This document summarizes the key points about biodiversity loss and its impacts on human health and medication development. It discusses how biodiversity provides benefits through natural products that have led to many current medications, especially antibiotics and anticancer drugs. Loss of biodiversity limits these benefits as it reduces available natural compounds for medication research and development. This can increase health risks by reducing effective treatments for diseases. The document calls for policies to preserve biodiversity and incentivize natural product research to maintain these health benefits for current and future generations.

1. Biodiversity, Ethics, and Human
Health
Matthew A. Butkus, PhD
McNeese State University
April 24, 2009

2. Overview
The human brain is a wonderful thing. It
g
starts working from the moment you are
born and never stops until you stand up
p y p
to speak in public.
-Sir George Jessel

3. Overview
Basic assumptions
Ethical basis for obligations to future people
Current biodiversity loss
y
Current medication development
Biodiversity loss impacts antimicrobial
medications
Biodiversity loss impacts anticancer
medications
Ethical and Policy Implications

4. Basic Assumptions

5. Basic assumptions
Environmental ethics is ideologically diverse
◦ Should we conserve species or ecosystems?
◦ Is there a single principle that trumps others?
◦ Should we be more concerned about pragmatic
solutions than ethical principles?
◦ Does nature have value in itself, or does it have
value because it is useful to us?

6. Basic assumptions
My warrants
◦ Nature has intrinsic worth, but human-centered
approaches will likely be more effective
◦ Assumptions about the audience
Some have genuine interest
Some are apathetic
Some care more about health than the environment
Some are skeptical about the impact of biodiversity loss

7. Obligations to future people

8. Is there an obligation to future
generations?
Much of contemporary ethics involves
contemporaneous agents
Several important questions to ask
◦ How can we have obligations to non-existent
people?
◦ How do we know what their values and needs
will be?
◦ How can we compare their values and needs
with real, existent people?
◦ Why should we care about posterity?

9. Is there an obligation to future
generations?
Objection #1: The Argument from
j g
Ignorance
◦ We do not know whether there will be
anyone actually existing in the future or what
their needs might be.
◦ Past attempts to project into the future
produced wildly inaccurate pictures

10. Is there an obligation to future
generations?
Objection #1: The Argument from Ignorance
◦ Response: While some concerns may be
mysterious, others are considerably less so.
y y
We have maintained a generally constant interdependent
relationship with other organisms
We have maintained a generally constant vulnerability to
disease and infection
We have maintained a generally constant set of
biological
bi l i l needsd
We do hold people responsible for their past actions,
which allows us to extend responsibility for current
actions into the future

11. Is there an obligation to future
generations?
Objection #2: Disappearing beneficiaries
j pp g
◦ The people who exist in the future are
pp
directly dependent upon the choices we make
◦ We can’t be said to “harm” people
considering that they would not exist were it
not for our choices

12. Is there an obligation to future
generations?
Objection #2: Disappearing beneficiaries
◦ Response: First, rights transcend particular
people
l
The existence of concepts like justice and rights are
not dependent upon the existence of any particular
person
It does not matter which people will exist simply
exist,
that people will exist
This makes us liable for rights violations against
future people

13. Is there an obligation to future
generations?
Objection #2: Disappearing beneficiaries
j pp g
◦ Response: Second, comparison of types of life
p , p yp
make particular people irrelevant
Objectively, lives of happiness are better than lives
of suffering
We are wrong to place future people into
conditions of suffering when we could put them in
situations of sufficiency or abundance

14. Is there an obligation to future
generations?
Objection #3: The argument from
j g
temporal location
◦ We cannot know if or what harms may result
far in the future

15. Is there an obligation to future
generations?
Objection #3: The argument from
j g
temporal location
◦ Response: It does not follow that this negates
responsibility for action
There is more to moral agency and responsibility
than i
h intentions
i
Known risks do not excuse liability

16. Overall trends
It seems reasonable to suspect that future people
will have the same basic needs, basic rights claims
needs claims,
and the same ability to suffer
Actions that cause harm along these lines to
current people can cause harm to future people
We act unethically when we intentionally cause
these harms
Human disease offers a clear model of benefits
and harms

17. Current biodiversity loss

18. Current destruction of diverse
ecosystems
Estimates vary on the rate of destruction
Broadly speaking, major taxonomic losses
are increasing (International Union for the
Conservation of Nature statistics)

19. Current destruction of diverse
ecosystems
Human population is currently increasing (U S Census Bureau)
(U.S.
◦ Global population currently over 6.7 billion
◦ Increasing strain on limited resources (population outstripping
production with finite supplies)
◦ Population densities increasing in major urban areas
◦ Suburban sprawl increasing the overall land area of population centers
◦ Greater incursion into ecologically diverse areas (producing ‘hotspots’ –
Conservation International)

20. Current medications and derivation
from natural sources
Common k
C knowledge examples (Rishton
ld l (R h
2008)
◦ Digoxin from foxglove in 1785
◦ Morphine from poppies in 1806
◦ Aspirin from salicylic acid in willow bark in 1897
◦ Penicillin from mold in 1928

21. Current medication development

22. Current medications and derivation
from natural sources
Current World Health Organization list of 300 “Fundamental
Fundamental
Medicines” (Jones, Chin, and Kinghorn 2006)
◦ 44 are unmodified natural products
◦ 25 are semi-synthetic derivatives
◦ 70 based on/mimic natural products
◦ Natural advantages: great diversity, biologically selected, excellent
gg y, g y ,
source of novel compounds, offer insight into cellular
mechanisms, can guide drug design (Knight et al. 2003)

23. Current medications and derivation
from natural sources
Food d Drug Ad
F d and D Administration
◦ Between 1981-2002 1051 new chemical entities
1981-2002,
approved for testing
◦ 685 b d on natural products (NPs, semi-
based l d (NP i
synthetics, derivatives, vaccines, peptides, and
proteins)
◦ Evolutionary pressures favor natural product
research and development
p

24. Current medications and derivation
from natural sources
Currently used popular
medications derived from natural
products (Grifo et al. 1997)
◦ Levothyroxine (Synthroid)
◦ Lisinopril (Zestril)
◦ Digoxin
◦ Famotidine (Pepcid)
◦ Amoxicillin and clavulanic acid
◦ Atenolol (Tenormin)
(Augmentin)
◦ Cephalexin
p
◦ Albuterol
◦ Codeine
◦ Medroxyprogesterone acetate
◦
(Provera) Ipratropium bromide (Atrovent)
◦ Metoprolol tartrate (Lopressor) ◦ Erythromycin
◦ Ciproflaxin (Cipro) ◦ Hydrocodone & APAP (Vicodin)
◦ Warfarin Na (Coumadin) ◦ Prednisone
◦ MPH human insulin (Humulin N) ◦ Oxycodone

25. Current medications and derivation
from natural sources
Chemical differences between natural products and
synthetics (Koehn and Carter 2005)
◦ Greater number of chiral centers in natural products
◦ Generally more oxygen atoms in natural products (more
nitrogen, sulfur, and halogens in synthetics)
◦ Lower ratio of aromatic ring atoms to total heavy atoms
◦ More solvated hydrogen bond donors and acceptors
◦ Greater molecular rigidity
◦ These differences produce great compound diversity, activity, and
the potential f more bi l i ll validated l d compounds
h i l for biologically lid d lead d
◦ Historical production involved cooperation between medicinal
chemistry and cultural anthropology

26. Current medications and derivation
from natural sources
Natural product research no longer the emphasis
in current chemical research (5 sources)
◦ Initial difficulties in production incompatible with
market pressures for efficiency and competition
◦ Less emphasis on antimicrobials and more emphasis
on lifestyle medications
y
◦ Impurities in natural samples undermined ease of
analysis
li

27. Current medications and derivation
from natural sources
◦ Combinatorial chemistry
Traditional approach slow and low yield: A + B AB
Combinatorial approach rapid and yields much more
diversity: {A} + {B} {AB}
Computer modeling assists combinatorial methods
◦ High-throughput screening
Rapid screening of a large volume of compounds against
a particular biological target
Produces high volumes of hits that may yield future
medications

28. Current medications and derivation
from natural sources
◦ In principle, combining combinatorial
chemistry and high-throughput screening
should yield major breakthroughs and novel
classes of medications
◦ Empirically, this theorized delivery has not
occurred, producing calls for a return to
d di ll f
natural product bases (5 sources)

29. Biodiversity loss impacts
antimicrobial medications

30. Biodiversity impacts drug resistance
in infectious agents
Infection a recurring issue in human history
◦ Black Death in Europe (bubonic, pneumonic, and
septicemic)
◦ Battlefield injuries as vectors for infection
◦ Germ theory and modern infection control have
helped to dd
h l d t address thi
this

31. Biodiversity impacts drug resistance
in infectious agents
Significant concern in contemporary
Sf
medicine is the resurgence of medication-
resistant infectious disease (9 sources)
◦ Antibiotics becoming less and less effective as
microbial resistance evolves (Barker 2006)
Mutations in the target drug site
Modifications in cell permeability
Mutagenesis of porins
M f
Up-regulation of efflux pumps
Inactivation of drugs by enzymatic degradation

32. Biodiversity impacts drug resistance
in infectious agents
◦ Hospitals major sources of bacterial infections -
nosocomial infections (Bonten, Willems, and Weinstein
2001; Rice 2001; Appelbaum 2006)
VRE
MRSA/VRSA
C. Diff
Hospital infections account for nearly 80 000 deaths per year
80,000
(Jones 2001)
Hospital infections now occurring in community settings (Wijaya,
Hsu,
Hsu and Kurup 2006; McKinnon 2007)

33. Biodiversity impacts drug resistance
in infectious agents
◦ Drug-resistant tuberculosis is now emerging in
more virulent forms (Ducati et al. 2006)
1 in 3 people on Earth is infected with tubercle bacilli
Responsible f 8-10 million new cases and 3 million
R bl for 8 10 ll d ll
deaths per year
As transportation infrastructure improves, this is
becoming a global problem (Sharma and Mohan 2006;
Ernst, Trevejo-Nuñez, and Banaiee 2007; Wells et al.
2007)

34. Biodiversity impacts drug resistance
in infectious agents
Natural products aid antimicrobial drug development
◦ Targetting RNA replication
◦ Cell wall biosynthesis
◦ Metabolic pathways
◦ Cellular division
◦ Virulence factors
◦ Ribosomal sites of protein synthesis and modification
p y

35. Biodiversity loss impacts anticancer
medications

36. Biodiversity impacts research on
cell pathways and anti-cancer
anti-
medications
Cancer has an enormous impact on human health
(Tan et al. 2006)
◦ Globally, 11 million new cases and 7 million deaths
annually
◦ 25 million people living with the disease at any given
time
◦ In the United States, 1 in 4 deaths is due to some
form of cancer, accounting for 500,000 deaths
annually
y

37. Biodiversity impacts research on
cell pathways and anti-cancer
anti-
medications
Natural product research has been key in
the understanding of the cellular division
g
process (Cragg and Newman 2001)
NP’s have offered insight into pathway
aberrations in malignant cell growth
growth,
providing avenues of research (5 sources)

38. Biodiversity impacts research on
cell pathways and anti-cancer
anti-
medications
New avenues of research are emerging, with
several biological compound types showing
promise
◦ Turpenes (Modzelewska et al. 2005)
◦ Microtubule inhibitors (Altmann and Gertsch
2007)
◦C
Cyanobacteria d i ti
b t i derivatives (Tan 2007)
(T

39. Biodiversity impacts research on
cell pathways and anti-cancer
anti-
medications
◦ Turpenes (Modzelewska et al. 2005)
30,000+ terpenoids have been identified
Sesquiturpenes (conjugated 15C chains) involved as
part of plant interactions with insects and
pathogens
Found to have antimicrobial, antitumor, and
cytotoxic effects

40. Biodiversity impacts research on
cell pathways and anti-cancer
anti-
medications
◦ Microtubule inhibitors (Altmann and Gertsch
2007)
Microtubules critical in cell membranes, organelle
and vesicle transport, and cellular division
transport
Taxol increases microtubule polymerization,
inducing cellular apoptosis
Many novel cytotoxic compounds have been
identified of varying efficacy

41. Biodiversity impacts research on
cell pathways and anti-cancer
anti-
medications
◦ Cyanobacteria derivatives (Tan 2007)
100+ marine alkaloids have been identified and are
being explored
Additional research occurring in hectochlorins
hectochlorins,
lyngbyabellins, apratoxins, and aurilides

42. Ethical and Policy Implications

43. Ethical and policy implications
Preserve existent biodiversity
◦ Failure to preserve biodiversity generates future
health problems
◦ Empirical basis: Global Seed Vault established by
p ca bas s: G oba S au t stab s
NORDGEN (Denmark, Finland, Iceland, Norway,
and Sweden) at Svalbard
◦ Goal is to minimize loss; complete avoidance of
biodiversity loss is unlikely
y y

44. Ethical and policy implications
Develop economic and agriculture
alternatives to development in ecosystem
‘hospots’
◦ Use market forces to incentivize
environmental responsibility and biodiversity
maintenance
◦ Aid programs to reduce incentive to develop
diverse areas for agriculture

45. Ethical and policy implications
Revision of chemical research techniques
and economic incentives
◦ Improve efficiency of natural product research
Screening processes already more efficient
Manipulate biosynthetic pathways
Use NP’s as the building blocks of other molecules
Use NP fragments for recombination
fra ments f r rec mbinati n
Complete synthesis of NP analogues
Use NP scaffolds to develop new chemical entities
Develop NP libraries

46. Ethical and policy implications
Revision f h i l
R i i of chemical research t h i
h techniques
and economic incentives
◦ Use market forces to increase incentives to
develop natural products
Tax incentives
Extension of drug patents
Regulation to protect intellectual property and research
regions
Incentives to explore biologically active leads
State and federal assistance in refitting laboratories and
databases

47. The last conclusion we would like to draw is
that mother nature, whether you conceive
of her as the process of evolution or with
religious or pagan conviction, is a far better
conviction better,
more ingenious chemist (and many other
things as well) than we will ever be. So until
g )
we can know which bits of nature hold
which information, we are playing roulette
each time a species goes extinct.
hi i i
- G if et al. 1997
Grifo l

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El t iS
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April 22, 2009).
22 2009)
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(
(Accessed April 22, 2009).
p )