The Emperor of All Maladies

The following is a re-upload of a post in my previous blog (which was destroyed by mistake).


I first heard of the book The Emperor of All Maladies some time back in a NUS whispers post. It is a book by Siddhartha Mukherjee, an Indian-born American physician and oncologist1. An oncologist is a doctor that treats cancer.

While I did not read the book, I watched the 3-part documentary series (Part 1, Part 2, Part 3) that was based on it. It gave a brief history of cancer - the problems, the advances, the treatments, etc, It is accompanied by narratives of cancer patients, and insights from doctors/researchers.

Here are some of my takeaways:

Causes

Virus

This line of thought was first motivated by the study of the Rous sarcoma virus, where Peyton Rous attempted to inject chicken with cancerous cells (See the paper here). It was the first experiment which showed that cancer cells can be transplated to induce cancer in healthy beings.

If this was true, then Science already has an answer: vaccines. While cancer vaccines had limited success, scientists soon found out that not all cancers were due to external agents attacking the body (such as viruses), but something borne internally.

Chemicals

Mustard gas and cigarette smoke have in World War I, and smoking have undeniably induced cancer in many patients.

Mutations in genes

The theory of mutation unifies the above-mentioned theories together: The viruses/chemicals that cause cancer do so because they cause mutations in genes! A gene that can potentially cause cancer is known as an oncogene. For example, the sarcoma (src) gene in chickens and ras gene in humans.

Treatments

Surgery

The idea is simple:
1) Remove the cancer cells from the body
2) Body is now cancer cell free
3) ...
4) Profit!!!

This thinking dominated medical treatment for years. In breast cancer treatment, it was pushed forward by French surgeon Bernard Peyrilhe in the form of radical mastectomy.

Mastectomy is the surgical removal of a breast. Radical refers to "root" - cancer cells have a root and they spread from there. The idea of radical mastectomy is then to carve out ever larger chunks of meat from the chest area in hopes of removing all cancer cells that caused a breast cancer. It was grotesque and does not always cure breast cancer in patients, but it was the state-of-the-art.

Later on, using randomised trials, Fisher showed that just cutting out a small lump (a.k.a. lumpectomy) was more suitable than radical mastectomy as it has similar survival rates and way less disfiguring.

Radiation

As opposed to surgery, radiation has the ability to reach areas that cannot be easily reached via physical surgery. Unfortunately, the usage of radiation also caused other kinds of cancer and death in patients and pioneer researchers.

One notable researcher would be Marie Curie. While she did not specifically worked to use radiation on cancer, she died researching on radiation due to insufficient protection - No one knew how dangerous it could be at that time!

Chemicals

Another approach to cancer treatment is to use chemicals. The hope is that chemicals only targets specific cancer cells and spare the rest. There has been limited success (such as Herceptin that targets HER2/neu) but cancer cells evolve quickly and grow immunity (think antibiotics). To combat drug resistance, researchers looked into using different combinations of such chemicals, also known as Combination drug therapy (See Nature for more).

To better understand cancer genes and develop better targetted drugs, scientists conducted cancer genome sequencing. One prominent project is the Cancer Genome Atlas.

Immunotherapy

A less invasive treatment is to use human's immune system to combat cancer. William Coley injected compound of infectious bacteria into tumors to trigger fever that overwhelm the cancer, hoping that the immune system will take over and cure everything.

In this area, two prominent researchers are Steven Rosenberg (on T cells) and James Allison (on drugs to removes immune system inhibitors).

Palliative care

There is always a cost to prolonging a patient's life - money and suffering. Be frank with patients from the very start so that they have time to deal with cancer, and let them make informed decisions.

Prevention

As the saying goes, "Prevention is better than cure".

Smoking is one of the main causes of (lung) cancer. It has an interesting history of how it permeates society and how it persisted despite medical harms (for example, it is likely to cause lung cancer). By eradicating smoking, we can prevent unnecessary onset of cancer in smokers.

On this "line of attack", researchers find out causes for cancer, such as smoking and obesity, then lobby for efforts to eradicate them. Unfortunately, there still exists many unexplained causes of cancer and Science has not fully understood cancer yet.

Final thoughts

  • Cancer was surprisingly more common than I previously believed.
  • Clinical trials and medical research are painfully slow processes that take months/years of hard work. This makes it really hard to iterate through ideas quickly (cf. In Computer Science, we can just throw implementations onto servers; In Mathematic, idea iteration is throttled only by one's thinking speed.)
  • Doctors are often conflicted when giving treatments. Sometimes the positive effects of a treatment are not clear and/or the negative effects are huge, but they are obliged to still give it to the patient. On a related note, should doctors lie to their patients? These are tough decisions to make on a daily basis.
  • In this part of the video, I was reminded of the min-cut graph problem --- Find the cheapest way to cut a cancer pathway. Could this be one possible way where Computer Science can help in cancer research?
  • Cigarette companies can really be assholes... Maybe this is human nature? :(
  • I tried to read up a bit further in current cancer research but could not get past all the jargon. I wonder if that is how others view papers in Computer Science and Mathematics. Hm...

Going further

There are also some related videos that I've watched:

  • A talk where Siddhartha gives snippets from the book and describes his writing journey.
  • An interview where Siddhartha talks about how cancer is a lens to understanding society, that we should always remain skeptical, and that our society seems to be distracted/not focused on tough problems.