71 pages • 2-hour read
Siddhartha MukherjeeA modern alternative to SparkNotes and CliffsNotes, SuperSummary offers high-quality Study Guides with detailed chapter summaries and analysis of major themes, characters, and more.
In the opening chapter of Part 2, Mukherjee turns to cell anatomy. A cell has three primary parts. The first is the cell membrane, which encircles the cell’s outer boundary, helping define and protect the cell. The cell membranes are made from proteins and fatty-acid-based lipids. They’re porous, which enables the transport of nutrients into the cell and the transport of toxic materials out of the cell.
The fluid within the cell, which is variously called cytoplasm, cytosol, or protoplasm (Mukherjee uses the term “cytoplasm” going forward), represents the second part of the cell. It’s enclosed by the cell membrane but external to the nucleus. Cytoplasm is highly organized. The cell’s cytoskeleton, which is responsible for its structure and cytoplasm, appears as “ropelike structures” made of protein scaffolds.
Ribonucleic acid (RNA), which is present in all living cells, is found in cytoplasm. It has a complex shape and is composed of “four subunits: adenine (A), cytosine (C), uracil (U), and guanine (G)” (79). The nucleus produces RNA. RNA’s principal role is to carry instructions for controlling the creation of proteins. The site of protein synthesis is the ribosome. Ribosomes contain both RNA and protein. Proteins in cells are important because they “control the chemical reactions of life” (80). Proteins die in the proteasome, the “cell’s trash compactor” (80).
Cytoplasm contains organelles, or a cell’s mini-organs. There are several different types of organelles, including the nucleus, ribosomes, mitochondria, and endoplasmic reticulum. Mitochondria produce chemical energy, meaning that they’re “the cell’s fuel generators” (80). A cell can produce energy in two ways. The first is the fast route, whereby enzymes break down molecules into smaller sizes in cytoplasm. This reaction generates energy, and the end product is a chemical known as adenosine triphosphate (ATP). Mukherjee notes that “ATP is the central currency of energy” (81). The second way a cell generates energy is by burning sugar in the mitochondria. This represents the slower route, and its end product is glycolysis.
Endoplasmic reticulum (ER) is a network of membranes in the cytoplasm. ER facilitates the movement of proteins and directs them to the Golgi apparatus, another organelle. The Golgi further processes and sorts proteins so that they end up in the correct location in the cell.
The final part of the cell is the nucleus, “which is the most essential, and still the most mysterious, of organelles” (88). The nucleus is located inside the cell membrane of plant, animal, and human cells. Bacteria don’t have nuclei. The nucleus controls and regulates cellular activities (e.g., metabolism and growth), contains most of the cell’s genetic material (its genome), and produces RNA.
The genome is made of the double-helix-shaped deoxyribonucleic acid (DNA), which represents the entire set of a cell’s DNA instructions. Tightly bundled coils of DNA are called chromosomes. Similar to cytoplasm, the nucleus is highly organized, although little is known about its structure.
Mukherjee ends the chapter by emphasizing that understanding cellular anatomy is the key to restoring “the function of a diseased cell in its narrative anatomical location in the human body” (95).
In this chapter, Mukherjee focuses on “the most monumental event in the life cycle of a cell” (96), which is when a cell divides and produces daughter cells. There are two types of cell division. The first is mitosis, which German scientist Walter Fleming discovered in the late 1800s by staining chromosomes with dye and watching them divide under a microscope. Under mitosis, one cell (the mother) divides to produce two new daughter cells. These daughter cells are genetically identical to the mother cell. Each daughter cell has 46 chromosomes.
The second type of cell division is meiosis, which leads to “the birth of new cells, sperms, and eggs for the purpose of reproduction” (97). In humans, cells contain two sets of chromosomes because one comes from each parent (known as diploid). To maintain this state, eggs and sperm must have only a single set of chromosomes (known as haploid), each containing 23 chromosomes, prior to fertilization. During meiosis, each diploid cell divides into four haploid daughter cells. These daughter cells are called gametes. Fertilization between two gametes (egg and sperm) produces a zygote that has 46 chromosomes. The zygote includes a combination of DNA from each gamete.
Cell division has four phases. The first consists of Gap 1 (G1), in which the cell starts to grow larger, makes copies of organelles, and collects the molecules it will need later in the process. It represents the first resting phase. The second phase is synthesis (S), in which the cell synthesizes new DNA in the nucleus. The third phase, which is the second resting phase, is called Gap 2 (G2). In this phase, the cell continues to grow, produces more organelles and proteins, begins to reorganize its internal structure in preparation for dividing, and makes sure that the DNA strand has no mutations or damage. The final phase is mitosis (M), when the cell splits into two daughter cells.
Mukherjee introduces English geneticist Paul Nurse and English biochemist and molecular physiologist Tim Hunt. Both were interested in the cell cycle, particularly what controls it. Through studies on mutant yeast, Nurse found that cyclin-dependent kinase (CDK) enzymes were associated with cell division phases. Hunt, through studies on sea urchins, found that a protein called cyclin was associated with the cell cycle too. They realized that these two proteins “act in concert to regulate the transitions in the phases of cell division” (105).
Next, Mukherjee turns to in vitro fertilization (IVF), a form of cellular therapy that “artificially or medically assist[s] human reproduction” (107). Several different scientists worked on this issue, including Landrum Shettles, Robert Edwards, Patrick Steptoe, and Jean Purdy. IVF was first achieved in 1969, although a baby wasn’t grown from this process until a decade later. The discovery faced immediate backlash from the medical and religious communities and the public. Louise Brown was the first “‘test-tube baby’” (115), although Mukherjee takes issue with this term since test tubes weren’t used during the fertilization process.
Mukherjee focuses on the story of Chinese professor and biophysicist He Jiankui (nickname JK) in this chapter. First, however, he provides some context. Since the late 1960s, researchers were interested in whether they could detect chromosomal abnormalities in the embryo. The technique of preimplantation genetic diagnosis (PGD), invented in the 1990s, turned this interest into a reality. PGD involves testing an embryo for particular genetic disorders before it implants on the uterine wall. Mukherjee calls this process a negative process because it doesn’t entail creating a new embryo from new genes.
Scientists soon began exploring whether a positive process, or “the addition or alteration of a gene” (121), was possible. Scientists could do this with animal embryos, but the technique wasn’t easily adapted to human embryos. The 2011 discovery of gene editing, which enables scientists to change a living organism’s DNA, changed this story.
The most commonly used gene editor is the CRISPR-Cas9 protein. It derives from a naturally occurring bacterial defense system. Mukherjee notes that “Cas9, when combined with a piece of RNA to guide it, can be directed to make a deliberate change in the human genome” (123).
Mukherjee returns to the story of JK, who was interested in editing a gene, specifically CCR5, in a human embryo. CCR5 is a gene for a protein on immune cells that HIV uses to enter and infect the cell. Humans with a natural mutation called delta32 on the CCR5 gene are resistant to HIV. Mukherjee notes that this gene choice didn’t make sense. While the father did have HIV infection, the risk of HIV transmission from the sperm to the egg was zero because the sperm is washed during the IVF process. In addition, disabling CCR5 could have dangerous consequences for the immune system. Whether the couple was informed about the possible risks associated with the gene editing procedure is unclear.
JK conducted the gene editing process—despite potential issues, including that it wasn’t the same as the natural mutation—and implanted edited embryos into the womb. He announced the healthy birth of the first two gene-edited babies at a conference in 2018. Scientists grilled JK during the question-and-answer session on his methods for recruiting participants, whether he obtained informed consent, the potential risks associated with gene editing, and more. Mukherjee describes the session “as among the more surreal moments in medical history” (127). JK was unable to answer most of the questions. He was sent to prison for several years and banned from performing future research on IVF. Despite the backlash that JK faced and the current lack of rules and standards to govern human gene editing, other researchers are diving into this work.
The chapter ends by focusing on how single-celled organisms (e.g., yeast, slime molds, and algae) become multicellular organisms. Several experiments have demonstrated that single-celled organisms are “singularly drawn to form multicellular clusters” (134). The reason for this remains unknown, although it may be tied to size and movement. Regardless, the evolution of multicellularity was intentional, especially given that some cells are programmed to self-sacrifice to help create multicellular aggregates.
Mukherjee describes the process of fertilization. While it’s now known as the correct biological process to create life, people in past centuries held different beliefs. One belief, known as preformation (see Part 1), held that humans appeared in the womb as miniature versions of a person. They simply had to grow. Aristotle was one of the first thinkers to break away from this idea. He argued that humans were sculpted from menstrual blood. Albertus Magnus, a German friar in the mid-1200s, agreed with Aristotle. However, he also identified the formation of distinct organs in the embryo. It took another 500 years for researchers to advance this idea. The notion that organs underwent continual change during fetal development finally won over scientists, demolishing preformationism. This idea has been further honed under cell biological theory, which established that “all the anatomic structures of a developing embryo are formed by dividing cells, creating different structures and performing various functions” (138).
Once fertilization happens, the cell divides. This division continues until it creates billions of new cells. During the embryonic stage, these cells form three cell layers. The first is the ectoderm, or inner layer, which gives rise to the nervous system, skin, hair, teeth, and nails. The second is the mesoderm, or middle layer, which dictates the development of key cell types (e.g., connective tissue, muscle, blood, heart, and bone). The third is the endoderm, or outer layer, which forms the linings of the respiratory and digestive systems and some organs (e.g., the liver, lungs, intestines, and pancreas).
These three layers are followed by the formation of the notochord, a flexible rod similar to cartilage. Mukherjee notes, “The notochord will become the GPS of the developing embryo, determining the position and axis of the internal organs as well as secreting proteins called inducers” (139). By adulthood, the notochord turns into pulp in between human bones.
Experiments on frog embryos in the 1920s helped uncover what drives the phases of development for different organs during embryonic development. At each stage of development, already existing cells secrete proteins and chemicals that tell emerging cells where to go and what to develop into. It’s an extremely complex process with interplay among all the different signals.
The title of this section, “The One and the Many,” helps explain its purpose. Mukherjee generally focuses on “cells in isolation” (151). He explains the anatomy of the cell, the processes related to cell division, and how the understanding of both has transformed reproductive technologies. However, he begins to hint at something larger—specifically, that it takes an entire system of cells to support humans, who are multicellular organisms. The author notes that scientists are like cells: While they often do their work alone, they also coalesce into different scientific communities depending on their research niche. These communities, in turn, attempt to make breakthroughs that impact the broader human community. As Mukherjee notes, “There is the one and the many, and also the ‘many many’” (146).
Mukherjee continues to document Breakthroughs in Biology and the Evolving Understanding of Cells. The discovery of the anatomy of the cell was itself transformational. A cell comprises different parts, which work together to enable the very basics of human life. When one of the parts malfunctions, it’s important for researchers to pinpoint exactly what’s wrong so that they can determine the correct treatment.
As one example, past treatments often targeted the breakdown of a particular organ. However, understanding the anatomy of a cell has allowed doctors and nurses to target malfunctioning cellular organelles, such as a gene in the mitochondrion of a retinal ganglion cell that causes blindness. Researchers are currently testing whether replenishing the mitochondrial function of this gene will reverse blindness. Decades of advances are now enabling science to target the building blocks of sight. While this won’t benefit people who’ve already lost their sight, it could be life-changing for those who are slowly losing their sight.
In addition, researchers transformed the understanding of cell division by inventing ways to see the process. German scientist Walter Fleming discovered mitosis by staining chromosomes with blue dye. He realized that previous researchers weren’t actually looking at the inside of the cell but at the outside, which was why they couldn’t explain the phases of cell division. By staining the chromosomes, he could document what was happening internally under a microscope. Researchers continued to refine Fleming’s observations, further illustrating Mukherjee’s point that science is not done in a bubble but as part of a community.
Within this section, Mukherjee further explores What It Means to be Human. He devotes time to cell autonomy because this is where humanness begins. Mukherjee notes how “that autonomy, in turn, enables an essential feature of living systems: the capacity to maintain the fixity of an internal milieu—a phenomenon termed ‘homeostasis’” (90). Without homeostasis, living organisms, including humans, wouldn’t exist.
Mukherjee highlights several inequities and ethical dilemmas within the scientific community related to important breakthroughs. One example is how science routinely fails to recognize the contributions of women. British nurse Jean Purdy was one of the pioneers of IVF. She even performed the experiment that achieved the first example of IVF. However, a paper describing this accomplishment didn’t credit her. While the paper’s authors later tried to acknowledge her contributions, they initially joined a long list of male scientists who didn’t credit the work of women scientists. Mukherjee discusses Jean Purdy to emphasize her critical role in the birth of IVF. By doing so, he helps “garner the scientific recognition due to her” (113).
Another ethical dilemma is the role of pharmaceutical companies in promoting breakthroughs. A German pharmaceutical company created a sedative and antianxiety medicine called thalidomide, which mostly targeted pregnant women, “who, given the casual misogyny of the time, were often considered ‘anxious’ and ‘emotional’ and therefore needed to be sedated” (142). Forty countries quickly adopted the drug. However, when the company tried to bring the drug to the US, the FDA commissioner Frances Kelsey stopped them. Kelsey previously worked for a pharmaceutical company and understood that no drug was without risks. The creators of thalidomide claimed that their drug had no adverse effects, which immediately made Kelsey suspicious. After a long battle, Kelsey finally won, especially after increasing evidence showed that the drug caused horrible birth defects and even stillborn births. Kelsey bravely stood against a major corporation. In doing so, she saved the lives of countless children and demonstrated the importance of thoroughly examining test data from any breakthrough to ensure that it’s reasonably safe for people.



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