i Fatty acids are the building blocks of the fat in our bodies and in the foods we eat. When you digest food, your body breaks down fats into fatty acids, which can then be absorbed into the blood. Fatty acid molecules are usually joined together in groups of three to glycerol, forming a molecule called a triglyceride.

ii At the moment, the only obesogens that have a well-established mechanism of action are those that act through PPARγ, such as TBT, the fungicides triphenyltin and triflumizole, the antidiabetic drug rosiglitazone (also known as Avandia), and another fungicide, tolylfluanid, which acts via the glucocorticoid receptor. All of these chemicals lead to weight gain in animals. Avandia and a related drug called Actos cause weight gain in humans and serve as important proof of principle for PPARγ activators as obesogens in humans.

iii One could make the argument that HFCS is disrupting hormonal signaling in a different way that the EPA should be considering. Their view of endocrine disruption is too limited. Disrupting any of the many hundreds of hormonal signaling pathways (for example, leptin, insulin, growth hormone, and more) has adverse biological consequences that need to be accounted for. Perhaps even more important, disrupting any type of cellular signaling pathway, even if it is not a hormone-regulated pathway, can disrupt biological functions and lead to adverse consequences. My Japanese colleague Jun Kanno has introduced the concept of “signal toxicity” ⁹⁷ to identify chemicals that disrupt any sort of receptor-based, cellular signaling pathway. This concept greatly broadens the field of endocrine disruption; therefore, the field needs to incorporate signal toxicity (or signaling disruptors) into the growing framework of metabolism disruptors. ⁷

iv The toxicology community is fond of such contrived debates. For example, I was invited to the Society of Toxicology Annual Meeting in 2015, where one night they staged a debate about whether low-dose, non-monotonic dose responses existed or not. Of course the audience voted that they did not exist because industry and government toxicologists, who made up the bulk of the audience, believe that all dose responses should be linear and that there is always a dose (usually a high dose) below which no adverse effects can be detected, as discussed elsewhere in the book. While one might not see the harm in a spirited debate, facts are not debatable, only theories and opinions are. Senator Daniel Patrick Moynihan put it best when he said, “Everyone is entitled to his own opinion, but not to his own facts.”

v Perhaps the most accurate story about the science of the genetic material and all of the players involved was related by Horace Freeland Judson in his classic book, The Eighth Day of Creation, ¹⁰³ but it is also useful to read James D. Watson’s The Double Helix ¹⁰⁴ and Francis Crick’s What Mad Pursuit ¹⁰⁵ for a full appreciation of all the challenges and successes along the path to discovering the structure of DNA.

vi The Soviet biologist Trofim Lysenko fomented his own version of Lamarckism and used his influence with Josef Stalin to impose his views on Soviet science. Lysenko rejected the concept of genes, of Mendelian inheritance and natural selection, and his influence with Stalin led to the jailing, firing, or execution of scientists opposed to his teachings. Lysenko’s version of Lamarckism essentially led to the destruction of genetics in the Soviet Union. It was not until 1964 that Lysenko’s influence was finally removed. As you can easily imagine, Lamarck’s theory was conflated with Lysenko’s and, rather than being treated as an alternative theory for consideration and scientific debate, was emphatically dismissed along with Lysenko’s twisted version. Mike Skinner has written a very thoughtful article describing a unified theory that accommodates both genetic and epigenetic inheritance. ⁹²

vii Niles Eldredge and Stephen Jay Gould introduced the concept of punctuated equilibria to make the Darwinian idea of natural selection more consistent with the fragmentary nature of the fossil record. In their view, populations had lots of variability but were stable over time (that is, in stasis or equilibrium) until some large environmental disturbance—the punctuation—led to the seemingly rapid changes observed in the fossil record. ¹¹² One example of such a large-scale change would be the asteroid impact that coincided with the mass extinction of the dinosaurs about sixty-six million years ago.

viii A symbiont is an organism that lives together with another, a process called symbiosis. Symbiosis can be mutualistic, where both benefit, commensalistic, where one benefits but the other is not harmed, or parasitic, where one benefits and the other is harmed.

ix A meta-analysis is a large-scale analysis that focuses on the results of previous studies. They are frequently performed on genome-wide association studies (GWASs), large-scale analyses that seek to link particular genetic regions with diseases, to derive more information from the increased statistical power of many studies.

x Under sections 201(s) and 409 of the Federal Food, Drug, and Cosmetic Act, any substance that is intentionally added to food is a food additive and subject to premarket review and approval by the FDA, unless the substance is generally recognized, among qualified experts, as having been adequately shown to be safe under the conditions of its intended use, or unless the use of the substance is otherwise excepted from the definition of a food additive. The term “qualified experts” is open to interpretation, and in my opinion, GRAS should actually be interpreted as “generally recognized as untested, but perhaps safe.”

* A small amount of sweet corn, papaya, and summer squash sold in the United States is grown from genetically modified seeds. Buy organic varieties of these crops if you want to avoid genetically modified produce.

xi At the federal level, bottled water must comply with the Federal Food, Drug, and Cosmetic Act (FFDCA) (21 U.S.C. §§ 301 et seq.) and several parts of Title 21 of the Code of Federal Regulations. Section 410 of FFDCA requires that the Food and Drug Administration’s bottled water regulations be as stringent and as protective of the public health as the EPA’s tap water standards.

xii Depending on the manufacturing processes, lauryl sulfates may be contaminated with measurable amounts of ethylene oxide and 1,4-dioxane. The International Agency for Research on Cancer classifies ethylene oxide as a known human carcinogen and 1,4-dioxane as a possible human carcinogen. Ethylene oxide can also harm the nervous system, and the California Environmental Protection Agency has classified it as a developmental toxicant based on evidence that it may interfere with human development.