For the past 40 years, I have been exploring the mysteries of metabolism and how diet can control metabolic efficiency.   Why?  Metabolism controls every aspect of human existence.  It controls how we convert food into energy, turn inflammation on and off, our immune response, gene expression, and ultimately our rate of aging.

Exploring the mysteries of metabolism has been greatly aided by genetic engineering.  However, Metabolic Engineering® makes those discoveries applicable to practicing better medicine today and far into the future.

Before the Zone
My early scientific background had little to do with nutrition.   In 1976, I started one of the first biotechnology companies in the country to develop new injectable synthetic lipids for use in intravenous cancer drug delivery systems. In particular, those patented lipids made possible the only nanotechnology cancer drug (Doxil^®) ever approved.  To date, the cumulative sales of this cancer drug have exceeded more than 5 billion dollars, and it continues to sell more than  500 million dollars annually.   In addition, the identical lipids I patented in the early 1980s are essential to produce the current mRNA Covid-19 vaccines.

The beginning of the Metabolic Engineering®
My scientific direction changed entirely in 1982.  That was the year the Nobel Prize in Medicine was awarded for understanding how a group of hormones known as eicosanoids were the molecular drivers of inflammation.  Although most eicosanoids are highly pro-inflammatory,  a few are anti-inflammatory.  I hypothesized that if I could generate a better balance of these eicosanoids by dietary manipulation, it could impact every disease related to chronic inflammation.  Furthermore, if I were successful, the potential stakes would be much bigger than continuing to develop intravenous cancer drug delivery systems.   So, I changed the focus of my research to seek a possible solution to inflammation using nutrition instead of drugs. 

My initial strategy was to find a botanical source of the necessary fatty acid building block for these anti-inflammatory eicosanoids. Then, I had to learn how to grow industrial quantities of it, process the oil, and then manipulate its metabolic pathway in the body to make more “good” anti-inflammatory eicosanoids and fewer “bad” pro-inflammatory eicosanoids. This would take a lot of work, but by 1988, I was ready to start testing my theory.  

Discovery of the Zone diet
Since my goal was to reduce inflammation, I started working with elite professional athletes who live in a world of inflammation by choice because of the intensity of their training.  I started first with NFL football players and professional triathletes. The results were extraordinary, so I knew I was on the right track. Looking for additional athletes to study, I then started working with the Stanford University swim teams.  Several of their swimmers were training in Japan in the summer of 1989, so I ensured they and their coaches were well supplied with the same products I used with the professional athletes.  The reports from Japan were just as enthusiastic as those I had received from professional athletes.

Unfortunately, within a few weeks after the swimmers returned to Stanford, I received phone calls from both coaches stating that something was happening to their swimmers. Their performance is going downhill as they are constantly physically and mentally exhausted. Oops. I knew I had better find the answer quickly, or it was back to intravenous cancer drug delivery systems.

I discovered the answer in the bowels of the MIT library.  There, I found an obscure article showing that excess insulin in the blood could disrupt the careful balance of good and bad eicosanoids I was trying to achieve using only fatty acids.  I realized that once the Stanford swimmers returned from Japan, they started eating standard dorm food rich in carbohydrates that would increase insulin and disrupt the careful balance of the eicosanoids I had developed.  In simple terms, they were now producing more of the bad eicosanoids, thus causing physical and mental fatigue.  I then realized that the years I had spent developing the elegant dietary fatty acid technology wasn’t going anywhere unless I could control insulin levels with the diet.

However, which diet? A little more research provided the answer. It had to be a calorie-restricted diet with adequate protein and balanced with enough carbohydrates to keep insulin in a zone—not too high but not too low.  I felt like Doc Brown discovering the flux capacitor in the movie Back to the Future.  In this case, I had found the Zone diet. 

However, I still had to work out some basic details.  Once that was done, I went back to Stanford to try again.  The coaches used themselves as guinea pigs and were convinced enough to give me a second chance with their swimmers as the 1992 Olympics were coming up in Barcelona.

Although the coaches were wholly convinced, only a few of their swimmers were willing to change their diets. Those who did so won seven gold medals in the Olympics—not bad for one country but extraordinary for one university.

Soon afterward, I filed a patent for the Zone diet as a drug to treat insulin resistance, which was issued eight years later.  This marked the start of Metabolic Engineering® .

The Public Awareness of Metabolic Engineering®
Outside of a few professional athletes and the Stanford swim teams, virtually no one knew of my concepts. That changed with the 1995 publication of my first book, The Zone.  In that book, I described how a calorie-restricted diet with the correct balance of protein, carbohydrates, and fat could generate the hormonal balance needed to achieve a better balance of good and bad eicosanoids.  If successful, the result would be reduced inflammation in every organ in the body.  The Zone diet was like a combination lock to get that appropriate eicosanoid balance to keep inflammation in a zone, not too high, but not too low.  To the surprise of everyone (including the publisher), this highly technical book became a #1 New York Times bestseller and sold over two million copies.

I continued my research and my writing. In 1999, I wrote The Anti-Aging Zone, which demonstrated that combining the Zone diet with even higher levels of omega-3 fatty acid intake could slow aging.  The OmegaRx Zone, published in 2001, described how increased intakes of higher purity omega-3 fatty acids could generate a recently discovered class of hormones known as resolvins that could reverse inflammation. This book marked the beginning of the omega-3 fatty acid revolution.

I discussed the growing knowledge of the role of inflammation in chronic disease in my 2005 book, The Anti-Inflammation Zone.  In 2008, in my book Toxic Fat, I discussed the role of insulin resistance in many chronic disease conditions and how the combination of the Zone diet and high-dose omega-3 fatty acids could reverse it.  

That book was followed by The Mediterranean Zone in 2014, in which I explored the role of polyphenols in activating AMPK, the master regulator of metabolism.  This understanding of the role of polyphenols was the last step I needed to complete my evolving concept of  Metabolic Engineering® .

The Resolution Zone was published in 2019.  In this book, I provided a more detailed understanding of the role of Metabolic Engineering® to activate AMPK to influence inflammation, immune function, gene transcription, and the repair of damaged tissue.

The Future of Metabolic Engineering®
The concept of the Zone continues to evolve as genetic engineering provides new tools to explore the mysteries of metabolism.  My next task is to explain how Metabolic Engineering® can reprogram your metabolism to eliminate senescent cells.  Senescent cells are transformed cells that ultimately cause the development of chronic disease and accelerate aging.  Thus, their removal using Metabolic Engineering® can usher in a new era of medicine. The details will be explored in my next book, The Wellness Zone.  

But you don’t have to wait for  The Wellness Zone to be published to start reprograming your metabolism in each of your 30 trillion cells; keep visiting DrSears.com for the newest updates in Metabolic Engineering® .

Reaching the Zone will be the key to 21st-century medicine. However, to reach and stay in the Zone, you need to follow Metabolic Engineering® as if it were a drug to maintain wellness, better manage chronic disease, and slow aging.

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