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Book review: Transformer: THE DEEP CHEMISTRY OF LIFE AND DEATH by Nick Lane

Transformer is a fascinating book by Nick Lane explaining the chemistry involved in keeping cells alive. It offers some fascinating insights into the ways in which cells work well and also ways in which they can go wrong.

When researching health and wellness, I read a lot of well-intentioned information that lacks insight from real experts in their field. Nick Lane is one such expert who really knows his field of biochemistry.

He is a Professor of Evolutionary Biochemistry at University College London, and among his many accolades, his previous book, Life Ascending, won the 2010 Royal Society Prize.

What is it about?

The question on the back cover reads, “What is it that animates cells and sets them apart from non-living matter?”. This is a very broad question which takes us on a grand tour of biochemistry.

Transformer charts the rise of the living world and the deep logic of life as a chemical phenomenon. Focusing particularly on the metabolic processes that give life by transforming lifeless chemical ingredients into living, energetic organisms.

The quality of Transformer makes it a fantastic guide to the biochemistry of life and a platform on which to help understand health and disease. I enjoyed Transformer because it is written in a very accessible manner by someone very comfortable with the complexity of the topic.

A short review

This will be a relatively short review giving you a flavour of the book and sharing some key takeaways. I am new to writing book reviews so I don’t know what I can quote within copyright laws so please bear with me.

While reading the book, I found some excellent insights that I really wanted to share, so I duly noted them down. Then, when coming to write this review, I realised I may be sharing too much. So I have done my best to share without revealing too much. I have included page numbers to help you find the information for yourself.

4 things I learned

I learnt so much from this book that I cannot put it into words. I have chosen 4 key insights that were notable enough for me to write down.

The question I asked is how can the understanding of life’s metabolic pathways and mechanisms provide optimum performance and/or help us prevent disease?

This is a common question I ask during research, so I have a habit of noting anything that may provide an answer. Just one insight is good from a book, and in Transformer, I found 4 valuable sections to add to my research, which highlights how useful I found the book.

So, what did I learn, and how does it all fit in with the wider picture? Let’s find out.

Cancer cells act like fermenting yeast cells 

On page 197, Nick Lane has some fascinating insights into cancer cells and their propensity to act like yeast cells. He references the work of Otto von Warburg, who noticed that cancer cells have a tendency to behave like fermenting yeast cells. They tend to metabolise glucose and convert this to lactate, preferring the less efficient oxygen-less energy pathway.  

“the tendency of cancer cells to behave like yeast, fermenting glucose rather than respiring, even when oxygen is present.”

Nick Lane

This insight is something I have heard from many different places. The way Nick presents this finding as part of a very long set of research going back decades if not centuries. I love seeing how everything connects to everything else.

The way biology works is very much like the proverbial butterfly flapping its wings and creating a storm elsewhere in the world. The same concept is true in biology, where one small change in a cell membrane or in this example, cancer cells using a fermentation-based energy cycle because they do not have access to the oxygen they need.

many diseases are encouraged by Krebs cycle flux

For decades I have been reading about problems in energy flows in biology leading to disease. Nick summarised recent research on this and clarified how important energy cycles are in maintaining healthy cells, healthy biomes and healthy people.

The detail behind this is on Page 214 where I discovered that “succinate gives delicately balanced real-time feedback on the status of the respiratory system as a whole.”

the number of conditions that come down to impaired Krebs cycle flux is astounding.

Nick lane 

Nick goes on to say “Even slight impairments in Krebs-cycle flux give a read-out of succinate levels, which are counteracted through changes in gene activity. The list of medical conditions where this mechanism turns out to be relevant is sobering.”

Every time I learn about health and disease, I am reminded that when the essential energy pathways of life are disrupted, disease will occur.

Now that we have overcome the common pathogens of the pre-modern age, such as smallpox and cholera, it is, therefore, no surprise that the biggest diseases of the modern age come from inside our own cells due to a breakdown in the complex chemical reactions that make up our metabolism.

These chemical reactions are not simple pathogens we can destroy. They are fundamental processes in every cell. Therefore, there is no simple chemical solution as there has been for other diseases.

Nick ends this analysis with a powerful quote as follows

just think for a moment about the common disorders where oxygen delivery to tissues becomes compromised. Stroke. Heart attacks. Dementia. Arthritis. Organ transplants. Succinate accumulation is central to them all.’

Nick Lane

Energy use and its related chemistry are still critical areas of research in the search for ways to control and reduce cancer and many other diseases.

What happens if you eat too much and don’t exercise? 

The next insight came on page 224 where Nick begins to analyse what may happen if you eat too much and don’t exercise. 

The genes switched on drive cell growth and proliferation – another signal that says grow! The context reinforces this epigenetic switch. 

Nick Lane

The depth that Nick goes into in this analysis is impressive. He talks about a group of enzymes known as the Sirtuins, their effect on the cell growth signal and their relationship with the availability of NADH.

The lesson here matches what I have seen in all cancer research. The growth signal is turned on due to Krebs cycle misregulation, which encourages cancer and other diseases.

The problem in cancer is that reverse Krebs-cycle flux triggers the same signal because cancer cells have lots of NADH from aerobic glycolysis and lots of acetyl CoA from citrate. So the growth switch remains jammed on.

Nick Lane

Cancer can lead to muscle breakdown

The final insight is found on page 227 where I discovered a disease and cell process that was new to me. Normally, these kinds of books are a more up-to-date version of the science I have already read elsewhere.

Only recently, though, have I been learning about Cachexia, also known as wasting syndrome. It is a condition seen in Cancer that scientists are struggling to understand.

Cancer can lead to muscle breakdown because glutamine has two amine groups and ends up as toxic ammonia not safe urea

NIck Lane

We go on to learn that the urea cycle is the only pathway here that is of no use to cancer cells. However, that does not mean the body should use the urea cycle instead of glycolysis. The problem with the urea cycle is the production of ammonia

the release of ammonia from glutamine in cancer cells actually promotes the breakdown of proteins in distant muscles. 

NIck Lane

Nick goes on to explain

“This works because glutamine is unusual in having two amino groups. To mop up the ammonia, muscle proteins break down and release their amino acids. “

After a more detailed explanation Nick summaries the problem.

“Overall, raised levels of ammonia circulating in the blood are mopped up by the synthesis of new glutamine, through muscle breakdown, hiding behind the medical term caches. This is one of the deepest horrors of cancer, as the disease Is known as the start of cancer, cachexia”

My thoughts

The challenge in health is primarily that all the excellent disciplines involved rarely talk to each other. This has been my frustration ever since I discovered my love of biology. I continually notice that if all the disciplines talked together and shared information to learn from each other, then all the common diseases of modern life would be solved by now.

This is not fantasy. The causes and fixes of many diseases, particularly Diabetes, insulin resistance and obesity are very well understood. The problem is very much that

  1. the answers are distributed across different fields that do not talk to each other
  2. we are not good at behaviour change, getting people to do the things they need to do

Lack of sharing

Sharing knowledge and behaviour change is where health promotion falls down. We as societies have never been good at getting people to do things that are good for them.

Transformer is a perfect example of this statement. You can hear throughout the book that Nick has a deep and fundamental understanding of the causes and potential fixes of the major disease of our time.

Yet, what I find most fascinating about this is that he doesn’t understand quite how to use his knowledge to reduce his risk factors for the diseases he talks about. 

He knows why poor metabolism leads to disease. But he doesn’t know how to improve his metabolism. So, he has the knowledge but not the answers. Therefore, he cannot overcome his biology and is trapped inside it. 

Studying exercise science taught me how to improve metabolism, which is key to exercise performance. We went into similar levels of detail to understand how exercise restores balance to the body through homeostasis in the process of recovering from each challenge.

Sadly, I was the only student interpreting the science this way because I was the only student focused on public health in the physiology lectures. Everyone else was just focused on exercise performance, not health. So the lessons were missed.

It is the same story across all disciplines and industries, which is why progress is so slow. Exercise science isn’t talking to biochemistry or physics, and biology all keep to their own niches, too. The result is that there is no joined-up thinking. Only experts in their field explaining in ever more detail the limited understanding of their field and and missing the power of joined up knoweldge.

An excellent summary

This analysis is an incredible, up-to-date, and detailed summary of what has been known for decades. That lack of exercise, too much food and bad metabolism increase the risk of disease. But the book doesn’t explain how to resolve this problem in a modern world with an enjoyable lifestyle 

As a result, this analysis follows the general medicinal and research-based approach and ignores your needs and desires. So it gives you the biochemical explanation of the problem but no tools to solve it which is a real shame.

As a summary of how chemistry powers life, it is fantastic. Getting such a clear, consistent explanation of the problem is very helpful.

It is the research of world-class experts such as Nick that I use to educate others about their inner strengths and the power that lies within them.

My approach starts with happiness and your needs and desires to find ways to address this deep science.  

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