The Master Builder: How the New Science of the Cell Is Rewriting the Story of Life

by Alfonso Martinez Arias

A leading developmental biologist argues that cells, not DNA, hold the key to understanding life’s past and present     What defines who we are? For decades, the answer has seemed our genes, the “blueprint of life.” In The Master Builder , biologist Alfonso Martinez Arias argues we’ve been missing the bigger picture. It’s not our genes that define who we are, but our cells. While genes are important, nothing in our DNA explains why the heart is on the left side of the body, how many fingers we have, or even how our cells manage to reproduce. Drawing on new research from his own lab and others, Martinez Arias reveals that we are composed of a thrillingly intricate, constantly moving symphony of cells. Both their long lineage—stretching back to the very first cell—and their intricate interactions within our bodies today make us who we are.   Engaging and ambitious, The Master Builder will transform your understanding of our past, present, and future—as individuals and as a species. 

Genres: Science, Biology, Nonfiction, Genetics, Audiobook, Popular Science, Nature

352 pages, Hardcover

First published August 1, 2023

Reviews

[Laura · Rating 3 out of 5]

As a biochemist with a PhD in protein biochemistry applied to cancer biology, I hesitate about diagnosing this book bold, or not yet fully baked. Mind you, I'm not a developmental biologist, which would make me better equipped to critique (and citicize?) this book. Overall, I'm uncertain if this was a 2 star, or 3 star read. Because while the author advanced some really good points about cells being 'the master builders' he also ignored important feedback loops, redefined the 'genome' according to his own preference, and switched terms around probably in an effort to simplify the story for the lay reader to the detriment of current scientific knowledge. And speaking of the lay reader: I doubt they can easily follow this book; I definitely struggled to follow the author's point at times, and that was after 10 years of education in biology and 14 years of lab work.

The thesis of the book is that our gene-centric view of life is inaccurate, and life should be seen as cell-centric, with genes representing essential tools that cells used to survive and (where appropriate) build an organism. The book is thus a rebuttal of Dawkin's "The Selfish Gene" which I haven't yet read but must. To be fair, the author brings forth some very interesting and compelling arguments: not every physical trait is explained by genes (see fingerprints distinct even between identical twins), traits that are no longer useful and would otherwise be discarded can still be revived (e.g. chicken that can grow teeth like primitive dinosaurs), cell's interaction with the environment and each other is paramount to forming a healthy living individual and the same cell with the same DNA placed in distinct conditions will lead to different structures, and the existence of complex multicellular organisms with protracted or limited reproduction cycles. All these observations fly in the face of the simple "gene is king" hypothesis. The strongest argument is best summarized in the following paragraph:
"the fundamental logic of life defies the selfish gene thesis. If as Dawkin’s suggest, life is a battle between individual genes for the price of replicating themselves into eternity, why bother building contraptions as baroque as a eukariotic cell? Why create the marvelous permutations of a moles foot, a bat's wing, a horse's leg, our own hand? Why create forms that require increasing amounts of energy and other resources, some with long periods between birth and sexual maturity, when they can finally serve their purpose of having offsprings to carry half of their genes to the next generation? I do not like “why" questions; the law of evolution is that if it works, it will be kept. The complexity and beauty of the traits I have mentioned are obvious and the question lurks in the background. According to Dawkin’s hypothesis, genes should stick to simple single celled options, (...) or better yet viruses.(...) Single celled organisms would be far more energy efficient vehicles for time traveling genes.” (...) "while every other type of cell in the body harnesses the genome for further multicellular cooperation, the germ cells and gametes are harnessed by the selfish genome, which uses these special cells as their vehicle for time travel, untouched by the creative processes associated with the generation of the organisms. From the point of view of this cell and the organism, the genome is a toolbox that cells used to make a hen, and the egg is simply the hen’s payment for accessing it."

I expected there would be a discussion on prions--meaning proteins that are deformed and can in turn deform other healthy proteins in a new organism without ever affecting the genome. How that fits into this cell-centric theory (it definitely contradicts the gene-centric one) would have been interesting to discuss, but the author didn't touch it.

However interesting the author's thesis was, it wasn't always supported with proper arguments. He insists that genes are not the master builders, but then brings the story back to genes (like when he discusses about somite formation and the roles gene mutations play in damaging this embryonic step). He talks about the importance of proteins in building a body: "It is proteins not genes that give cells the ability to organize themselves in time and space in new ways.” Agree! But proteins are the products of genes! He also forgets to discuss about how proteins loop back to the DNA and alter it in response to external stimuli, which gives a bit more weight to the selfish gene hypothesis. He equates gene copying into mRNA (transcription) with gene expression, which is wrong. Gene expression starts with transcription, but it also requires splicing regulation, translational control (which affects how the mRNA is turned into a protein), as well as post-translational modifications which alter not only the protein's life, but most importantly its function. He talks about genes from different species executing the same function, which is not always the case. He conflates embryonic stem cells with induced pluripotent stem cells, even though they've been shown to not be identical (and while I understand this may have been done for easier reader comprehension, it came at the cost of overstating a scientific discovery and probably muddled the waters even more for a non-specialist audience). The biggest trespass for me was the way he redefined the genome. Take the example of identical twins Isabella and Olivia who both harbored a genetic mutation that fused two genes together and predisposed them to cancer. Only one of the identical twins got cancer however. "; The zygote that would become Olivia and Isabella had not carried either cancer causing gene mutation. Then at some point shortly after gastrulation while their body plan was being constructed, the two genes fused in a blood stem cell in Isabella. Because the twins had shared circulation that stem cell passed on to Olivia and established itself in her bone marrow, where it underwent the second fatal mutation. Ultimately Olivia's leukemia was caused by the two mutations but they lay not in her genome but in the malfunction of one of her stem cells, which had its origin in her twins sister's body." But the mutation WAS in her genome, it just wasn't in all of her cells! The way this paragraph pretzels logic and current knowledge is very confusing, and also I believe scientifically incorrect. This is on top of already confusing sentences that I had a hard time understanding as a practicing biochemist with a good knowledge of genomics; I don't expect the lay audience will comprehend those points easy (for e.g. when we discuss the autosomes versus the sex chromosomes).

Overall, this is an interesting theory, and it's definitely supported by some strong data. I believe the either/or approach of this books or other science communicators like Richard Dawkins is more narrow than it needs to be, and I expect a more balanced "both cells and genes" are paramount for life hypothesis to be closer to the truth. The author raised some important points on how our over-reliance on genetics is making us overstate the importance of small DNA mutations, and overstate the importance of "nature" in general. This can indeed lead to some dystopic futures, which are already beginning to unfold. But the overall complicated presentation, the occasional incorrect information, and the misuse of scientific terms make me hesitant in recommending this book.

PS: One thing that stuck with me was the way he defined plant versus animal cells, based on whether or not 'they move.' It struck me as highly unscientific, and more appropriate for a middle grade audience (for whom this book is way too advanced). The difference between plant and animal cells lies in their COMPONENTS (plant cells have cell walls made of cellulose, they deposit glucose resources as starch instead of glycogen, they don't make or use cholesterol for cell membrane structuring, and they most often than not have chloroplasts which can turn light into biochemical energy), not in whether or not they move.

[Mario · Rating 4 out of 5]

La noción de los genes siendo responsables de *todo* en la vida ha prevalecido por décadas. Aquí, Martínez nos lleva de vuelta a la célula. Sí, sí, los genes son los planos con los que se construye la vida: pero la célula es la encargada de leer esos planos, elegir las herramientas necesarias, establecer cada proceso biológico que conlleva el desarrollo de otras células y subsecuentes tejidos. Es decir, sin la célula los genes son inservibles.

Maravilloso.

[Brett · Rating 4 out of 5]

Lots of great details and information. Despite repeating it every other page I didn't come away fully convinced by the main thesis, which is that DNA is just a dumb toolbox and that the cell is what is most important in determining what happens. Clearly DNA alone can't do anything, but the cell without DNA also can't function normally. The whole argument over which matters more seems like a professional ego thing more than a fact about nature. That said, some facets of the argument are more compelling: That DNA has received too much attention relative to the rest of the cell, and that the genome does not contain a complete procedure that dictates everything that happens.

[Mike Foreman · Rating 5 out of 5]

This is a must read for those interested in how life works. It is the logical successor to Siddhartha Mukherjee's "The Gene" and "Song of the Cell". My take is that the science of medical biology is growing at an exponential rate with new discoveries every week. This book covers a lot of recent developments as well as some of the author's 40 years of work as a geneticist at Cambridge. The essence of the book is that cells are in charge and use genes as tools in a toolbox, depending on their environment and intercellular signals. The only time genes are in charge is in cancer.

[Ali · Rating 4 out of 5]

"When genes became components of cells, they had to abide by the terms and conditions of the cells ever afterward. Their selfishness was curtailed."

Arias has a basic contention here - that our zeitgeist vastly overestimates the determinism of genes - but in the journey there, this is an excellent primer on cellular biology. It would pair well with Mukerjee's The Song of the Cell, also a book written about cells during the Pandemic. This trend is fabulous, a positive response to growing unease with how far from easily explicable modern biological technologies have become.
But the point for Arias, even if not the main work of the book, is to contextualise the role of DNA. Arias does well - or I at least I found it pursuasive - in explaining that DNA is a tool used by cellular structures. And those structures obey they own laws of functioning, set by physics and chemistry. In essence, we grow, not from a single strip of deoxyribonucleic acid, but from a gamete, itself formed by existing cells. Without cells to place DNA in, we have no person - you can't create cells just from DNA. Cells call upon DNA to provide a blueprint, but many factors can alter the process as they build it. Without an understanding of cellular functions, we cannot understand how we form. And much of this function is adaptable to our environment, changeable and geared towards cooperation between, at least, parts of us. In other words, our genes are part of who we are, but there is a lot more to it as well.
There are some other foci along the way. Arias is engaged in research into how human embryos form, and he explains clearly the ethics and how they are negotiated, including how very, very fine some distinctions are between 'real and ártificial', 'viable' and not. This section challenges readers to think beyond simple rules and into murkier elements of moralism. What is it to be human? Is it about potential, capacity to feel, and capacity to interact? And is humanity the only relevant line for experimentation?
This is a fascinating book from someone whose specific answers hint at much bigger questions.

[Blair · Rating 4 out of 5]

“The Master Builder” presents a point of view that the cell is life's prime contractor, and not DNA.

Ever since Watson and Crick’s team uncovered the shape of the DNA molecule, the world has been convinced that genes are most important determinant of life – whether it be bacterial, insect, plant, animal, or human. DNA is seen to determine and define all, so much so that the term has been used to describe cultural characteristics of people, countries, and even companies and brands.

To see this, consider how many times have you heard that “It’s in our DNA” to think or act in a certain way? This book approaches this subject by saying that genes are important, but it’s cells that are more important.

I was impressed with the “hook” that the author set at the beginning of the book, when it described the woman who needed a kidney transplant but found that 2 of her 3 sons had different DNA from her - not because the hospitals in which they were born made a mistake, but because she had two sets of chromosomes. How did that happen? Pursuing this answer kept me focused on completing the book and showed me once again that hooks are important when storytelling.

While I had studied genes in my biochemistry courses at the University of Toronto many years ago, and have read widely about the subject in recent books such as Siddhartha Mukherjee's "The Gene" and "Song of the Cell" this book by Alfonso Martinez Arias both solidified some of my thinking and taught be new things. In terms of confirming by thinking, I now better understand that cells are composites of other cells.

For example, animal-based eukaryote cells came into being when archaea cells consumed bacterial cells and the two types of cells learned to live symbiotically. Similarly, plant-based eukaryotic cells consider of cells that ingested bacteria that could perform photosynthesis. These eukaryotic cells then learned to live in colonies that became the tissues and organs that make up our bodies.

Further I learned that higher level beings such as humans have very common systems such as fruit flies, fish, frogs, and mice, and this is why all our embryos look alike.

I also learned that the DNA throughout our bodies is not the same throughout our bodies. That's because different parts of our bodies replicate at different rates and there are almost always mutations through each replication.

Moreover, I learned how an unborn foetus can cooperatively share its cells, and hence its DNA, with its mother through the same channels that the mother shares cells with the foetus. This is probably why the woman at the beginning of the book did not share the same DNA in all her cells as her sons.

These are some of the things I hadn’t considered before.

There was nothing I didn’t like about the book; however, it did stimulate many new questions in me. For example, does a cell build up new molecules from scratch when it needs them or does it salvage what is available to it. Further I wanted to know how nutrients like calcium and other elements facilitate or hold back cell growth. The book could have provided another chapter to explain this.

This was a very interesting read. I recommend it.

[Fadel Fakih · Rating 4 out of 5]

Alfonso Martinez Arias is a brilliant scientist with immense impact and a deep grasp of the field of cell biology. This is evident both from the book itself and his 26K+ citations of his research (according to Google Scholar). Thus, if there is someone to take over the mission of discussing this topic, he is definitely one of the first names that comes to mind.

The book provides a beautiful narration of the history of cell biology. It highlights how the thinking of brilliant scientists has shaped our knowledge of cell biology and development. The book challenges the gene-centric view of life, which places genes at the center of natural selection and the evolutionary process. The gene-centric view also emphasizes the role of genes in giving cells their identity. The book successfully confronts this idea with convincing examples from embryology. I particularly liked the idea: “Genes create time and cells create space.”

I read this book immediately after finishing Richard Dawkins’ “The Selfish Gene.” Both are brilliant biology books; however, they represent opposing extremes—gene-centric versus cell-centric views. Martinez takes a more conservative stance regarding the role of genes in how life operates. I personally prefer staying in the gray zone when it comes to biological laws. I disagree with characterizing life as strictly either gene- or cell-centric. Genes are certainly the blueprints of life, and they build the tools for cells to use. Yet, the relationship is not unidirectional. The cell, along with its niche, guides genes to determine the cell’s identity through the transcription of a specific set of genes.

In the book, it is mentioned that with DNA alone, you can’t build life. This is true, but it is equally true that without a cell, DNA alone cannot build life (at least in nature) because an organism would not be able to pass its catalogue of information to the next generation. The book also states that genes provide the tools while the cell decides what to keep and what to discard. However, it is ultimately the genes that create these tools, and if signaling feedback modifies the expression pattern, the regulation of gene expression adjusts the tools accordingly.

In conclusion, this book is definitely a must-read. It opens our eyes to developmental biology and offers an intriguing alternative to the gene-centric view. However, I think it presents yet another extreme in imposing laws on biology. I believe the whole process is far more dynamic and dependent on the interaction of multiple factors.

[Brenda Greene · Rating 5 out of 5]

An excellent overview of the way cells form embryos, including the human embryo, starting with the genome. It is quite a technical read, and assumes some understanding of the cell and how it works.

While the day to day genome mainly transcribes proteins from activated (or deactivated) genes, during multicellular embryo development, HOX genes lay down the structural blueprint for cell differentiation. Cells then communicate with each other, sense their own position in time and space (up, down, inside, outside) and interact with the genome through complex chemical feedback loops.

These interactions enabled life to evolve from single celled plants and animals to organisms due to a process called emergence over long periods of geological time. There are trade offs during the evolution of form, driven by energetics and the constraints of the environment.

In the womb or in eggs, the timing and structure of embryo development differs between species. Humans, for example, look nearly identical to fish embryos at early stages of cell division - further evidence of common ancestry.

There were gaps in the narrative, both stated and unstated and some specifics were generalised. As life is extraordinarily complex, this is not surprising. Alfonso has carefully pitched his narrative so that the reader mostly sees the woods and sometimes the general form of the trees.

Of course, there is discussion about in vitro fertilisation, cancer and aging as well as the ethics and morality of this type of research and intervention. The penultimate chapter summarises his own research.

There are complex diagrams throughout and many references to the science and ideas around cell biology. It is written in a clear and engaging style, focussed on the idea of the cell and its genome in a complex and ever changing interplay with its external and internal environment.

Brilliant.

[Taveri · Rating 4 out of 5]

the author demolishes Dawkins' notion of the Selfish Gene in showing that cells make decisions on growth without using genetic code, although doesn't explain what the cues are, just that it derives from within the cell, for instance how cells decide which become specialized or that our legs or arms each become the same length independently.  Mice have 97% the same DNA as humans (chimpanzees 98%) making their genes suitable for testing human diseases. [Although 99% of DNA is non-coding so saying they are alike is like saying all homes are 99% alike when including the yard contents and atmosphere above the yard and house.]

Although i had to read many sections twice it is not a difficult read and addresses issues of ethics on using embryos in research.

[Ram Vasudeva · Rating 4 out of 5]

This is a book for the ages. Without much spoilers here, it provides a perspective of how cells remain central to the how traits and organisms are put together (cell-centric view) taking on the conventional idea that genes drive everything (gene-centric view). The author is a researcher, scientist who presents evidence from his own work and those of collaborators to drive home the point that cells remain critical to the understanding of all life on earth. In doing so, genes are not sidelined, it remains a critical tool that the cells use, is his premise and some of the evidence provided in the text are compelling. A good read, is written for the specialist reader and the text did not come across as a book for a non-specialist audience. Recommended

[Stven · Rating 1 out of 5]

I'm going to read the reviews, because somebody out there was able to follow this guy's logic, and for me he's just not connecting. Page 24 he introduces the concept of RNA and says it is a messenger for DNA. He talks about the shape of RNA compared to the shape of DNA. He says RNA can leave the cell, which DNA can't, but that it doesn't live as long as DNA. He talks about different kinds of proteins. He says "expressed" is "shorthand for transcribed." But he doesn't ever get down to brass tacks and tell me what the RNA does. Or maybe he does and I just miss it because he's so chatty that I can't find where he gets to the point.

[Andrea · Rating 5 out of 5]

The book begins with what felt like a fairly lengthy review of basic cell science but then moved seamlessly into newer material. The premise is that we have given rather too much emphasis to the role of DNA in “telling” the cell and from there the organism how it must develop and function. The new science emphasizes the interaction of individual cells with each other and the environment. As a non expert it is hard for me to explain how interesting this was and how much new materialI learned quite effortlessly.

[Mick de Waart · Rating 4 out of 5]

As a layman, I found myself both captivated and challenged by this book. It introduced me to insights and ideas I had never encountered before, which was enriching and enlightening. While I occasionally felt out of my depth, I still gained some profound and interesting knowledge. Though I likely missed some of its deeper nuances, the experience was undoubtedly worthwhile. Surely worth my time but probably even more so for those with a background in the field.

[Arvind Balasundaram · Rating 5 out of 5]

A brilliant piece of science writing, where the author makes a compelling argument on why we need to shift our focus from an over-reliance on genes to a better understanding of cells and their biology. The book is exhaustive in its scope, and though written for the lay-reader, it does not compromise details around important concepts like emergence, gastrulation, etc.

[Douglas Perry, PhD · Rating 5 out of 5]

This book is written by a geneticist who eventually saw the light and became a cell biologist. What was the reason for his conversion? To paraphrase his answer, "Consider what goes in to making a house, then consider an organism. Genes give the blueprint, proteins are the bricks, but who is the builder? The cell."

[Paul · Rating 4 out of 5]

Obviously not a textbook so limited in how detailed the explanations can be but I did emerge seeing genetics from a different viewpoint. Just as another book made me realise our mind is not limited to our brain so this book made me realise inheritance is not limited to DNA and the cell is not just a carrier of the code. Once the chain is broken trying to restart from DNA only is not equivalent.

[Duncan Clark · Rating 5 out of 5]

Who knew cellular biology could be so intriguing? This was a surprisingly readable book. It was informative, eye-opening and always interesting. The author obviously has a passion for the subject and that passion comes through clearly.
Even if you have no deep or professional interest in the subject, I'd be surprised if anyone who read this book didn't find it both engaging and educational.

[Kevin Marshall · Rating 5 out of 5]

Don't believe in selfish genes

Cells in larger organisms cooperate unless they are cancerous. Genes are the toolbox, cells are the craftspeople.

Studying cells is harder than counting genes, but genetics alone cannot explain much. Really.

[Vella · Rating 4 out of 5]

Fascinating story of cell biology, all in powerful service of reminding readers how the myth of gene-centered development is actually far more complicated. Great read!

[Jorge · Rating 5 out of 5]

Se avecina una revolución en la biología.

[Dstrichz · Rating 4 out of 5]

3.5 rounded up

[Bako S · Rating 5 out of 5]

So good, one of those perspective-shifting books

[Finlee Rice · Rating 4 out of 5]

Fantastic. Really enlightening. Could have been so much shorter, like a 30 page scientific paper instead of a 300 page book. Wonderful info nonetheless.

[Rosa · Rating 5 out of 5]

Biology is dominated by reductionist ideas- as Dr. Arias puts it, "The gene is well within our scientific comfort zone. We can describe its structure and rules of action in precise molecular terms."

However, it is becoming increasingly clear that the genome does not hold all the secrets to life. Dr. Arias describes the genome, not as a blueprint for organisms, but as tools that cells use to build organisms.

Dr. Arias does a great job in describing the recent scientific advancements to study cells, some from his own lab, such as embryoids and gastruloids.

"The cell is the unit of life and emergence is its secret. At a higher level of organization as cities emerge from interactions between humans and cells from interactions between molecules, organisms emerge from interactions between cells."

[Lea · Rating 5 out of 5]

Las arquitectas de la vida, es el nombre indicado para definir las células, el autor lo deja claro al centrar su narración con este enfoque celulocentrico. Las protagonistas son bien conocidas por todos, pero creo que no imaginamos cuan esencial es su trabajo de orquestar la construcción y mantenimiento de las diversas formas y expresiones de vida que existen. Además, de enfatizar en el papel de la célula como un arquitecto el autor alude a los genes como herramientas, sin restar importancia, nos cuenta como las células pueden valerse del uso de su caja de herramientas impresas en sus núcleos. Con toda la información que proporciona la lectura nos va integrando en este movimiento "Vitalismo Celular".
Quiero terminar comentando lo que más me marco de esta entretenida lectura, fue el poder analizar mejor la multicelularidad, como esta permitió a las células cual Davinci crear. Las células pueden utilizar sus interacciones para controlar la actividad del genoma, así construir y funcionar correctamente y pensar que con las mismas herramientas (genes) las células pueden crear multitud de funciones (diferentes órganos, sistemas, tejidos...) y seres (plantas, animales, hongos...), lo verdaderamente asombroso sería que algún día la ciencia pudiera desvelar el secreto de cómo se crea un ser humano, con todo lo que ello implica, programas genéticos, lenguaje celular, interacción (espacio, tiempo y comunicación), uso y despliegue de genes, factores de transcripción, gradientes moleculares... para poder replicarlo, pero creo que ese es otro cuento en donde tratamos de igualar a la naturaleza, dudo que se logre al 100%.

[Philemon - · Rating 5 out of 5]

It's amazing how much science acts as if DNA and genetics totally determine who we biologically are. That is a misconception that this book seeks to correct.

As Arias argues, DNA can do nothing outside a cell. And not any cell, but the zygote's inherited germ cell and its mitotic descendants. Does science have a handle on everything the cell (outside the genome) contributes to instantiate and maintain life? Absolutely not. Cell biochemistry is unimaginably complex. Think of long, intricate rows of dominoes that go in and out the genome and interact with other cell components. As Arias shows, there's no appreciable rhyme, reason, or algorithm for what goes on in the cell. It's the product of everything that went before in history that happened to work, going back billions of years to the first protocells (experimental one-celled life forms).

It's mind-blowing to realize that all life on Earth is related through germ lines stretching back to bacteria and beyond; we are almost certainly distant cousins of everything that's ever lived on this planet, all products of egg- and stem-cells handed down through countless generations, all stemming from one common ancestor cell that miraculously emerged from the primordial soup. Even without considering DNA, any mushroom you see on your path is your biological cousin through the germ line. And unlike DNA, which consists of the abstract data of sequenced nucleotides, the germ line is representable only in the physical world, one complete, living cell handed down from another.

Richard Dawkins's selfish-gene theory fails to give due honor to the germ cell and its four-billion year history. Science understandably recoils from the inscrutability of the cell as considered in toto. It's too big and complex to model. It just is.

Richard Feynman wrote on his Caltech chalkboard, "If I can't create something, I don't understand it." He could have been writing about the cell.

The germ cell, and cells in general, deserve more respect than they've been getting. This book eloquently helps to address that.

[Ricardo · Rating 4 out of 5]

Las células altruistas frente a los genes egoístas. Muy interesante y entretenido, casi como una novela.
A veces algo técnico, muy pocas, se puede seguir muy bien.
K