The strategy of the Institute to Improve World Health will be to achieve four specific aims:


The La Jolla Project seeks to utilize the data from the Human Genome Project (HGP) and protein databases to define, for the first time, the order of disappearance of proteins during early forms of protein deficiency that occurs in humans who suffer from chronic degenerative diseases that are associated with the Metabolic Syndrome, including obesity, type-2 diabetes, lipid disorders, cardiovascular disease, brain disease, autoimmune disease and cancer. Early forms of protein deficiency have been newly defined as “Selective Protein Deficiency Syndrome,” or “SPDS,” which is a metabolic condition characterized by the early disappearance of proteins according to their charge characteristics.

The data will be used to determine the imbalance in metabolic pathways that occurs during selective protein deficiency syndrome, which may lead to chronic degenerative diseases associated with the Metabolic Syndrome. This project will ultimately define the diet-related limitations in metabolic pathways that result in metabolic disease, chronic degenerative disease, accelerated aging and even premature death.



In 1975 Dr. Scheele invented 2D gel electrophoresis for the high resolution separation of proteins in higher animals including humans (1). This discovery allowed, for the first time, separation of all the proteins in the human body (est. 20,000). This technique allowed for the study of protein expression and adaptation in all organ systems on a protein-by-protein basis. In the 80s and 90s Dr. Scheele’s laboratory focused on the study of pancreatic digestive enzymes and defined all the major adaptation patterns in response to changes in carbohydrate, fat and protein in the diet of experimental animals (2).

These studies greatly extended the original studies of Pavlov demonstrating that selective feedback mechanisms are important in shifting from one digestive pattern to another as the composition of the diet changes and showed conclusively that adaptation of the body to changing environmental conditions (diet) is one of the fundamental laws of nature and at the heart of homeostasis. The research further demonstrated the hormonal- and signal-transduction mechanisms that are responsible for these adaptive changes (3).



However, under conditions of early protein deficiency Dr. Scheele showed that serious disruptions occur in the feedback mechanisms that regulate pancreatic adaptation to changing diets. Under conditions of selective protein deficiency, positive-charged proteins initially suffered (disappeared) more than negative-charged proteins. The synthesis of negative-charged proteins continued but the synthesis of positive-charged proteins was greatly diminished to levels that were more than 90% diminished from levels observed in health. These changes in protein expression appear to result in serious impairments in cellular function (2,3).

Dr. Scheele believes that selective impairments in protein expression in humans may result in serious disease states, including overweight disorders, high blood pressure, high cholesterol levels, type 2 diabetes, cardiovascular disease, brain disease, autoimmune diseases, cancer and other diseases characterized by numerous risk factors and symptoms associated with the Metabolic Syndrome (4).

The high resolution analysis of proteins spread on 2D gels, provided the first diagnostic test for changes in protein patterns due to early protein deficiency. The dramatic decreases observed in the expression of positive-charged proteins within 10-12 days of placing experimental animals on protein deficient diets, served as a wake-up call suggesting that protein health may be more difficult to maintain than previously thought.

From analyses of these studies, it became abundantly clear that the vulnerable shoulder of the food chain is represented by positive-charged amino acids. It also became abundantly clear that reversal of the early forms of protein deficiency could be most effectively combated by providing the essential and positive-charged amino acids that are crucial to the diet of higher animals and humans (4).

From Dr. Scheele’s extensive studies using 2D gel electrophoresis on groups of enzymes, we know that early forms of protein deficiency in laboratory subjects (e.g. rats on a protein deficient diet for 10-12 days) result in a dramatic loss of positive-charged proteins (up to 90-95%) without alterations in negative-charged proteins. The major impact of these findings is that early forms of protein deficiency may result in dramatic changes in enzyme-induced metabolic pathways that constitute a serious threat to human health (4).



This disruption in health appears to be due to the constitutive deficiency of essential amino acids in the food chain that lead to deficiencies in enzymes that drive metabolic pathways. Furthermore, the patterns of protein deficiency (loss of positive-charged proteins) observed in the exocrine pancreas can be expected to occur in other organs and physiological systems throughout the body, including those that regulate inflammation, blood pressure, cholesterol metabolism, glucose metabolism, resistance to infectious organisms, weight control and the like.



Given that early forms of protein deficiency (selective protein deficiency syndrome) may be observed throughout the body, we are now in a unique position to map the consequences of early protein deficiency in all organ systems in the human body.

Because most of the human genome has been sequenced on all 23 chromosomes, it will be relatively easy to use computer analytics (Systems Biology) to fractionate the human proteome according to protein charge (isoelectric point or pI) and display these fractions as lists according to those that will disappear in order (first, second, third…last) under conditions of protein deficiency. This will also allow biologists to define the order by which individual steps in metabolic pathways become impaired.

The major benefit to mankind in this study will be to organize the structural information achieved in the human genome into a map of function (in this case loss of expression resulting in metabolic disease) that may be used to understand the role of low-protein diets in major disease conditions, like those associated with the Metabolic Syndrome and Alzheimer’s Disease, that may define most of the health care crises in this country and around the world.

Using figures from the Center for Disease Control and Prevention (CDC), more than $2 trillion in health care spending goes to treat “diet-related chronic disease” each year. This includes “preventable” diseases such as obesity, diabetes, high blood pressure, cardiovascular disease, autoimmune disease, dementia syndromes and certain types of cancer.


The La Jolla Project, supported by the Institute to Improve World Health, represents the #1 opportunity to convert the structural information of the HGP into functional information that will have direct, meaningful impact on the health and disease of the people around the world.

The proposed project has the following distinct advantages:

  • It is a doable project in that there are no technological limitations to the rapid completion of Specific Aim #1 in 3 to 5 years.
  • The budget of the project is modest in absolute terms and miniscule in terms related to the direct impact on health care costs.
  • The project, which harnesses structural aspects of the human genome and functional aspects of human biology, will provide important information that defines the role of early protein deficiencies in preventable metabolic disease.
  • It will provide a wealth of functional information that may explain many of the causes of chronic diseases associated with the Metabolic Syndrome. It is estimated that these chronic degenerative diseases are responsible for up to 80% of aging health care costs.
  • It will provide important information that will stimulate efforts to construct a map of all metabolic pathways in the human body and pinpoint which of these pathways, including their individual steps, will be impaired by diets that are low in protein that lead to metabolic disease, loss of human productivity, accelerated aging and premature death.
  • It will revolutionize the dietary recommendations that regulatory bodies publish on healthy diets around the world.
  • The ultimate impact will be on substantially lowering the health care costs across America, so that these costs, which currently represent almost 18% of the GDP may possibly be lowered to 10% of GDP or even less.
  • In short, this is the project that will have the greatest impact on the health of people around the world.
  • This proposal is also “smart” in that it leverages the $3 billion that was spent to sequence the human genome and the mountain of genomic data that was generated in this monumental effort. Now this data can be converted into functional data that may be focused directly on the greatest health care needs of the American people: Metabolic Disease.


Accordingly, we believe that the La Jolla Project is the most important health-care project of our time.


  1. Scheele, G. (1975) Two dimensional gel analysis of soluble proteins – Characterization of guinea pig exocrine pancreatic proteins. J. Biol. Chem. 250: 5375-85.
  2. Schick, J., Verspohl, R., Kern, H. and Scheele, G. (1984) Two distinct genetic patterns of response in the exocrine pancreas to inverse changes in protein and carbohydrate in the diet, Am. J. Physiol. 248: G611-616.
  3. Scheele, G. (1993) Regulation of pancreatic gene expression in response to hormones and nutritional substrates, In The Pancreas, Biology, Pathobiology and Diseases (V.L. Go, J.D. Gardiner, H.A. Reber, E. Lebenthal, E.P. DiMagno, G.A. Scheele, eds.) Raven Press, New York, NY pp 103-120.
  4. Scheele, G. (2011) The Obesity Cure. 2011. Link:
  5. High Protein Supplement: U.S. Patent No. 7,982,066 B2 issued on July 19, 2011.

The scientific writing team will publish the findings of the La Jolla Project in appropriate scientific journals.

Specific Aim #1 will take 3 to 5 years


The second aim will be to develop specific assays that are capable of accurately measuring early forms of protein deficiency for individual protein markers in specific metabolic diseases. This effort will include two kinds of tests. Both will be contracted out to academic laboratories through research grants.

  • A generic test for deficiency of positive-charged proteins in patients who suffer from metabolic disease. This test should be simple to perform and should compare levels of positive-charged and negative-charged proteins in a given tissue or body fluid. It may be performed on blood samples or it may be performed on an easily accessible body fluid like saliva, where positive- and negative-charged proteins appear in abundance. Ratios of positive- and negative-charged proteins may be most easily detected with isoelectric focusing gel separation procedures.
  • Individual tests conducted on target proteins identified in Specific Aim #1 that associate with specific metabolic diseases. For each disease we anticipate that a minimum of two to three target proteins need to be identified and studied.

Specific Aim #2 will take between 5 and 8 years.


Specific Aim #3 will conduct Phase 2 and 3 placebo-controlled FDA clinical trials on several metabolic diseases that appear to associate with the loss of positive-charged proteins. The metabolic diseases of greatest interest at the present time are:

  • Obesity
  • Type2 Diabetes with hyperglycemia
  • Cardiovascular Disease with hypertension and lipid disorders
  • Brain Disease resulting in dementia or Alzheimer’s Disease
  • Autoimmune Disorders

These studies will examine the effect of Factor4 Weight Control® on the clinical parameters in these five areas of metabolic disease. Each of these clinical trials will be contracted out to clinical research organizations (CROs).

Factor4 Weight Control® has already been shown to be a promising treatment for obesity in an open-label clinical study conducted on 25 obese subjects. Ninety six percent of the subjects lost weight within the first 3 months. The pilot study was then extended for up to 12 months. The results showed an average weight loss of 8.4 pounds in 3 months, 16.2 pounds in 6 months, and 33.4 pounds in 12 months. These time points represent 4.5%, 8.2% and 16% of body weight. The FDA considers a 5% reduction in body weight significant for weight loss claims.

Specific Aim #3 will take up to 5 to 10 years.


Specific Aim #4 will publish articles in the academic and lay press as part of intensive educational, advocacy and legacy programs to show how diets and innovative dietary supplements or medical foods, specifically Power Amino Acids® (essential, positive-charged and satiety amino acids), may be used to stem the tide of four epidemics that are currently crippling the world. The four epidemics are:

  • Obesity and overweight disorders
  • Metabolic disease associated with the Metabolic Syndrome
  • Brain disease, including early dementia and Alzheimer’s disease
  • Dependency and addiction disorders

The methods to effect widespread social change related to nutritional health and wellness are discussed under “The Operating Plan” and underscore the importance of legacy efforts funded by the nonprofit corporation to Improve World Health.

Chief among these efforts will be a book franchise and a series of honorary lectures, academic prizes and media events to educate the populace on the importance of nutritional health in the following areas:

  • Healthy Lifestyles with increased satiety, improved diet, exercise, sleep, attitude, and less dependency on sugar, caffeine and alcohol.
  • Weight Control with lower body weight, improved body definition, and increased pep, energy, activity, stamina, endurance and performance.
  • Metabolic Health with lower levels of blood cholesterol, triglycerides, sugar and less metabolic disease, including overweight disorders, hypertension, type 2 diabetes, cardiovascular disease, cancer, osteoarthritis, and gallbladder, liver & kidney disease.
  • Aging Health with increased longevity and quality of life evidenced by reduced chronic degenerative disease and enhanced feelings of comfort, satisfaction, and well-being.

The educational program will show how nutritional substrates determine metabolic health. Chief among these concepts is the importance of (i) limiting refined sugar and processed carbohydrates in the diet and (ii) enhancing the intake of essential, positive-charged and satiety amino acids. These two important concepts are discussed in The Obesity Cure.

The educational program will further explain how dietary supplements like Factor4 Weight Control® can potentially lower health care costs at home and abroad.


The Role of Factor4 Weight Control® in Lowering Health Care Costs

The role of Factor4 Weight Control technology in lowering health-care costs around the world may be described as follows:

Factor4 Health products, including Factor4 Weight Control®, contain essential, positive-charged and satiety amino acids (Power Amino Acids®), which correct diet-related deficiencies in amino acids, proteins, metabolic pathways and body health. The key to Factor4 health is that the technology prevents the loss of positive-charged proteins due to protein-deficient diets. At the same time power amino acids serve to tame appetite by working directly on the appetite centers in the brain and stomach. The ultimate benefits of Factor4 Weight Control® in preventing/treating obesity and metabolic disease may be described as follows:

  • When appetite is tamed, eating disorders, including overweight disorders and obesity are tamed. At the same time that appetite is reduced, Factor4 provides the high-quality nutrients that are essential for nutritional health.
  • When eating disorders are tamed, it is now easy to achieve healthy lifestyles, weight control, metabolic health, revitalized youth and aging health as well.
  • When metabolic disease is tamed, America’s productivity may be dramatically increased and health-care costs may be significantly decreased.
  • When health-care costs decline from current levels of almost 18% of GDP to less than 10% of GDP, the unrestrained climb in National budget deficits will be tamed as well.

Specific Aim #4 will continue as an ongoing effort to educate the public on the importance of nutrition in improving metabolic health around the world. These efforts will be guided according to the research findings generated by the “Institute to Improve World Health.”