Notes on The Emperor of All Maladies

For work I’m reading and taking notes on my blog about cancer biology texts.

The following are notes on most chapters of The Emperor of All Maladies by Siddhartha Mukherjee. Some of these are not actual chapters (e.g., “Leukemia” is not a chapter).

I listened (during many episodes getting a kid to sleep in the middle of the night) to this book borrowed from my local library with the Libby app.

Leukemia

• Book started off with author taking about his treatment of a leukemia patient. Noting that is a special type of cancer, in that it is of white blood cells, so can be quantified, and it is rather rare, but especially vicious and deadly.

Remote Sympathy

• At one point “remote sympathy” was a suggested treatment, practice sympathy and palliative care
• Anesthesia: first used in 1846
• Antiseptic: first used in 1860s
• Those two creations (anesthesia and antiseptic) paved the way for surgery to remove tumors that wouldn’t be a major risk to the patient (less pain during, and not dying from infection afterwards)

A Radical Idea (Halsted and radical surgery)

• “radical surgery”: Halsted started this originally as digging up the root of the tumor, but then went into removing not just the tumor but muscle and bones and glands behind it, often permanently disfiguring people - this apparently took hold after he showed evidence that it worked well for local tumor removal - even though patients most often still died within 3 years because the cancer spread despite the radical surgery

Radiology (the hard tube and the weak light)

• someone noticed (about 1890?) that certain things gave off x-rays and would be able to give a picture of the insides of the human body. radium was one of these - which lead to the watch maker situation where women died of cancer from radium. But cancer treatment of radiation came from this and still used today.

Dyeing and Dying

• The industry involved in dyeing fabrics led to many discoveries, including
  • Treatments for bacterial infections in humans
  • Paul Ehrlich came up with concept of chemotherapy though he used the phrase “curative substances”
  • Paul Ehrlich came up with some of the first antibiotics from these dye chemicals
  • After tackling diseases of humans caused by bacteria, Ehrlich wanted to address cancer, but could not find any chemicals that worked
• 2 years after Ehrlich’s death, mustard gas was used by germans (and maybe others) in World War 1. A pair of people studied the affects of this gas on the few that survived, and published their results which should have interested cancer researchers, but because of war wasn’t picked up until much later

Poisoning the Atmosphere

• 70 tons of mustard gas was on an allied battle ship in WW2 and germans attacked, and the mustard gas killed a lot of people (an “own goal”)
• From that event two researchers were curious if mustard gas would be effective against white blood cells because they attacked

VAMP

• A four drug regimen for leukemia in children, idea was radical at the time, thought was you give one drug at a time then try the next etc
• Happened at the NCI
• Fry and Fryberg led the trial
• Most had remission but then all but 5% died after leukemia passed through blood brain barrier into the brain

an anatomist’s tumor

• started describing two cases: hodgkin’s lymphoma, and pancreatic cancer - where the first had a high chance of recovering and the latter very little chance
• then told story of a tiny woman with a huge personality that had some cancer, that they treated but realized they had nothing else to try
• told story of hodgkin who described hodgkin’s lymphoma - how he came to study anatomy and the importance of his work
• story of Kaplan who focued on treating hodgkin’s lymphoma with very intense xrays adapted from a linear accelerator - and get some success maybe curing very early stages of hodgkin’s lymphoma in a randomized trial

An army on the march

• no notes

Moonshot for cancer

• right after landing on moon so coined moonshot
• Legislation was a independent federal agency but it got watered down to just a couple hundred million I think
• Cancer group that promoted it gave up

the smiling oncologist

• no notes

knowing the enemy

• no notes

Halsted’s Ashes

• no notes

counting cancer

• stories of quantifying cancer
• shocking realization that death from cancer was not decreasing but increasing
• realization that perhaps prevention needed to be made more important because fighting cancer when it’s already in the body is not easy

prevention is the cure

• no notes

the emperor’s nylon stockings

• big study on cause of lung cancer on doctors in the UK.

a thief in the night

• no notes

a statement of warning

• ftc was going to be a warning on cigarettes but industry asked for congress legislation instead and it was much softer
• fairness doctrine: young lawyer thought it up, but then industry voluntarily removed tv ads so they didn’t have to suffer negative ads
• Vignette of a woman victim with lung cancer: that was used to sue tobacco companies for not sharing everything they knew and court let them see lots of internal communications which lead to lots of embarrassing things even though case was mostly lost
• Despite major victories in the us, companies have just moved to other countries where they’re paying off politicians etc and doing the same thing

curiouser and curiouser

• discovery of hepatitis b virus by someone
• originally thought it was a genetic linked trait but then found that a person changed from negative to positive and so couldn’t have been genetic
• They then found a vaccine for it
• gastritis investigation: helicobacter pylori was found, apparently gastritis can predispose to cancer, researcher infected himself to confirm it,

a spiders web

• Papanicolaou came up with Pap smear originally from studying pig menstruation
• screening tests for breast cancer: history of screening trials for mammograms, fraught with many bad trials that messed up the randomization

stamp

• megadose chemotherapy - just means giving very large (larger than previously used) doses - can’t find mention of the term specifically, but there is high-dose chemotherapy

the map and the parachute

• megadose chemotherapy took hold and even insurers started paying for it but trials finally happened and all but one showed it wasn’t worth it
• That one trial was in South Africa and megadose was probably egged on by that trial alone. In 1999 Americans went to South Africa to look at the data. It was poorly kept and the doctor didn’t turn over everything, and many patients that were called cured or in remission were missing or dying, And there were ethical issues too as it appeared the patients may not have known what they were having done

a distorted version of our normal selves

• Mendel and peas
• 1909 word “gene” coined but no understanding of what it was
• Thomas Hunt Morgan : proposed that genes were on chromosomes
• Oswald Avery: bacteriologist, 1926 genes could transmit laterally between bacteria. In 1944 they found that genes was actually dna
• a student of Morgan’s George Beetle studied slime molds and figured out the dna to protein pathway
• A few others figured out that rna was in between dna and proteins
• morgan former student had a theory of mutagenesis that potentially all cancers were due to mutations in genes but wasn’t widely accepted

under the lamps of viruses

• Rous of rsv had a very strong personality and pushed the field away from any explanation of cancer causation other than viral
• Howard Temin researching RSV postulated that it could turn rna into dna, but years later finally via a post doc got proof for that happening - these viruses that make reverse transcription happen are called retro-viruses
• Massive hunt for proof of retro viruses causing cancer but only 1 case found a rare cancer
• But retro virus research paid off as it was found as cause for HIV

the hunting of the sarc

• [[oncogene]]: a gene capable of causing cancer
• endogenous SARC found in cells
• virus rsv probably just picked up SARC from a cancer cell originally
• lesson was that radiation or other exogenous factor caused cancer by activating endogenous proto oncogene

the wind in the trees

• a scientist found that a CMS leukemia had chromosomal translocation, the heads of chromosomes 9 and 22 were swapped
• This kinda changed the thought of cancer from chaos to organized chaos
• retinoblastoma: two forms: inherited form and non inherited sporadic form, inherited always has tumors in two eyes and always one in sporadic form.

a risky prediction

• many labs raced to isolate an oncogene , one was the Weinberg lab
• All extracted the same gene: RAS
• RAS carefully modulates a protein in normal cells but goes crazy in cancer cells
• br gene 🧬
• Brca1 gene, brca2 gene 🧬
• Transgenic mice in mid 80s came along
• Mice for studying cancer were used afterwards . Oncomouse

the hallmarks of cancer

• vogelstein: research trying to find how many changes are required to create a cancer cell
• RAS to mec to ERS pathway
• resists can death signals
• Can activate pathways to accumulate blood delivery to itself to grow faster, tumor angiogenesis
• By early 90s cancer researchers could model a cancer type by its underlying genes
• paper written: hallmarks of cancer

the fruits of long endeavors

• anecdotes about authors patients and Jimmy fund person comes forward after 50 years

new drugs for old cancers

• no notes

a city of strings

• recombinant DNA was the technology that started Genentech
• Genentech started 1976
• Most of early wins were production of old drugs that were hard to collect from animals
• 1984 [[HER2]] found by Genentech scientists. But they didn’t know what to do with it. (“neu” was the predecessor found in Weinberg’s lab)

drugs bodies and proof

• chapter covered [[HER2]] positive drug created at Genentech
• A woman died waiting to get access to the drug set off protests at the south San Francisco office, and then company agreed to a trial
• Trial was a huge success and drug was approved

a four minute mile

• BCR-ABL gene is a fusion of two separate genes caused by a translocation of chromosomes 9 and 22 that causes chronic myeloid leukemia (CML)
• gleevec: name for a drug targeting CML
• Gleevec made by Novartis
• Druker had to beg Novartis to release some of the drug
• first person treated was a train conductor
• CML used to be fatal and live for 3-6 years but with gleevec they can likely survive rest of their life taking it the whole time

the red queen’s race

• CML became resistant in some patients to gleevec and BMS made a new drug that acted different and it works for those patients
• Framingham long term study following everyone living there
• Social network study of the above: found that smoking was best explained by the social network, with isolated people facing the worst unlikely to quit smoking
• red queens race https://en.wikipedia.org/wiki/Red_Queen's_race?wprov=sfti1

thirteen mountains

• quote: “cancer is a genetic disease”
• returned to story of his patient Carla. Visited her to declare that they beat her cancer
• cancer genome atlas project released in 2008
• most cancers have a lot of mutations, e.g, 50 or so, but some cancers have very few, only a half dozen or so, and are more easily treatable. On the other hand if there’s very few for a cancer maybe it takes less damage/time for a cancer to start? https://bsky.app/profile/longreads.com/post/3lkefphassh2i
• passenger mutations are ones that have no effect
• driver mutations are ones that potentially contribute to cancer - mutations to an [[oncogene]]

Attosa’s war

• Attosa, an Achaemenid princess (who lived 550–475 BC) , who had cancer, was used as a way to say how she would have been treated through time (referenced in her wikipedia article) - rather through distinct changes in cancer treatment through time - this was a very cool way to summarize parts of the book and cancer treatment history
• story at very end was about a women with cancer and how she didn’t make it in the end, but author realized later after she’d died what certain things meant (at least what he thought they meant)

end thoughts

This is the only book I’ve read about cancer- having said that, it was a great book. Maybe if I knew more about cancer already I’d have a more discerning palate and more to say.

Anyway, it’s an odd time to read this book - and an odd place to work right now - when science/research is completely under attack in the US; at least research can continue in other countries 🤷🏽

notes

• FYI: Internet Archive link to all of the text