“Here’s the rule: Each of us humans, but also animals, and…yes, and plants, everything that is alive, struggles to stay alive and doesn’t know why. Th
“Here’s the rule: Each of us humans, but also animals, and…yes, and plants, everything that is alive, struggles to stay alive and doesn’t know why. The why is written in each cell, but in a language that we don’t know how to read with our minds. We do read it, though, with our beings, and we obey the message with our entire behavior. But the message can be imperative. The species in which the message is imprinted deeply and clearly survive, the others are extinct.”
~ Primo Levi
Siddhartha Mukherjee really ticks me off. I’ll admit to a wonderous envy, not wanton anger. I’ve met and gotten to know a number of medical experts—some are geniuses, some just brilliant—in my professional life. As smart as they are, their breadth of knowledge and interests are very narrow, with Everest-like spikes of the subjects they know really well. But most of them don’t know much else. Generally speaking, they’re not widely read, have few deep interests outside their fields, and what they do tends to have a superficial, game show-esque quality. They mistake traveling widely for conferences and building in sight-seeing and vacations for depth. Mukherjee seems to be different. Just perusing the bibliographies of his books reveals a number of clues. Mixed in with the predictable professional literature are works by Giovanni Boccaccio, Lewis Carroll, Emily Dickenson, Kazuo Ishiguro, Philip Roth, Carl Sandburg, Walt Whitman, and other assorted poets and writers. He cites them with carefully connected tangents, never losing the logical threads of his scientific arguments. It’s really not fair that such a good, clear, well-read writer is also a noted physician and researcher. Leave some crumbs for the rest of us!
There are two ways to approach this book: as a stand-alone or introductory work to Mukherjee’s books or as the third of an unintentional trilogy. It works either way. I choose to see it as the conclusion of a trilogy. The first, The Emperor of All Maladies, which focuses on cancer, is the most accessible volume. The second, The Gene, seemed to be motivated by the dramatic developments taking place in genetically-targeted therapies after publication of his first book and might be a bit much for lay readers. The Song of the Cell falls somewhere in between. If you’re interested in the latest developments in medicine and sure you’re not going to read any of the others, you can’t go wrong. But I do think there is great value in reading them all; if one is interesting, the other two will be as well.
The cell might well be the most interesting concept in biology, a building block for a larger being and a complex system of a smaller, vitally important system to the larger being. Mukherjee breaks down the primary cells of the human body in both logical and engaging ways, always balancing potential with actual tasks and purposes of each. And his conclusion demonstrates the political is never far away from the biological:
The human body functions as a citizenship of cooperating cells. The disintegration of this citizenship tips us from wellness into disease…Beyond understanding cells in isolation, deciphering the internal laws of cellular citizenship—tolerance, communication, specialization, diversity, boundary-formation, cooperation, niches, ecological relationships—will ultimately result in the birth of a new kind of cellular medicine.
I have mixed feelings about this book, a comparative biography of Carl Linnaeus and George-Louis Leclerc de Buffon, contemporaries who never met who wI have mixed feelings about this book, a comparative biography of Carl Linnaeus and George-Louis Leclerc de Buffon, contemporaries who never met who were in a “race” to classify all living things and other tertiary sciences like geology, and the consequential legacies they left. I became aware of it through an episode of the BBC podcast History Extra which, in turn, spurred me to purchase it. But much as a child let down by the reality of Christmas because it can never live up to the anticipation, the book did not add much to the podcast. Indeed, after listening to the podcast again, it makes the case the book does, but much more succinctly and accessible.
One thing that stood out in the podcast as compared to the book were the questions raised by Roberts about the legacy of Linnaeus’s rather glib, pithy, and wrong comments in classifying human life into four arbitrary classes. He addresses it in the book, but as a list of differences, not as a central point. I think he missed a huge opportunity. (I’ll write more about this in coming weeks on my Substack and will link to it here when the time comes.) For example, when Roberts writes:
Declaring just four varieties of humans (or subspecies; Linnaeus was never clear on the matter) was to Buffon an error of the highest magnitude. To affix inherent attributes to them was repugnant.
one might expect a more detailed discussion about what made “affix[ing] inherent attributes” so “repugnant.” Instead it was inferred, almost as if a thorough delving into the assertion made might be too controversial, forced to use uncomfortable language, or reopen festering wounds. But that should be the point, I think, about the importance of writing about such a potentially divisive historical fact. It’s the least understood topic that everyone has an opinion about – vocal or not – and the fact that it may be grounded in a seemingly flippant, overly biased categorization in an academic book is worthy of a lengthy treatise in and of itself.
But that may well be my problem. Roberts’s book does have interesting stories, reminding the reader of how things once considered to be existential somehow lose their luster while remaining as consequential as ever....more
To read a review of this book, click here to see my comments on my Substack page.To read a review of this book, click here to see my comments on my Substack page....more
I've started a Substack on the history of myeloma, a rare cancer of the plasma cells, which I hope will help me in writing a history in lay language. I've started a Substack on the history of myeloma, a rare cancer of the plasma cells, which I hope will help me in writing a history in lay language. Here is a link to my thoughts about this remarkable book, but from a narrow point of view.
This is one of best non-fiction books I've read in quite some time....more
Alfred Nobel’s last will and testament funded five prizes in his name—in chemistry, physics, medicine, literature, and for “advanc[ing] fellowship amoAlfred Nobel’s last will and testament funded five prizes in his name—in chemistry, physics, medicine, literature, and for “advanc[ing] fellowship among nations,” the latter known more commonly known as the Peace Prize—to recognize “those who, during the preceding year, have conferred the greatest benefit to humankind.” Despite “the preceding year” provision, for the first three-plus decades of the Prizes’ existence, they were very much lifetime achievement awards. By the time Wilhelm Röntgen was awarded the physics prize in 1901, the first year they were given, it was for his 1895 discovery of x-rays. Although he made the discovery, Röntgen had little to do with the development of the technology. Scientists around world had rapidly improved his achievement to make it more effective and accessible by the time he received the Prize. Over time, Nobel’s bequests combined recognition of seminal achievement with a goal of increasing public awareness to improve and proliferate them.
A once unseemly practice of lobbying for the Prize, subtle and not-so, became more common after a worldwide campaign to confer the 1935 Peace Prize to Carl von Ossietzky, editor of a German magazine opposing the rise of Naziism in Germany. A worldwide committee that included Albert Einstein and a young Willy Brandt hoped to use the Prize to publicize the realities of Hitler’s Third Reich and save Ossietzky’s life. Ossietzky was arrested the night of the Reichstag fire. The 1935 Prize was not awarded, Ossietzky was selected in 1936. He was denied permission to travel to Oslo to receive it and died shortly thereafter due to illness exacerbated by abuse inflicted on him in the fledgling concentration camps.
Nils Hansson, a Nobel Prize historian based at the Heinrich Heine University in Düsseldorf, described this in a lecture about how not to win a Nobel Prize. He opened with an anecdote about a Stockholm-based hematologist, Gösta Gahrton, who was a member of the Prize’s selection committee between 1988-1997. “Many times,” said Nilsson, the expert “was invited to other nations to give lectures. But when he got there, he soon realized his lectures were not the reals reasons for his invitations. Instead, his hosts often had their own detailed lectures, presented after his, apparently designed to heighten their chances and lobby for the Nobel Prize." In his conclusion, Nilsson highlighted three “rules” that generally had to be met to enter that small circle of eligibility for potential Prize winners. First, “ideally, discoveries must open up a brand-new field of research.” Second, “one shouldn’t walk on well-worn paths” of fields that are filled with activity, making it difficult to differentiate between great insights or achievements. And a counterintuitive third: to not “be too visionary” or far ahead of one’s time, making the achievement comprehendible to wide audiences.
E. Donnal “Don” Thomas’s singular pioneering of bone marrow transplantation (BMT) to make incurable diseases curable embodied those preconditions. But rather than lobby for the Prize, his work and quiet leadership had been speaking for itself for more than three decades and was just beginning to take root when he received the Nobel Prize for Medicine in 1990. The practical implications of his vision were attracting interest from ambitious researchers and physicians. Institutions around the world were investing millions of dollars in new infrastructure and staff. He gave birth to a paradigm-changing revolution.
Born in 1920, Thomas was the only child of a rural Texas physician who made house calls in a horse-drawn wagon. Although self-described as “not an outstanding student,” (quotes excerpted from Thomas’s Nobel lecture) Thomas went from a one-room schoolhouse to the University of Texas at Austin to the Harvard Medical School, where he earned his MD in 1946. In Boston, he worked with Sidney Farber, whose trailblazing work on chemotherapies in childhood leukemia created the foundation for modern cancer research and treatment (The Emperor of All Maladies explains Farber’s impact on modern cancer research and treatment). This relationship “intensified” Thomas’s focus on bone marrow and leukemia, but a difference in philosophic approaches to cancer treatment led Thomas to Cooperstown, New York in 1955, where he “began to work on marrow transplantation in human patients and in the dog.” At that time, even the idea of using animal models to develop and test drugs for human use was less than two decades old.
Although he had little tangible success in the form of surviving patients, Thomas’s research at Cooperstown in the late 1950s to early 1960s drew researchers from around the country to see observe what he was doing and learn. Colleagues invited him to speak, to share his theories and lab results. He didn’t have a lot of positive results to report, but they recognized, to put a reverse spin on Gertrude Stein’s aphorism about Oakland, that there was definitely some there there.
From the advent of the history of medicine, it has been recognized the immune system could be assisted. Herbs and plants had been known to have medicinal qualities for centuries. In the late 19th/early 20th century, therapeutic syrups and pills using new discoveries in chemistry began to proliferate. Acetyl-salicylic acid became aspirin, arguably the most used drug in history. Paul Ehrlich’s discovery of chemically synthesized salversan to treat syphilis fed an optimism that many more “magic bullets” to treat disease would be identified inevitably. While there were discoveries and applications over the first half of the 20th century, the pace was frustratingly slow. A young Don Thomas posited that there might be a better way: to somehow manipulate bone marrow by taking some from a healthy patient and introduce it to another whose immune system was weak or compromised.
BMT transplants do not have the immediate, visceral recognizability of organ transplants that can be visualized by lay persons. The “action,” so to speak, takes place at the genetic and cellular levels. Bone marrow creates all the components of blood which, in turn, are the engine of the body’s innate immune system. Macrophages, monocytes, neutrophils, platelets, and other cells generated by bone marrow act as emergency responses to protect, identify, and repair damage caused by genetics, viruses, or injuries. Together, they form the communications network of the body. The primary function of lungs, to take just one example, it to breathe in order to process oxygen; blood is the delivery system that allow it to do so and connect it to the functions of other organs. Sometimes this system does not respond as it should or is inadequate, which can be impaired for a variety of reasons. The trick for therapy was to make the immune system adaptive. Manipulating the function B cells and T cells, for example, to identify and fight disease.
Transplanting bone marrow from one person to another, known as allogeneic transplant, proved to be “very difficult.” The donated marrow often became an aggressive, incompatible “invader” of sorts, causing graft-versus-host-disease (GVHD), a common side effect in which donated marrow would attack not only disease, but healthy tissues and organs with potential with toxic, often fatal consequences. But his research found promise in patients who were identical twins. The graft, the donated marrow, would become part of the host, working in concert, not at cross purposes. Once Thomas began to understand, implement, and have success with a handful of BMT transplants using identical twin donors to potentially cure incurable diseases like aplastic anemia, leukemias, and certain types of renal (kidney) failure.
Serendipitous events and a growing reputation took Thomas to Seattle’s Public Health Service Hospital in the early 1960s, allowing him to continue and expand his work. Thomas’s entire lab moved to the Fred Hutchinson Cancer Center (The Hutch) in 1975 when the federal government decided to close the nation’s public health hospitals. It was one of eight comprehensive cancer centers first created by President Nixon’s War on Cancer initiative and was focused almost exclusively on BMT research and treatment. Around the same time, progress being made by worldwide in identifying and learning how to separate stem cells—the blood-generating elements in plasma cells in bone marrow—known as autologous stem cell transplant, in which a patient’s own cells were extracted and manipulated before being reintroduced into the same patient as therapy.
Growing understanding and acceptance of transplant procedures spurred medical institutions throughout the United States and Europe to invest billions in facilities, staff, and education. The Hutch became the worldwide Mecca for patients seeking transplants, and more significantly, for physicians to spend time in Seattle to bring knowledge and experience back to their clinics.
GVHD continued to be a stubborn, Medusa-like enemy. And much like Perseus, Thomas had the single-minded focus to take on the challenge of its oft fatal complexity. But it required more than a single stroke to conquer; it required a coordinated team, time, money, and, most of all, a persistent vision. His leadership attracted a staff who cherished and carried out their assignments. One of his closest collaborators, Rainer Storb, a German researcher-scientist, joined him on a Fulbright scholarship in 1965 and never left despite dozens of offers over the years from universities throughout the U.S. and Europe. Storb was freed from what he saw as useless administrative drudgery to do lab work with a kennel of dogs and translate his experience into treatment of patients. Thomas also found key administrators, physicians, lab assistants, and most importantly, dedicated nurses who became as and more valuable than any clinicians. One of them was Fred Appelbaum, this book’s author.
Appelbaum doesn’t shy away from criticisms and controversies Thomas encountered during his career. His narrative also provides a cursory insight into new cellular therapies like CAR T and bispecific antibodies, different methods to assist the bone marrow to function as advertised. They and other related therapies are beginning to enter clinical practice and may, one day, make BMT obsolete. But that day is not today. The success of BMT as therapy has spawned programs like Be the Match and other national marrow donation programs throughout the world. Through them, people can register their own bone marrow type and be linked with suitable patients anywhere in the world. Today the registries have more than 40 million participants willing to donate their own marrow to complete strangers. It was less than one million when Thomas received the Nobel Prize. For some diseases, like multiple myeloma, generally resistant to allogeneic transplants except in the case of identical twin donors—which is still the best BMT therapy known—autologous transplants have become standard treatment many patients. In general, however, cost is as much of an access issue as it has ever been. One must be well-insured or have wealth to access them.
Any visitor to The Hutch today cannot help but be overwhelmed by the simple, tasteful entrance, an appropriate shrine to the impact of Thomas and the people who made his work tangible for posterity. Appelbaum joined Thomas in the mid-1970s, eventually being elevated to a leadership role at The Hutch and instrumental in many roles in the cancer community. His at times charming account of Thomas’s work and influence covers all the essential bases for lay and professional readers, a rarity in medical writing. He chronicles and puts into context how Thomas stubbornly and deliberately trod his intellectual footprints, where the various practical paths led, and how still more continue to be discovered and understood. Appelbaum’s book conveys this emotion; one doesn’t have to go to The Hutch to experience it. Cancer patients and experts are not the only audiences for this story. Anyone curious about medicine should consider picking up a copy. Its lessons are precisely what Alfred Nobel hoped his legacy would enlighten....more
The history of industrialization is entwined with disease and disability. Seemingly every technological development brings with it unintended—often prThe history of industrialization is entwined with disease and disability. Seemingly every technological development brings with it unintended—often predictable in hindsight—health-altering, existential consequences. Examples abound: brown lung diseases of women working in the Lowell, Massachusetts textile factory system, coal miners’ black lungs, Radium Girls pointing brushes with their mouths to apply radioactive paint to glowing watch faces, and on and on. Cost-benefit rationalizations translate these collateral damages into “being part of the job.” Legalisms transform evidence of probable harm into fictions of uncertainty. Jim Morris’s relatively short and profoundly concise arguments in The Cancer Factory weave those varying strands into a substantive narrative tied together by the stories of real people: workers—and their families—at a Goodyear chemical plant in Niagara Falls, New York. They were exposed to ortho-toluidine, “a colorless to pale yellow liquid that turns dark on exposure to air or light…used to make textile dyes, rubber chemicals, pharmaceuticals, and pesticides”.
The chemical was essential to Goodyear’s bottom line, making its tires and other rubber- and plastic-based products more durable. If not handled safely, it poses a toxic risk. Subsequent research proved it set time bombs of potential catastrophic disease within the bodies of the workers who came into contact with it. Protective measures were minimal, actually nonexistent. And their families who were exposed to residue transported home on clothing and skin. It could years or decades for exposure express itself in disease; bladder cancer being the most common. This period of latency fed defense arguments centered on creating doubt, willful amnesia, and time to contrive confusion and justify uncertainty. Legal strategies were buttressed by state and federal legislative and executive branches to create laws and to further limit liability and avoid responsibility. The U.S. has a long, sordid history of creating agencies and commissions to protect workers, consumers, and vulnerable persons. Virtually all adhere to the same template: overpromise, underfund, understaff, and create an appearance of actually doing something substantive while doing nothing of the sort. Agencies created to address worker safety were undermined by corporate political donations and stonewalling to deny staff and funding to implement rules. Science-based evidence would be diluted and hindered by bureaucratic stalling. The few times workers prevailed was mostly due to union representation and a few committed individuals whose lives were devoted to science and justice. On the other hand, when cancer is a major part of the story, and when the abdication of corporate responsibility is in the mix, a verb like “prevailed” might be a bit strong.
Damaged genes cause every cancer, whether inherited, sparked by an external contagion, or some combination of both. Compromised genes tip the first of many biological dominoes that inevitably lead to catastrophic damage to infiltrate cells, organs, and other life-sustaining biological systems. As they crowd out healthy tissue, they become efficient suicidal terrorists. Some move slowly, others rapidly. If they are “successful,” they will die together with the host they menace. The older we get the more likely parts of the body begin to break down; aberrant genes cause normally functioning cells to lose the ability of the innate immune system to detect, target, or fix potential causes of malignancies. That somewhat explains why almost half of all cancer patients are older than 70. Most childhood cancers and significant percentages of more prevalent cancers like those of the breast are built into some people’s DNA, relayed generation after generation, sometimes more so in particular ethnicities, racial categories, and/or geographical locations.
Environmental exposures of varying intensity inevitably infiltrate genes of certain people to generate a type of cancer (or other diseases and disabilities, but for the purposes of this essay, the focus will be on cancer), a trend that has been accelerating and multiplying since the advent of the industrial revolution. Knowledge that a variety of cancers are likely linked to known toxins raises public awareness, sometimes creating political pressure to enact public policies closely tied to overwhelming sympathy. These can lead to insuring access to treatment and perhaps even compensation if their misfortunes are tied to proximity and timing, such as Vietnam Veterans exposed to Agent Orange or September 11 first responders and others around Ground Zero. But for the most part, cancer patients are pretty much on their own. Rich and well-insured persons will have advantages, many more won’t. Cancer is often political and always economic. Which brings money and opportunism—as well as power and greed—into the cancer equation.
People who are exposed to harmful, cancer-causing risks through their employment are “ambushed by a preventable, chronically induced illness that could not be blamed on lifestyle, genetics, or rotten luck.” They are, by definition, victims. Profit motives fed by consumer demand leads to an indifference of the human costs making them possible. Manipulation of information and scientific evidence lead to willful ignorance and indifference. Cold cost-benefit calculations such as the percentages of “allowable, safe” levels of exposure to chemicals known to have carcinogenic effects on humans are used to justify immoral outcomes. Legalisms based on cynical, contrived fictions create weak—or more often than not, non-existing—standards and practices to keep affected employees ignorant of the hazardous nature of their jobs. This fed the "myth…that "safe" levels of carcinogens could be determined” when in reality “[t]here were no safe levels." Medical evidence, research known to employers, was routinely, intentionally hidden or manipulated or appear of inconclusive, resulting in workers being hit by “an adversary they couldn't see, one that weakened untold numbers of them over time and lopped years off their lives.” In playing down the risks of handling ortho-tuluidine, by carelessly exposed workers and their families and neighbors, Goodyear was responsible for setting off the genetic trigger of bladder cancer.
At the same time I was reading The Cancer Factory, U.S. Sen. Sherrod Brown (D-OH), a purported progressive, coincidentally demonstrated the depths of hypocritical cynicism Morris writes about. Brown, chair of the Senate Banking Committee, likes to sell himself publicly as a champion of common people. To be honest, he once seemed to be, but as the only state-wide elected Democrat with an electoral constituency that has been fine with its descent to Republican-style proto-fascism, he walks a political tightrope with a frustrating balance for people like me. On December 6, 2023, he issued a press release excoriating CEOs of the eight largest banks in the U.S. for opposing regulations to require higher capital reserves to protect the system and consumers against Wall Street speculation. Brown noted their “banks touch almost every aspect of our financial system and working Americans’ money – even if they are not your customers” and “accused them of “hav[ing] one thing in common: corporate lobbyists [who] pushed for weaker rules, less oversight.” He noted the crucial role of having “financial watchdogs in place who are getting serious about the need for these protections.”
On the same day, Brown touted his leadership in opposing rules proposed by the Environmental Protection Agency (EPA) to regulate emission standards of steel plants. He quoted a union leader[emphasis in original], “The EPA’s proposed amendments to the National Emission Standards for Hazardous Air Pollutants presents significant challenges to an already heavily regulated Steel Industry”, and the CEO of Cleveland Cliffs, one of the largest steel manufacturers in the nation, “If promulgated, the regulations would put at risk good-paying, middle class union jobs in the steel industry. We are grateful to Senator Brown for leading this U.S. Senate letter to EPA raising serious concerns about the proposed rules.” None of them, however, acknowledged facts like the documented impact air pollution generated by steel plants that lead to higher incidences of asthma and other respiratory diseases in people who work and live in the vicinity of them. Nor did they mention the criticism of environmental organizations that the proposed EPA rules were too weak and did nothing to alleviate the “irreversible damage they have caused to people’s health.” Obviously, Brown did not see the ironic connection of the press releases he put out on the same day. Tension between the two mindsets demonstrate, as Morris writes, “industry bending the narrative to its commercial needs,” too often at the expense of public health. Other examples can be easily Googled but are hardly new.
Approximately 104 million people worldwide are living with cancer right now. Almost 20 million people will be diagnosed with cancer from the time this sentence is read through the next year; 20 million families who have no idea what will hit them. More than 10 million will die in that time. Regardless of whatever progress will be made, because of a growing worldwide population and the relentless certainty of aging—nearly half of all patients are older than 70—it is estimated to increase by 55 percent by 2040.
The Cancer Factory is more than a history, more than a story about workers at a Goodyear chemical plant in Niagara Falls, New York, and much more than another polemic. It is a parable that will only become more relevant in the coming years because cancer is a disease of modern life. We cannot avoid the air we breathe, the foods we eat, the jobs we have. We don’t yet know how, for example, microplastics, forever chemicals, or the consequences of climate change might damage our genes or those of future generations to set off the chain reactions to create new cancers, diseases, or disabilities. Uncertainty will be exacerbated by new political, social, and economic incentives. The unavoidable moral of who gets a cancer diagnosis invariably linked to employment? Profits are privatized, costs are socialized, misery is individualized. Of that much we can be confidently pessimistic.
Addendum: I received a pre-publication copy of this book from Beacon Press through a Goodreads giveaway entry (yes, Virginia, people do win). I sincerely hope this book will be a great success and read widely. It is profound, expansive in scope, concise in writing, lasting in memory, and frustrating in fact. I hope it motivates more people to pay attention to the world around them....more
What little of Alan Lightman’s work I’ve read, I’ve truly enjoyed. I should think about him more when thinking of the next thing. He writes dense, yetWhat little of Alan Lightman’s work I’ve read, I’ve truly enjoyed. I should think about him more when thinking of the next thing. He writes dense, yet simply accessible essays about why different matters of science should matter to non-scientists. But there’s enough to entice the more intellectually curious of those for whom the science is elementary. In this collection, Lightman ponders the wonder of being a student doing truly original research, the kind of which had likely often been attempted but not yet achieved. He also gives us substantively concise thumbnail sketches of significant physicists and explains their philosophical differences in understandable sentences.
This would be a great book to give as a present to a young high school-to-early medical school student who thinks deeply about their career choices or are in the process of doing so. It conveys the message that becoming enthralled in and with your subject is more than half the battle toward being satisfied with the choices you will make. And for older fogies like me, wish these kinds of insights had been around when I was younger....more
Life is a matter of probabilities. Ask any cancer patient.
Having treated many types of cancers and hematological diseases over the course of his careeLife is a matter of probabilities. Ask any cancer patient.
Having treated many types of cancers and hematological diseases over the course of his career, Prof. Heinz Ludwig from Vienna, Austria, is used to getting the question “How long do I have?” immediately after diagnosing people with a cancer. Ludwig does “not think much of giving concrete information about expected survival time. These are average values that say little about an individual patient’s prognosis.” But he understands wanting to know is a normal human reaction.
“If patients do not ask, then I do not mention any concrete figures…Instead, I tell them about cases in which people have coped particularly well with their illness,” wrote Ludwig in Living Longer, Living Right: 5 things we can do to stay healthy. “If, however, they insist and want an answer to the question, I draw a survival curve that shows how different the course can be. It shows that there is an average, but that some patients die very early and others survive unexpectedly long.”
Ludwig is the longtime director of Vienna’s Wilhelminen Hospital Cancer Research Institute and director emeritus of its Center for Oncology, Hematology, and Palliative Care. And he’s one of the world’s foremost authorities on myeloma, having received the Robert A. Kyle Lifetime Achievement award in 2007. He became a pioneer in patient-centered approaches to medical care while treating the full range of diseases seen in his department.
Patient-centric has become an overused marketing term in recent years, but for Ludwig it’s been a part of his outlook since his days as a medical student. Imagine being able to spend a few hours alone with Ludwig to talk about the lessons he’s learned and what it all means – or more precisely, what the probabilities tell us they might mean. You can actually do that, sort of, by downloading a copy of his book or audiobook (see bottom of article).
Living Longer, Living Right is a summation of Ludwig’s ideas about what people can do to improve the odds of experiencing a life lived well. And with life – as with disease – there are no guarantees or absolutes, only probabilities. Some do better than the average, some worse, and most are somewhere in between.
Ludwig writes “not with the purpose of producing a book of advice that will guarantee a healthy life to everyone who follows it blindly.” His views are centered around principles that “are fundamental to our humanity, they pervade our entire life, and they influence our physical as well as our mental health.” People should live their lives, not just survive.
*
If central casting put out a call for a Viennese professor, few would fit the bill better than Heinz Ludwig. Seen from a distance, he can seem as intimidating as the stereotype implies. Upon closer inspection, however, it’s immediately obvious that’s all wrong…sort of. He’s definitely refined; tall, a quiet baritone voice, a slight, enduring smile. But in no way stuffy or aloof.
Ludwig’s intensity isn’t intimidating; it comforts. His explanations are simple and illuminating. His approach is collaborative; when he says patients are partners, he means it. This conviction also led him to forge a very different path to becoming a noted myeloma specialist, one very different than followed by everyone else of his stature: he did it outside of traditional academia.
Coming out of medical school, Ludwig studied for three years at the University of Vienna’s Institute of Immunology, making him a sought-after candidate for internal medicine training at two of Vienna’s universities. He chose the “less prestigious” one because of its emphasis on “the interpersonal aspect,” they focused more on patient need than publishing scientific papers. Following his internal medicine fellowship, Ludwig decided to work in one of Vienna’s large city hospitals.
In Europe, medical universities form the backbone of national health systems, as we saw in previous articles about France. Ludwig is an exception to the rule. He established the top myeloma research and treatment clinic in the nation while leading a comprehensive department with a reputation for patient-centered care.
Living Longer, Living Right helps explain why. The evidence he presents is empirical, based on personal clinical experience and an incredibly eclectic range of studies. And he does it in plain language meant for regular people, not in the scientific jargon of scientific papers.
*
Ludwig opens with anecdotes about two patients that helped him to conceptualize the book. Martha had a breast cancer diagnosis that had an average of two-to-four-years survival. She wanted to live long enough to see her twelve-year-old daughter graduate from school. In six years. Not only did she live to see her daughter graduate, she got to see her get married and held her grandson before succumbing to the disease.
Robert was a successful Austrian business man in the United States who returned to Vienna after a metastasizing colon cancer diagnosis, in part because of American health care costs. He lived the life he wanted, but it left him alone, without a support network of family and friends. Instead of setting a goal to live, he wanted to die; but the euthanasia for which he hoped was illegal in Austria. As his case worsened, Ludwig put him in palliative care for a few days before he died. Alone.
Martha set goals and outlived the odds, dying peacefully among her loved ones. Robert felt his life had been lived as he wanted and he wasn’t living for anyone else. Each was on the opposite side of their respective survival curves; one lived longer or the other died sooner averages indicated. Perhaps there was more to it than medicine alone, Ludwig concluded.
Martha and Robert represent thousands of patients Ludwig has cared for in his career, leading him to ask fundamental questions, "what it is that makes us the persons we are. How important are our genetic makeup, our life experiences, our surroundings?” On the one hand, the latter two have nothing to do with medicine as such. On the other, they have as much or more to do with patients’ diseases and the treatments as any medical fact.
Ludwig distills his thoughts into five L-concepts “so they might easily be remembered:” loving, laughter, learning, lifelong fitness, and lighter eating. Much like diversity medicine, the ideas intersect in different ways for different readers.
*
Loving is an expansive and all-inclusive concept, encompassing everything from individual passion to familial bonds to community engagement. The key is to make an effort to be connected and engaged, to bond with others. Ludwig explains various studies confirming linkages between poor health and disease to individual isolation or, more importantly, the opposite: health benefits come with social connections.
One study demonstrating remarkable health outcomes in the close, socially cohesive community of Roseto, Pennsylvania, noted “loneliness is exactly as harmful as smoking 15 cigarettes a day.” A lack of loving bonds – family, intimate relationships, pets, colleagues, friends – adds to stress, which is known to exacerbate the effects of harmful bacteria in the stomach as well as “pain [which] can also be triggered by psychic factors alone.”
Methods to foster love include making active, consistent efforts to be involved with the important people in your life and finding passion in the activities you find most interesting. Physical contact ranging from casual handshakes and hugs to the sexuality of intimate relationships have been shown in studies to have beneficial effects. Our connections and interactions matter greatly to our health.
Ludwig cites studies showing how laughter is healthy for the heart and circulatory system, reduces stress, changes biochemical processes, and improves oxygen distribution.
If we succeed in making humor a part of our lives, this will contribute to our health…it provides medical benefits similar to those of positive social contacts, which are, in brief: Our blood pressure and our heart rate decline, which is good for, among other things, our arteries and our heart, and the cortisol level also decreases. Our immune system can therefore do its work more effectively and proceed against a great variety of disease-producing microorganisms – such as bacteria, viruses, parasites, molds – or tumor cells.
One should never mistake that authenticity of laughter to morph into “the harmful dogma of positive thinking” to obscure or crowd out realism. That could be “seriously naïve and, worse yet, extremely counterproductive.” Humor should never obscure the truth, and can often confirm it. And a true appreciation of humor requires a certain amount of knowledge.
Unfortunately, the speed and pace of modern life have complicated learning. “Some five hundred years ago,” Ludwig writes, “a person was born into approximately the same world as that in which he died. And his grandparents and grandchildren lived much as he did.” An average myeloma patient today has lived through times going from rotary dials to touchtone phones to faxes to the internet to social media.
Change is now an expected part of life. Our societal demands for learning do not abate. That’s especially true for a cancer patient. Worse yet, writes Ludwig, “I have come to know many people who did not start to look inward until they suffered a serious health crisis…And so they wanted to determine whether and what they might have done wrong up to that point and what they could do better in the future.”
Regardless of how cancer patients learn, a certain amount of education is required in order to have constructive discussions about with their physicians. That doesn’t mean they need to become experts. They should know enough to ask questions and request explanations when they don’t understand. Patients who do so generally do better in the long run.
But for Ludwig, as important as knowing about their disease is, learning is more of a life activity, one that keeps the brain active. Exercising the brain, regardless of topic, is as important as physical exercise.
Lifelong fitness is easier said than done. It’s hard for a myeloma patient who has been physically inactive to start an exercise routine. It is, however, common knowledge now that a fitter patient will have more options and, on average, better outcomes than one who is not. For example, myeloma expert Jens Hillengass from Roswell Park Comprehensive Cancer Center in Buffalo, New York is studying how exercise and fitness impact cancer incidence and treatment.
When it comes to exercise for patients, Ludwig has “a simple rule of thumb…exercise should be carried out for half an hour at least three times a week” reach pulse rates of “180 minus the age of the patient, which for a 50-year-old would mean 130 beats per minute…it would be preferable to do a bit more rather than a bit less.”
Indeed, Ludwig “recommend[s] almost all of my patients to consider physical training as one of the most effective drugs, with the least side effects and also among the most reasonable in cost, and to ‘consume’ this drug several times a week” to boost the immune system.
With this mindset, food could also be considered a drug. Lighter eating, historically speaking, was a normal part of the human condition.
In the history of mankind a regular feeling of hunger was the normal condition for very long periods of time. This actually helped people survive because they were compelled to stock up to be better prepared for periods when access to food was extremely limited, such as during extreme drought or long, cold winters. It is not surprising that, with this adaptation, which evolved early in the history of man, our body is still so organized as to want to put on reserves. In our present-day culture this is, of course, not only not necessary, it is out and out harmful.
His insights on food and nutrition align very closely to research currently being conducted by Urvi Shah at Memorial Sloan Kettering Cancer Center in New York. Less meat, especially red meat, more fruits and vegetables, less processed food, more whole grains, less sugar. Eat less. Not so often. Drink more water. Eat real food, not supplements.
For many of us, as obvious as it seems, this is not an easy transition. Not only do decades-long habits die hard, according to Ludwig, advertising makes it harder still:
Modern food trends, such as light products or power foods, are not really much more than clever sales arguments of the industry, with which it turns to profit our hopes for an alternative to self-control. It allows us to cherish the hope that we could change something about ourselves without having to make an effort. We buy “light” products whose advertising suggests that we could lose weight just by eating them. We gladly pay a bit more for that. If it then turns out that it doesn’t work, we don’t blame the manufacturer of the product, we blame ourselves. Then we have simply not eaten enough of it or have once again indulged too often or both.
Most importantly, Ludwig writes, “We should be orienting ourselves on ourselves. We should always start from where we are; otherwise the danger is too great that after a few days on a new nutritional plan we just give up.” That’s wise advice to be applied, in my view, to the first four L-concepts as well.
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Living Longer, Living Right largely discusses universal themes. One Ludwig mentions is “economic security. To have to fight every day for our livelihood is an enormous burden.” It’s hard to do anything about the five L-concepts if you’re worried about basic economic needs. But starting here, the American context is quite different from that in Europe.
Medical bankruptcies don’t exist in western Europe as in the United States, where it is a real fear for perhaps a majority of Americans, whether they are cancer patients or not . And while European patients may not have access to the latest cutting edge drugs outside of clinical trials, they do get effective treatments and their survival curves are similar and, in some cases, slightly better than those in the United States.
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“It’s up to us,” concludes Ludwig. That alone makes the idea of personal change so difficult. But then again, cancer is difficult.
As I reflect on the book, though, I think the intended audience of cancer patients and older adults who want to do something about disease should pick up a copy, read it, and pass it on to their children and grandchildren. Or at least get copies to them.
These are lessons and suggestions that are more easily learned and adopted at a young age, preferably long before the possibility of disease. And while doing something about the five L-concepts will increase the range of probabilities for many patients, the real goal of adopting them is to stop the onset of disease in the first place – to prevent it from ever occurring.
The odds that reading this book will cure anyone of disease is not realistic. But it would greatly increase the probabilities of living longer, and, if not living right, definitely living better....more
Upon reflection after a couple of years, I have to downgrade this to one star and would make it lower if I could. This is a pretentious waste of time.Upon reflection after a couple of years, I have to downgrade this to one star and would make it lower if I could. This is a pretentious waste of time. I recently Googled some examples of pilot checklists and looking them over for 20-30 minutes was a much better than time spent on this "book." Amazing what drivel passes for insight.
Original review:
This is short book with a fairly straightforward message: checklists matter in a world of increasing complexity and may be essential to navigating parts of it successfully. I really have no problem with the message. But as short as the book is, it’s just too long with too many self-serving anecdotes. It would have made an interesting extended article in the New York Times or a magazine. Not sure it needed a book with a $33 list price for the hardback.
We do live in a world that values and rewards expertise—as long as you’re not a teacher—more so if one needs teams to accomplish a repeatable project or task because “when it comes to the mundane, routine matters [that] are easily overlooked under the strain of more pressing events”, things can go wrong. Gawande waxes examples to underscore his thesis. My problem is that he seems to denigrate the concept of autonomy too easily. He uses the Ibsen-esque metaphor of the Master Builder to declare, “a supreme, all-knowing expert with command of all existing knowledge—autonomy is a disaster.” I think is jumps to his all-encompassing conclusion a bit too quickly. Yes, the examples he dwells on throughout the book about surgeries, constructing tall buildings, and airplane pilots make sense. But I also think there’s a danger of taking the analogy too far. Take teaching, for example. They must simultaneously navigate two worlds: one of administrative expectation—which is too often divorced from practical reality—and another of actually teaching students in a classroom, where professionalism, autonomy, and discretion are key to to expressing each individual teacher’s potential.
There is, however, a time and place for checklists, because sometimes “trust in the ability of the experts to manage the complexities” of some procedures can falter on occasionally missing or overlooking the most minor and obvious tasks, especially in retrospect. Team checklists need “pause points” for the team to assess what they have done in order to proceed to the next stage. This leads to “[e]mbracing a culture of teamwork and discipline.” This teamwork gives the seemingly minor positions greater importance, they act as a check on the so-called experts, the ones who are normally unquestionably in charge. Moreover, checklists can “improve…outcomes with no increase in skill.” And that’s quite an important observation. Like a chain, teamwork is only as strong as its weakest link; but in this case weakest is the wrong, even condescending, term. Gawande make clear that the use of a checklist, giving everyone an equal voice in making sure the tasks are carried out. There is a hierarchy of expertise, the is not one for process.
Gawande does, however, find the balance in the limits of checklists in his conclusion of the example of the “Miracle on the Hudson” use of checklist procedures when Capt. Sullenberger and his crew crash landed a plane on the Hudson river with no loss of life after hitting flock of geese on take-off. The checklist and the adherence to it created two things, a process for the team to implement when a crisis occurred, and “vital procedures when it mattered most, to remain calm under pressure, to recognize where one needed to improvise and where one needed not to improvise.” The ultimate lesson about the value of checklists: they remind us of what we need to do regardless, and this give us the opportunity to use our innate talents and skills when things don’t go according to plan.
It’s a good story and lesson. I just don’t think this was worthy of a book, however short is was. Gawande could have used a checklist to tell his important story much more concisely....more
Greed. That’s basically the story of Bad Blood. It’s what lies under it that makes this a compelling read. Not only is it about raking in vast amountsGreed. That’s basically the story of Bad Blood. It’s what lies under it that makes this a compelling read. Not only is it about raking in vast amounts of money and accumulating power, it’s about doing so by tapping into and exploiting the biggest personal fear we all share: the fear of disease. I guess that’s a storyline most everyone can relate to these days. And this story begins and ends with Elizabeth Holmes.
Who is Elizabeth Holmes? In 2004 she was a young Stanford University dropout who was inspired by Steve Jobs to emulate him or be even bigger. She received a patent the year before for the concept of a patch that collected blood to conduct other medical tests, thus eliminating the need for needles and vials of blood for medical tests. Holmes parlayed her patent, social connections from growing up in the DC area, and new ones made through Stanford—most important a relationship with a shadowy Pakistani man in his forties that she met there, Sunny, who would become her lover and collaborator—to raise millions of dollars in start-up money for her idea in less than a year. She refined a contrived charisma to convince investors with power and influence to open their wallets. Her easily grasped idea, potentially diagnosing a wide range of diseases easily without the discomfort of drawing large amounts of blood, combined with the prospect of making money and being a major disrupter in health care was too appealing. Combinied with rapidly advances in biotechnology, it seemed so logical. Holmes took the fear of needles and monetized it with an understandable analogy: If we can make computing power smaller, faster, and with more capacity, why can’t we apply it to medical tests? Everyone wanted to believe her.
Inspired by the simple elegance of her idol's iPhone design, Holmes had a similar portable testing housing designed that could easily fit on a table, “the Edison.” Over the coming years, she accumulated a Who’s Who board membership that included former presidential cabinet members George Schultz, Henry Kissinger, and William Perry, former senator Sam Nunn, and General-soon-to-be-Secretary of Defense, Jim Mattis. Theranos enlisted large pharmaceutical companies to do small studies and drug store giant Walgreens, to reconfigure its business and floor plans around its simple blood tests, which “they could rely on them to make medical decisions”, or so they thought. And the stock went up to become a Silicon Valley titan as corporate headquarters continued be upgraded, jets were purchased, and major magazine cover stories proliferated.
Outside of Elizabeth and Sunny, no one suspected it was all built on lies and deception. Ambition was fine, lies, not so much. Especially with billions at stake. The warning signs were there; the management problems alone were so obvious in hindsight. For example, “Elizabeth liked to keep information compartmentalized so that only she had the full picture of the system’s development [as] she siloed the groups off from one another and discouraged them from communicating…” She “demanded absolute loyalty [and] could turn on [employees] in a flash” and she “and Sunny regarded anyone who raised a concern or an objection as a cynic and a naysayer.”
What were the problems? First and foremost, many of her former employees cited a “loose relationship with the truth…” Employees drawn to Theranos in large part by idealism became more conflicted. Patients with terminal diseases made themselves available for clinical trials, not because they thought it would help them, but in the hope that “no one would have to say goodbye to loved ones too soon.” But Theranos employees slowly came to the realization that was far from reality. More often than not, the public demonstrations always seemed to rely on the very technology their public relations machine said would become obsolete. One oversight lab later “deemed the problems grave enough to put patients in immediate danger.” People were also misdiagnosed with false positives that required follow up visits and often unnecessary medical procedures, not to mention the stress “both the emotional and financial toll of a health scare brought on by inaccurate results.” Holmes and Sunny would not allow independent testers to examine the Edison. Nor did they permit the company’s tests to undergo peer review, arguing that their processes were proprietary like, you know, the formula to Coca-Cola. By the time the emperor’s new clothes were completely revealed, it was “suggested the Edisons’ results were no better than guesswork” and “that not a single one of the blood tests run on its proprietary devices could be relied upon.”
The consequences were predictable and are still playing out with Holmes scheduled to go to trial this summer. Yet the real issues won’t be considered for legal action. Those touched by the fear of disease want to have trust, hope, expectation, and confirmation of cures. Holmes instinctively tapped into power and wealth, even as her lies were beginning to be exposed, to build and lose a Ponzi-scheme because greed combined with hope can attract many people in its wake. They desperately want to believe the lie. Holmes figured that out. Perhaps that’s part of her genius.
She seems to have genuinely thought she would get away with it. Time will tell. With Holmes’s trial looming this summer, schedule willing, I have a gut feeling the COVID crisis will awaken more interest than it would have normally. It won’t be a mostly investor/business and biotech startup audience. Now more people understand what it means when someone tries to get rich by selling snake oil, no matter what form it takes or when it happens. We'll still fall for stuff, but how we prepare and respond when people’s lives are at stake—or might be—is important. Perhaps that’s why many of us are fascinated to see how this plays out and what the long-term consequences will be for business and policy. The answer will tell us more about ourselves that it ever will about Theranos and Holmes. Writing as an American, I’m not hopeful....more
Immunotherapy is the most simple and obvious idea in medicine. Get your body to heal itself by dispatching its immune system whenever needed to fight Immunotherapy is the most simple and obvious idea in medicine. Get your body to heal itself by dispatching its immune system whenever needed to fight disease. Immunotherapy is also the most difficult and elusive idea in medicine. Trying to apply it to individual patients is the most difficult problem in medicine. Getting your body to accept manipulated corrections to your immune system to figure out how to fight disease without fighting or hurting the things you need: that’s the medicinal Holy Grail of this age. Finding the right balance to know when to turn on, turn off, and create lasting, enduring responses is what its all about. And as old as the general theory is, the actual applications were not possible until this time and they’re only getting better and more refined. The big problem with applying immunotherapies in patients is not as much the identification of targets that cause cancers and other diseases as it is in sending a signal to cease action once the targets have been eradicated. This ends up causing what is called cytokine release syndrome (CRS), which is similar to graft-versus-host-disease (GVHD), in which healthy, functioning cells become the targets of immune cells that have run out of bad things to attack. The body’s immune system knows how to do that as well as remember an immune response should the same bad thing target the body. Science still has to figure that out.
A Cure Within looks simultaneously at the periphery and some of the specific challenges to the field of immunotherapy through the lens twenty-five uneven—which is not meant to be a critcism—biographical sketches of various pioneers in the filed of immunotherapy. Some of the profiles are matter-of-fact about science, others go into personal stories, all of them touch on what contributions each has made. Every chapter begins with a sketch on a scrap of paper, notebook or cocktail napkin of a schematic of the discovery, made by the subject of the essay. Some are kind of easy to understand, others require a PhD and years of training.
It is certainly worth a read if immunotherapy is important to you, your family members, and/or your friends. But you really have to long for it. My hope for this book is that it finds the audience it needs that would benefit from reading it. And there’s the rub. Which patients and caregivers would benefit from reading it? I think it’s a good book for the scientifically literate ones who actively engage in learning about diseases they are interested in and who want to know more about the fundamental concepts underlying them. To be honest, there aren’t that many of them. But for those few, this is an excellent resource to lead to more in-depth reading of specific topics. Which scientists would benefit? Probably young people who are considering or choosing to pursue careers in immunotherapy. I hope this book will find its audience. As the author points out, when Siddhartha Mukerjee’s The Emperor of All Maladies was published in 2010, it did not contain a word about immunotherapy. Given its importance in treating cancers and blood disorders, that fact alone gives this book relevance....more
This past spring was a particularly great time to view woodpeckers in northeast Ohio. I got this book as a gift after I made a comment about woodpeckeThis past spring was a particularly great time to view woodpeckers in northeast Ohio. I got this book as a gift after I made a comment about woodpeckers to my sons. It’s a quick afternoon read that contains many interesting facts about woodpeckers: how they select their trees, the types of enclosures they carve out for mating seasons, how to identify marks on trees to determine differing types of woodpeckers, and what foods might attract them for closer viewing.
There are few sights more entertaining than a pileated woodpecker in flight.
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And they are truly spectacular when at work. This year I saw two at the same time on parallel trees.
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More common and full of energy is the northern flicker.
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And if you are lucky enough to get a view of their undersides, it’s a treat.
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The red-headed woodpecker is more common.
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As is the downy woodpecker.
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If you live in the eastern U.S. or Canada and like to watch woodpeckers, this is a nice book to have in your collection. I’ll be returning to it this fall as I welcome old friends on their way south....more
At the same time I reached the midway point of Siddhartha Mukherjee’s The Gene: An Intimate History, the satellite Juno entered the atmosphere of JupiAt the same time I reached the midway point of Siddhartha Mukherjee’s The Gene: An Intimate History, the satellite Juno entered the atmosphere of Jupiter. But that feat pales, in my view, to the story about genetic journeys that are taking place within our individual, biological selves, especially since “genes provide the context to understand development and fate” of every human life. As I finished the book today, the New York Times reported that a clinical trial using a promising type of genetically engineered cells—made, coincidentally, by a company called Juno—had to be halted after three patients died because of swelling in the brain. It is a sobering reminder of, despite its promise, how far we still have to go to understand and harness the promise of genes to lessen the burdens of disability and disease.
It’s hard not be overly enthusiastic about how the manipulation of genetics might make things like birth defects, cognitive issues, mental illness, and diseases like cancer, Alzheimer’s, and hemophilia things of the past, especially considering Mukherjee’s masterful, precise overview of the history of scientific progress to understand how the gene works. Yet his combined gifts of scientific expertise and literary brilliance—which he also demonstrated vividly in The Emperor of All Maladies—provide a dose of reality of how difficult the steps from theory to practice will be. There is an overriding sense, however—like Martin Luther King, Jr.’s vision of the Promised Land—that we just might get there if we keep trying.
In writing about the evolving history of the gene from Pythagoras to Darwin to Mendel and their intellectual progeny through today, Mukherjee has taken what is usually a dry subject with the prose of a gifted novelist. He interweaves the story of the gene with his own family’s history of mental illness, leaving unsaid his fears of genetic predisposition that might one day affect him, his children or other loved ones.
From a lay perspective, it is most interesting that the basic knowledge of the gene is built on studies of things like fruit flies, worms and yeast. (Keep that in mind the next time you hear a member of Congress complaining about “wasteful” spending on research he or she cannot comprehend.) By understanding the basic mechanisms of genes, which are within chromosomes and synthesize DNA to RNA to proteins in these smaller, “simpler” organisms, researchers could better understand how these processes work in humans. Two fly geneticists, for example, “understood that mutations [in genes] are just variations...that convey…essential and profound truth[s]. A mutation…is a statistical entity, not a pathological or moral one.” In other words, when we impose our personal, social, or political views on things like race, a person’s disability or disease, or anything caused by genetic variation, for that matter, it tells us more about our subjective humanity than it does about objective reality.
This explains why he doesn’t shy away from the history of the misuse and deliberate misinterpretation of genetics for purposes of political ideology or social engineering. In taking on subjects like eugenics, the monstrous “racial” policies of Nazi Germany, Murray and Herrnstein’s book The Bell Curve, and then brings them together through the telling of the story of Carrie (to whom this book is dedicated) and Emma Buck, a daughter and mother who were forced to undergo state-sanctioned sterilization in the name of an evil policy built on a combination of junk science and misguided notions of morality.
In telling this story, Mukherjee intertwines contextual definitions with simple rhetoric. Genes are much more complex than carriers and purveyors of heredity; to evolve, genes express things like variation, adaptation and mutation, the latter which he sums up as, “A chicken…was merely an egg’s way of making a better egg.” An essential concept is the genome, i.e., “all genetic information within an organism.” The interplay between genes within any organism’s genome is what makes up the stuff of life. It is an uneven, pragmatic process, or has Mukherjee explains more clearly, “Beautiful laws were often killed by ugly facts.”
The ugliest of facts is: even when genes and genomes are distilled to their most simple elements, answers on how to manipulate them is elusive. Scientists must understand the interplay of a variety of factors. “A genotype is an organism’s genetic composition. It can refer to one gene, a configuration of a gene, or even an entire genome. A phenotype, in contrast, refers to an organism’s physical or biological attributes and characteristics—the color of any eye, the shape of a wing, or resistance to hot or cold temperatures.” Or as he puts it more simply: “genotype + environment + triggers + chance = phenotype.” Some genetic information about disease can be distilled down to one gene defect as in diseases like chronic myelogenous leukemia (CML), hemophilia or Huntington’s disease. “But most common human diseases do not arise from single-gene mutations. These are not genetic illnesses as much as genomic illnesses: multiple genes spread differently throughout the human genome, determine the risk for the illness.”
The next most important steps to address these issues will be to sequence genomes; to figure out what genetic information is transmitted in particular places at particular times. “Cancer,” for example, is “a genome that becomes pathologically obsessed with replicating itself” and, depending on the type, it can require multiple—perhaps tens or hundreds of distinct operations at the genetic level—approaches to alter blood cells have them match up with the disease causing mutations within each individual’s body, something that Juno’s clinical trial tried unsuccessfully to do. Yet, Mukherjee’s opus leads me to believe that when we understand why these trials have failed, the news will be much bigger than interplanetary exploration and much, much more significant to our lives.
Mukherjee is a trained oncologist. These folks are usually very dry and hyper-focused; they aren’t well-read outside of their fields nor do they know much about art, poetry or history. But Mukherjee is different. He can write with an eloquent simplicity that makes complex issues completely clear to someone like me who was never crazy about science. First he writes what is arguably one the best nonfiction books ever written, The Emperor of All Maladies, and then he follows it up with an eloquent masterpiece on a subject that is much more complex to explain. He is incredibly gifted. Much like Carl Sagan, he should be considered one of the great medical minds of our or any generation if only because of his gift of being able to convey such complex, relevant ideas to lay persons everywhere....more
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