Books that mattered to me this year – The Cancer Letter

Over the past year, I noticed several books written by giants in our field, people everyone knows, people I am honored to know personally. I was interested in what they wrote, and I thought their books would be of general interest to The Cancer Letter community.

Going beyond merely recommending the books, I set out to write in a book review format, providing critiques that would enable everyone to appreciate more of the details (and want to read the books).

Because of my interest (or because I know the subject matter and, in some cases, am acquainted with the authors), I included reflections on the aspects of the books I found interesting, adding perspective or insight when appropriate.

You will find a lot of interesting history and fascinating tidbits within these volumesincluding the personal human side of science and medicine. Perhaps I got a little carried away with the number of words, but I wanted to do these books justice. I know my colleagues will be eager to read every word. And maybe some will be inspired to do similar thingsmaybe we could start something new here.

Perhaps it was an unusual year for those types of books that I gravitated toward. Rather than sticking with my typical diet of sci-fi, social justice, history, and entertainment, I gravitated toward important and timely social and ethical issues in science and oncology.

I hope the reader gets all the way down to the bottom of the list (especially the book my daughter Julie is reading), and, finally, I wish there were more hours in the day.

The books reviewed here are:

Other books on my reading list are:

And a book my daughter, Julie, is reading:

When a Nobel Laureate like Paul Nurse stops to ask what it means to be alive or what defines life, one can be sure that something interesting and important will be learned.

The basic unit of matter is the atom. The basic unit of life (the first step), the cell varies widely in size, for example 3,000 bacteria add up to a mm, while a single nerve cell from the spine to the big toe can be a meter long. Virchow Omnis cellula e cellula, or all cells come from other cells, is pretty profound.

We all were single embryonic cells; life does not ordinarily arise from inert matter. At the core of cells are the genes, and their history dates back to before it was known what genes were. Gregor Mendel studied inheritance patterns in pea plants and referred to pairs of elements and specific patterns he observed were later understood to apply to all sexually reproducing species. Microscopy was used by Anton van Leeuwenhoek, and later by Matthias Schleiden and Theodore Schwann in the late 1830s to observe cells.

By the 1870s, Walther Flemming observed threads in cells that separated as cells divided, later called chromosomes, physical manifestations of genes, the heritable particles proposed by Mendel. While it became known that chromosomes contained deoxyribonucleic acids, work of Oswald Avery in the early 1940s, most biologists thought that DNA was too simple and boring a molecule to be responsible for such a complex phenomenon as heredity.

Nurse recounts how the structure of DNA was transformational as were its implications for heredity. The gene is the second step in understanding the biology of life. He got to know Watson and Crick and describes how they were and how they complemented each other.

The genetic code was broken in the late 1960s and early 1970s. Nurse describes Sydney Brenner as having interviewed him for a job he didnt get, during which he compared his colleagues to the crazed figures in Picassos painting Guernica, which hung on the wall of his office.

Genetically modified bacteria were developed by the late 1970s and instructed to produce insulin, while Fred Sanger worked out methods to sequence DNA, and the human genome was sequenced by 2003. Nurse goes into how the control of mitosis and the cell cycle to ensure faithful replication and cell division is what makes life possible for a cell. He recounts laborious work with yeast mutants that led him to identify the small wee mutants, at least 50 of them, and then the cdc2 mutant that unlocked a fundamental mechanism of cell division.

Nurse recounts a personal story about his own genetics with shocking revelations for him as he was moving to become president of Rockefeller University. Youll have to read his book for that information.

The book turns to evolution, natural selection as an important feature of life (the third step), ideas of Lamarck and (Charles) Darwin (and his grandfather Erasmus who was also a doctor and poet). He mentioned others before them and also described the influence of artificial selection used by humans, such as breeding pigeons or dogs, on directed evolution.

Even the error rate of DNA replication is subject to natural selection. Nurse describes life on our planet as all connected, and recounts an experience on a visit to Africa with a gorilla and then the amazing conservation in cell cycle control between yeast and human cells, at least as far as cdc2.

It is interesting to me, that four decades after its discovery, there has not been a description of a yeast p53 homologue or a cell cycle checkpoint mechanism like p53 activation of the mammalian CDK inhibitor p21(WAF1)/CDKN1A, one of my most favorite genes that mediates growth arrest to allow DNA repair in damaged or stressed cells.

Nurse gets into another (the fourth step) aspect of life through chemistry and chemical reactions. He describes insights by Pasteur that chemical reactions are expressions of the life of the cell. Metabolism is the chemistry of life is something that many cancer researchers in 2021 are focused on.

He points out that enzymes are catalysts that support life. The compartmentalization within cells is viewed as a way that a vast array of chemical and metabolic reactions can occur to sustain life. Life is also powered by ATP made in mitochondria. Finally, Nurse describes a key aspect of life (the fifth step) as information, sensing, responding and adapting, and posits that purposeful behavior is a defining feature of life.

The book discusses much more about the organization and regulation that makes life possible. Nurse includes a chapter about changing the world with new ideas and technologies, and how the world has changed as a result of all the progress that has been made through science. He ends the book with his approach to defining life by providing essential principles that build upon the five steps, recounts ideas of others, and offers some of his own speculation about the origin of life.

I read this book while in medical school, but became interested in it this past year, as I think it brings back a history of medicine and a kind of explorer who has been lost in the modern era.

If bureaucratic heads would roll in Washington, the answer from the FDA would have to be no as far as starting human studies with thymidine as a cancer therapeutic without preclinical evidence of safety.

Thus, Dr. Beppino Giovanella wrote a clinical protocol for himself, and took thymidine orally in increasing doses. He developed diarrhea and couldnt absorb enough to reach high blood levels. So, he injected himself with IV thymidine and went to the FDA with evidence of safety and they reversed their decision to allow clinical testing in patients with terminal cancer. But not all chemotherapy works

Dr. Horace Wells, a dentist and inventor in Hartford, CT, was successful but felt his profession was unpleasant because of the pain his patients had to endure. He observed a demonstration of the effect of laughing gas when a circus performer hurt himself and felt no pain. He set up a demonstration on himself of what would be a painless tooth extraction.

His demonstration in Boston to the Harvard surgeons didnt go smoothly because of his nervousness and their arrogant skepticism. He abandoned dentistry but was urged by his family to patent the nitrous oxide gas.

He wouldnt give his former student Morton, in Boston, the gas, and Morton eventually experimented with ether, also being talked about at the time, on his dog and goldfish. Morton eventually made a demonstration for the surgeons at Harvard and it went well for the removal of a neck tumor painlessly.

The story gets interesting with disputes in 1846 between Wells, Morton, and Jackson each claiming they made the invention. Desperation, anguish, and madness are part of this story and eventually credit for the discovery of anesthesia is settled but not before a human toll is taken. Read about it to find out what happened.

Several other guinea pig doctor stories are included about cholera, yellow fever, tubes inside the bodywhether its the heart or kidneys combined with X-rays, to push back the frontiers of medicine. One story I read in the 1980s is about Dr. William J. Harrington, who was chair of medicine at University of Miami, who was also head of hematology and on the faculty while I was a student there.

I met him at the end of my hematology rotation and remember, to this day, that when examined by a hematologist, one should always have in the back of their mind that the answer might be to do a bone marrow examination.

Dr. Harrington had met a young patient who was bleeding when he was a medical student in Boston. His patient had no platelets and died from surgery to remove her spleen. Later, as a hematology fellow at Barnes Jewish Hospital in St. Louis, he would inject himself with a pint of blood from a patient with severe ITP who had not improved despite a splenectomy.

Bills own platelet count went down to zero for 5 days and he had bleeding around his ankles and in his stools. He had multiple blood and bone marrow examinations during the days that followed until his platelets recovered. His self-experimentation was the first example of a demonstration of autoimmune disease.

Interestingly, the book recounts that other staff members, secretaries, medical students and physicians in the summer and Fall of 1950 participated in similar experimentation with transfusions under more controlled settings. Dr. Harrington presented his paper at the 43rd annual meeting of the American Society for Clinical Investigation.

It was quite a treat for me to read this book, as I had met Dr. [Suzanne] Koven during medicine house-staff training at Johns Hopkins, and in fact she was my chief resident (the third woman in the departments hundred-year history and the only married woman or woman with a baby to be selected for this honor.) during my senior medical resident year.

Dr. Koven, who was an English major in college, and had wanted to become a journalist, has an incredible talent for writing and flowery language. She recounts her journey with a special kind of humor. The only thing I remember from my introductory chemistry course is that Einstein calculated Avogadros number (6.022 x 1023) using grains of pollen. I never understood what Avogadros number was, but I enjoyed picturing the wild-haired genius with his loupe and tweezers painstakingly dissecting the sex organs of flowers.

The Letter she wrote to a young female physician is about what to expect in a male-dominated medical world, with many challenges from sexism, some infuriating, some merely annoying, serious and damaging discrimination, imposter syndrome and ends with recognition of a mature state of humility, and self-reflection for the benefit of her younger colleagues.

She quotes Sir William Osler: There are three classes of human beings: men, women, and women physicians.

Koven admits her complicity in a system that had so little regard for me, and states perhaps the reason I didnt rebel against the culture of my medical training was that I loved it.

Dr. Koven writes about her father who was an orthopedic surgeon with whom she spent time in the office after school.

What I wanted, I think, during those afternoons when I dipped x-rays into vats of sharp-smelling chemicals and held down limbs as the circular saw screeched through plaster casts, was to be close to my father, about whom I was endlessly curious.

On why she didnt become a psychiatrist, which she considered at one time, she mentioned a joke her father, the surgeon, told her The internist knows everything and does nothing, the surgeon knows nothing and does everything, the psychiatrist knows nothing and does nothing, and the pathologist knows everything and does everything a day too late.

She writes in a chapter entitled Things shameful to be spoken about: Ive always been a talker. Mrs. Sylvia Krensky wrote on my otherwise unblemished first-grade report card: Suzanne must learn to let the other children speak. I never did. To this day Im a chronic interrupter and conversation hog.

In her book, Dr. Koven shares much about her personal life through various transitions and some of what she went through, with wisdom, knowledge and poetry interspersed.

In her own words, she shares her tribulations, the idea that Id misdiagnosed my mother due to my incompetence was too painful for me to dwell on for too long. I quickly moved on to another theory: that my mothers diagnosis had eluded me for the same reason it had eluded her internist in Florida during the many months shed complained to him about fatigue and left-shoulder pain; she was a woman.

Dr. Koven recounts meeting a patient with leukemia during her clinical skills training as a medical student at Johns Hopkins. Her interview at that point captures when the patients illness became apparent, during an afternoon when he was coaching his grandsons baseball team and suddenly became light-headed.

He held on to the chain-link fence to keep from falling and as he looked at his fingers, wrapped tightly through the metal wire, he noticed how pale they were.

Months later, on an inpatient rotation when the patient was much sicker when she reviewed the notes from her earlier encounter I tossed my old note back in the folder with my essays on Black House and Mrs. Dalloway, having concluded that it was, like they were, useless.

Then, she wrote this sentence that resonates a bit in the modern era of sometimes fragmented and impersonal medicine (although probably not the intended takeaway): Then I wrote my new note as if Id never met Mr. Blake before, as if Id never heard his story.

Dr. Koven wrote a chapter about Mnemonics, that every medical student will appreciate. She tells her friend, another English major she had met at Yale: The pancreas! I cried. I dont understand the pancreas!

In a chapter entitled We Have a Body, Dr. Koven describes an experience with a patient with terminal ovarian cancer on a rotation at the old Baltimore City Hospital. Youll have to read the book, but Dr. Kovens compassion and the art of medicine come to mind as she looked into the patients social history (a good thing for any doctor to do to understand more about their patient as a person) and what she did to spend time at the bedside.

Dr. Kovens book has much more, and every medical student and doctor should read it. It recounts a history important for anyone interested in social justice in the medical field as well as addressing sexism in medicine.

She reflects on her first experience with death. It seems preposterous to me now, as a mother and as a doctor, that any responsible adult thought it was a good idea for our AP biology class to take a field trip to the Medical Examiners Office of the City of New York to witness the autopsy of a nursing student from the Bronx whod been stabbed to death the night before by her boyfriend.

She says this, among other things about her experience in anatomy. At the end of the course there was no memorial service, there were no candles, no songs, and no prayers of gratitude, as there often are in medical schools today, to honor the people our bodies had once been.

Dr. Koven also addresses racism drawn from her experiences at Johns Hopkins.

Dr. Taussig pointed to the blood bank and stated aloud what everyone knew: that the blood of Black people and the blood of white people were stored separately there. She then asked Henry (one of Dr. Kovens mentors who told her the story): Doesnt this strike you as very wrong?

Pediatric cardiologist Dr. Helen Taussig invented the blue baby operation known as the Blalock-Taussig, shunt and which should really be called the Blalock-Thomas-Taussig shunt in recognition of Blalocks lab technician, a black man named Vivien Thomas, the grandson of a slave, who played a key role in perfecting the procedure.

Reading further about Dr. Kovens experiences and reflections, I thought she would have made an exceptionally great oncologist incorporating extensive clinical expertise and perhaps her own special impact on the field of palliative care to help patients. Who knows, maybe there would have even been a Kovens syndrome.

In a chapter about Lineage, Dr. Koven says My true lineage, I now think, included Blackwell and Haseltinenot to mention Oprah, and my motherat least as much as Osler. The House of God comes up a few times, along with a novel called Woman Doctor written by Dr. Florence Haseltine with English professor Yvonne Yaw, at around the same time as Samuel Shems bestseller.

Unlike The House of God, though, no ones heard of Woman Doctor. Its out of print. My copy has a tacky 70s cover featuring a grainy photograph of a glamorous, dark-eyed, long-lashed woman in full surgical garb who looks nothing like Dr. Haseltine as she appears in her author photo.

I was able to find a copy of Woman Doctor that I bought on Amazon, $6.55 Hardcover (for some reason, the paperback is listed from $38.50 and Mass Market Paperback $902.81).

Dr. Kovens book has much more, and every medical student and doctor should read it. It recounts a history important for anyone interested in social justice in the medical field as well as addressing sexism in medicine. It is a classic by a masterful author who is a complex individual with very important messages and legacy. Her Letter to a Young Female Physician book is already a best seller.

On a personal note, by 1989, when Dr. Koven was my chief resident, she had encyclopedic knowledge of medicine, the poise and equanimity that the Osler Marines aspire to and never appeared as an imposter per personal observations.

It is hard to know why we remember certain things, but I do recall a scene one morning on our Osler rounds where our team had an admission on Halstead 5, the famous step-down cardiology floor at Johns Hopkins.

As we were outside a patients room discussing the case, the patients heart stopped and they needed immediate resuscitation. Dr. Koven, chief resident and medical attending of record, very calmly picked up the paddles, and then passed them on to another team member to perform the electrical cardioversion. This was when she was fairly late in her pregnancy but functioning very admirably as our leader. As she handed the paddles off she had a smile or more of a smirk that all who know her would recognize, and then she said perhaps someone else should do this.

This was an intense time during residency training in an era without work-hour rules, or balance between learning and service. There were other memories and even conflicts, mostly suppressed but not all forgotten.

My colleague, John Marshall, who leads the Division of Hematology-Oncology, is a leader in our field, articulate, and well-known for his sense of humor. He directs the Otto Ruesch Center for the Cure of GI Cancer along with his wife Liza, who is a survivor of breast cancer. In this book, published in 2021, John and Liza share personal storiesand we can be grateful they shared them.

John begins the first part of the book entitled Hail to the Queen (referring to breast cancer as the queen of all cancers) by giving his perspective early in his career I quickly came to see the ubiquitous pink ribbons as the enemy, a symbol of unfair focus in our field. Breast cancer comes first, and the rest of us get the leftoversI preached my gospel of resentment and jealousy of breast cancer to anyone who would listen.

He would say things in lectures such as what color is the colon cancer ribbon? Come on, you in front? Brown? God, I wish it were a brown ribbon (and the comments went downhill from there, not to be repeated here).

He reminds the readers about how the Department of Defense came to fund breast cancer research, and how politically incorrect it would be to cut it even though it doesnt kill most of those in the military. He felt an injustice towards the high mortality of some of the many patients he saw, including young people, with advanced GI cancers.

He says other funny things, like, hematologists are full of themselves, a bit like peacocks or GI oncologists are the Gryffindors of the cancer world. We are by far the best humans God ever created His resentment was not helped when Georgetown recruited Marc Lippman as Cancer Center Director, and where breast cancer ruled.

Some chapters are written by John, and others by Liza. Liza found out she had breast cancer when a colleague of Johns walked into his office to share results of Lizas breast tissue pathology that showed cancer cells in the lymph system, and Liza was on the phone speaking with him.

This was no joke. Lizas previous experience with a close friend Holly in her mid-40s had shown the aggressiveness and deadliness of breast cancer a few years earlier. For Liza, John intervened to help her get scans quickly and even chipped in by showing up to a school activity so she could get away.

John had a difficult time in his teenage years with his mothers cancer and familys financial downturn. As he excelled in school, he would often hear from his dad, If a boy like you doesnt succeed, who will?

He recounts his spiritual life as a Baptist, and how with singing in the choir and other public speaking opportunities, he discovered his love of an audience and entertaining others. He lost his mom from Non-Hodgkins Lymphoma before she was 40, when he was 13.

His father remarried, he went to boarding school and then to Duke University. Without much structure, he faced a low point in his life until he met Liza, then went to med school while she went to law school.

Liza recounts the testing she had with scans and how she and John handled telling their family, especially their children and other friends about the breast cancer diagnosis. Liza had to deal with hearing the diagnosis of triple negative breast cancer, and that while cancer was seen in the lymphatic system in a core needle biopsy, the doctors didnt know where the primary tumor was and couldnt see it on her scans.

Liza would hear about the need for mastectomy surgery, chemotherapy, radiation, prosthetic breast, and the prospects of lymphedema. There were many options that were overwhelming, and some options that werent discussed with Liza that she wished were discussed. The existing friendships made the doctor-patient relationships more complicated. John recounts what he observed, knew, wished he could say but didnt, how he remembers telling Liza, and his transition from physician to caregiver for Liza.

He says other funny things, like, hematologists are full of themselves, a bit like peacocks or GI oncologists are the Gryffindors of the cancer world. We are by far the best humans God ever created

John lectures about cancer and how it develops. He included a lecture from 2010 where he spoke about cancer vaccines as an area of interest, including combining vaccines and how NIH grant reviewers rejected his grant three times suggesting nothing would come of the research. In his lecture he said Our microbiome is part of usit might actually be the location of our souls. Profound statement, and then he suggested in 2010 that if NCI wouldnt fund vaccine research, they certainly wouldnt fund research on poop. He discusses diet and cancer and the why me question in his lecture.

It is interesting to read what John says: Wherever two or more are gathered, I cannot keep my mouth shut. If an idea pops into my head, I express it. I have gotten better at not stepping in when others are talking, but Im not perfect even with significant effort.

Here, he was referring to experiences with Lizas doctors. For those of us who know and work with John in national oncology activities, he is actually a great leader and expert moderator of discussion; one of the best Ive seen (and not mansplaining despite what he says).

He says it is easier for him to make decisions about whats best for him than whats best for someone else. Maybe, although it is easier to be objective when trying to help others. In academia, Ive found it much easier to help others with their grants than to help myself.

For medical decisions, it can be very difficult in the middle of the storm to know whats best, and the input of others can be incredibly helpful. At the time Liza needed to make her decisions in 2006, less was known about triple negative breast cancer, and while a clinical trial of neoadjuvant therapy (chemotherapy before surgery, now standard of care for her case) was available, there was concern about waitingand so she went ahead with surgery because surgery would happen either way. Within the chapters, both John and Liza discuss issues of intimacy and sexuality in the setting of mastectomy and breast cancer.

Liza recounts her surgery, more revelations about her diagnosis, and the experience of being at a teaching hospital, her admiration of George Clooney, more about the post-op period and their life together.

John writes about some of what happens to people in real life as cancer gets diagnosed at inopportune moments. He goes into oncology healthcare delivery, successes as a physician, realities and disappointments in medicine, competitiveness and the business of medicine, among other topics.

John declined the special invitation to attend the breast tumor board when Lizas case was being discussed. He spoke about how he started looking at patients differently when he sees them in the hospital every day, and how the experiences have affected how he does his job.

Liza describes learning about the pathology from her surgery, what others knew it meant, and complicated options in clinical trials for what would happen next. She goes into how and why John, who certainly knew much more, didnt necessarily say much beyond answering all her questions.

John recounts his struggles and reactions to Lizas illness as he became caregiver. For reasons he couldnt explain, he found himself not looking into details of the SWOG trial, the scans and pathology reports, asking a lot of questions, or attending lectures on TNBC even if pizza was served!

John presented a lecture about finding value in cancer care, where he discussed healthcare economics and drug company profits from U.S. taxpayer funded research. He discussed red cell growth factors that he administered to Liza and information from trials that showed adverse outcomes.

He goes into dilemmas of being in the middle of an illness where you want to do everything no matter the cost, and value in healthcare, where ultimately, we as a society all pay the bills. The book goes into issues important for patients with breast cancer and their caregivers. The impact of a cancer diagnosis, especially one with a poor prognosis, and how it affects a family are discussed. Giving a shot of Neulasta even for an experienced physician is complicated if you dont let it warm to room temperature, dont give the shot slowly, and dont read the instructions.

One chapter I particularly appreciated was one John wrote about his perspective on funerals as an oncologist, and how he handles communications with family and caregivers after the death of a patient.

He tells a story at Hollys funeral, where an elderly U.S. senator passed out (how he dealt with it, and how the balance of power in the U.S. Senate was changed for a moment) and recounts his first experience with a cancer funeral at the age of 13 when his mother died.

He speaks about how he personally handles the loss when a patient dies. John writes about how oncologists maintain hope, spin their message, think about quality of life, statistics, and clinical trials. He speaks about his interactions with colleagues after going public. He goes into a cryptic message from Marc Lipmann (who had left Georgetown for the University of Michigan at that time) your wife needs a platinum, Marc, and other discourse with Neil Love.

This is followed by a chapter entitled Platinum, but not the pretty kind. Liza thinks Marc Lippmans message may have saved her life. There is more so take time to read, enjoy, and learn from this book.

I was excited to see this book about the CRISPR revolution written by Kevin Davies. I first heard of Kevin Davies in 1992 during my postdoctoral fellowship, as he was the founding editor of a new journal called Nature Genetics.

I will always be grateful to Kevin and that journal for accepting my first paper from the Vogelstein lab on defining the DNA-binding consensus sequence for the tumor suppressor protein p53. Nature Genetics published it on page 45 of that first issue, after Nature rejected it, and it has stood the test of time.

The book begins by describing Kevins arrival to Hong Kong on Monday November 18, 2018, to attend a conference on CRISPR when news broke on Twitter that babies genetically altered by CRISPR might have already been born#CRISPRbabies was trending, and news of YouTube videos made by 34 year old Chinese Scientist He Jiankiu described what he had done and that two beautiful little Chinese girls, named Lulu and Nana, came crying into this world a few weeks ago.

Kevin had a front row seat to He Jiankius presentation and questioning at the conference that was seen by many around the world. Unlike what someone said on social media that Jiankiu was being inappropriately celebrated, Kevin felt we were watching a dead man walking.

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Books that mattered to me this year - The Cancer Letter