STEM Tuesday: GENE by Siddhartha Mukherjee

I heard this on NPR’s “Fresh Air.”  Actually, I heard bits of it on two separate trips. It’s one of those broadcasts that fascinated me so, I had to find it on the internet and listen again.

Siddhartha won the Pulitzer Prize in General Non-fiction for The Emperor of all Maladies:  A Biography of Cancer in 2011.  He’s like the Carl Sagan of medicine.  He explains things in a way that both simplifies and enthralls.

First a little biography on Siddhartha:  He’s an oncologist and a cancer researcher.  He has a PhD from Stanford University of Oxford where he studied cancer-causing viruses and he’s a graduate of Harvard Medical School.  Siddhartha works on discovering new treatments for cancer using innovative biological methods.

Clicking on this photo will direct you to Amazon.

“Fresh Air” talked to him about his new book The Gene:  An Intimate History.  I took notes from the 45-minute podcast to create my post. Although this new book has a strong cancer component, it encompasses much more.

According to Siddhartha, the “Centerpiece of the book is that biology is not destiny. But some aspects of biology and some aspects of destiny are commanded very strongly by genes.”

We used to think of disease as something to us.  In other words, us reacting with the something from or in the environment.  However, new research indicates that  many diseases are dependent on interception of genes and environment. If you leave one of these out, won’t know how to treat the disease.

Siddhartha goes on to break that dependence into three categories or what he calls “penetrance:”

  1. Strong:  Diseases that have a strong genetic component like Cystic fibrosis or Huntington Disease: The genes linked to these diseases he classifies as highly penetrant.
  2. Mid:  These are diseases that have a powerful genetic influence or interaction between multiple genes, and the environment environment. Diabetes, obesity, and even schizophrenia  fall into the mid-level penetrant category.
  3. Low:  Many infectious diseases fall into this category.  HIV susceptibility and influenza both show an interaction between your genes and the environment influence whether you will get the disease and how acute an infection will be.

These discoveries make scientists and physicians rethink how we look at cancer. Although we’ll probably continue to think about ‘breast cancer’ or ‘lung cancer’ or ‘liver cancer,’  some  of these cancers have the same mutations. For example some of the genes particular to breast cancer are also in lung cancer.

A mutations in the cancer cell produces proteins that are disease drivers. These drivers act as a commander in the cell causing them to behave abnormally.  The trick into create molecule that turns off command center.  Because normal cells don’t have the same command center protein, they are left unharmed.  (Unlike chemo that affects both the cancer and the healthy cells.)


[tweetthis]One drug targets the command center acts “like an arrow that pierces the heart of the abnormal protein.”[/tweetthis]

Siddhartha reminds us that when a single gene mutates it  rarely causes cancer.  Instead, several cells must mutate and start what he calls a “whisper campaign” to co-opt the normal behavior and change the way  the cell behaves.

Some very promising work focuses on the core network that controls the cell behavior.  Physicians see extraordinary success in multiple myeloma.  In this disease, in theory, the protein waste disposal system doesn’t work properly drug The drug used doesn’t target the cancer mutation. Instead it targets what Siddhartha calls its Achille’s Heel, the core network

Another avenue is to turn the body’s own immune system against the cancer cells.  Although this is not a new idea, it is accomplished in new ways.  CRISPR technology allows scientists to genetically modifying T-cells in the immune system. The work is  very preliminary.  Siddhartha and his group want to find ways to bring the work forward into  [re-clinical studies.  Another aspect of the work is to change how the cancer cells “cloak” or protect themselves from the body’s immune system.

CRISPR can now do the work that even five years ago seemed insurmountable. If you imagine the “human genome as information that’s contained in 66 sets of Britannica, CRISPR allows us to go  in and change one word and leave most of rest untouched.  We can erase and change one word.”

As you can imagine, this raises many ethical question centered around “what is disease?”

Siddhartha believes that if we need to ask three important questions:

  • “Is there truly extraordinary suffering associated with the condition?”
  • “Is there one to one penetrance?” We often don’t know the complexity of the genetic influence.
  • Is there justifiable choice? In other word, we need to make sure the human has a choice.

“As long as stick within the triangle, know that we’re not tampering in a totally unsafe way.”

There’s a lot more about epigenitics, environment, sexuality, and gender identity that scientist are discovering.  I’ll save that until next week.

I know it’s super-nerdy stuff, but so, so interesting.  Don’t you think?