Basic Facts About Human Population Growth and Its Consequences

MOLECULAR MECHANISMS OF warming, increased ozone in urban areas, acidic ENVIRONMENTAL TOXINS oceans, etc.

BSCI 273 01 Spring 2007

COURSE SYLLABUS Professor Wallace M. LeStourgeon [email protected] Office (Biological Sciences Bldg 5269) Phone (2- 2588)

This introductory information presents some of the themes and fundamental issues in the field of public health and environmental toxicology. Today, considerable pessimism exists in the minds of many environmentalists and scholars in the field of environmental toxicology and ecology. More specifically, many believe that within the next 80- 100 years the biosphere, as we know it today, will About 50 years ago it was thought that the world be largely destroyed. This pessimism stems from could not feed 6 billion people. Now, it appears we the fundamental problems presented below, from can if we are willing to convert natural habitats into powerful economic pressures that foster a cavalier farm land and deplete global fisheries. While we attitude regarding resources and environmental worry about the ever increasing loss of land and pollution, from mass public naivety and, according resources and the ever increasing rates of pollution, to some, intrinsic flaws in human behavior. we often overlook a major consequence of more and more people in a defined space. Namely, the The First Fundamental Problem need for more and more laws that restrict behavior and personal freedoms. The The earth is 4.57 billion years old. While bipedal industrialists argue that growth is good but they primates have existed for 4-6 million years, until are the same people that complain about about 8000 years ago, modern primates (humans) regulations and the loss of personal freedoms. existed in small dispersed groups rarely exceeding a few thousand individuals. In the past 200 years In the ascent of mankind, an inescapable fact of (quicker than a hiccup in geological time) the social development is that economic growth is human population entered an exponential growth directly proportional to and therefore encourages phase. In 1650, about 500 million humans population growth. This is the major reason our inhabited the earth. In the following 200 years, the borders have been open to immigrants for the past population doubled to 1 billion. The population 30 years. Modern cultures do not know how to doubled to 2 billion between 1850 and 1930 and uncouple population growth from economic growth. again to 4 billion by 1975. Today there are about 6,925,486,602 humans on the planet and this As the current inhabitants of spaceship Earth, we number is increasing at a rate of 3 people per are motivated to understand the biological problems second or about 95 million people each year. Y6B arising from high population density due to the occurred October 12, 1999. 95 million new people severity of its consequences. For example: As a each year corresponds to more than eleven new result of human activity, in the last 30 years the New York cities per year on the earth’s surface. It atmospheric CO2 concentration has increased is thus important to consider the explosive rate of significantaly. Microbubbles in the Greenland ice land and resource consumption necessary to support cap reveal that CO2 concentrations were stable for this expansion and also, the added pollution of the many thousands of years (at 280 ppm) until about biosphere. By 2050, nine billion people will 1800. Recently, a 19.4% increase occurred in the inhabit the earth. At no time in earth’s history has a mean CO2 concentration, from 316 parts per million single species so dominated the biosphere. More (ppm) in 1959 to 377 ppm in 2004. The 1997-1998 importantly, we now move mountains, redirect increase of 2.87 ppm represents the largest single rivers, farm desserts and rain forests, and alter yearly jump since the Mauna Loa record began in atmospheric chemistry on a global scale (the ozone 1958. Fossil fuel combustion (oil, coal) alone now hole, 20% increase in CO since 1959, global 2, adds over 7 billion tons of CO2 annually to the atmosphere. Of equal significance, human The Fourth Fundamental Problem activities now fix nitrogen from the atmosphere at a rate near 120 million metric tons per year. It is There are three types of toxic reactions, acute, estimated that in 1940 human activities fixed almost chronic, and subliminal. We are familiar with acute no nitrogen and that half of all the nitrogen ever toxicity because it frequently leads to death. fixed by human activities has occurred since 1980. Chronic toxicity almost always causes perceptible

Ultimately, CO2, methane, and nitrous oxide (N2O)- symptoms but rarely leads to immediate death. induced earth warming (the green house effect) will However; today, the most dangerous form of impact the quality of life on the planet. The toxicity is completely subliminal (not perceptible). preceding three decades were back to back the In other words, we feel nothing when a cell in our warmest decades in recorded history. liver suffers a mutation leading to cancer or to an autoimmune disease like lupus, myasthenia gravis, The Second Fundamental Problem or rheumatoid arthritis. Today 46% of all white males will be diagnosed with cancer in their Between the ages from 5 and 10 years, each new lifetime. The numbers are only slightly less for generation accepts what they see in their black males. Only about 2% of all cancers are environment as “normal and natural”. They simply caused by the inheritance of a defective gene from have no other frame of reference. A new shopping our mothers or fathers. Rather, about 98% of all mall or a new road through a forest seems cancers are caused by mutations induced by irrelevant. Thus, in this context, there is no environmental factors (mostly mutagenic motivation to curb urban sprawl, consumption of chemicals and background irradiation). resources, and the continued destruction of the Remember, DNA is a chemical and the only way to biosphere. In an effort to appreciate the modify a chemical is with another chemical. The remarkable recent change in our environment, non-perceptible nature of mutations is a huge imagine for a moment what a native American from problem because, if people feel “fine” they do not about 1850 would recognize if he or she were worry about low levels of chemicals in the water transported to the parking lot of a large shopping they drink, the food they eat, and the air they mall (answer = nothing!). Now, imagine the global breathe. This leads to great apathy, to indifference, resources that have been consumed to achieve our and to a cavalier attitude about increasing levels of present level of urban sprawl (about 40% of the environmental toxins. As a testament to this fact, Earth’s total resources). the 46% incidence of cancer in white males is several times higher than the great plagues of small The Third Fundamental Problem pox, polio, aids, the black plague, yet the general public is completely unaware. Of greater concern, Western cultures are mentally conditioned to accept the general public does not know that we the replacement of “God’s creation” with “man’s accumulate mutations in our cellular DNA as we creation” and we call it “progress”. Not only are pass through life and that the rate of accumulation we paving the earth but already, all of the streams corresponds with the age of cancer onset. and lakes in Wisconsin and one third of the streams in Tennessee contain such high levels of methyl The Fifth Fundamental Problem mercury and/or pesticides that the public is warned not to swim in, or eat fish from the streams. How Developmental biologists and psychologists argue often do we hear this fact discussed in the popular that man’s evolutionary history plays a major role media? Consistent with this fact, the FDA has in our present day behavior. A major behavioral cautioned pregnant women not to eat more than phenomenon seen in almost all creatures is termed one, 6 ounce can of albacore tuna per week - again, the “territorial imperative”. It is an individuals due to methyl mercury contamination of the drive to possess adequate space and resources for biosphere. Some believe it is man’s Biblical survival and reproduction. In ancient times, the destiny to destroy the biosphere and that, at the end, scarcity of people, their lack of technology, and a redeemer will remove them to a better place. plentiful resources rendered the issue irrelevant. Some of these individuals argue that we should Today we are still motivated by our ancestral egos hasten the destruction of spaceship Earth to speed and greed to consume resources and acquire wealth the return of their savior. Others believe that they far beyond our personal needs (60 foot yachts, 6000 are instructed by their religion to protect and sq.ft. homes, large energy-consuming cars, etc. preserve creation. etc.). Many environmentalists argue that mankind has simply run out of time to mentally evolve beyond his biology-based greed. It is Organic” to be sure that chemicals have not been interesting to note that a central theme of the added to the product. So, it is easy today to find Worlds great religions has been to consistently “organic” foods at supermarkets but the public preach against avarice, greed, and vanity. Question doesn’t know that it has been snookered for the – how hard is it for a rich man to get into heaven? sake of increased profit. As a second example, the Does anyone believe it? Can a true capitalist be a global food producer Altria has a bill in the Senate true Christian? (S. 3128) that will remove all state warning labels on foods that contain chemicals like mercury that The Sixth Fundamental Problem can lead to severe birth defects and a higher incidence of cancer. The public does not understand that “longevity” or “life expectancy” does not relate directly to the life More than 63,000 chemical compounds are span potential of an individual. We have heard commonly used in the U.S. today. No information repeatedly that in the past 60 years “life exists on the biological effects of more than 50,000 expectancy” has increased from 57 to 76 years. of these chemicals and about 1,000 new chemicals However, “life expectancy” is the “average” age at per year are waived into common use without death for a population group. The public also does testing for their effects on human and not understand that the increase from 57 to 76 years environmental health. The majority of these is entirely due to antibiotics, vaccines, and much chemicals or halogen-containing molecules for improved diagnosis and treatment procedures. A which modern species have no mechanism for person living 10,000 years ago would have exactly detoxification and which are highly stable in the our “life expectancy” if they lived today. As an environment. The EPA’s latest “Toxics Release example, this Summer, a new vaccine against Inventory” shows that more than 23,000 industrial human papilloma virus became available. The virus facilities in the US alone release 3.2 billion pounds is responsible for the majority of deaths from of known toxic pollutants into the air, soil and cervical cancer. When the majority of young waterways per year. This figure is derived from women are vaccinated against the virus, it will voluntary reports by only the largest corporations significantly increase our Nation’s “longevity” but on just 300 or so chemicals. Estimates of the US’ it will in no way affect the intrinsic life span total yearly emission of toxic chemicals from all potential of women. The publics misunderstanding sources, legal and illegal, are in the neighborhood of this point is a problem because it fosters a of 25 billion pounds. The intent of the Clean Water cavalier attitude on “hate radio” regarding public Act enacted in 1972 was “zero discharge” of known health and environmental destruction. The more toxic agents. However, in response to powerful important question becomes, “How long would we global corporations and to a sympathetic live on average if we had today’s technology and administration, this act has been quietly gutted by the pristine Earth of 150 years ago?” Congress during the past 5 years. More recently the Bush administration has proposed to no longer The Seventh Fundamental Problem require industries and businesses to report the type and amount of chemicals released in local Those who try to educate the public about communities. If the public is denied knowledge it environmental and public health issues are referred can not know the origin of a pollutant nor the health to as liberal professors, environmentalist wackos, consequences of exposure. tree huggers, and they are ignored. As a testament to their lack of influence, over the past 6 years, the regulatory agencies charged with protecting public health (The EPA, FDA, and USDA) have become staffed by lobbyists for the chemical, pharmaceutical, and agricultural industries. Stated more specifically, large global corporations now Course Objectives: control our federal regulatory agencies. As one example, the USDA has recently defined While the above presents several reasons for “ORGANIC” as any food that contains 5% added pessimism, it also points to obvious solutions. Our chemicals or less. Thus, foods labeled “organic” specific focus this semester will be to study today may possess more pesticides and compounds that have significant public health preservatives than before the new USDA definition. effects and that are major threats to the long term One must look for a label that states “100% USDA sustainability of the biosphere. These compounds are of anthropomorphic origin (created by human semester can be found in the references listed at the activities). We will come to understand how these end of this syllabus. compounds act to interfere with normal biochemical processes at the cellular, organismal, and ecosystem Course Grade: The course grade will be based on levels. three 50 minute in-class exams and the final exam. The exams will each comprise 23% of the course In order to understand the action of environmental grade and the final exam grade will comprise 31%. toxins in organisms, it is first necessary to identify One question on the final exam will require that you their subcellular targets (i.e. the cellular receptors or remember the seven problems stated above and the molecules) that are bound by, or act upon the under their impact on public health. toxic agent. Secondly, it is important to understand the forces that direct binding specificity and that LECTURE TOPICS AND IMPORTANT determine binding affinity. With this information DATES in hand it is often possible to identify the metabolic pathway involved and to predict the physiological January magnitude of the toxic effect. While detailed biochemical information is available for only a few Wed. 10 Introduction, Course Objectives, The of the thousands of environmental chemicals, we Fundamental Problems often can make good predictions as to a new Fri. 12 The SEER Database: What good data molecules toxicity and mode of action by can show. The fundamental question. comparing its molecular structure and chemical Mon. 15 An overview of major environmental properties to those of well characterized toxins. issues and their impact of public health. It is not an objective of this course to berate Wed. 17 Basic toxicological concepts: industry or industrialists. We will; however, Concentrations their use, misuse and consider the conflicting positions of “industrial significance. conservatives” and “environmental conservatives”. Fri. 19 Mechanisms that drive We will also consider examples of overt directed biomagnification (bioconcentration) efforts to misinform the public in an effort to Mon. 22 Biotransformation and the cytochrome maintain and grow profit margins (i.e., lead in P450 enzymes gasoline and paint, methyl mercury, pesticides, Wed. 24 First pass metabolism and phase I and alcohol, nicotine, formaldehyde, Tylenol, Vioxx, II bioactivation. food preservatives, sweeteners, government- Fri. 26 Receptors, ligands, binding affinities sanctioned false labeling of organic foods, industry- and specificity, binding assays. funded youtube uploads, S. 3128, and many others). Mon. 29 Receptor-activated pathways and The adage “caveat emptor” is as valid today as in ligand-receptor interactions. the past. However, in the past this advice applied to Wed. 31 Mutagens (chemical carcinogens) - the individual. Today it applies to mankind. These types and mechanisms - risk discussions will constitute the “Science and Society assessment, mutagens and the dose - Perspectives” component of the course. response relationship. The TD50 assay vs. modern molecular cellular Some details: assays.

We will use one book and class handouts for February documentation of the political methods and economic forces at work in the field of Fri. 2 EXAM 1 environmental toxicology. Crimes Against Nature (by R. F. Kennedy) is available in the bookstore. Mon. 5 Heavy metals (lead, mercury, arsenic, The book is written from the perspective of cadmium) industrial sources and environmentalists and, from time to time emotional contaminant levels and/or judgmental comments can be found. Wed. 7 Methyl mercury, bioconcentration and However, the information presented is factually mechanisms of toxicity correct. Didactic presentations will be Power Fri. 9 Toxic synergy via heme synthesis and Points. Copies of each presentation will be handed environmental carbon monoxide. out in class and posted at the OAK site. Much of Mon. 12 Chemicals acting at synaptic and the basic scientific information presented this neuroeffector junctions. The sympathetic and parasympathetic State of the World: Our Urban Future. A nervous systems. Worldwatch Institute on Progress toward a Wed. 14 Continued. Sustainable Society. W.W.Norton & Co. New Fri. 16 Neurotransmission - axonal York, 2007 conduction, chemical blockade, National Report on Human Exposure to specific neurotoxins and pesticides. Environmental Chemicals, The Center for Mon. 19 Cholinergic transmission Disease Control and Prevention, 2005 Wed. 21 Adrenergic transmission and Molecular Biology of Cancer. L. Pecorino. Oxford desensitization University Press. Oxford, New York. 2005 Fri. 23 Chemicals that interfere with Mechanistic Toxicology. Urs A. Boelsterli. Taylor acetylcholinesterase, and Francis Group. London and New York, organophosphates and other pesticides 2003 Essentials of Toxicology (Casarett and Doull’s). Mon. 26 EXAM 2 Curtis D. Klaassen and John B. Watkins III, eds. McGraw-Hill, 2003 Wed. 28 Air pollutants and solvents Guide to Cytochromes P450 (Structure and Fri. 30 Solvents continued. Function). David F. V. Lewis. Taylor and Francis Group, London. 2001 March 3 – 11 Spring Break Reactive Oxygen Metabolites, Chemistry and Medial Consequences. Manfred K. Eberhardt. Mon. 12 Pesticides CRC Press 2000 Wed. 14 Pesticides continued. Principles of Biochemical Toxicology (3rd Ed.). Fri. 16 Endocrine disrupters. John Timbrell. Taylor and Francis Press. 2000 Mon. 19 Xenobiotics, immunotoxins, and Environmental Toxicology and Chemistry. Donald autoimmune disease G. Crosby. Oxford University Press. New York Wed. 21 Continued 1998 Fri. 23 Autoimmune disease continued, Pathology of Environmental and Occupational Mutagenic pharmaceuticals. Disease. John E. Craighead. Mosby-Year Book, Mon. 26 Continued Inc. St. Louis. 1995 Wed. 28 Continued Molecular Toxicology. P. David Joseph. Oxford University Press, New York, N.Y. 1997 Fri. 30 EXAM 3 Disposition of Toxic Drugs and Chemicals in Man. (4th Ed.). Baselt & Carvey, eds. Chemical April Toxicology Institute, Foster City, CA. 1995 Perspectives in Environmental Chemistry. D.L. Mon. 2 Bisphenol-A and phthalates in plastics Macalady, Oxford University Press, Inc. New Wed. 4 Acrylamide in fried foods. York. 1998 Fri. 6 Atrazine Goodman and Gilman’s The Pharmacological Basis Mon. 9 Bromine-containing flame retardants of Therapeutics. J.G. Hardman and Lee E. Wed. 11 Continued Limbird editors in chief. Ninth Edition. Fri. 13 Radon McGraw-Hill. 1996 Mon. 16 TBA Medical Toxicology. Matthew J. Ellenhorn. Wed. 18 TBA Williams and Wilkins, Baltimore. 1997 Fri. 20 TBA Handbook of Carcinogenic Potency and Mon. 23 Course overview, information for final Genotoxicity Databases. L.S. Gold and E. exam. Zeiger, eds. CRC Press, New York. 1997 Origins of Human Cancer. H.H. Hiatt, J.D. Final Exam: Friday April 27 @ 3:00 P.M. (no Watson, J. A. Winsten, eds. Cold Spring Harbor alternate will be given). Graduating seniors with A Press. Cold Spring Harbor, N. Y. 1977 averages are exempt. Clinical Management of Poisoning and Drug Overdose. Second Edition. L. M. Haddad and J. References: F. Winchester, eds. W.B. Saunders Co. Philadelphia 1990 Exposure Analysis. W.R. Ott, A.C. Steinemann, Toxic Deception. D. Fagin and M. Lavelle. Birch and L.A. Wallace, Eds., Taylor and Francis, Lane Press. 1996 2007 Fertility on The Brink. The National Wildlife Federation, Washington D.C., 1994 Cancer at a Crossroads: A Report to Congress for the Nation. National Cancer Advisory Board. 1994 The Environmental Safety Guide: Hazardous Chemical Waste Management - Guide for Vanderbilt Personnel. Department of Institutional Safety. Environmental Safety Section. 1994