The Cell

Rating

7/10 This is a book that you read slowly and thoroughly. Not because it’s that amazing and you will want to retain every single piece of information, but because it’s dense and if you don’t pay proper attention you will put it down after the 2nd chapter. That’s nearly what I did… but then I reread the 2nd chapter again and on the second pass it made much more sense. The book is dense, using a lot of nomenclature that tests your memory and recall. The author also uses a lot of repetition to introduce new terms, which is a great practice, but it still gets a bit hard to remember what exactly a mannose-6-phosphate receptor is when mentioned half a page after it was first introduced.

This hopefully also gives you an idea about the depth of the explanation. It’s deep! And I loved it for that. The author didn’t shy away from going to the nitty gritty details of how cells actually work. It turns out it’s all just different proteins interacting with each other. Enzymes are proteins. Antibodies are proteins. Receptors are proteins. Histones are proteins. It’s proteins all the way down - literally!

I thought I had a pretty good idea about what a cell is and how it roughly works - I did not. Ignorance is a real bliss. If you’ll read this book, and you are not a cellular biologist, you will probably come away with an above average understanding of what cells are and how they work; and you will also come away with the feeling that what this book taught you is just the tip of an iceberg and there is a Marianna trench of knowledge to still learn about cells. In that sense, the author has accomplished the quest he set out to accomplish - make lay people appreciate science and get excited by it. Or at least it worked for me, but then again, I would consider myself to be on the edge of general lay population. But for the category of cellular biology I am as lay as they come.

Synopsis

A deep dive into what cells are, how they work, and what makes them live and die. Also a deep dive into the juice microscopy science behind how we actually see not just the surface of cells but also what goes on inside them.

Notes

Chapter 1 - First people seeing cells

• in 1660s Robert Hooke, an English polymath, was among the first people to use an elementary microscope built by Christopher Cock to observe that at a microscopic level a piece of cork wood is composed of tiny empty spaces separated by walls. These spaces reminded him of cells in which monks slept and so the word cell was born
• at the same time, Antoni van Leeuwenhoek, a Dutch linen draper, developed his own specialized microscopes as his hobby and saw things at even tinier scales than what Hooke was ever able to see
• this was the beginning of humans seeing the microscopic world
• in 1665 Hooke also published a book called Micrographia that features detailed drawings of what he saw

Chapter 2 - A very detailed tour of a cell

• “As atoms are to matter, cells are to life”
• a cell is a bounded space filled with a liquid called cytosol in which organelles, different compartments, including the nucleus, reside
• the cell is bounded by a plasma membrane which is solid but permeable barrier (proteins and molecules can penetrate it) that separates the organelles from plasma, the liquid component of blood
• different proteins float freely both inside the cell, within organelles and cytosol, and outside it in plasma
• a special class of proteins that perform some energy-dependent chemical changes, e.g. moving molecules from, within, or into the cell are called enzymes
• these enzymes use the cell’s cytoskeleton to move various molecules around
• the cytoskeleton is composed of another class of specialized proteins that form supporting structures for the enzymes; one such structure is a microtubule protein
• the most important organelle inside a cell is its nucleus where chromosomal DNA resides
• DNA is the genetic code that’s responsible for replication and transcription - production of RNA. Replication is equivalent to cell division; when a new cell is born from the current one by creating a new identical copy of the existing DNA. Transcription is the process of creating RNA from the DNA which is a precursor to functional proteins that perform some work for the cell as directed by the information encoded inside the DNA
• these two processes happen within the nucleus. The transcription, which directs the cell’s activity, begins by creating and sending out new messenger RNA (mRNA) into the cytosol where it is translated into functional proteins by ribosome
• the mRNA exits the nucleus through a nuclear pore complex which is a channel through which the boundary of the nucleus can be exited, otherwise the nucleus has an impenetrable barrier to e.g. prevent viruses from implanting their DNA into ours
• cytosolic ribosomes are little spherical bodies inside the cell that perform translation of all mRNA into functional proteins; every protein starts its lifecycle on a ribosome
• although called cytosolic, many ribosomes are not floating freely inside the cytosol. Instead they are attached to the endoplasmic reticulum (ER), which is a large membranous compartment. The proteins destined to form the membrane of the cell or those destined to be send out of the cell, are produced here
• ER is also the place where protein folding occurs. Ribosomes first form all proteins as linear chains of amino acids and then fold them into their functionally desired 3D shape
• after folding, the proteins follow a channel called secretory pathway out of the ER along which post-translational modifications by already existing enzymes occur
• all of this activity is powered by molecules called adenosine triphosphate or ATP, which are the basic unit of cellular energy. All ATP is produced from carbs, fats and proteins inside the cell’s power plants called mitochondria
• the mitochondria produce the ATP by a process closely resembling a water wheel; protons flow in and out of mitochondria due to chemiosmosis: the movement of molecules through a barrier from a place with low concentration to a place with high concentration, like water filling up a dried fruit. This movement stimulates an enzyme that in return secretes ATP
• finally, the cell dies thanks to a process called apoptosis - programmed cell death. This occurs when the membrane/barrier of the mitochondria becomes leaky, thus impairing the ATP production, which in turn starves the cell of energy and kills it

Chapter 3 - Basics of the genetic code

• “DNA becomes RNA becomes protein”
• a human genome is all of the DNA inside the cell’s nucleus
• a human DNA consists of 23 chromosomal pairs, within each chromosome are many genes and since the chromosomes come in pairs, we all have a maternal and paternal copy of every gene
• having a maternal and paternal copy of every gene is a safeguard against mutations. Mutations come as dominant or recessive. If a mutation is recessive, the unmutated copy of a gene will overpower the function of the mutated gene. However if the mutation is dominant, it will itself over power the unmutated copy and potentially cause disease
• when a new protein is being created, DNA is transcribed into appropriate RNA; the first step in this process is translating each individual gene, a small part of the long DNA, into its corresponding RNA transcript. Not whole of DNA is transcribed in a single piece!
• both DNA and RNA are polymers: linked chains of small molecules called nucleotides
• the nucleotides for DNA are: thymine (T), adenine (A), guanine (G), and cytosine (C)
• for RNA they are the same except for thymine being called uracil (a very similar molecular structure)
• the DNA is wound up in a double-helix, a twisting ladder, while RNA is a single polymer chain. The connections between nucleotides of the DNA are stronger along each of the two chains than across them
• the double-helix allows only specific pairs of nucleotides to be chained across the two strands: the allowed pairs are A-T and G-C
• the cross connections are weaker so the double-helix can separate and serve as a template for the complementary RNA strand to be polymerized. When this happens, one separated strand of DNA is used as a template to create its corresponding paired RNA which is subsequently used in the production of the functional proteins
• the proteins themselves are then created as long chains of amino acids held together by peptide bonds. But they don’t remain as long polypeptide chains. Instead they are folded into complex 3D shapes from which their function follows

Chapter 4

• “antibodies are proteins created by our immune system to mark and identify foreign invading pathogens”
• during cell division, the double-helix separates along its base pairings and new complementary strands are synthesized for each polymer chain. These are then connected to the original halves of the double-helix and two new cells are born. Thus each new cell contains one of the two original polymer chains of the DNA from the mother cell

Chapter 5 - Epigenetics explained

• DNA doesn’t just freely float inside the nucleus. Instead it tightly winds, like a spool of thread, around proteins called histones. This is an efficient way to package up the roughly 3 billion nucleotides that compose the human genome
• the tightness with which the individual segments of DNA are wind around histones regulates how accessible they are by polymerase which is responsible for their transcription; thus tightly wind DNA is less likely to be transcribed into RNA which is thus less likely to produce functional proteins corresponding to the genes in this part of the genetic code
• therefore, which proteins are generated is not controlled only by genes themselves but also by how tight they are wind around histones - this winding can be controlled by processes such as histone acetylation or DNA methylation
• these mechanisms that control gene expression are heritable and we refer to such inherited mechanism as “epigenetic” - they don’t directly change the genes, but alter their expression
• what makes a nerve cell a nerve cell and a blood cell a blood cell is which genes are expressed and which aren’t

Chapter 6 - Phenotypes and long/short alleles

• the phenotype is a physical manifestation of which genes are expressed; e.g. whether the flowers of a pea plant are white or purple
• different phenotypic traits are general independent of each other, e.g. flower color and stem length. This is because different genes are responsible for their manifestation
• an organism always has two copies of a gene and each copy has a part that we refer to as an allele. A long allele is dominant, while short allele is recessive. An organism with both alleles the same is called homozygous, while an organism with two different alleles is called heterozygous. All heterozygous organisms will display the phenotypic trait connected with the long allele, the dominant trait. A homozygous-dominant organism will also display this trait and only an organism with two copies of the short allele with display the recessive trait
• thus the recessive trait is only displayed in 25% of offspring (given it is controlled by a single gene, less often if it is connected with other short alleles of different genes)

Chapter 7 - PCR: polymerase chain reaction

• PCR, polymerase chain reaction, is a process by which we multiply specific small chunks of DNA
• during PCR we use a small chain of nucleotides called a primer that is equivalent to a chunk of DNA that is right in front of the segment we are interested in
• this primer serves as a starting point for the polymerase enzyme that then acts on the subsequent nucleotides and generates copies for us

Chapter 8 - Genome sequencing

• the price of genome sequencing is getting so low that soon it might cost as much as an MRI to sequence your entire genome
• but there isn’t very much that we can functionally do with this information

Chapter 9 - Genome and personalized medicine

• basically there is very limited progress on this front
• lot of money was poured into using genetic information to come up with treatments but with very little and limited success
• and the author raises a good point about how ethical is it to invest vast amounts of money into research of very rare diseases when we live in and era were even the access to basic medical treatment is plagued with class division, politics and heavy profit-seeking

Chapter 10

• nothing notable

Chapter 11 - Genetic-environment covariance

• genetic-environment covariance is the idea that while there appear to be some effects for which genes are responsible, e.g. claims of black people having lower IQs, the actual reason is covariance of the gene responsible for dark skin with the environment into which you are born and opportunities you are afforded because of this environment
• the general idea can be summarized as genes mediating how the environment acts on you - e.g. girls being less likely to become mathematicians because of the environment subconsciously discouraging them to pursue this path

Chapter 12 - Fluorescence explained

• flurophores are molecules that regularly and predictable absorb and release photons; they are responsible for the effect of fluorescence
• so for a flurophore to emit light it has to first absorb some; the absorption and then subsequent emission is not without heat loss, thus the light that’s absorbed is of higher frequency than the light that’s emitted - this is why a flurophore excited by an invisible ultraviolet light shines visible blue (blue light has the highest frequency on the visible spectrum and ultraviolet is right above it)
• we are able to use fluorescence to mark any part of a cell thanks to a specialized fluorescent protein found in jellyfish. This protein has been genetically engineered to attach to any other protein of choice without impairing its function. Thus we can control to which protein the fluorescent protein attaches and then we can watch where and how the target protein moves and functions

Chapter 13 - How we see into living cells

• microscopy is basically like holding a dry leaf to the sun and seeing the structure of veins that make up its shape; the denser parts block more light making them appear darker. The most basic microscopes work on the same principle; but they also magnify the sample with some powerful lenses
• using oils as a medium through which light passes, rather than air, allows us to achieve higher magnification. This is because oil has a higher refractive index than air. It essentially bends light more, focusing more of it into one spot which we can then pass through a lens. In other words, there is less light scattering to random directions in oil than there is in air
• but there will still only be a small portion of light that’s truly in focus. For this reason we use confocal microscopes that essentially just have a small pinhole after the lens which lets through only a tiny fraction of light that’s in focus, all the out of focus light gets filtered out by a barrier

… to be continued… maybe… the rest of the book was mostly about microscopes and some more niche cell topics like specific organ cells, diseases and general state of the microbiology research