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.
