Life is Emerging: Review of Siddhartha Mukherjee’s Song of the Cell
The DNA double helix is often the image spiraling at the center of 21st century advances in biomedicine and the growing bioeconomy. And yet, DNA is molecularly inert. DNA, the code for genes, is not alive and is not strictly necessary for life. Ought life be at the center of our communication of living systems? Is not the Cell a superior symbol of life and our manipulation of living systems?
A code for life isn’t a code without the life that instantiates it. A code for life must be translated. The cell is the basic unit of that translation. The cell is the minimal viable package of life as we know it. Therefore, cell biology is at the center of biomedicine’s greatest transformations, suggests Pulitzer-winning physician-scientist Siddhartha Mukherjee in his latest book, The Song of the Cell: The Exploration of Medicine and the New Human.
The Song of the Cell begins with the discovery of cells and of germ theory, featuring characters such as Louis Pasteur and Robert Koch, who brought the cell “into intimate contact with pathology and medicine.” This intercourse would transform biomedicine, leading to the insight that we can treat disease by thinking at the cellular level. The slightest rearrangement of sick cells might be the path toward alleviating suffering for the organism: eroding the cell walls of a bacterium while sparing our human cells; inventing a medium that coaxes sperm and egg to dance into cellular union for in vitro fertilization (IVF); designing molecular missiles that home to the receptors decorating the exterior of cancer cells; teaching adult skin cells to remember their embryonic state for regenerative medicines.
Mukherjee uses the bulk of the book to elucidate key cell types in the human body, along with their “connective relationships” that enable key organs and organ systems to function. This includes the immune system, the heart, the brain, and so on. Mukherjee’s distinctive style features compelling anecdotes and human stories that animate the scientific (and unscientific) processes that have led to our current state of understanding. In his chapter on neurons and the brain, for example, he integrates Santiago Ramon y Cajal’s meticulous black ink sketches of neurons into Mukherjee’s own personal encounter with clinical depression. In one lucid section, he interviews Dr. Helen Mayberg, a pioneering neurologist who takes seriously the descriptive power of her patients’ metaphors, as they suffer from “caves,” “holes,” “voids,” and “force fields” that render their lives gray. Dr. Mayberg aims to stimulate patients’ neuronal cells in a manner that brings back the color.
Beyond exposing the insight and inventiveness that has arisen out of cell-based thinking, it seems that Mukherjee’s bigger project is an epistemological one. The early chapters of The Song of the Cell continually hint at the potential for redefining the basic unit of biology as the cell rather than the gene. The choice to center biomedicine around cells is, above all, a conspicuous choice not to center it around genes (the subject of Mukherjee’s previous book, The Gene), because genes dominate popular science communication.
This choice of cells over genes is most welcome. Cells are alive. Genes are not. Letters—such as the As, Cs, Gs, and Ts that represent the nucleotides of DNA, which make up our genes—must be synthesized into a word or poem or song that offers a glimpse into deeper truths. A key idea embedded in this thinking is that of emergence. Whether in ancient myth or modern art, creation tends to be an emergent process, not a linearly coded script. The cell is our current best guess for the basic unit of life’s emergence, turning a finite set of chemical building blocks—nucleic acids, proteins, sugars, fats—into a replicative, evolving system for fighting stasis and entropy. The cell’s song is one for our times, for it is the song of biology’s emergence out of chemistry and physics, into the “frenetically active process” of homeostasis.
Re-centering our view of biology has practical consequences, too, for how we think about diagnosing and treating disease, and for inventing new medicines. Centering cells presents a challenge: which type of cell to place at the center? Rather than default to the apparent simplicity of DNA as a symbol because it represents the one master code for life, the tension in defining the diversity of cells—a mapping process still far from complete in cutting-edge biology laboratories—can help to create a more thoughtful library of cellular metaphors to shape both the practice and communication of biology.
Further, effective problem solving is often about operating at the right level, or the right scale. The cell feels like appropriate level at which to interrogate many of the diseases that ail us, because the senses that guide our own perceptions of sickness and health—the smoldering pain of inflammation, the tunnel vision of a migraine, the dizziness of a fluttering heart—are emergent.
This, unfortunately, is sort of where Mukherjee leaves the reader, under-exploring the consequences of a biology of emergence. Many practical and profound questions have to do with the ways that each scale of life feeds back on the others. In a tome on Cells and “the future human” I wished that Mukherjee had created more space for seeking the ways that cells will shape and be shaped by the future, of humanity and otherwise.
We are entering a phase of real-world bioengineering that features the modularization of cellular parts within cells, of cells within organs, of organs within bodies, and of bodies within ecosystems. In this reality, we would be unwise to assume that any whole is the mere sum of its parts.
For example, when discussing the regenerative power of pluripotent stem cells, Mukherjee raises the philosophical thought experiment of the Delphic boat, also known as the Ship of Theseus. The boat is made of many pieces of wood, each of which is replaced for repairs over the years, with the boat’s structure unchanged. Eventually none of the boat’s original wood remains: Is it the same boat?
Mukherjee raises the Delphic boat in one paragraph at the end of the chapter on stem cells, as a metaphor related to the possibility of stem cell-enabled regeneration in perpetuity. He does not follow any of the threads of potential answers. Given the current state of cellular engineering, about which Mukherjee is a world expert from his work as a physician-scientist, this book could have used an entire section dedicated to probing this question and, importantly, the ways this thought experiment falls apart.
We are entering a phase of real-world bioengineering that features the modularization of cellular parts within cells, of cells within organs, of organs within bodies, and of bodies within ecosystems. In this reality, we would be unwise to assume that any whole is the mere sum of its parts. Wholeness at any one of these scales of life—organelle, cell, organ, body, ecosystem—is what is at stake if we allow biological reductionism to assume away the relation between those scales.
In other words, Mukherjee succeeds in providing a masterful and compelling narrative of the lives of many of the cells that emerge to enliven us. Like his previous books, it is a worthwhile read for anyone curious about the role of cells in disease and in health. And yet, he fails to offer the broader context of The Song of the Cell.
As leading agronomist and essayist Wes Jackson has written, “The sequence of amino acids that is at home in the human cell, when produced inside the bacterial cell, does not fold quite right. Something about the E. coli internal environment affects the tertiary structure of the protein and makes it inactive. The whole in this case, the E. coli cell, affects the part—the newly made protein. Where is the priority of part now?” [1]
Beyond the ways that different kingdoms of life translate the same genetic code, the practical situation for humanity today relates to the ways that the different disciplines of modern life use values and culture to influence our genes, cells, bodies, and environment. It may be that humans will soon become a bit like the Delphic boat, infused with the buzz of fresh cells to repopulate different niches within our bodies, for healthier, longer lives. But in biology, as in writing, a mixed metaphor can cause something of a cacophony. For we are not boats with parts to be replaced piecemeal. And nor are whales, nor alpine forests, nor topsoil. Life isn’t a sum of parts, and neither is a song that rings true.
[1] Wes Jackson, "Visions and Assumptions," in Nature as Measure (p. 52-53).
When a patient is diagnosed with early-stage breast cancer, having surgery to remove the tumor is considered the standard of care. But what happens when a patient can’t have surgery?
Whether it’s due to high blood pressure, advanced age, heart issues, or other reasons, some breast cancer patients don’t qualify for a lumpectomy—one of the most common treatment options for early-stage breast cancer. A lumpectomy surgically removes the tumor while keeping the patient’s breast intact, while a mastectomy removes the entire breast and nearby lymph nodes.
Fortunately, a new technique called cryoablation is now available for breast cancer patients who either aren’t candidates for surgery or don’t feel comfortable undergoing a surgical procedure. With cryoablation, doctors use an ultrasound or CT scan to locate any tumors inside the patient’s breast. They then insert small, needle-like probes into the patient's breast which create an “ice ball” that surrounds the tumor and kills the cancer cells.
Cryoablation has been used for decades to treat cancers of the kidneys and liver—but only in the past few years have doctors been able to use the procedure to treat breast cancer patients. And while clinical trials have shown that cryoablation works for tumors smaller than 1.5 centimeters, a recent clinical trial at Memorial Sloan Kettering Cancer Center in New York has shown that it can work for larger tumors, too.
In this study, doctors performed cryoablation on patients whose tumors were, on average, 2.5 centimeters. The cryoablation procedure lasted for about 30 minutes, and patients were able to go home on the same day following treatment. Doctors then followed up with the patients after 16 months. In the follow-up, doctors found the recurrence rate for tumors after using cryoablation was only 10 percent.
For patients who don’t qualify for surgery, radiation and hormonal therapy is typically used to treat tumors. However, said Yolanda Brice, M.D., an interventional radiologist at Memorial Sloan Kettering Cancer Center, “when treated with only radiation and hormonal therapy, the tumors will eventually return.” Cryotherapy, Brice said, could be a more effective way to treat cancer for patients who can’t have surgery.
“The fact that we only saw a 10 percent recurrence rate in our study is incredibly promising,” she said.
Few things are more painful than a urinary tract infection (UTI). Common in men and women, these infections account for more than 8 million trips to the doctor each year and can cause an array of uncomfortable symptoms, from a burning feeling during urination to fever, vomiting, and chills. For an unlucky few, UTIs can be chronic—meaning that, despite treatment, they just keep coming back.
But new research, presented at the European Association of Urology (EAU) Congress in Paris this week, brings some hope to people who suffer from UTIs.
Clinicians from the Royal Berkshire Hospital presented the results of a long-term, nine-year clinical trial where 89 men and women who suffered from recurrent UTIs were given an oral vaccine called MV140, designed to prevent the infections. Every day for three months, the participants were given two sprays of the vaccine (flavored to taste like pineapple) and then followed over the course of nine years. Clinicians analyzed medical records and asked the study participants about symptoms to check whether any experienced UTIs or had any adverse reactions from taking the vaccine.
The results showed that across nine years, 48 of the participants (about 54%) remained completely infection-free. On average, the study participants remained infection free for 54.7 months—four and a half years.
“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments,” said Gernot Bonita, Professor of Urology at the Alta Bro Medical Centre for Urology in Switzerland, who is also the EAU Chairman of Guidelines on Urological Infections.
The news comes as a relief not only for people who suffer chronic UTIs, but also to doctors who have seen an uptick in antibiotic-resistant UTIs in the past several years. Because UTIs usually require antibiotics, patients run the risk of developing a resistance to the antibiotics, making infections more difficult to treat. A preventative vaccine could mean less infections, less antibiotics, and less drug resistance overall.
“Many of our participants told us that having the vaccine restored their quality of life,” said Dr. Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who helped lead the research. “While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game-changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”