24: Antifragile; Gene editing; Why we age
Hi. Hope you’re doing okay.
I am dropping a copy of my book reviews on Goodreads on here just in case Goodreads ceases to exist. Here are 3 recent reviews:
1- Antifragile
Since you are a complex biological system, your goal in life should be striving to become Antifragile, the term Taleb coins as he looked and looked and, to no avail, couldn't find it in the lexicon of modern people. Taleb identifies a spectrum he calls the Triad that is composed of Fragile, Robust,and Antifragile. He gives the analogy of the fragile as the package that warns you to "plz, avoid exposing the item to stressors and harm" as opposed to the Antifragile package that begs you to expose it to stressors and volatility. We already know what robust is; something that is immune to stressors and volatility, but,Alas,lacks the ability to gain or benefits from these stressors(disorder). Complex systems, be it biological or man-made need stressors and volatility to thrive in an increasingly uncertain world. The need for stressors is evidenced by the negative black swans( hidden small risks accrued over time) these fragilized systems collapse under. So what modernistic, procrustean-bed type societies are commiting is denying these systems their natural right of having constant exposure to stressors and volatility and this has to change if we want our systems to attract more positive black swans instead of negative ones. The author suggests the barbell strategy, an important mechanism to manage risk and avoid big losses. The strategy goes as follows: on one side of the barbell, you play it extremely safe putting 80% of your resources in safe bets and 20% in speculative type of deals. That way, you are antifragile to big losses, likely incurring high gains. A lot of important terms are worth mentioning here in passing as they help drive the point home further. Iatrogenics, which Taleb expounds on in the part about medicine. The idea is that of harming through unneccessary interventionism( via positiva), instead of doing the right thing and letting things take their natural course, in healing from a mild sickness, say. The second term on our list is Hormesis, exposing the system to stressors( up to a point) to make it immune against harsher conditions in the future. Subtractive knowledge. The idea of knowing more by subtracting(via negativa) instead of adding as more data=more noise and the path to true knowledge is in debunking false theories and exposing the false instead of adding more. Lindy effect. The idea that unperishable stuff( written word, artifact, historical monuments, selfish genes, ideas..) increase in value as they age as opposed to perishable biological systems whose lifetime decrease as thy age. Convex thinking vs concave thinking. I don't think i understood these two terms very well. The way I see it is an Antifragile system is represented on a graph by showing postive convexity effects: Assymetry and nonlinearity over time. For instance, the number of cars on the road with respect to intensity of traffic. Past a certain point, one additional car one the road can have a very non linear/asymetric/exponential ( convex?) effect on the system making traffic non linearly more congested. Overall an enjoyable read with an important central idea that I can now carry over to my individual life in order to become Antifragile. For instance, to become Antifragile as a person, 1-avoid medicine unless the case is severe, 2-use the barbell strategy when taking risks, 3- induce stressors and volatility in your life, for example lift weights, run sprints, eat non linearly( not in 3 meals), fast, walk slowly for hours in a natural habitat as opposed to on a smooth surfaced treadmill, 4- be a rational flaneûr; live a non narrative/ anti tourstificated life. You don't abide by a plan, you update your decisions as you go, based on new information from the environement, 5- Avoid the news(noise), read the classics, avoid sugar, expose yourself to uncertainties. Make small mistakes and learn from them( stressors=information) so that you don't live under the illusion that you're safe(while small,hidden risks b are being accumulated in the background till the day they explode into a prominent black swan and makes you exit the genepool).
2- Lifespan: Why we age- and why we don’t have to
Aging has always been a taboo subject to bring up in social circles. We have grown accustomed to seeing people drop dead around us( mostly the elderly) and we never bother to ask as a society if this is how the normal course of things should be: grow old and start developping diseases and spend the last decade or two of your life fighting diseases, in a state of frailty and debility. If you are lucky you make it till 80 amd then the lights go off. In this book, the author is positing a novel way of looking at aging. He is simply on a mission to proseltyze the world to recognizing aging as a disease that can be treated or at least delayed with the added benefit of giving healthy livespans till the last breath. The author starts off by identifying the hallmarks of aging: cellular senscense, telomere shortening, DNA damage, and others. Through the experiments they are performing in their labs, Dr Sinclair and his brilliant army of researchers think that technologies such as cellular reprogramming, gene therapies, organ printing using stem cells, biotracking techs to detect any fluctuations in biomarkers amd possible diseases, cas9 DNA editing tech, and a host of drugs like metformin, NADboosters, resvesatol and upcoming drugs like senolytics that promise to rejuvenate or kill zombiecells represent only the tip of the iceberg in terms of what lies ahead of longevity inducing tech. The author argues that we can make it to 120 with our current bodies if we can follow the necessary steps in keeping our life healthy: these steps which are proven to trigger our survival circuit response include 1- intermitternt fasting; 2- exposing to cold; 3- limiting dairy, pasta, and follow a diet rich with veggies and fruits; 4- excericsing regularly; 5- minimizing stress. Now, the author also suspects that some drugs might be beneficial to longevity like metformin,and NDN but there is no definitive conclusiom yet. These steps are things anyone can do on their own but the promise of the future if aging were to be identified as a disease amd funding started pourimg in is technologies that will prolong healthy life for at least a couple of decades. Imagine a world where everything you use can work for your favor: a car equipped with a seat that monitors your health amd alerts your doctor for any inconsistencies in your bodily functions; a hand watch that can monitor a multitudinous number of biomarkers, which help identify any possible future disease long before it happens. Imagine a world where every decade you go to the doctor amd get vaccinated for cellular aging, gaining 10 or 20 more years in physical and mental health. This, as the author repeatedly promise,is not sciemce fiction. It is already happening. The revolution is coming and pro-longevity society will rise from the ashes of pro aging society that is entrenched with the idea of aging being a natural/ meaningful part of life. There is no biological law that says aging is not reversible. The world in which aging is being reversed is a world where a lot of money spent on taking care of the elderly will be freed to focus on rejuvenating techs that would prevent the mother of all diseases, the disease that will prevent all other diseases, Aging. Ageism would be obseolescent. You wouldn't he able to make how old people are. The old will still work amd give back to society even after they turn 100. If aging is simply the loss of information over time( DVD accumulating scratches) and if what Claude Shannon theorized in his mathematical theory of information can be tramsfered to the biology of aging( finding corrective information, correcting agents, backup data_ the genes of the young is preserved till a very old age so it can be accessed_.). The genome preserves info in digital form and the epigenome works in analog. Many roads could lead to solving aging and the analogy of computers seem to be a promising route. There are a lot of ethical issues discussed in the book from overpopulation, medical personal data, unemployement...etc. The author manages to convince us that the way to a better future is through fighting diseases and reversing aging. I felt really excited reading this book. I mean, the momentum is real and there is no going back, these techs and therapies seem to be in the offing. I really dom't understand why some still choose to turn a blind eye to what is possible. I am upset by our tentative tendency as a society to change our views on things. Why should old people suffer and grow weak where they could stay healthy and sharp with promising technologies. I can not wait for a future with health as a the defining attribute of the times, no matter the age.
3-A crack in creation: Gene editing and the power to control evolution
A fascinating profile of the history of biohacking, as in how tinkering with Biology has transformed over the years, and the various research and experiements conducted in the field that culminated with the accidental discovery of a revoluionizing molecular genome editing tool, CRISPR, thanks to the immune system fighting mechanism found in a bacteria against a certain virus. Humans have been engrossed in the business of changing what is "natural" for ages. They trued to enhance yields by selective breeding and reproduction, but they didn't get far. In recent decades, all sorts of gene splicing, gene editing, and gene therapy were starting to show promise in the midst of families of the genetically diseased. If the mutated gene(s) responsible for the wrong expression of the protein that ends up causing the disease can be fixed by tinkering with the genome why not do it, but you see, these techs were limited and benefitial only to a fortunate few. Now, with CRISPR, the concerns of old bioediting techs were reduced many folds and it is only left to the collective's imagination to imagine the possibilities. With a far accurate editing tool, and a much cheaper and easier to use, the tinkering with the human genetic code is now up for grabs for little to no cost. Curing diseases, enhancing genomes, producing healthy yields, and ridding the subsequent generations of all sorts of defects( using germline editing) is now in sight and the tech can not just be undiscovered. Talking about the joy of discovery, the work in the lab,and the various challenges of being the stewardships of such revolutionizing biotechnologies, the author expresses a sense of urgency at the dangers of not wielding this new found technology right, while simultaneously, fills us up with hope and excitement about the various possibilities available at our fingertips if we collaborated our efforts wisely. I pretty much enjoyed reading this book and having had an insder's view of what is going on in the lab and what we're on the cusp of in terms of human-directed evolution, so to speak.
Some important takeaways: *The genome is made up of a molecule called deoxyrybonucleic acid or DNA, which is constructed of just 4 different building blocks. Known as nucleotides, these are the familiar letters of DNA: A,G,C, and T, shorthand for the chemical groups(also known as bases) of adenine,guanine,cytosine,and thymine. DNA, as it turns out,is much like a secret language, each specific sequence of letters provides instructions to produce a particular protein inside the cell. To transform the instructions contained in DNA into proteins, cells use a crucial and closely related intermediary molecule called ribonucleic acid, or RNA, which is produced from DNA template via a process called transcription. This overflow of genetic information from DNA to RNA to protein- is known as the central dogma of molecular biology,amd it is the language used to communicate and express life. The human genome comprises about 3.2 b letters of DNA,with around 21000 protein-coding genes. The human genome is composed of twenty-three distinct pieces called chromosomes,that range in length from 50 to 250 million letters. Simplest mutation is a substitution, the replacement of one nucleoitide for another, which can disrupt the gene and cause to produce a defective protein. DNA sequencing is a process that enable scientists to record the contents of the human genome,letter by letter. Gene therapy( fix genetic mishaps by adding helathy genes) while gene editing( repair the defective genes themselves)
ON HOW CRISPR WORKS:
CRISPR, clustered regularly interspersed short palindromic repeats, can be described as a pair of designer molecular scicssors because of its core function: homing in on a a specific twenty two letter DNA sequence and cutting apart both strands of the double helix. ....CRISPR's greatest attributes was fantastically easy to target specific genes. All you had to do was select the desired twenty two DNA sequence to edit and then convert that sequence into a matching twenty two letter code of RNA. Once inside a cell, the RNA would couple with its DNA match using base pairing,amd cas9 would slice apart the DNA.