effects killed people faster than the cancer. They would not have known why until the true causes of cancer were revealed at molecular level, same physical presentation caused by different gene alterations. Only until the mechanisms of cancer are better understood can we design the right remedy to conquer that, medicine and science need to collaborate closely, that’s when the cure becomes tangible.

Scientific discovery is not a linear process, it often involves steady non-progressive phase with burst of breakthroughs. However, government policy, public opinions, and private funding can greatly change the landscape of things, for better or for worse. During World War II US government centralized many scientists to solve specific problems to win the war, the task forces made great breakthroughs in physics and engineering and medicine very effectively. After World War II the strategy was changed to more basic research and understanding of nature. Later, Sydney Farber working with Mary Lasker motivated the public and persuaded Nixon to declare the war on cancer. When there’s more public or private funding on specific cancers that would typically give a boost to speed up the solution. However, when compassion comes before science, it may lead to the opposite effect. Such is the case when a breast cancer patient sued the insurance company demanding certain therapy in the late 1980s before the national trial was completed. Patients ended up with non-effective therapy and devastating result, and at the same time the trial was delayed for people not wanting to be randomized into the control arm. Sadly, at the end the trial concluded that such therapy had no additional benefit.

For me, personally, while reading the book I was also excited to see a lot of familiar names of the scientists who made major contributions to cancer research. But reading this as a history of discovery I gained a better understanding on the background of their discoveries, some serendipitously and some with bold leap of faith, and of course there were also missed opportunities. Having a big picture and dare to think is always important in research and discovery because we are venturing into the unknown. As Howard Temin did when he discovered reverse transcription, if the data did not fit the dogma, then the dogma – not the data – needed to be changed.

Cancer research has made great breakthroughs over the last two decades. Now we understand that cancer arises from genetic alterations within certain cells that enables them to grow uncontrollably, but the process leading to that point may take a couple of decades. It is not something happens overnight and often there’s no single silver bullet to cure it. Some causes of cancer have been identified, such as certain genetic mutations and environmental carcinogens (eg. smoking), others remain unknown. What has proven effective include health monitoring with pre-screening to enable early diagnosis and targeted therapy which scientists are continuing to discover and develop. Cancer is not as formidable as it used to be. With current research effort we hope the cure would come in the near future.

Get your copy of the book or watch the PBS show.


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