ENVIRONMENTAL RESEARCH: LINK TO HUMAN HEALTH Mar4n Cormican, Centre for Health from Environment Ryan Ins4tute, Na4onal University of Ireland, Galway An#microbial Resistance and Microbial Ecology Group School of Medicine, NUI Galway What Will I Say In 45 Minutes ?
•  Humpty Dumpty & Words
•  Health & Disease
•  Water & Disease
•  The End of the World as we (microbiologists) know it
•  Disease & Disability Care & Environment
•  Environment & Health
•  Stewardship
•  The planet does not need saving
Lewis Carroll
Through the Looking Glass
•  “When I use a word”,
Humpty Dumpty said, in
a rather scornful tone, ‘it
means just what I
choose it to mean –
neither more nor less’
The Old Chestnut: Health ?
“a state of complete physical, mental and
social well-being
and
not merely the absence of disease”.
WHO Definition
4
The Other Word: Environment ?
Centre for Health from Environment
• All that is external to the human host: it can be divided
into physical, biological,
social, and cultural spheres”.
• (Last 1995)
• Mike Depledge even wider definition
5
So By This Definition It Would Seem
You Are Responsible for Protecting
Life, the Universe & Everything
6
The Other Word: Environment
• 1992 & 2003 Acts
• Refer to “the preservation of the quality of the environment
as a whole”.
• Define environmental protection, environmental pollution,
environmental medium and environmental quality standard
but not environment
• Probably more emphasis on physical & biological rather than
directly on social & cultural but
7
Smoking at home may cause as many fatalities as road
crashes
Dr. Marie Coggins. Irish Times 21-05/2013
http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0668.2011.00755.x/abstract
8
The Environmental Media
Atmosphere
Waters
&
Land
9
Waters & The Challenge of Focusing on
Health from Environment
The basis for health & life
The basis for prosperity
We have a lot of it
But so what ?
10
Stuff in Water & Disease from Environment
• Mostly we talk about threats & perceived threats
• 1. Pathogens: VTEC, Cryptosporidium, Giardia, Hepatitis
A virus, Norovirus, Legionella & More
• 2. Antibiotic Resistant Microorganisms
• 3. Compounds – Arsenic, Aluminium, Fluoride
11
Stuff in Water & Disease
• So we tend to focus on taking known bad things out of
water to get good water
• But there is a lot of other stuff in water
• Claimed benefits in terms of taste & health (“minerals”)
• Other water microbes & hygiene hypothesis
• We don’t much know about what we do to the other
microbes in water treatment systems
12
Stuff in Water & Disease
• Does it matter for health if water is perceived as
unpalatable ?
It sure matters to sense of wellbeing
You can measure how much it matters in €
13
Water & Microbes & Disease
•  How do we communicate to the public about faecal
contamination of water ?
•  Kamal Kar
•  Tell people “there is s**t in the water”
•  http://www.communityledtotalsanitation.org
14
Finding Out if there is S*** In the Water
• Culture of indicator organisms E. coli & Enterococci
• Detection of pathogens: VTEC, Norovirus
• Detection of antimicrobial resistant indicator bacteria
in water
15
What’s Good About Our Traditional / Legal
Indicator Organisms ?
• E. coli
• General Coliforms” [Enterobacteriaceae]
• Enterococci
• C. perfringens
• 1. Gut microbes = faeces (not so much with GCC)
• 2. Fast & Easy to grow (for decades)
• 3. Mostly killed by chlorination (not so much for
Clostridum spores)
16
What’s Not so Good About Our Traditional /
Legal Indicator Organisms
• 1. Standards generally based on small volume grab samples
(100ml)
• 2. Implicit assumption that microbial faecal contamination
does not matter if you kill/inactivate bacteria so they can not
be grown (dead s**t doesn’t matter)
• 3.We don’t know who’s gut they came from (human/cow?)
17
A Added Dimensions to Traditional Indicator
Organisms ?
AMR in the Aquatic Environment
18
Antimicrobial Resistance
The Latest Concern CPE
Carbapenemase
Producing
Enterobacteriaceae
(CPE/CRE)
Some resistant to all but
a few difficult to use
antibiotics
19
Antimicrobial Resistance
The Latest Concern
20
You Don’t Need to Go to New Delhi
The Latest Big Worry
Carbapenemase
Producing
Enterobacteriaceae
21
Antimicrobial Resistance
The Latest Concern
22
AMR & GiSMOs
• GiSMO
• Genetically Self Modified Organisms
• Natural Genetic Modification in Bacteria is a constant natural
process that generates novel variants
• Powerful selection forces result in rapid displacement of
established forms by novel variants (invasive species)
23
Experimental Generation of AMR Variants
• Imaginary Experiment -1
• A CPE producing K. pneumoniae
• CPE gene & multiple other AMR genes on a plasmid
• Conjugative transfer into Salmonella Typhi (Typhoid fever)
• Salmonella Typhi Resistant to essentially all know effective
treatments
• That is not a GM micro-organism
24
Experimental Generation of AMR Variants
• Imaginary Experiment -2
• E. coli K1 with a plasmid encoding a gene that makes it
dependent on a specific nutrient
• To force it to retain the plasmid you want to build a blaTEM
(ampicillin resistant) gene into the plasmid & grow E. coli in
presence of Ampicillin
• That is a GM micro-organism
25
Experimental Generation of AMR Variants
• Imaginary Experiment -1
• Generates a profoundly dangerous organism if it escapes into
a setting of poor sanitation & selection pressure
•  Not a GM Micro-organism
• Imaginary Experiment -2
• Generates a pussy cat that probably can’t live unless you
mind it
• Is GM Microorganism
26
Is the GMO Contained Use Directive
Scientifically Misdirected ?
•  We have a whole series of GiSMOs that have become
established as threats to human health because of anthropic
selection, (perhaps aided by effluent discharges)
•  Has this happened for any GMO ?
27
Is the GMO Contained Use Directive
Scientifically Misdirected ?
•  It appears to be predicated on the assumption that genetic
recombination in bacteria is largely a human activity
•  It appears to focus on process (how the variant is made)
over product (the potential of the variant to do harm)
•  It appears to give priority to genetic variation over
selection (variants even if they escape will disappear if
not selected)
28
Genetic Modification in Bacteria
• If you build it they will come
• If we make the selection force the bacteria will do the genetic
modification
• In the absence of selection the genetic modification does not
matter
29
What’s Not so Good About Our Traditional /
Legal Indicator Organisms
•  Absence of Indicator Organisms Does not Ensure absence of
pathogens
•  Vero-Toxigenic E. coli ( does not come out as E. coli on many tests)
•  Cryptosporidium (Galway 2007, Roscommon 2013)
•  Norovirus
30
CAPE – CAPTURE, EXTRACT, AMPLIFY: A RAPID METHOD FOR MONITORING LARGE WATER VOLUMES FOR PATHOGENIC CONTAMINANTS Na4onal University of Ireland, Galway An#microbial Resistance and Microbial Ecology Group School of Medicine, NUI Galway Vero-­‐toxigenic E. coli (VTEC)? S > 535 VTEC no4fica4ons in 2012 S  251 in 2011 S  194 in 2010. S  Two variants of VTEC O157, O26 cause most disease in Ireland S  But there are other VTEC’s S  E. coli 0104 caused a major foodborne outbreak origina4ng in Northern Germany in 2011: 3821 cases, 14 countries, 793 cases developed HUS and 47 deaths. An#microbial Resistance and Microbial Ecology Group School of Medicine, NUI Galway VTEC infec4on In The News An#microbial Resistance and Microbial Ecology Group School of Medicine, NUI Galway Finding Vero-­‐toxigenic E. coli (VTEC)? S  It is a lot like other non pathogenic E coli S Looking for V. cholerae in faeces /
feacally contaminated water is looking for a needle in a haystack S Looking for VTEC in faeces/ faecally contaminated water is looking for a slightly different needle in a needle stack An#microbial Resistance and Microbial Ecology Group School of Medicine, NUI Galway Linking VTEC in the Water With Disease S
Molecular Typing – how similar is the DNA in the VTEC needles (1) in the water and (2) in the pa4ents faeces ? S
PFGE Banding Paierns An#microbial Resistance and Microbial Ecology Group School of Medicine, NUI Galway CapE Project Aim To develop, validate and implement a convenient and effec4ve method for harves4ng microbial nucleic acid from large volumes of water for molecular detec4on of human pathogens, e.g. VTEC An#microbial Resistance and Microbial Ecology Group School of Medicine, NUI Galway ISO method for detec4on of VTEC S
Grab a litre of water S
Filter to trap bacteria on filter paper S
Culture bacteria in liquid S
DNA amplifica4on on liquid to look for VTEC virulence An#microbial Resistance and Microbial Ecology Group School of Medicine, NUI Galway CapE Plan S
Filter a large volume on site
S
Then A (Culture Dependent)
S
Culture the filter in liquid
S
DNA amplification to look for VTEC
virulence
S
and B (Culture Independent)
S
Extract DNA direct from filter
S
DNA amplification to look for VTEC
virulence
An#microbial Resistance and Microbial Ecology Group School of Medicine, NUI Galway The Story So Far S
We have found VTEC (O26) in the river Corrib by culture
dependent examination of large volume filters
S
We are working on direct comparison with conventional
Grab samples
S
Culture dependent at present has a lower limit of
detection than Culture Independent
S
So why pursue working with direct DNA amplification ?
An#microbial Resistance and Microbial Ecology Group School of Medicine, NUI Galway Why Pursue Direct DNA Detec4on ? The Future S
Direct detec4on could be faster S
We hope to lower limits of detec4on S
It may have applica4ons in assessing water where culture is imprac4cal (remote areas) S
BUT MOST OF ALL – The Rumsfeld Factor An#microbial Resistance and Microbial Ecology Group School of Medicine, NUI Galway The Rumsfeld Factor Stuff we Don’t Know Enough About S
Free DNA/Phage/Protozoan parasites/Pathogenic Viruses that do not grow in conven4onal culture S
Vast majority of other microbes in water do not grow in conven4onal laboratory cultures (and they may maier for health) S
Can look for par4cular targets with specific DNA/RNA Amplifica4on to iden4fy micro-­‐organisms of interest An#microbial Resistance and Microbial Ecology Group School of Medicine, NUI Galway For Example: Molecular Source Tracking
Finding Out Who’s S*** In the Water
42
Finding Out Who’s S*** In the Water
The End of World As We Know It S
Next Genera4on Sequencing An#microbial Resistance and Microbial Ecology Group School of Medicine, NUI Galway The End of World As We Know It •  No more gel electrophoresis based
typing, or phage typing or serotyping or
biotyping ?
• Whole genome sequencing (WGS)
• All 5 million nucleotides
• Compare the sequences of the isolates
The End of World As We Know It
The Next Wave : Metagenomics
•  “The term metagenomics is applied to
the open-ended sequencing of nucleic
acids recovered directly from samples
without target-specific amplification or
enrichment” Lohman et al.
The Next Wave : Metagenomics
1.Extract all the DNA
2. Enzymatically break it into millions of
little bits (tagmentation)
3. Sequence all the little bits
4.Vast data file of reads of 100- 250 base
pairs
Metagenomics 1: Making the Library
Breaking Up the DNA from the Filter
Metagenomics 2: Sequencing All the Little
Pieces
ANIMATION
http://www.wellcome.ac.uk/stellent/groups/corporatesite/
@msh_publishing_group/documents/video/WTX056031.swf
And That’s the Easy Bit
Millions of Little Bits of Overlapping Sequence
Who remembers Hot Chocolate
put you together again
Assembly
Millions of Little Bits of Overlapping Sequence
Metagenomics Assembly
•  1. The assembly phase,
•  2. The alignment phase
•  3. The phylogenetic phase
The End of the World As We Know It ?
•  “It’s tough to make predictions especially
about the future”
•  Yogi Berra
The End of the World As We Know It ?
•  It will soon be difficult to publish research that involves
bacterial typing methods other than WGS/NGS in first ranked
journals
•  All bacterial typing method other than WGS/NGS could be
obsolete within 5 to 10 years
•  Culture could be largely a supplementary method for many
samples within 5 to 10 years
The End of the World As We Know It ?
•  Bacterial culture may be almost obsolete well within my working life
•  Maybe even specific DNA target amplification will be obsolete within my
working life
•  The limiting factors, increasingly focus is on computational power, data storage
and band-with
•  Doing the sequencing may be the easy & cheap bit ( if you have the instrument)
•  [ If fact some people are now exploring DNA synthesis as a method for long term
data archiving]
•
Applications to Water
• Total microbial DNA from a single sample
interrogated for sequence markers for indicator
organisms, pathogens, antimicrobial resistance
determinants, animal species specific bacteria
• Maybe even sequences of DNA from pig/human/
cow/dog if you capture that DNA
Applications Also to other Environmental
Media & Biodiversity
Atmosphere
Land
58
Bringing My Head Back Above Water
Why A Centre for Health from Environment?
59
The Broader Issues
Health – Environment – Disease
Talking About Health in
Ireland
- Trolleys in ED
- Waiting lists
- 5 year survivals
- Screening programmes
- Medical cards
60
What The Healthcare Services Do
1. Diagnosis of Disease & Disability
2. Treatment & Management of Disease & Disability
3. Screening for Early Diagnosis of Disease
4.  Some Health Promotion
(Largely Advice on Disease Avoidance)
61
So Healthcare Services is a Misnomer
Disease & Disability Detection &
Management Service
(D&DDMS)
which is really important when you need it
62
& Then There is the Disease Promotion
Sector
An anxiety about every ache
A test for every trouble
A diagnosis for every difficulty
A pill for every problem
63
Disease Promotion
64
Disease & Disability Detection &
Management
Is a pillar of a humane society
but unwanted impacts are /may be
substantial and not adequately questioned
65
Disease & Disability Detection &
Management
Unwanted impacts
1. Environmental Impact of this Sector
Energy / Resources / Discharges
2. Disempowerment & Negative Impact on Sense of Health &
Wellbeing
3. Health Opportunity Costs
66
The Disease & Disability Detection &
Management Sector
Why Impacts are Unquestioned
Who Can Question the Saving Lives
But
No Lives Were Saved Anywhere Today !
67
Measuring the Good Stuff from Disease &
Disability Detection & Management Sector
Quality Adjusted Life Years (QALY’s)
1 Year of Life in Full Health = 1 QALY
1 Year of Life in Poor Health < 1 QALY
(difficulties of quantifying the “deduction”
for poor health”)
68
Measuring the Good Stuff from Disease &
Disability Detection & Management Sector
Quality Adjusted Life Years (QALY’s)
Restores a dying newborn to full health –
lots of QALY’s
Keeps me alive to go back to a nursing
home with profound cognitive and physical
impairment – few QALYS
69
Measuring the Cost of Disease & Disability
Detection & Management Sector
Environmental Impact
Opportunity Costs
Greatest towards the end of life when the
QALY’s gained are least
70
The Disease Promotion Sector
Environmental & Wellbeing Impact
Opportunity Costs
With little or no evidence of any QALY’s
71
Live’s Can’t Be Saved
Life can Be Enhanced
Life can Be Extended
Life Can Be Eased
A Life can be Spent
72
Live’s Can’t Be Saved
A Life can be Spent
in freedom to do the things you “have
reason to value” [ A. Sen]
And then we all die
73
Recycling Ourselves
Dealing with Human Mortality is a
Fundamental Issue for the Environment &
for Health Equity in the 21st Century
“Golden lads and girls all must
As chimney sweepers, come to dust”
74
Questioning the D&DD&M & Disease
Promotion
A powerful environmentally unsustainable
vested interest
It takes attention & resources from much
more effective measures for health
e.g. physical, biological, social & cultural
environment
75
What Determines Health?
“whether people are healthy or not, is determined by
their circumstances and environment ---whereas the more commonly considered factors such
as access and use of health care services often have
less of an impact”.
76
Is There Hope of Change
Healthy Ireland 2013
Health is much more than
an absence of disease or
disability, and individual
health, and that of the
country, affects the quality
of everyone’s lived
experience.
Healthy Ireland 2013
Healthy Ireland 2013
Health is an essential
resource for everyday life, a public
good, and an asset for health and
human development.
Placing Human Health at The Centre of
Environmental Policy
80
Misantropic Environmentalists
The perception that some in the environmental
movement are interested primarily in butterflies and
bats and hostile to people & “development”
” rather shoot a human than shoot a snake"
Edward Abbey
81
Anthropocentric Environmentalists
Emphasise human and environmental interdependence
Health
Ecosystem services
82
Pragmatic Environmentalists are
Anthropocentric
Homo sapiens are the dominant species
We are profoundly self interested
We are not outside of the “natural environment”
We are not an invasive /alien species
“one of the main reasons the world faces a global
environmental crisis is the belief that we human beings
are somehow separate from the natural world in which
we live”. Kofi Anan
83
Pragmatic Environmentalists are Anthropocentric
Stewardship accepts human influence on the global
environment to meet human needs
Reserved/preserved ecosystems are and will be
relatively small & becoming smaller
(11 billion by 2200)
And will only be supported by communities if their basic
needs are met
And they are seen to be of value to communities
84
Global Stewardship & Environmental Justice
Poverty and inequity are both consequence and a cause
of poor health and environmental degradation
Real progress on environmental stewardship can not be
made without addressing justice
85
Why a Centre for Health from
Environment at the Ryan Institute
•  To provide a focus for those (small numbers)
already interested in the area
•  To try to draw more people to a environmental
perspective on health and an anthropocentric
view of the environment (your support is & has
been very valuable)
•  To develop scholarship and research in these
areas in Ireland
86
Environmentalism for this Century
•  Its not about saving the
planet
•  The planet doesn’t need us
•  Its about saving human
civilisation
87
With Thanks To Some of the
Enthusiasts
•  Diarmuid O’Donovan
•  Martina Prendergast
•  Colin Brown
•  Sarah Knight
•  Dearbhaile Morris
•  Maurice Mulcahy
•  Sandra Galvin
•  Brian Quinn
•  Siobhan Kavanangh
•  Eoghan Clifford
•  Mark Healy
•  Su-ming Khoo
•  Marie Coggins
•  Miriam Byrne
•  Henrike Rau
•  Enda Cummins
88
The End Quote
Sustainable Development is not a New Idea
•  “The produce of the earth is a gift ------ to the inhabitants, and
to impoverish the earth now to support outward greatness
appears to be an injury to the succeeding age.”
•  John Woolman 1772
89