Early proto-eukaryotes of planet Earth were sustained by a largely oxygen-free atmosphere. Their survival was threatened as blue algae acquired photosynthetic activity and began to release large quantities of oxygen into the atmosphere. Lynn Margulis proposed in 1960s that mitochondria and certain other cellular organelles evolved from certain oxygen-utilizing prokaryotes, which migrated into the bodies of proto-eukaryotes. In this symbiotic relationship, the proto-eukaryotes provided prokaryotes a safe environment. The prokaryotes, in turn, saved protokaryotes from oxygen toxicity. This theory was validated by subsequent studies.

In the mid-sixties, Bjorksten and Harmon put forth their theories of protein cross-linking and free radical injury, respectively, as the basic mechanisms of the aging process. Evidently, protein cross-linking and free radical injury result from oxidative molecular injury. Spontaneity of oxidation in human tissues, and oxidative molecular injury, which follows as its natural consequence, may be regarded as the true nature of the aging process in man. Tissue capacity for antioxidant generation, determined by certain genetic and acquired factors, provides the essential molecular counterbalance to spontaneous oxidation. The evidence for this viewpoint is drawn from a large body of clinical and experiemental data.

What are the clinical implications of this viewpoint of aging in man? Oxygen is a molecular Dr. Jeckyll and Mr. Hyde. Life-sustaining aspects of oxygen are well understood in clinical medicine. Life-terminating capability of oxygen is generally ignored. Man today faces extinction by accelerated oxidative molecular damage much like protoeukaryotes did during an earlier era. This accelerated oxidative stress is caused by the impact upon his genetic make-up of an enormous overload of aging-oxidant molecules on his internal and external environmnet. What are the best strategies for health promotion and reversal of chronic immunologic and degenerative disorders? These are the strategies that address all aspects of accelerated oxidative molecular stresses with clinical management protocols of nutritional medicine, environmental medicine, medicine of self-regulation and medicine of fitness. Integrated applications of these management protocols is the clinical practice of molecular medicine.

Inactivity of the liver mixed-function oxidase enzyme system and conjugase enzyme system results in reduced capacity to detoxify endo- and exotoxins. Cytochrome P450-MFO is upregulated by exposure to xenobiotics, endogenous sterols, endotoxins, alcohol, or phenol compounds. This upregulation depends upon hepatic activation of ribosomal function by specific nutrients. Research with patients suffering from chronic fatigue-immune deficiency syndrome (CFIDS) reveals suppressed MFO and conjugase activity. Baseline MFO activity and glycine conjugation is determined by measuring salivary caffeine clearance and urinary hippuric acid excretion. A nutritional approach that supports upregulation and ribosomal synthesis of cytochrome P450 and conjugase enzymes, and provides precursors for activation of mercapturic, hippurate, and glucuronic acid pathways supports increased clearance of endo- and exotoxins in these patients.

Thirty-five CFIDS patients who demonstrated reduced salivary caffeine clearance and urinary hippuric acid output after oral benzoate challenge participated in an intervention trial to evaluate a nutritional approach for upregulating hepatic detoxification. Symptoms in the treatment group significantly declined after intervention, while those of the control group did not. The study demonstrates that nutritional upregulation of hepatic detoxication can occur in chemically distressed patients and a unique nutritional intervention program can provide significant improvement in symptoms and function of affected patients.

The purpose of the study to be presented was to begin development of a psychological profile for environmental illness patients. Test scores were drawn from a pool of 89 patients diagnosed with environmental illness by physicians who specialize in Clinical Ecology. The patients were administered a Mental Status Exam, portions of the Wechsler Adult Intelligence Scale-Revised, and the Profile of Mood States by psychologists or graduate students trained in test administration.

The results of the study indicate a primary pattern in environmental illness patients consisting of fatigue and reduced mental functioning. There was also a lack of psychotic or personality disorder indicators. The psychological tests objectively verified the subjectively reported psychological symptoms of environmental illness patients.

Immunological and endocrinological correlates of various anger conditions were investigated. Serum cortisol, peroxidase activity of white blood cells, percentages of total T-lymphocytes and their subtypes, suppressor-T cells and helper T-cells, as well as the ratio of helper-T to suppressor-T cells were measured. Significant differences were found between males and females in two anger scales, Anger Control and Anger Expression. Results strongly indicate that men and women differ in biopsychological responses to anger. In the female group, significant correlations were found between various anger scales and total-T cells, suppresor-T cells, and helper-T cells. In the male group, significant correlations were found between various anger scales and myeloperoxidase activity of white blood cells. Serum cortisol levels were not significantly elevated in relation to anger for males or females. The influence of ecological conditions in terms of psychoimmunological disruption will be discussed.

Clinical observations indicate memory deficits among EI patients. The kind of deficits and their extent have not been sufficiently delineated. The purpose of this study is to verify objectively the memory dysfunction among these patients. Results validate the existence of such deficits and find them common in EI patients. Long-term memory remains generally intact. While there was some inconsistency in measurements between certain of the standardized tests (Wechsler Memory Scale-R, WAIS-R, and Harrell-Butler CNS), certain areas of memory dysfunction were found among EI patients and could be reliably measured. Primarily there were problems in such areas of memory as short-term, logical sequencing involving memory and performance, vision, and attention and concentration.

Aging is associated with a functional decline of sensory systems, memory, problem-solving capacity, with increased latency to visual and somatic stimuli, with a loss of neurons, a decrease in neuronal plasticity and in some neurotransmitter levels, receptor number and affinity and with alterations of membrane fluidity and deposition of abnormal proteins in the neurons and the glial cells.

Many of these degenerative changes appear to be linked to endogenous and exogenous stressors like oxygen free radicals, xenobiotics, or environmental toxic agents. For example, a high level of noise contributes to hearing loss and an acute stress episode to loss of memory.

I will describe how nutritional tools can stimulate protective mechanisms against neurological and endocrinological degenerative processes.

It is well known that the secretion of the testicles arises at the top around twent-five to thirty years and decreases progressively after this age. The secretion of male hormones falls sometimes dramatically in a few months at any age. After forty, every man will be concerned, some time or other, by the male climateric. Below a critical amount of daily hormonal production, all sexual functions are declining.

The libido becomes lukewarm and the frequency of sexual intercourse decreases. Lack of testosterone induces impotency, slerosis of the corpus cavernosum, and disturbances of ejaculation and micturition. Those conditions are the sexual expressions of the male climateric.

The diagnosis is easily made by hormonal blood tests. In the majority of the cases, hormonal treatment with male hormones is sufficient to recover all sexual functions. The treatment must be continued forever.

Environmental sensitivity can be due to two mechanisms (a) classical allergy, which is immunologically mediated, usually through IgE, and (b) chemical sensitivity, which is nonimmunologically mediated as in lactase deficiency causing intolerance to milk. The second group is also known as Clinical Ecology or Environmental Medicine. Although usually thought of as distinct, the two systems do interact.

The classical allergic disease, Hay Fever, is usually thought of as being due to exposure to pollen in a subject with an inherited allergic tendency. Hay Fever is, however, more common in towns than in the country and first appeared in the 19th century coincident with the start of the Industrial Revolution. This suggests that toxic damage to the nasal mucosa is necessary to initiate the allergic process. Thus, chemical sensitivity plays a major role in this classical allergic disease. Similarly, asthma is becoming more common in industrialized societies, and this is probably due to the effects of industrial pollution on the bronchial mucosa. IgE tends to be slightly higher in smokers, and this could be due to damage to the mucosal surfaces allowing more ready access to antigens. Glomerulonephritis is more common in male industrial workers, and accumulating epidemiological data suggests that this is due to heavy exposure to solvents, which damage the kidney and predispose individuals to a secondary immunolgical reaction.

Taken together, these examples suggest that many classical allergic or immunological diseases are dependent on chemically induced surface mucosal damage, which facilitates the entry of antigen and then causes an immunological reaction in genetically predisposed individuals. These observations suggest a mechanism for the increase in allergic disease in modern industrialized societies.

Waning immunity has long been recognized as a concomitant of normative aging. The main features include impairment of cell-mediated immunity (skin anergy, delayed graft rejection, and impaired in vitro lymphocyte transformation); impaired humoral immunity (reduced antibody response to those antigens requiring T helper cell support); a plyclonal increase in immunoglobulins and increased autoantibody production (secondary to impaired suppressor cell functions). Although impaired immunity is aggravated by nutritional deficiency and may also occur secondary to a variety of disease states that are increasingly common in old age, much of the deterioration is thought to be a primary aging effect. It has been postulated that the primary change is thymic involution. An alternative hypothesis is that the immune deficiency of aging is a secondary aging effect and occurs as a result of adverse environmental influences. It is postulated that a variety of age-related changes result in bacterial colonization and production of various mediators such as endotoxin. Endotoxin functions as a polyclonal activator inducing the various immunological change as described. Finding spontaneous lymphocyte transformation and circulating endotoxin in otherwise healthy elderly individuals supports this hypothesis. Endotoxin, postulated to be produced from abnormal bacterial colonization, is probably only one such polyclonal activator. It is well recognized that noxious environmental incitants can also result in a variety of nutritional deficiencies. It is suggested that the immune changes of aging and the devleopment of frailty be looked at more closely from an environmental perspective.

The phagocytic killing cascades of 70 environmentally sensitive patients with recurrent infections were investigated. These patients presented multiple manifestations to chemicals, food, inhalants, and recurrent infections. Of these, 88% were found with dysfunctions. Treatment, especially with transfer factor and autogenous vaccines, showed significant improvement in total T cells and phagocytic killing.

In autopsies of elderly humans, pituitaries have often been found showing diffuse fibrosis. Studies point also to decreased responsiveness of target glands and organs to pituitary hormones. All by all, with age, a certain degree of hypopituitarism develops. Attention should be paid to this clinical diagnosis. Treatment by means of adequate replacement therapy might help to put a brake on the overall aging decline. Although success will be limited by the aging accelerating effects of environmental or other aggressors as chemical toxics, infectious agents, chronic stress, and so on.

The author insists on the importance of precocious treatment of the perimenopause and related hypoovarian states, years before the actual menopause occurs, as precocious gonadal aging and it corresponding troublesome symptoms start in the perimenopause. In this lecture successful treatment of perimenopausal states with natural hormonal replacement therapy is exposed. A quick overview is given on the various side effects of synthetic non-natural hormones, which can greatly be avoided with the proper use of natural hormones. Three types of treatment are discussed:

Treatment of uncomplicated menopause generally consists, following the author, of the combination of three hormones: estradiol, progesterone (even when a hysterectomy has been accomplished), and an androgen. Adjusting these treatments is more complicated and time-consuming than giving combined estroprogestative pills, but results are not only physiologically but also psychologically more satisfying. Fundamental is to obtain a correct balance between estradiol and progesterone. Diagnosing these different perimenopausal states needs investigation by blood samples taken on specific days of the cycle, but emphasis is put on the symptoms of each hormonal deficiency., which enables the physician to make the best diagnosis and obtain the most adequate hormonal balance in the treatment. Treatment of the perimenopause may well prevent unnecessarily precocious aging, with a corresponding improvement in quality of life, and, possibly, an extension of life span. This lecture is documented with multiple experimental and clinical data.

Cases of chemically hypersensitive individuals resulting from a specific chemical exposure will be presented. Testing procedures, including blood analysis, cognitive function, neurological function, and chemical booth challenges will be discussed. These results will be correlated with functional brai imaging (SPECT scanning).

Restricting the food intake of rats to 60% of the intake of ad libitum fed animals retards the aging processes as well as many age-related phenomena. That the aging processes are retarded is based on the following evidence: life expectancy is increased; maximum life span is increased; the mortality rate doubling time is increased; a spectrum of physiological processes is maintained in a youthful state and age-associated diseases ranging from nephropathy and cardiomyopathy to a spectrum of neoplastic diseases are either eliminated or delayed to more advanced ages. This anti-aging action is primarily, if not solely, due to restriction of energy intake rather than a reduced intake of a particular nutrient or toxic dietary contaminant. However, it is not the result of a reduction in metabolic rate. Rather, it appears to be due to the way these altered characteristics use fuel. For example, a high rate of glucose used as fuel occurs in dietary restricted rats at lower plasma glucose and insulin levels than required for ad libitum fed rats. Also, the same rate of oxygen utilization causes less damage in dietary restricted rats than in ad libitum fed rats. The nervous and endocrine systems appear to be involved in the coupling of the reduced energy intake to thes ant-iaging actions. However, it is also possible that dietary restriction has ins anti-aging actions not be retarding one or more primary aging process(es) but by having a general protective action. In this regard, dietary restricted rats have through the life span daily periods of elevated plasma corticosterone levels compared to ad libitum fed rats. Glucocorticoids are a double-edged sword with appropriate levels being protective in regard to meeting challenges and excessive levels being damaging. Dietary restriction may act by providing a life span of appropriately protective levels. Clearly, progress has been made in understanding mechanisms underlying the action of dietary restriction.

We have reported that magnetic wave from cathode ray tube (CRT) aggravates experimentally induced allergic conjunctivitis.

Our next concern is the actual damage of the cells besides the above functional change. Our previous study showed that the cornea of CRT workers frequently revealed superficial erosive change. This change was found even after continuous working of VDT for four hours. In order to elucidate its mechanism, animal experiments were conducted. BALB/C mice were exposed in front of CRT (30 cm) of television. Effect of heat, light, charged particles, and noise was excluded by other experiment. Epithelial injury of the cornea was confirmed by fluorescein positive staining 24 hrs after CRT exposure. Epithelial injury was located mainly at the most superficial layer of the corneal epithelium. The corneal epithelial defect was further examined with a scanning electron microscope. The impaired area increased in a dose-dependent manner with exposure to CRT. Defect increased in two hours of CRT exposure and attained its maximum by twelve hours exposure. The corneal epithelium has good repairing ability. Therefore, the defect may not leave permanent damage on the corneal epithelium in young animals. But organic derangement may be possible to be produced on the diseased cornea such as senile degenerated cornea and so forth.

A market research survey of 100 patients who have attended the Breakspear Hospital was conducted by an independent market research company, ISIS. This shows the efficacy of environmental medicine. A proportion of these patients are in the geriatric age group, and despite their conditions being denoted as due to their age, considerable improvement was demonstrated. The details of the research will be discussed.

Of 20,000 chronically ill private patients manifesting physical and/or mental illnesses followed during the past forty years since the chemical susceptibility problem was described, 80-90% have improved by the time of their third office visit after their case had been summarized.

The main emphasis has been finding and avoiding demonstrated environmental incitants and perpetuants of chronic ilnesses, especially specific foods, environmental chemical exposures and such inhaled materials as dust, mites, danders, pollens and molds. There has been a minimal emphasis on drug therapy of the effects of illness. Food allergy tends to be labile in that the majority tend to tolerate specific foods on a rotary diversified diet after a few months of specific avoidance. Avoidance of incriminated environmental chemicals is far less effective in reducing the degree of individual susceptibility. Results of handling inhalant allergy by means of the Lee -Miller of Rinkel techniques are approximately the same as reported by others.

Many similarities are found to occur between pollutant injury in the chemically sensitive and the aging process. Free radical generation occurs with chemical injury in the chemically sensitive as well as during the aging process. Damage may occur to the mitochondria, nucleus, peroxsisomes, endoplasmic reticulum, and lysomes. Evidence is that the glutathione replenishing mechanisms are damaged in both. Gut flora and absorption are altered in both conditions. In animals under feeding prolongs life where it also improves the chemical sensitivity. Transport mechanisms may be altered in both, and other problems with metabolism may be altered like renal reabsorption, conjugation, and repair. There are many similar therapies that may be beneficial that have been devised for either. Certainly, research in one field may aid in understanding the other. Studies at the Environmental Helath Center-Dallas have suggested that there are nutrient pool changes in vitamins, minerals, and amino acids and both groups of patients. Immune deregulation may occur in both.

The total load has always incorporated looking at least for food, chemical, and mold sensitivities as well as nutrient and hormonal deficiencies.

Some unusual and highly resistant cases, many of which had also been to ecologists, responded dramatically to the macrobiotic diet with nutrient and/or hormonal corrections. These include reversal of sarcoidosis, acute myelogenous leukemia, chronic fatigue of 12 years, pesticide poisonings, chemical sensitivities, chronic prostatitis, amblyopia, recurrent anaphylaxis, metastatic myeloma, and more.

This presentation stresses the importance of never losing sight of the total load regardless of the improvement that the tools we are accustomed to using daily can bring about. It also stresses that, regardless of how seemingly hopeless a condition may be, the final cure seems to be limited only by our imaginations.

Transfer Factor (TF) is a biologically active component of dialysates of leukocyte extracts, which has substantial immune-stimulating properties. Evidence suggests that it appears to be primarily produced in T-helper (CD4 cells).

This paper will give a review of the experience of the Environmental Health Center-Dallas with the use of TF in the treatment of patients with immune dysfunction/deregulation and chemical sensitivity. Data will be presented on treatment results focusing on improvement in cell-mediated, delayed hypersensitivity parameters, increase in the total numbers and subsets of lymphocytes, and improvement in clinical status of the patients.

Representative case histories will be presented as an illustration of the effects of TF treatment within the context of a comprehensive environmental approach.

Implications for treatment of the immunological involution seen with aging will be explored.

The politics and science of pesticides in the Florida Keys ecosystem is reviewed, both in microcosm and macrocosm. This tropical experience can be applied to numerous other locations and has global implications.

Even though over 95% of the land in the Florida Keys (Monroe County) is in park status (the highest ratio in the country), pesticides banned in the early 1970s are found in the water, sediments, natural sea slicks and even the corals in the reef, which have in their tissues the highest levels ever reported worldwide.

These continued chemical assaults represent yet another challenge to the endocrine system of all animals (including seafood eating mammals) in this maritime environment.

With increasing average lifespan, there is increasing interest in geriatrics and in measures which can promote useful longevity rather than dependent old age. Several excellent books on nutrition and aging, and my own personal experiences, suggest that there are about a dozen factors that can be helpful in promoting useful longevity. These will be described with special attention to the trace mineral, zinc.

Discussion will involve development of SPECT Scanning and its current uses in evaluating a variety of patients including environmentally triggered disease processes.