Ravenous by Sam Apple

Ravenous is truly a wild, crazy story, and a fascinating, breezy read from an excellent writer. I’ve always felt like I knew a a fair amount about World War II, the Nazi’s, Germany, etc., but I had no idea their fascination with ending cancer, Hitler and other SS officer’s obsession with health and diet, and the role Otto Warburg played in all of this. Warburg was a gay, German/Jewish scientist of wide renown in the early 1900’s, regarded as one of the most important biochemists of the twentieth century. He was convinced — and had the Nazi’s convinced at every turn imaginable — that he could cure cancer, and he was one of the only Jewish scientists to survive the Nazi onslaught of mass murder before and during World War II. Warburg not only managed to survive the Nazi era, but Apple punctuates his book with stories of Warburg’s defiance, stubbornness, and downright ignoring of any Nazi official who stood in the way of the work that he was doing in his tightly controlled lab. Far from a heroic character, Warburg is portrayed by Apple as stunningly aloof, mean-spirited, recalcitrant, and obsessed with his work to the point that he had few allies in the scientific field — especially when he defiantly chose to remain in Germany while his colleagues were being deported to concentration camps. Apple manages to tell Warburg’s incredible story while also explaining a whole host of science along the way, mainly tracking how cancer research — and our understanding of it — has evolved and changed in the past century, and shows that Warburg’s research has come full circle after being ignored for decades after his death. Apple is a wonderful storyteller, and my notes were a pleasure to compile as they are not only informative, but also easy to understand for those that are interested in the evolution of cancer research over time.

• in 1934, at a moment when Hitler had already begun sending Germans to concentration camps, Otto Warburg, a gay man of Jewish descent, wanted Nazi laws rewritten according to his personal needs
• 1941, Warburg learned that he would be allowed to continue working at his institute so long as he focused on cancer research
• Nazi’s interest in Warburg was rooted in the most respectable science of the time — cancer
• interfering with a cell’s use of oxygen and forcing it to ferment glucose — likely cause of chemicals causing cancer
• that cancer cells typically eat enormous amounts of glucose and ferment much of it was confirmed by other researchers in the decades after Warburg made his discovery
• by the final decades of the 20th century, Warburg’s work was no longer of any interest, but it came full circle eventually
• a cell turning to fermentation when oxygen is available is now known as aerobic glycolysis, or “the Warburg effect”
• more glucose being consumed by the cancer cells, the worse a patient’s prognosis is likely to be
• today, approx. 600K Americans die of cancer every year, an increase that vastly outstrips population growth — defining illness of our time
• cancer is linked to modernity
• many cancers are closely tied with being overweight
• obesity is a consequence of our cells ending up with more food than they should — Warburg discovered that cancer cells overeat
• cancer is a disease of bad information, a disease of damaged DNA providing cells with the wrong instructions
• Germans believed in the transformative power of science
• by 1900, Germany had the largest economy in Europe, world’s leading scientific nation
• cancer was the one challenge Germany could not overcome
• cancer deaths were going up and up
• German researchers launched what amounted to the original war on cancer, becoming the first to identify one carcinogen after another, from sun exposure, to various industrial chemicals to secondhand smoke
• among native populations, cancer was either rare or unheard of, or in those that hadn’t adopted western lifestyles
• disease of civilization
• prior to 19th century, cancer was very rare, also almost completely absent in written sources from antiquity
• explained in how we live, not necessarily our length of lives
• unnatural and excessive food, unhealthy surroundings, sedentary occupations, mental anxiety and worry
• Klara Hitler, Mom, died of cancer, also had a Jewish doctor
• Ehrlich, anticipating today’s thinking on nutrition and growth factors in cancer — proliferation depends in the first place on the avidity of the cells for the nutritive substances
• starving of transplanted tumors = athreptic immunity, Greek word for malnutrition
• 1913, Cornell published experiments had done on enough animals to eliminate any doubts that carb free diets made more rodents more resistant to tumor growth
• 1910, questions in biology — how food and oxygen combine inside us to sustain life — remained unanswered
• first world war would likely have never happened if not for the ascension of the recklessly militant and volatile Wilhelm, who took over for Kaisier Fredrich
• German Jews signed up to defend the fatherland by the tens of thousands, enthusiastic about a new sense of German unity
• as they assimilated, Germany’s Jews came to think of themselves as fully German
• animosity toward Jews only spread and turned more virulent
• for German scientific racists, gravest threat was that they were assimilating and marrying non Jewish Germans
• by the time the war was over, 2 percent of all German Jews had died defending the fatherland
• prior to the war, Hitler had not been overtly anti-semitic
• what little money Hitler made himself often came from selling his paintings to Jewish merchants
• 1918, Hitler was awarded the Iron Cross, First Class, received the honor on the recommendation of Hugo Gutmann, highest ranking Jewish soldier in his regiment
• fermentation, according to Pasteur, was a backup process that activated and sustained the life of microbes when oxygen wasn’t readily available
• fundamental relationship between between respiration and fermentation is now known as the Pasteur effect, and it was Warburg who named it
• soreness we feel after intense exercise is a by product of the lactic acid our fermenting cells produce
• Warburg Effect: if a cell had access to oxygen and nevertheless chose fermentation, it could only be because something fundamental was broken and preventing the cell from using the oxygen properly
• as respiration decreased, fermentation increased
• cancer cells were fermenting, sucking up glucose and spitting out lactic acid
• for Hitler, what Germany needed was not merely better agricultural methods, but the will to fight and conquer more Lebenstaum, or “living space”
• German East — Ukrainian grain fields
• by linking cellular breathing to a specific part of a specific molecule, Warburg had launched a new era in science
• German Romantics thought that superior German traits were being diluted amid the departure from nature and the mixing of races in modern cities
• cancer had arisen during the period of industrialization, when Germany left its “natural” state, fit perfectly with this racist fantasy
• late 1920’s, Germans were arguably more concerned with the connection between diet and cancer than any other nation in the world
• Frederick Hoffman, 1937, published Cancer and Diet, a 767 page book where he noted that the rest of the world had fallen behind the Germans in their research into nutrition’s role in cancer
• Germany’s lead in focusing on the relationship between diet and cancer
• perhaps the medical establishment would have taken cancer diet connection more seriously had the thinking not fallen into the wrong hands and been forever tainted
• cancer terrified Hitler the most, amongst his many phobias
• collapse of stock market, 1929, German economy nosedived again, and no one would benefit more from the return to instability than Hitler
• Hindenburg had appointed Hitler chancellor on the assumption that he and other German conservatives could contain him
• first year of Civil Service Law, estimated 2600 scientists and other scholars, almost all of them Jewish, fled Germany
• Warburg emerged as a gay man from a famous Jewish family and survived, provoked the Nazi’s at every opportunity
• fleeing Hitler wouldn’t only lead to shame and a loss of identity, but it would be an implicit acknowledgement of having been mistaken about Germany itself — he was a patriot in that way
• Nazis referred to Germans with only one or two Jewish grandparents as Mischilinge, a derogatory term that translates to something like “mongrel”
• Warburg was declared a first degree Mischling, stranded between two worlds: half Jew, half Aryan, half oppressed, half oppressor
• church prohibitions against money lending led Jews into such professions, even as they were barred from many other lines of work
• Nazi’s saw the eternal Jew as a metaphor for the Jew’s never ending malice — a character who, in his refusal to vanish, justified the famous German slogan, “The Jew is our misfortune”
• Nazi’s accelerated campaign against cancer
• Hitler’s focus on diet and cancer only intensified after he became chancellor
• many Nazi leaders were strangely focused on cancer
• 1937, prisoners at Dachau were forced to drain marshlands and then to plant and run an industrial sized organic farm on 200 acres — largest research center of its kind in the world
• SS had additional gardens planted at other concentration camps
• figure out which blood markers might signal cancer, at Dachau, they did the first medical experiments on prisoners
• Warburg unintentionally discovered why vitamins are so critical for our health
• because our bodies can’t produce these critical engine parts, we need to obtain them from food
• also discovered that nicotinamide played a critical role in respiration
• white tablets of nicotinic acid could wipe out a disease called pellagra, which was a miracle back then
• Koch’s postulates, if a microbe is the cause of a disease, it must be present in every last case of the disease
• in one sense, Koch shaped Hitler’s life simply by proving that germs cause disease
• as the years passed, Hitler became increasingly fearful of germs
• Hitler borrowed from Koch’s bacteriological jargon; in 1920, Hitler described Jewish influence on German life as “racial tuberculosis”
• Jews as the bacillus and ferment of all social decomposition
• Warburg never doubted that Hitler’s fear of cancer made it possible for him to survive
• Barbarossa, secret plan to invade the Soviet Union had initially been known by another name: Operation Otto
• in 1933 when the Nazis came to power, there were more than 100 scientists at the prestigious Kaiser Wilhelm institutes who qualified as Jewish; Warburg was the only one to maintain his position until the very end
• in the last months of his life, Hitler had the strength left for only three topics: dog training, stupidity of the world, and diet
• chemotherapy, drugs attacked rapidly dividing cells, cancerous or not
• chemo turned out to be a validation of Warburg’s broader belief in the fundamental importance of metabolism
• vast majority of Nazis moved seamlessly back into German life, those that weren’t tried and convicted
• as late as 1957, almost 80 percent of the officials in the justice ministry were former Nazi Party members
• German public’s fear of cancer was also largely unchanged after the war
• William C. Hueper left Germany in 1923, concern that artificial chemicals were responsible for many cancers was growing more pervasive in America
• Hueper achieved a level of fame when Rachel Carson wrote about him in Silent Spring in 1963, sold hundreds of thousands of copies and inspired a generation to think more seriously about the environment
• Carson’s book changed America in a way that few others ever have
• Carson was also undergoing treatment for breast cancer, died two yers after book publication, before she could witness the tremendous influence of her work
• Hueper’s Nazi sympathies can come as a shock to those who remember him as a crusader for public health
• researcher most qualified to identify the prime causes of cancer in the 60’s was not Warburg but Richard Doll, the most celebrated British epidemiologist who had linked smoking to cancer in the 50's
• between 1930 and 1944, lung cancer deaths among English men had increased sixfold
• Doll and Hill turned to epidemiology, the study of health and disease patterns among populations
• that did the most to ease the burden of the diseases in the 19th and early 20th centuries
• first to definitively link smoking to cancer by means of a modern scientific study
• Germans were more than a decade ahead
• Nazis launched the world’s most aggressive anti smoking campaigns, nicotine free cigs, counseling, workplace bans
• 1981, by Doll and Peto’s estimates, artificial chemicals in our air and food accounted for only 2 percent of all cancer deaths
• black and white world of smokers and non smokers is impossible to reproduce in studies of nutrition, which is one reason why so many different foods have been shown to cause cancer in one study and to prevent it in the next
• Fritz Haber, Wilhelm Society, plan was to secure the German food supply by solving the nation’s nitrogen problem
• cannot live without nitrogen; without enough of it, crops will not grow and humans will not eat
• ammonia, naturally reacts with oxygen to form the nourishing molecules plants need
• Haber’s ammonia producing process was one of the most important inventions of the 20th century
• little or no interest in Warburg’s cancer research by the 60's
• two conceptions of cancer, one metabolic, one genetic, emerged, and the genetic conception prevailed, and Warburg was erased from cancer science for a time
• organized death of cells, programmed cell death, or “apoptosis”, from the Greek for falling off
• during the development of an embryo, apoptosis, like a sculptor chipping away at a stone to reveal a human form, helps shape our bodies
• approx 10B cells are thought to die in a person every single day
• mitochondria were directing apoptosis
• body gets rid of unwanted cells, cutting off growth factors and starving the cells into suicide
• Cancer cells that ate whenever they felt like it, cells that couldn’t be starved into suicide, even though they had no purpose in the body
• getting more glucose than you want might be what the Warburg effect is
• if a cell can eat all it wants isn’t yet cancerous, it is an emerging threat to its neighbors
• when an individual cell alters the state it’s in by expressing different genes, it is known as an epigenetic change
• a cancer cell behaves like a growing single celled organism that is binging on glucose
• when they see food in their environment, they move to capture as much as they can
• when that food exceeds their need to survive, they begin to make copies of themselves
• search for a new living space is metastasis, the spread of the disease from one place in the body to another, and it is typically why cancer kills us
• with each new advance showing that cancer is tied to how our cells eat, researchers studying cancer trends were arriving at advances of their own showing that cancer is tied to being overweight
• 90K Americans losing their lives to cancers linked to being overweight or obese
• studies to know show that obesity causes cancer
• rise in diabetes deaths occurred alongside the rise in cancer deaths didn’t go unnoticed in the late 1800's
• parallel to cancer, diabetes was not becoming common everywhere
• as soon as they adopted western lifestyles
• since 1960, diabetes rate in U.S. has increased 800 percent
• 2010 report showed that people with diabetes are significantly higher risk for more forms of cancer
• same effect: blood coursing with glucose that our cells are unable to eat, Yalow
• calculate the amount of insulin in a sample = radioimmunoassay, revolutionized modern medicine
• insulin tells our fat tissue to take up and hold on to nutrients was clear to diabetes doctors from the moment they began to inject the hormone into their patients
• people who have high insulin when they are diagnosed with cancer also tend to have worse outcomes
• elevated insulin is a risk factor for cancer even in the non obese
• insulin’s role is to whisper encouragement into the ear of an incipient tumor
• some types of cancer could survive without the insulin, but many others could not
• interplay of genetics and bad luck will always lead to some portion of cancers
• question is now whether too much insulin explains our modern epidemic of cancer, but whether it is the crucial factor we have long overlooked, the missing piece of the puzzle that best explains why prevention efforts continue to fail
• insulin levels are determined by what we choose to eat
• keto diet — might make traditional therapies more effective in fighting some cancers
• prevalence of metabolic health in American adults is alarmingly low, even in normal weight individuals
• candy, ice cream, chocolate, soft drink industries all stem from the mid 19th century, as does the expectation of a sweet dessert at the conclusion of every lunch and dinner
• Emerson — first to show sugar consumption in the West had risen together with diabetes beginning in the 19th century and also sugar consumption fell during WWI, diabetes rates in the following years fell as well — only a correlation
• belief that animal products were the true threat had crystallized into accepted wisdom in the 80’s and 90's
• fructose appeared so benign by 1979, Glucose had been singled out as its evil twin
• recent data suggest that fructose will directly turn on the genes responsible for making fat in the liver
• basic concept — that carbs fatten the body — has been well understood for centuries
• as fat accumulates in the liver, makes its way into the pancreas and even into our muscles
• misplaced fat drives inflammation and interferes with how our cells respond to insulin
• no choice but to secrete more insulin, a dangerous cycle, makes us fatter, more misplaced fat and greater insulin resistance
• Cantley, high consumption of sugar almost certainly responsible for the increased rates of a variety of cancers in the developed world
• fructose is the perfect food for a growing cancer precisely because it helps cancer cells to survive in the low oxygen environments
• we need far more research on the health effects of sugar
• Hitler was addicted to it, as his madness grew, so did his taste for sweets