Books that mattered to me this year

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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. 

Wafik El-Deiry
Wafik S. El-Deiry, MD, PhD
American Cancer Society Research Professor, director, Cancer Center at Brown University;  Director, Joint Program in Cancer Biology, Brown University and Lifespan Cancer Institute;  Attending physician, hematology/oncology, LCI, Mencoff Family University Professor, Brown University;  Associate dean, Oncologic Sciences, Warren Alpert Medical School, Brown University

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 volumes—including 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 things—maybe 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:


What is Life? Five Great Ideas in Biology

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 1830’s 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 1940’s, “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 didn’t get, during which he compared his colleagues “to the crazed figures in Picasso’s 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. You’ll 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.


Guinea-Pig Doctors: The Drama of Medical Research Through Self-Experimentation

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 couldn’t 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 didn’t 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 wouldn’t 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 body—whether it’s 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. 

Bill’s 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. 


Letter To A Young Female Physician: Notes from a Medical Life

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 department’s 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 Avogadro’s number (6.022 x 1023) using grains of pollen. I never understood what Avogadro’s 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 didn’t 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 didn’t 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:” “I’ve 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 I’m 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 I’d 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 mother’s diagnosis had eluded me for the same reason it had eluded her internist in Florida during the many months she’d 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 patient’s illness became apparent, during an afternoon when he was coaching his grandson’s 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 I’d never met Mr. Blake before, as if I’d 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 don’t 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. You’ll have to read the book, but Dr. Koven’s compassion and the art of medicine come to mind as she looked into the patient’s 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. Koven’s 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 Examiner’s Office of the City of New York to witness the autopsy of a nursing student from the Bronx who’d 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. Koven’s mentors who told her the story): “‘Doesn’t 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 “Blalock’s 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. Koven’s 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 “Koven’s syndrome.”

In a chapter about “Lineage,” Dr. Koven says “My true lineage, I now think, included Blackwell and Haseltine—not to mention Oprah, and my mother—at 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 Shem’s bestseller. 

“Unlike The House of God, though, no one’s heard of Woman Doctor. It’s out of print. My copy has a tacky 70’s 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. Koven’s 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 patient’s room discussing the case, the patient’s 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.


Off Our Chests: A Candid Tour Through The World Of Cancer

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 stories—and 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 leftovers…I 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 doesn’t 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 John’s walked into his office to share results of Liza’s breast tissue pathology that showed cancer cells in the lymph system, and Liza was on the phone speaking with him. 

This was no joke. Liza’s previous experience with a close friend Holly in her mid-40’s 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 mother’s cancer and family’s financial downturn. As he excelled in school, he would often hear from his dad, “If a boy like you doesn’t 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-Hodgkin’s 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 didn’t know where the primary tumor was and couldn’t 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 weren’t 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 didn’t, 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 us—it might actually be the location of our souls.” Profound statement, and then he suggested in 2010 that if NCI wouldn’t fund vaccine research, they certainly wouldn’t 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 I’m not perfect even with significant effort.” 

Here, he was referring to experiences with Liza’s 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 I’ve seen (and not ‘mansplaining’ despite what he says). 

He says it is easier for him to make decisions about what’s best for him than what’s best for someone else. Maybe, although it is easier to be objective when trying to help others. In academia, I’ve 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 what’s 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 waiting—and 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 Liza’s 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, didn’t necessarily say much beyond answering all her questions. 

John recounts his struggles and reactions to Liza’s illness as he became caregiver. For reasons he couldn’t 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 don’t let it warm to room temperature, don’t give the shot slowly, and don’t 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 Holly’s 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 Lippman’s message may have saved her life. There is more so take time to read, enjoy, and learn from this book.


Editing Humanity: The CRISPR Revolution And The New Era Of Genome Editing

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 Kevin’s 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 Jiankiu’s 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.”

Kevin recounts discoveries by Emmanuelle Charpentier, Jennifer Doudna, Feng Zhang at Broad and George Church, at Harvard. He touts the vast reaches of CRISPR and its impact on disease and life in general, and the “CRISPR Craze” as referred to by Science and the lay press. 

Kevin recounts his experiences as Nature Genetics editor, the BRCA1 discovery, the sequencing of the human gene and how the cost went from $2 billion to $1,000. He goes into ethical concerns with CRISPR, as well as the impact of basic science to lead to such an important discovery that is already showing impact on human disease.

CRISPR is a breakthrough of immense magnitude for gene editing. It allows “surgery” on the genetic code or for those who use it to “play God.” Davies describes comments by Nobel Laureate Bill Kaelin from a piece in the Washington Post championing basic research on cancer rather than “razzle-dazzle moonshots:” “The CRISPR gene-editing technology that will revolutionize medicine and agriculture emerged from studies of bacteria and their resistance to viruses.” 

Eric Lander, who now works for the Biden Administration, touts CRISPR as “the most surprising discovery, and maybe the most consequential discovery, in this century so far.” Much is riding on this, as Fang Zhang, who is a faculty member at the Broad Institute, has founded five companies in five years. 

James Watson credited Charpentier and Doudna with the biggest discovery since the double helix and further said, “If it’s only used to solve the problems and desires of the top 10%, that will be horrible,” and further stated, “we have evolved more and more in the past few decades into an inequitable society, and this would make it much worse.” 

Kevin Davies takes us on a treat to the Kavli Prize celebration, including some small talk, the event, Alan Alda, the sumptuous menu and the laureates mingling with King Harald of Norway. He notes something most probably haven’t thought about, that Doudna literally has the word “DNA” in her name. He takes us to the debate in the U.S. Senate in 2017, where Senator Susan Collins of Maine expressed concerns that science has outpaced policy. 

With a flurry of activities and multiple companies and patent disputes, the debate also reached the Vatican, where Pope Francis recognized scientific progress but also said that not everything that could be done is “ethically acceptable.” 

Steven Hawkings before his death predicted that gene editing would lead to “superhumans” and went on to say “once such superhumans appear, there are going to be significant political problems with the unimproved humans, who won’t be able to compete.”

And here’s a scary quote from Australian geneticist Daniel MacArthur, who tweeted, “my grand-children will be embryo-screened, germline-edited. Won’t ‘change what it means to be human.’ It’ll be like vaccination.” 

But in 2018, He Jiankui’s career crumbled overnight without fanfare. 

While NIH Director Francis Collins has been conservative, and leading scientists called for a moratorium, George Church has said “I just don’t think that blue eyes and [an extra] 15 IQ points is really a public health threat…I don’t think it’s a threat to our morality.” 

More shockingly, Steven Hawkings before his death predicted that gene editing would lead to “superhumans” and went on to say “once such superhumans appear, there are going to be significant political problems with the unimproved humans, who won’t be able to compete. Presumably they will die out or become unimportant. Instead, there will be a race of self-designing beings who are improving themselves at an ever-increasing rate.” Scary stuff, I must say.

Davies goes into the history of the human genome project and gives details of how CRISPR works and its broad classes and different nucleases. In her keynote at a Banff conference in January, 2020, Doudna proclaimed “precision editing of any genome is within reach.”

I loved reading the story of Francisco Mojica, a microbiologist interested in halophilic (salt-loving) bacteria, and noticed in 1992 repetitive sequences that make up 2% of prokaryotic DNA. By 2001 he came up with the CRISPR acronym that stands for clustered regularly interspersed short palindromic repeats. By October, 2003 he submitted a paper to Nature entitled “Prokaryotic repeats are involved in an immunity system.” The paper was declined by Nature and by PNAS, and a year later submitted to an evolution journal. 

Six months later he heard from the editor and three months later the paper was accepted. Mojica told Kevin Davies, “I remember those two years like a nightmare,” and said “when you have something so big in your hands and you send it to the very good journals—and all of them agreed it was not interesting enough to be published—you think is it me who is crazy or something else?” 

Another researcher, Gilles Vergnaud in Paris, had similar frustrations when doing research for the French Ministry of Defense, motivated by fears of Saddam Hussain’s use of bioweapons, submitted in 2003 a paper with CRISPR in the title and notions of defense mechanisms. This was passed on by PNAS and other journals until it was published in 2005. 

Most everyone in academia will sympathize with these experiences and acknowledge that the peer review system (and the grant review systems) have gotten much worse over the last 20 years.

Kevin Davies describes how he originally met Jennifer Doudna at a HHMI meeting in Chevy Chase, MD, back in 1998, when she was a young rising star and new HHMI Investigator. 

When she was 12 years old, Doudna’s father, an English Professor at University of Hawaii, left her a copy of The Double Helix which eventually captured her imagination. During high school, her guidance counselor told her “girls don’t do science,” which only intensified her interest in science. 

She earned her PhD with Jack Szostack at Harvard in 1985. Szostack, who was an RNA biochemist, won the Nobel prize—and it was during her research with him that she became very interested in RNA and its potential enzymatic activity. 

Doudna also worked with another Nobel Laureate and RNA biologist, Tom Cech (also former HHMI President), in whose lab she met her future husband. She eventually started a lab at Yale and then moved to Berkeley. More details are given about her brief stint as a VP at Genentech, and that she was allowed a return to Berkeley to reclaim her HHMI investigator role and work on CRISPR. Davies goes into Charpentier’s career and fame in Europe, more about Fang Zhang, and others.

Doudna and Charpentier met in March, 2011 for the first time in Puerto Rico. Charpentier, the more junior of the two, told Doudna about her upcoming results in Nature and offered to collaborate. Martin Jinek in Doudna’s lab worked on the collaboration and recounts the brainstorming that led to the idea of a single guide RNA that could be used to reprogram any sequence. In 2012, the collaborators submitted a paper to Science noting potential for gene targeting and genome editing that was accepted in 12 days.

Doudna and Charpentier went on to win the 2020 Nobel Prize in Chemistry for their CRISPR discoveries.

A bit of history I did not know: the founding editor of Cell (in 1974), Ben Lewin was a Nature Editor. He would sell the journal to Elsevier in 1999 for more than $100 million. 

As for the somewhat scary comments by Church and Hawkings, I hope our scientific and political leaders keep us safe from a strange dystopian future that might be inflicted by the CRISPR revolution.

I was grateful in 1993 that Dr. Lewin accepted my paper on WAF1 in Cell, and before Steve Elledge (now at Harvard) called Bert Vogelstein to tell him about a gene they cloned from a yeast two-hybrid system encoding a protein they called p21(Cip1) that inhibits CDK2. There was a brief time when Ben Lewin was the only one in the world who had the two papers with the same gene sequence for WAF1 and p21(Cip1) that would be published back-to-back in Cell in late 1993.

Davies’s book is an interesting history of many individual scientists and their contributions and collaborations to the CRISPR story. This story is also about the 7,000 or so genetic disorders described by the late Victor McKusick who edited “Mendelian Inheritance in Man,” and was the founder and leader of the Human Genome Organization (HUGO). 

I was fortunate to meet Dr. McKusick during my training at Johns Hopkins including a visit with him to the top of the Dome at the Johns Hopkins Hospital in 1994. It was an extremely rare honor for me at the time (arranged by my post-doc mentor Bert Vogelstein) as it has typically been reserved for the chief residents in medicine at Hopkins (it was also enjoyed by others in the lab who I invited to join us). 

Dr. McKusick was no longer chair of medicine at the time but would be seen occasionally at Medicine Grand Rounds on Saturdays when other giants of medicine, such as Dr. Harry Klinefelter (Klinefelter Syndrome), would be sitting there in the audience.

I later heard Dr. McKusick give a wonderful lecture at Hopkins that was recorded during an Interurban Clinical Club meeting. Davies writes “if he were still alive, the father of medical genetics would be in awe at the progress we’ve made in documenting the myriad ways in which our genetic software can be corrupted, not to mention the potential of delivering a patch to fix those errors.” 

Hopefully this clinical translation with CRISPR can be done safely for the treatment of genetic diseases as we are already seeing, and there would be more impact in cancer for example using CRISPR-engineered CAR-T cells. 

As far as embryo editing, I sincerely hope that this is completely outlawed and that we undertake a moratorium of several decades while we gain much more knowledge about collateral damage to the human genome. As for the somewhat scary comments by Church and Hawkings, I hope our scientific and political leaders keep us safe from a strange dystopian future that might be inflicted by the CRISPR revolution.


100 questions and answers about ovarian cancer

I have been at Brown University coming up on three years. We are building and growing our cancer center at Brown in pursuit of NCI designation during the coming years. 

I came here because of amazing colleagues doing great work in science, clinical care, clinical trials and community outreach. One of those amazing colleagues is Dr. Don Dizon, professor of medicine at Brown who leads the pelvic malignancies program at Lifespan Health System and has been spearheading our community outreach and engagement efforts at our cancer center at Brown. 

Don needs no introduction as a fellow of ASCO, leader in oncology education, LGBTQ advocate, and social media rockstar who also embraces new platforms such as TikTok—where he has made many public service announcements. He is also a national leader in bringing the potential for social media in oncology to fruition. 

I recently discovered the fourth Edition of his popular book about ovarian cancer, and felt that I should read it to learn something, and that I should take this opportunity to tell others about it.

The book is an incredible resource that has evolved over 15 years to the current fourth edition and is intended to help patients “with ovarian cancer, their families, significant others and loved ones.” 

Dr. Dizon writes “The fact is: We can cure ovarian cancer, but even when we cannot, we can help you live with it, too.” Much progress has been made and Dr. Broach mentions that the book provides information to answer “questions patients have while navigating their unique and often complex treatment plans.”

The first part of the book provides basic information about ovaries, their function, what it means to have cancer, cysts, including their different varieties. There are diagrams with details of the anatomy and descriptions of the physiology. 

A basic description of cancer and metastases in lay terms is provided along with dispelling some myths and misconceptions about what cancer is not. For example, cancer is not an infectious disease, and also if your mother had ovarian cancer, it doesn’t mean you will definitely develop the disease (although you may be at increased risk). The book provides information to dispel the myth that ovarian cancer is a death sentence. The patterns of spread of ovarian cancer are discussed. The Krukenberg tumor is explained.

The risk factors, diagnosis, and staging of ovarian cancer are covered in part II of the book. While the book focuses on epithelial ovarian cancer, non-epithelial ovarian tumors are mentioned. Recent knowledge about potential origins of ovarian cancer in fallopian tubes is discussed as are implications for whether removal of the ovaries might be needed to prevent the disease. 

The epidemiology and incidence of ovarian cancer are described as are the subtypes of epithelial ovarian cancer. Germ cell tumors, choriocarcinomas, sex cord-stromal tumors and teratomas are explained. Because the granulosa-cell tumors make hormones, patients become symptomatic at an earlier stage which generally portends a more favorable prognosis for these tumors due to their earlier detection. 

Gene mutations that can lead to ovarian cancer are explained including those that are inherited or acquired. The BRCA1 and BRCA2 genes are explained, including the risk of ovarian cancer they confer when mutated. Other genes that increase susceptibility to ovarian cancer are mentioned. 

Hormonal therapy and talc are covered. The many varied symptoms of ovarian cancer are discussed. Dee commented about her own diagnosis and experience in 2005 when she developed some non-specific symptoms. She makes the point that awareness of the symptoms is important. 

The authors explain Ascites, along with its treatment, and when it occurs as part of advanced ovarian cancer. The diagnosis of ovarian cancer is discussed, along with blood tests such as CA-125. Dee provided some of her experiences and anxieties with the CA-125 test. Dee also reflects on PET scans. 

The authors present the latest FIGO staging system of ovarian cancer, as well as the differences between stage and grade. Information about prognosis is provided. Dee comments about the benefits of second opinions.

The treatment of ovarian cancer is discussed in part III of the book. Dee described her strategy for care at a cancer center near her and the importance of access to a multidisciplinary team of specialists and ancillary services. The authors also address surgical options, including fertility sparing surgery. Dee comments about the availability of both IV and intraperitoneal chemotherapy treatments and how they are administered. 

Various treatments besides chemotherapy are discussed along with side effects, including angiogenesis inhibitors, and different available PARP inhibitors. The authors explain HIPEC, treatment monitoring, radiation and immunotherapy—including vaccines. 

Participation in clinical trials is explained. Dee explained her participation in a clinical trial and the reasons behind a later decision to not participate in a second trial for recurrent ovarian cancer. There is a discussion about ovarian cancer during pregnancy along with options for managing it. Complementary and alternative medicines are covered. Dee provided her valuable insights about these therapies.

Part IV deals with treatment-related side effects, diet while on treatment, treatment at older age, vitamins, growth factors, managing nausea, neuropathy, among other issues. The authors addresscConcerns about sex and intimacy in the context of cancer treatment, hot flashes, depression, and “chemo brain.” Part V is more focused on symptom management and palliative care and part VI is focused on relapse and options for treatment, and part VII addresses “if treatment fails,” hospice, DNR, TPN, health care proxy. Part VIII provides information about prevention, screening, and advocacy.

This is clearly an invaluable and rich resource with immense amounts of information to help patients and their loved ones. It is highly recommended for the entire continuum of the disease course. Other resources and organizations are mentioned as well as information about support for patients with ovarian cancer. This book about ovarian cancer is a model resource for patients and the lay public that should be emulated for other tumor types.


Rethinking Cancer: A New Paradigm for the Post-Genomic Era 

I have met Dr. Mina Bissell a few times in my career, and have invited her to speak in the past at an international conference I organized on the topic of drug resistance in cancer. 

She is a leader in the field of cancer research, the tumor microenvironment, and an inspiring woman scientist and mentor by all accounts. I was therefore very curious, as most people in the field should be, to see a book edited by her and her colleagues about the topic of rethinking cancer in the post-genomic era. We all need new ideas and different perspectives in oncology.

I appreciated in the preface the mention of reduced spending on cancer research, in this case in the UK, and the impact of the COVID pandemic on delays in cancer care. The genomics revolution and precision medicine need to fulfill their promise and so we need more fresh insights into how to prolong life for patients with advanced cancer. 

We have powerful molecular tools, computational methods, and more knowledge about cancer than ever before. But as most everyone knows, cancer is complex with heterogeneity between patients with the same disease or even within the different cells of the same patient. “This ubiquitous observation has led to the declaration of a ‘complexity crisis’ in the cancer genomics field.” 

Beyond genomics the many other ‘omics’ are now of much focus, hence “post-genomic” but now with a recognition that precision medicine in oncology is much more difficult than previously anticipated, and the system needs a “reboot,” “we’ve tried genomics, with only modest success in curing cancer, and now we need to move on to something else—but where to? That is what this book is about.” 

This, the editors point out, was “a failure clearly not due to lack of financial investments,” but rather “an incomplete or incorrect theoretical framework in our attempts to explain carcinogenesis.” The editors “are united by the view that it is paramount to revise the current somatic mutation paradigm if we are to make progress in finding a cure for cancer.” They acknowledge that less well represented in the book are the areas of inflammation and cancer immunology.

On the systems dimension of cancer, Dr. Strauss says: “What we have learned from complex systems, however, not only in biology, is the fact that their inherent nonlinearity often produces outcomes that seem counterintuitive to human ‘rational’ thinking. Thus, when human intervention interferes with such systems, the results can appear often ‘paradoxical,’ as for example when perturbing cancer with different treatment modalities.” 

This comments hits home because my own research is focused on killing cancer cells (every last one including by boosting the immune system): “Taking a complex dynamical systems logic into account from the start, seemingly paradoxical actions, such as not attempting to kill all cancer cells or choosing lower than the maximum kill dose of a given drug, make perfect sense and can deliver desired results in cancer treatments.” 

The concept of “cellular attractor” is introduced, as are ideas around cellular phenotypic traits, such as variable protein concentrations within a population of otherwise similar cells, plasticity, adaptive responses, and that there are millions of simultaneously occurring chemical reactions in an “ultra-high molecular density environment” within cells. 

“What a systems perspective of cancer teaches us is that we need to go off-piste a lot more than we normally do and explore many more areas outside the well-funded highways to professorship,” Dr. Strauss writes. He then points to the 99% of “junk” non-coding DNA, the so-called dark matter of our genome, as “highly relevant to our understanding of cancer genomics.” 

Evolutionary theory and single cell analysis have empowered the field to analyze heterogeneity and the temporal dimension of cancer. I would say that Darwinian theory does impact cancer research now especially with studies for example in our own work that focus on hypoxia, drug resistance, and other selection pressures in tumor evolution. 

[Mina Bissell] is a leader in the field of cancer research, the tumor microenvironment, and an inspiring woman scientist and mentor by all accounts. I was therefore very curious, as most people in the field should be, to see a book edited by her and her colleagues about the topic of rethinking cancer in the post-genomic era.

This too is near and dear to us and it is certainly appreciated the mention that there should be more of that in the field. I also appreciate the idea of evolutionary dynamics and unanticipated ways for how we may need to treat some cancers without aiming for maximal cell killing. I would say a good example is colorectal cancer and treatment with anti-EGFR agents. 

We do aim for maximal cell kill, in fact, I normally tell my patients that my approach in designing a treatment strategy is to “take our best shot at this.” I think this book would argue that taking our best shot may not mean killing every tumor cell when we might have the chance. 

In the case of anti-EGFR therapy, I am fascinated by the findings of Scott Kopetz (MDACC) and others that resistance mechanisms extinguish when patients are taken off therapy so that therapeutic re-challenge at a later time has efficacy. I do not believe this insight came from basic science but rather from the evolution of applied technologies such as liquid biopsies that could monitor the levels of KRAS resistance mutations for example (or others) and see over time that their levels extinguish suggesting the possibility of re-challenge therapy.

The idea that different tumor cells, depending on their evolutionary history of their own genomes will have different adaptive responses to selection pressures or microenvironment forces deserves more research focus (and of course is interesting). 

The idea that a goal should be “to induce cancer cells to switch their rewired cancer genome “back to normal” is great. But I would disagree that “clearly, such a systemic switch cannot be achieved by targeting single mutations in single genes.” 

I would argue that it can be achieved with targeting master regulators such as p53 that is the most commonly mutated gene in human cancer, and in fact we have worked for the last two decades to restore that pathway or its transcriptome to achieve a cancer therapeutic response. 

We have uncovered different ways this can be achieved from involvement of p73 to activation of a cancer-specific integrated tress response that bypasses p53 mutations and kills tumor cells. I would also argue that much has been achieved using those imperfect cancer cell lines that are no longer in vogue, including impact on patients who couldn’t wait for the better models. 

This in no way should keep us from developing better models, but also, we shouldn’t abandon ways that have led to success. I like to think that we will cure more cancers, but the reality is some advanced cancers may not be curable no matter what we do. 

And this comes from one who will turn every stone to find a treatment to help a given patient. I should add that I’ve seen one of my own patients get out of hospice a few years ago and live many months with ‘miraculous’ targeted therapy and think there needs to be some sort of reset in our field knowing things like that can happen—the progress is impacting people’s lives despite how advanced cancer gets.

The book is divided into sections that focus on different dimensions from redefining the problem through the theory dimension to the systems dimension, the time dimension, and the microenvironment dimension of cancer. There is an underlying tone in the book that the incredible impact of research on the tumor microenvironment and insights into the complexity of cancer has been underappreciated. 

While this may be perceived as such by some, I personally believe otherwise, that the contributions made by the TME field have been incredibly valuable and do shape the mainstream. 

I think it is common for clinicians in 2021 to fully understand the complexity of cancer and its microenvironment and to now blame that TME as well as tumor evolution, heterogeneity and the immune system, on why treatment fails. 

I like the idea that tumor heterogeneity has emerged as a “master hallmark” that we need to understand much better to develop better treatments. I would also like to say that reading this book, one gains a new appreciation that it is an understatement to say that cancer is “complex.” I think we need to build and we need breakthroughs. I would be careful with “reboot” because as a clinician I also believe in “do no harm” and that we shouldn’t necessarily abandon what we are doing until there is clear evidence that doing things differently will actually work better.

There is much to learn from this book, from different perspectives that we need to take seriously to actual insights about cancer gained from network science, plastic and rigid networks and how they are altered in cancer and how cancer stem cells are impacted.

The physical sciences have much to offer as does information science. They are helpful in providing different vantage points to try and make sense of complex biological systems. Dr. Huang refers to a “rigid mentality” and the “ceaseless quest for ever more powerful ways to kill cancer cells.” 

I am one of those, and would not mind doing something different (including collaborate with those who have a very different perspective) if I really believed it was better. I agree we need to be open-minded and I think our strategies have evolved in recent years to be much more purposefully tumor microenvironment-directed. 

I still think cancer stem cells are important and we shouldn’t forget them within all the complexity. I totally agree that ALL treatments have limitations in the cancer clinic, not to mention toxicities. But overall, there is forward motion. Yes, we need to do much better “to bend the curves” as clinicians often say about improving those Kaplan-Meier curves. I disagree that wrong strategies are perpetuated because we inadequately explain treatment failure. I think the whole field of oncology and translational cancer research is focused on understanding treatment failure and doing better, whatever it takes. 

This means working with colleagues with differing expertise and understanding more about cancer’s complexity—much is being learned now. There is much food for thought in this book about what we know and don’t know. Dr. Huang presents a case for formalizing a complex system as a network of interactions of its components. And that this is aided by new technology such as single cell RNA-seq. 

Dr. Huang describes systems dynamics, combinatorial interactions among components, the impact of constraints on interactions on characterizing a system, nonlinearity, the landscape of genetics and epigenetics, and the fact that most cancer treatments don’t work as desired. The point is made that treatment “also contributes to recurrence in an active manner.” 

Hyperprogression after cancer treatment (including by immune checkpoint blockade) is discussed and the impact of preclinical models on understanding effects that may be hidden in Kaplan-Meier curves. 

Dr. Huang also gets into an interesting topic of “Process Spontaneity: The Fundamental Inevitability in Multistable Systems,” and the concept of “attractor states.” A detailed theoretical framework is presented and then some molecular mechanisms are discussed. 

The author proposes “new research programs” such as ones to “elucidate the molecular pathways of stress-induced stemness,” “design and analyze experiments in a refined, quantitative, and theory-guided manner to uncover dose regimes of intervention that minimize the ‘backfiring’,” “examine the exceptional responders both in the positive (cure) as well as negative sense (treatment-induced progression) as real biological phenomena and not as statistical flukes,” and “we must be open to new schemes for trials that currently limit the early studies of novel classes of treatment to patients who have failed all therapies—precisely because previous treatment may have altered and diversified cancer cells on the epigenetic landscape, rendering them essentially untreatable.” 

There are good ideas here, although it remains to be seen whether actively trying to minimize ‘backfiring’ will impact on patients.

There is much to learn from this book, from different perspectives that we need to take seriously to actual insights about cancer gained from network science, plastic and rigid networks and how they are altered in cancer and how cancer stem cells are impacted. 

There is an interesting concept, that “different drug design strategies are required against early and late-stage tumors.” Early tumors have central nodes for targeting while late tumors have “more rigid cellular networks.” 

More exploration of predictions from network science are proposed. Dark matter, computational science, and Artificial Intelligence (AI) are further discussed. Drs. Scott, Basanta and Marusyk make a major point that Darwinian evolution rather than “mutationalism” is what is needed for new cancer therapies. 

“In contrast to the helplessness in dealing with the bad luck of mutation-driven process, embracing a Darwinian explanation enables a much more proactive attitude, as both diversification and selection could be subjects of clinical interventions.” Specific strategies are suggested for such interventions. “Rather than maximizing the short-term tumor cell kill rate, it might be possible to optimize chemotherapeutic treatments to increase the rates of genomic alterations, thus driving down fitness of populations of tumor cells.” 

Epigenetic drugs “can be potentially repurposed with an explicit consideration of the impact on phenotypic diversity and plasticity.” Consideration is given to “adaptive therapy scheduling based on evolutionary tradeoffs,” “to forestall the expansion of resistant sub-populations.” “Atavism’’ and “reversion to an ancestral phenotype” is covered in a chapter by Drs. Bussey and Davies. Specific directions are proposed for translation of the ideas that are discussed.

Dr. Larry Norton writes a chapter about “Time and Timing in Oncology.” Dr. Norton gets us to consider that while so much progress has been made, including with targeted therapies that attack the Achilles heel of some cancers and can work, when they don’t we don’t question the “original paradigm” or metaphor. 

“Achilles does not stand still.” This is the concept of time and change within a tumor. We need to learn better “how to shoot them [our arrows] at a target in motion.” “It is for this reason that the science of drug scheduling needs to progress in parallel with the science of molecularly targeted drug design.” 

He gets into the “log-kill hypothesis,” “Gompertzian-like sigmoid growth,” and makes the point that a high response rate does not equal cure. It is also nice to read an explanation of the Norton-Simon hypothesis “it is all about rates.” “Explicitly, a given drug at a given dose kills a higher fraction of cancer cells in faster- growing, small tumors than in larger, more slowly growing masses of similar biology.” Mathematical models, time, and timing are important, according to Dr. Norton.

Dr. Valerie Weaver and colleagues delve into desmoplasia, stiffness, mechanotransduction, metabolism, nutrient sensing, chromatin interactions as important areas for study in cancer. Metabolism, glycolysis, low pH of cancer is covered by Drs. Zdralevic and Pouyssegur. The Warburg effect is explained in detail as are some therapeutic opportunities. Immune evasion and ferroptosis are also discussed. A chapter on vascular corruption in cancer covers endothelial heterogeneity, tumor-endothelial cell interactions, various chemokine and growth factor pathways, and other chapters cover metastasis and the “niche.” 

The editors end with a glimpse of the future. This includes education and translation to get to “transformative innovation.”

Wafik S. El-Deiry, MD, PhD, FACP
American Cancer Society Research Professor; Director, Cancer Center at Brown University; Director, Joint Program in Cancer Biology, Brown University and Lifespan Cancer Institute; Attending physician, hematology/oncology, LCI, Mencoff Family University Professor, Brown University; Associate dean, Oncologic Sciences, Warren Alpert Medical School, Brown University
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U.S. Deputy Secretary for Health and Human Services, Andrea Palm, and Sweden's Minister for Health Care, Acko Ankarberg Johansson, signing the agreement. Credit: Joel Apelthun/Government Offices of SwedenThe United States and Sweden signed an agreement to step up collaborations in science and technology by focusing on cancer research.
Wafik S. El-Deiry, MD, PhD, FACP
American Cancer Society Research Professor; Director, Cancer Center at Brown University; Director, Joint Program in Cancer Biology, Brown University and Lifespan Cancer Institute; Attending physician, hematology/oncology, LCI, Mencoff Family University Professor, Brown University; Associate dean, Oncologic Sciences, Warren Alpert Medical School, Brown University

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