Genetics, biodiversity, agriculture

Environmental Health (5)Frumkin's textbook 3rd ed. Chapter 7, 18 & 19
2nd November 2023
Minato Nakazawa<minato-nakazawa@people.kobe-u.ac.jp>

1Chapter 7. Genes, Genomics andEnvironmental Health●

Key concepts– DNA, as the "blueprint of life", is the principal biological template thatallows all living organisms to reproduce and pass on their fundamental
attributes to offspring.
– Other factors than DNA, epigenetics, can modify how genes are

expressed.
– Environmental factors, including diet, chemical exposures, and lifestyle(e.g., smoking and alcohol consumption), may interact with both genetic
and epigenetic processes.
– Interindividual differences in susceptibility to environmental pollutants

may be determined by both genetic and epigenetic processes.
– Molecular tools (so-called omics technologies) that can quickly andcheaply acquire millions of biological data points have transformed how
scientists study the causal relationships between environmental
exposures and disease outcomes.
– Big data obtained by omics can be analyzed by mathematics, statistics

and computation.

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Basic Components of Gene and Genome●

Living organism uses a string of chemicals, called bases + deoxyribose = DNA(deoxyribonucleic acid)– 4 bases: T (thymine), G (guanine), C (cytosine), A (adenine)– DNA is double strand (complementary each other)– Fixed pairs of A and T, G and C– If a strand of DNA has the nucleotide sequence CGTCCGAT, the other must be

GCAGGCTA– Triplet theory: 3 bases (codon) code one amino acid → 2 or 3 different codons for the sameamino acid●

Approx. 3 billions of base pairs constitutes human genome●

Each cell has the same set of DNA, but expression is different by cell or tissue●

Gene is a specific sequence of nucleotides that contains information and that
controls some function in the cell●

Approx. 24,000 genes in human genome●

Genome (genes within it) is composed of discrete units (chromosomes)– Human has 46 chromosomes (22 pairs of autosomes + 2 sex-specific chromosomes), 23

from the mother in egg, 23 from the father in sperm– Females' sex-specific chromosomes are XX– Males' sex-specific chromosomes are XY.
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Y from father.

Within a chromosome, genes are located in the specific positions (loci).

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Human genome and elements of gene(cited from Frumkin's text Chap. 7)

Figure 7.1 & Figure 7.2

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Types of genetic variability●

Differences in single nucleotides in the same position of the same locus are the mostcommon type of genetic variability, single nucleotide polymorphisms (SNPs).
– Most of the SNP variability in the human genome is scattered throughout the large part of the

genome that is not part of a gene (intergenic regions) or located in noncoding (intronic)
sequences within genes: Among 3 billion human nucleotides, 95% are introns, 5% are exons.

– SNPs in exons can be classified as synonymous cSNP (c means coding) or non-synonymous

cSNP → as explained in "toxicology", there are many enzymatic polymorphisms.

– (e.g.) Naka I, Hikami K, Nakayama K, Koga M, Nishida N, Kimura R, Furusawa T, Natsuhara

K, Yamauchi T, Nakazawa M, Ataka Y, Ishida T, Inaoka T, Iwamoto S, Matsumura Y, Ohtsuka
R, Tsuchiya N, Ohashi J (2013) A functional SNP upstream of the beta-2 adrenergic receptor
gene (ADRB2) is associated with obesity in Oceanic populations. International Journal of
Obesity, 37: 1204-1210. https://dx.doi.org/10.1038%2Fijo.2012.206●

Other types of variability– Insertion or deletions of nucleotides (indels) in genes → When it causes a disease, it'sreferred as "mutation" rather than polymorphism●(e.g.) Kimura M, Tamam M, Soemantri A, Nakazawa M, Ataka Y, Ohtsuka R, Ishida T (2003) Distribution of
a 27-bp deletion in the band 3 gene in South Pacific islanders. Journal of Human Genetics, 48: 642-645.
https://doi.org/10.1007/s10038-003-0093-4– An entire gene is missing (deletion polymorphism; e.g. hGSTM1 gene exists in only 50%) or

occurs more than once in the same genome (gene duplication, copy number variation [CNV])– An entire chromosome appears 3 copies (triploid): e.g. Down's syndrome is 21 trisomy.

5Regulation of gene expression & epigenetics●

Transcription factors and promoter regulation of genes–

Phenotype is determined by the small part of genome–

The trigger to begin transcription is determined by
specific sequence of DNA in the 5'-flanking region(promoter region, Fig. 7.2.)– Specific proteins (transcription factors) bind topromoter region, then initiate the process oftranscription
Sometimes transcription factors need a small molecule(estrogen, testosterone, thyroid hormone) before moving to
the nucleus of the cell to bind to the binding site on a gene.
Such small molecule is "ligand".
●Some kinds of environmental chemicals mimics ligand tointervene this transcription process. Those are called as"endocrine disruptors".
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Figure 7.4 and Figure 7.5

Epigenetics– Methylation/accetylation of DNA is related with its

epression, those are modified by external molecule(Figure 7.4).
– Binding of microRNA (miRNA) to the 3'-terminal endsof mRNA inhibits transcription to decrease gene
expression– e.g. Maternal diet changes skin color of offspring inmice (Figure 7.5).

6Thrifty Phenotype as an example of epigenetics(Hales CN, Barker DJ (2001) The thrifty phenotype hypothesis. Br.
Med. Bull. 60: 5-20. https://doi.org/10.1093/bmb/60.1.5)
Odds ratio of metabolic
syndrome by birth weight(lb; 2.2lb=1kg) adjusted byadulthood BMI

Figure of hypothetical mechanism and graph to show odds ratio

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Omics technologies●

The study of the genome → genomics●

The study of the transcriptome (mostly mRNA) → transcriptomics

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The study of the proteome (entire population of proteins within acell or tissue) → proteomics
The study of metabolome (all parts of a cell constituting complex
metabolism) → metabolomics
The study of epigenetic factors → epigenomics
New computing approaches enabled to analyze huge datasets
obtained from omics → All possible combinations or comparisons
can be tested → Increase of type I error becomes problem,
adjustment of p-values in multiple comparison is needed → FDR
adjustment is applied. (cf.) LAMP (Limitless-Arity Multiple testing
Procedure), see, https://doi.org/10.1073/pnas.1302233110
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Gene-environment interaction●

Approaches– Garrod found alkaptonuria as genetic metabolic disorder. Bateson described

aggregation of such metabolic disorders in family.

– Single gene disorder is rare.

Rather too complex, resulted from geneenvironment interaction, diseases like type 2 DM and obesity are common.
●

Pima Indian living in Arizona shows much higher prevalence of obesity and type 2 DM than
Caucasians there, but Pima Indian living in Mexico shows low prevalence of obesity andDM.
See, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418458/pdf/nihms657043.pdf
https://www.youtube.com/watch?v=AwaHNy5cwdU– Genetic association study is widely conducted●

Examples– Drug responses: Primaquine causes severe hemolysis in people with low activitiy

variant allele of G6PD gene → Needs of Tailor-Made Medicine– Dietary exposures: alcohol (interact with ADH/ALDH – low activity ALDH2*2

holder is "flusher"), mercury (interact with CPOX and COMT)– Occupational exposures: benzene (interact with CYP2E1 enzyme)– Environmental exposures: some kinds of pesticides (interact with PON1 enzyme)
9Chapter 18. Pest Control and Pesticides●●

Note: "Pest" in Japanese usually means a specific diseasename of plague, but here "pest" has much wider sense.
Key Concepts– Pests are plants, animals, or microorganisms that threaten humanhealth– Each pest has specific biological and ecological characteristics– Pest control relies heavily on chemical agents– There are many different classes of pesticides– People are exposed to pesticides in many ways (incl. Residual

pesticides in foods)– Pesticide regulation is complex and relies on federal and states laws(in USA)– Integrated Pest Management (IPM) is a strategy combining

chemical and nonchemical methods
10History of pest control●●

Pests existed and were identified in ancientsocieties
Efforts to control pests also have long history– Past control measures: chalk, plant extracts, mercury,arsenic, lead and other compounds, in addition tosacrifices, prayers, rituals and dancing●

Chemicals– Paris green (copper acetoarsenite) was the first

insecticide widely used for agriculture

Figures 18.1 and 18.2

– DDT was found in 1939, widely used during WWII
– DDT-like chlorinated pesticides were developed– Public health and ecological researches revealed

problems ranging from human toxicity to wildlife toxicity
to ecosystem disruption → Rachel Carson's "Silent
Spring" (1962) altered the public and policymakers to
the risks associated with pesticide use– Damages caused by pesticides cost $12 billion in USA:

Loss of natural pest predators, crop pollinators,
honeybees, crops, wildlifes●

Today we are moving beyond exclusive reliance on
pesticides to the combination of chemical andnonchemical methods (IPM)

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Seven categories of public healthpests, defined by USEPA
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Cockroaches: asthma, allergies, food contamination
Body, head, and crab lice: skin irritations and rashes, louseborne diseases (typhus, trench fever, relapsing fever)Mosquitoes: mosquito-borne diseases (malaria [Anopheles],yellow fever [Culex], dengue fever [Aedes], some kinds ofencephalitis [mostly Culex])
Rats and mice: rodent-borne diseases, contamination of foodfor human consumption●

Microorganisms (bacteria, viruses, protozoa): pathogen itself●

Reptiles and birds: reservoir host of zoonosis, physical injury●

Various mammals: reservoir host of zoonosis, physical injury* Other pests include bedbugs, fleas, sand flies, termites, ticks, and so on. Recently
SFTS (severe fever with thrombocytopenia syndrome) is known as an emerging
disease, of which virus is transmitted by tick's bites,

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Control for insect pests●●

Insect repellent–

Preventing bites from biting insects (mosquitoes, ticks, fleas, chiggers, biting flies)–

It cannot prevent bites from stinging insects (bees, hornets, wasps)–

It doesn't kill but deter them from settling on skin and cloths–

DEET (10%-30%) is the most used one. Higher concentration means more long-lasting
effects (10%=2hr, 24%=5hr). Higher than 30% gives no additional protection and risk ofadverse side effects. Acute toxicity is very rare, but high-dose DEET may cause
neurological effects (suggested by animal experiment)–

Picaridin, lemon eukalyptus oil, 2% soybean oil are comparable with 10% DEET–

Permethrin or DEET impregnated clothing is used for military wear

Insecticides (a kind of pesticides)–

Sprayed on crops, alongside residential streets, poured on gardens, squirted along
baseboards and in basements, impregnated into clothing and bednets.
●–

Permethrin or deltamethrin impregnated bednets contributed to malaria control. Recently
LLINs (insecticides incorporated in the fibres of the net) like Olyset net[https://sumivector.com/mosquito-nets/olyset-net] and PermaNet[https://www.vestergaard.com/our-products/permanet] were developed and widely used for
malaria control.

World annual consumption of pesticides is about 2 million tons, 45% is used in Europe,
25% is used in USA; In applied rate basis, usage of pesticides in Korea, Japan and13
India are 6.6, 12.0, and 0.5 kg/ha, respectively.

Pesticides classified by target ormode of action (1)TargetMode of action

Algicides

Control algae in lakes, canals, swimming pools, water tanks, etc.

Antifouling agents

Kill or repel organisms attaching to underwater surfaces

Antimicrobials

Kill microorganisms (bacteria, virus)

Attractants

Attracts pests (lure an insect or rodent to a trap, etc.)

BiocidesKill microorganisms

Biopesticides

Pesticides derived from natural materials

Disinfectants andsanitizers

Kill or inactivate disease-producing microorganisms on inanimate
objects (latrine, table, etc.)

Fumigants

Produce gas or vapor intended to destroy pests in buildings or soil

Fungicides

Kill fungi (blights, mildews, molds, rusts)

Herbicides

Kill weeds and other plants growing in unwanted places

Insecticides

Kill insects and other arthropods

Larvicides

Kill larvae of insects← An example of well-known fumigants in Japan
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Pesticides classified by target ormode of action (2)TargetMode of action

Microbial
pesticides

Microorganisms that kill, inhibit or outcompete pests

Miticides(Acaricides)

Kill mites on plants and animals

Molluscicides

Kill snails and slugs

Nematicides

Kill nematodes

OvicidesKill eggs of insects and mites

Repellents

Repel pests (insects, birds, etc.)

Rodenticides

Control mice and other rodents (eg. strychnine)

Defoliants

Cause leaves or other foliage to drop from a plant, facilitate harvest

Desiccants

Promote drying of living tissues (for unwanted plant tops)

Insect growth
regulators

Disrupt the molting, maturing from pupal to adult stage

Pheromones

Disrupt the mating behavior of insectsPlant growth
regulators

Alter expected growth, flowering or reproduction of plants(excluding fertilizers and other nutrients)

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Organophosphates (OPs)
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Developed in 19C, utility was found in 1932.
Organophosphate pesticides are neurotoxin, inactivates acetylcholinesterase (regulatingneurotransmitter acetylcholine) → Some of those can be used as nerve gas (VX gas in
WWII, sarin in Tokyo subway attacks 1995), but major uses were insecticides likechlorpyrifos, diazinon, malathion, azinphos-methyl.
Unlike persistent organochlorine pesticides [https://dx.doi.org/10.1515%2Fintox-2016-0012] such as DDT, OPs degrade naturally in the environment after several days
Human exposure: unintentionally/intentionally, ingestion/inhalation– In USA, unintentional exposure with very low concentration is widespread: Eating freshly picked foods

contaminated with trace pesticide residues, inhaling household dust contaminated with pesticide
residue.

– In Cambodia, vegetables sold in markets sometimes contain higher level of pesticide residue thanmaximum safe limit [https://ejfoundation.org/resources/downloads/death_in_small_doses.pdf].

– In Ghana, some ready-to-eat vegetables contained higher level of OPs but were not considered as thecause of major public health problems [https://doi.org/10.1016/j.foodcont.2016.03.045][https://doi.org/10.1016/j.fct.2008.09.049] [https://doi.org/10.1007/s10661-015-4471-0].

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Alternatives– Carbamates: Inactivates acetylcholinesterase, but lower affinity than OPs and non-persistent– OCs (organochlorines): Less acute toxicity, but persistent.

pollutants, including DDT, PCB, etc.).

Major source of POPs (persistent organic– Pyrethroid pesticides: Synthetic version of natural pyrethrin, more stable than pyrethrin in theenvironment and toxic to the nervous system, but less toxic than Ops.

– Biopesticides: Lower mammalian toxicity, but more expensive.

e.g. canola oil and baking soda

16Herbicides
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Herbicides: The most widely used type of pesticide in the
agriculture, to reduce the effort to eliminate unwanted weedsfrom the farm by the farmers.
Top ten pesticides used (by weight) were mostly shared byherbicides, including glyphosate (Roundup by Monsant),
atrazine, metolachlor, acetochlor, 2,4-D, pendimethalin
Herbicides are also widely used in the home and garden,
industrial, commercial and government: 2,4-D and glyphosate
were most widely used active ingredients (USEPA, 2011).
Combination of genetically modified (GM) crops can facilitate
the use of herbicides like glyphosate-resistant crops withRoundup; A kind of integrated pesticide management (IPM)→ Widespread and controversial practice (see, Chapter 19)
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Pesticide regulation
Pesticide policy and law make up a complicated patchwork, addressing different
aspects of health, safety, and environment●
USA●– The principal pesticide law is FIFRA (federal insecticide, fungicide and rodenticide act) [https://www.epa.gov/laws-regulations/summary-federal-insecticide-fungicide-and-rodenticideact]. Major policies are:Requires product "registration" prior to manufacture, sales or use●
Requires toxicity data●
Requires specific labeling [https://www.epa.gov/pesticide-labels]●
Requires training of applicators●
Restricts handling and uses●

– Another important law in USA is FFDCA (federal food, drug, and cosmetic act)
– FQPA (food quality and protection act) of 1996 updated both FIFRA and FFDCA bymandating a single, health-based standard for all pesticides in all foods, based on"reasonable certainty of no harm"– For workers, WPS (worker protection standard), for wildlife, ESA (endangered species act)
have been set.
●Japan
– Agricultural Chemicals Regulation Act [https://www.acis.famic.go.jp/eng/hourei/]– Food Sanitation Law and Food Safety Basic Law [https://www.mhlw.go.jp/english/topics/foodsafety/positivelist060228/introduction.html]●

FAO and WHO establish MRLs (maximum residues limits), maximum levels of
pesticide residue that food can contain and still be expected not to harm human18
health: Member states can use these MRLs to develop national regulations.

Integrated Pest Management (IPM)●

Definition– "A comprehensive approach to pest control that uses combined means to reduce thestatus of pests to tolerable levels while maintaining a quality environment" (Pedigo, 2002)– "IPM is a decision support system for the selection and use of pest control tactics, singly

or harmoniously coordinated into a management strategy, based on cost/beneft analyses
that take into account the interests of and impacts on producers, society, and theenvironment." (Kogan, 1998
https://entomology.rutgers.edu/graduate/docs/papers/Kogan.pdf)●

Management and cultural practices to control pests: Farmers and public healthofficials use various management and cultural practice to reduce pest
populations or to make conditions less favorable for pests– Farmers: Planting crop when pest population is lower, using a cultivar more resistant topests, using a plastic mulch to reduce weeds, conserve moisture– Public health officials: Avoid standing water to reduce mosquitoes, control garbage

buildup to manage flies, recommend meticulous cleaning and waste management to
reduce other nuisance pests●●

Structural maintenance and monitoring are key to be sustainable
The use of chemical pesticides should be seen as a last resort. When used,comparatively less harmful ones to health and the environment should be chosen
19Chapter 19. Food systems, theenvironment and public health●

Key concepts– The food system, from initial inputs to production to distribution to

consumer choices, is a complex system, best understood using asystems approach– Green Revolution, including the use of fertilizers, pesticides andmachinery, and innovative crops, greatly altered methods of foodproduction and increased output, with some adverse consequences– In USA, most food is produced and distributed using large-scaleindustrial methods– A healthy food system is defined as "health-promoting, sustainable,

resilient, diverse, fair, economically balanced, and transparent"– Food safety is a traditional core function of environmental health,and practicing food safety is important for controlling bothbacteriological and chemical contamination and spoilage (However,the lecture of food safety is given later, not today)
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History of food system and now●

If the history of Homo sapiens werecompressed into a single year,– Farming started in the evening of December 13– Industrial agriculture started in the morning ofDecember 29●●

Modern food system is extremely large andpermeates many aspects of our lives.
In USA, food production accounts for over halfof land, 16% of energy, 80% of consumptive
water use; 13% of GDP is accounted by food
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Food
system●Food travels
through thelandscape via
food supply
chains ofvarying
lengths:
involvingproduction,
distribution,
consumption,
waste
disposal.

Figure 19.1

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Natural resources of industrial agriculture
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Soil: Healthy soils contain thriving ecosystems – up to a billion bacteria in eachteaspoon – and are resilient to drought. Once eroded, reconstruction needs
more than a century. Plowing, overgrazing, excessive fertilization degrade
topsoil much faster than it can be replenished. FAO reports 25% of the world
lands are severely degraded.
Water: Agriculture is the world's biggest freshwater user. Livestock products
use far more water than other agricultural activity. Much water is drawn fromunderground aquifer, which may be nonrenewable. Fertilizers and pesticides
degrade water quality.
Biodiversity: The existence of a variety of different species and organisms inan ecosystem is important for agriculture. Industrial agriculture is sometimes
monoculture (large expanses of the same crop): About half of USA cropland isused to grow genetically uniform corn and soybeans. Very vulnerable to pest
invations and plant diseases. (eg. Cavendish cultivar of banana shares about
half of global banana production, which suffers from new Panama diseasecaused by a fungi)
Energy: Much labor in agriculture is replaced by machinery, which consumes
fossil fuels. About 7-10 calories of input energy is needed to produce 1 caloryof food. Use of renewable energy including biomass power is encouraged.
Climate: Stable climate is also a "resource". Global warming and disasters
such as hurricane give damages to agriculture

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Manufactured agricultural inputs●●●

Pesticides → See, previous slides
Fertilizers: Traditionally farms had a mix of animals and crops, with theanimal's manure serving as fertilizer for the crops. Once science
discovered a way to fix atomospheric nitrogen to produce synthetic
fertilizers (Haber-Bosch process), animal manure became non-essential.
Since Green Revolution, crops take up only 30-50% of fertilizer nitrogen,
45% of phosphorus, then excess nutrients runs off the land and becomesnutrient pollution in marine ecosystems → causes eutrophication, deadzones, harmful algal blooms (toxins from HAB causes massive die-out offish and neurotoxic disorders or chronic diseases in humans)
Genetically engineered seeds: One of the most controversial
technologies. GM corn and soybean seeds came on the market in 1996,
but already account for vast majority of USA corn and soybean.
Roundup-resistant crops or Bt crops can reduce overall amount of
herbicide use. But roundup may be carcinogenic or cause birth defects,
Bt gene may transfer to wild plants and cause ecological pollution, or
pest insects gradually develop resistance against Bt.
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Industrial food animal production (IFAP)
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In USA, more than 9 billion foodanimals are slaughtered every
year.
Nearly all of the meat, milk andeggs consumed in USA are
produced in a system known as
IFAP (industrial food animal
production), which raises animals
in CAFOs (concentrated animal
feeding operations). IFAP model
has been exported to many othercountries including China, India
and Brazil.

Figure 19.3

CAFOs' biggest problem isroutine use of antibiotics →antibiotic-resistant bacterial
strains, which in turn may cause
antibiotics resistant humandiseases
IFAP animal waste is commonly
stored in large manure cesspits,then released to environment,
resulted in water and air
contamination

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