Biodiveristy, Ethics, and Human Health

Biodiversity, Ethics, and Human Biodiversity, Ethics, and Human Biodiversity, Ethics, and Human Biodiversity, Ethics, and Human HealthHealth

Matthew A. Butkus, PhDMcNeese State UniversityApril 24, 2009

OverviewOverviewOverviewOverview

The human brain is a wonderful thing. It gstarts working from the moment you are born and never stops until you stand up p y pto speak in public.

-Sir George Jessel

OverviewOverviewOverviewOverviewBasic assumptionsEthical basis for obligations to future peopleCurrent biodiversity lossyCurrent medication developmentBiodiversity loss impacts antimicrobial Biodiversity loss impacts antimicrobial medicationsBiodiversity loss impacts anticancer Biodiversity loss impacts anticancer medicationsEthical and Policy ImplicationsEthical and Policy Implications

Basic AssumptionsBasic AssumptionsBasic AssumptionsBasic Assumptions

Basic assumptionsBasic assumptionsBasic assumptionsBasic assumptionsEnvironmental 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?value because it is useful to us?

Basic assumptionsBasic assumptionsBasic assumptionsBasic assumptionsMy warrants

◦ Nature has intrinsic worth, but human-centered approaches will likely be more effective

◦ Assumptions about the audienceSome have genuine interestSome are apatheticSome are apatheticSome care more about health than the environmentSome are skeptical about the impact of biodiversity loss

Obligations to future peopleObligations to future peopleObligations to future peopleObligations to future people

Is there an obligation to future Is there an obligation to future generations?generations?

Much of contemporary ethics involves contemporaneous agents

Several important questions to ask◦ How can we have obligations to non-existent

people?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?◦ Why should we care about posterity?

Is there an obligation to future Is there an obligation to future generations?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

Is there an obligation to future Is there an obligation to future generations?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 organismsWe have maintained a generally constant vulnerability to disease and infectionWe have maintained a generally constant set of bi l i l dbiological needsWe do hold people responsible for their past actions, which allows us to extend responsibility for current actions into the futureactions into the future

Is there an obligation to future Is there an obligation to future generations?generations?Objection #2: Disappearing beneficiariesj pp g

◦ The people who exist in the future are p pdirectly 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

Is there an obligation to future Is there an obligation to future generations?generations?Objection #2: Disappearing beneficiaries

◦ Response: First, rights transcend particular lpeople

The existence of concepts like justice and rights are The existence of concepts like justice and rights are not dependent upon the existence of any particular personIt does not matter which people will exist simply It does not matter which people will exist, simply that people will existThis makes us liable for rights violations against future people

Is there an obligation to future Is there an obligation to future generations?generations?Objection #2: Disappearing beneficiariesj pp g

◦ Response: Second, comparison of types of life p , p ypmake particular people irrelevant

Objectively, lives of happiness are better than lives of sufferingWe are wrong to place future people into We are wrong to place future people into conditions of suffering when we could put them in situations of sufficiency or abundance


Objection #3: The argument from j gtemporal location

◦ We cannot know if or what harms may result far in the future


Objection #3: The argument from j gtemporal location

◦ Response: It does not follow that this negates responsibility for action

There is more to moral agency and responsibility h i ithan intentions

Known risks do not excuse liability

Overall Overall trendstrendsOverall Overall trendstrendsIt seems reasonable to suspect that future people will have the same basic needs basic rights claims will have the same basic needs, basic rights 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

Current biodiversity lossCurrent biodiversity lossCurrent biodiversity lossCurrent biodiversity loss

Current destruction of diverse Current destruction of diverse ecosystemsecosystems

Estimates vary on the rate of destruction

Broadly speaking, major taxonomic losses are increasing (International Union for the are increasing (International Union for the Conservation of Nature statistics)

Current destruction of diverse Current destruction of diverse ecosystemsecosystems

Human population is currently increasing (U S Census Bureau)Human population is currently increasing (U.S. Census Bureau)

◦ 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◦ 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)

Current medications and derivation Current medications and derivation from natural sourcesfrom natural sources

C k l d l (R hCommon knowledge examples (Rishton2008)

◦ Digoxin from foxglove in 1785

◦ Morphine from poppies in 1806

◦ Aspirin from salicylic acid in willow bark in 1897Aspirin from salicylic acid in willow bark in 1897

◦ Penicillin from mold in 1928

Current medication developmentCurrent medication developmentCurrent medication developmentCurrent medication development


Current World Health Organization list of 300 “Fundamental Current World Health Organization list of 300 Fundamental Medicines” (Jones, Chin, and Kinghorn 2006)

◦ 44 are unmodified natural products44 are unmodified natural products

◦ 25 are semi-synthetic derivatives

◦ 70 based on/mimic natural products

◦ Natural advantages: great diversity, biologically selected, excellent g g y, g y ,source of novel compounds, offer insight into cellular mechanisms, can guide drug design (Knight et al. 2003)


F d d D AdFood and Drug Administration

◦ Between 1981-2002 1051 new chemical entities ◦ Between 1981-2002, 1051 new chemical entities approved for testing

685 b d l d (NP i◦ 685 based on natural products (NPs, semi-synthetics, derivatives, vaccines, peptides, and proteins)

◦ Evolutionary pressures favor natural product research and developmentp


Currently used popular Currently used popular medications derived from natural products (Grifo et al. 1997)

◦ Levothyroxine (Synthroid)◦ Levothyroxine (Synthroid)◦ Digoxin◦ Amoxicillin and clavulanic acid

(Augmentin)◦ Albuterol

◦ Lisinopril (Zestril)◦ Famotidine (Pepcid)◦ Atenolol (Tenormin)◦ CephalexinAlbuterol

◦ Medroxyprogesterone acetate (Provera)

◦ Metoprolol tartrate (Lopressor)◦ Ciproflaxin (Cipro)

p◦ Codeine◦ Ipratropium bromide (Atrovent)◦ Erythromycin◦ Hydrocodone & APAP (Vicodin)Ciproflaxin (Cipro)

◦ Warfarin Na (Coumadin)◦ MPH human insulin (Humulin N)

Hydrocodone & APAP (Vicodin)◦ Prednisone◦ Oxycodone


Chemical differences between natural products and Chemical differences between natural products and synthetics (Koehn and Carter 2005)

◦ Greater number of chiral centers in natural productsGreater 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

h i l f bi l i ll lid d l d dthe potential for more biologically validated lead compounds◦ Historical production involved cooperation between medicinal

chemistry and cultural anthropology


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 medicationsy

◦ Impurities in natural samples undermined ease of l ianalysis


◦ Combinatorial chemistryTraditional approach slow and low yield: A + B ABCombinatorial approach rapid and yields much more Combinatorial approach rapid and yields much more diversity: {A} + {B} {AB}Computer modeling assists combinatorial methods

◦ High-throughput screeningRapid screening of a large volume of compounds against Rapid screening of a large volume of compounds against a particular biological targetProduces high volumes of hits that may yield future medicationsmedications


◦ In principle, combining combinatorial chemistry and high-throughput screening should yield major breakthroughs and novel classes of medications

◦ Empirically, this theorized delivery has not d d i ll f occurred, producing calls for a return to

natural product bases (5 sources)

Biodiversity loss impacts Biodiversity loss impacts antimicrobial medicationsantimicrobial medications

Biodiversity impacts drug resistance Biodiversity impacts drug resistance in infectious agentsin 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 h l d t dd thihelped to address this


S f Significant concern in contemporary medicine is the resurgence of medication-resistant infectious disease (9 sources)resistant infectious disease (9 sources)

◦ Antibiotics becoming less and less effective as microbial resistance evolves (Barker 2006)microbial resistance evolves (Barker 2006)

Mutations in the target drug siteModifications in cell permeabilityM f Mutagenesis of porinsUp-regulation of efflux pumpsInactivation of drugs by enzymatic degradation


◦ Hospitals major sources of bacterial infections ◦ 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 Hospital infections account for nearly 80,000 deaths per year (Jones 2001)

Hospital infections now occurring in community settings (Wijaya, Hsu and Kurup 2006; McKinnon 2007)Hsu, and Kurup 2006; McKinnon 2007)


◦ 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

R bl f 8 10 ll d 3 ll Responsible for 8-10 million new cases and 3 million 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)2007)


Natural products aid antimicrobial drug developmentNatural products aid antimicrobial drug development

◦ Targetting RNA replication

◦ Cell wall biosynthesis

◦ Metabolic pathwaysMetabolic pathways

◦ Cellular division

◦ Virulence factors

◦ Ribosomal sites of protein synthesis and modificationp y

Biodiversity loss impacts anticancer Biodiversity loss impacts anticancer medicationsmedications

Biodiversity impacts research on Biodiversity impacts research on cell pathways and anticell pathways and anti--cancer cancer cell pathways and anticell pathways and anti cancer cancer medicationsmedications

Cancer has an enormous impact on human health 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 annuallyy


Natural product research has been key in the understanding of the cellular division gprocess (Cragg and Newman 2001)

NP’s have offered insight into pathway aberrations in malignant cell growth aberrations in malignant cell growth, providing avenues of research (5 sources)


New avenues of research are emerging, with several biological compound types showing promisepromise

◦ Turpenes (Modzelewska et al. 2005)Turpenes (Modzelewska et al. 2005)

◦ Microtubule inhibitors (Altmann and Gertsch2007)

C b t i d i ti (T 2007)◦ Cyanobacteria derivatives (Tan 2007)

Biodiversity impacts research on Biodiversity impacts research on cell pathways and anticell pathways and anti--cancer cancer cell pathways and anticell pathways and anti cancer cancer medicationsmedications◦ Turpenes (Modzelewska et al. 2005)

30,000+ terpenoids have been identifiedSesquiturpenes (conjugated 15C chains) involved as part of plant interactions with insects and part of plant interactions with insects and pathogensFound to have antimicrobial, antitumor, and cytotoxic effects

Biodiversity impacts research on Biodiversity impacts research on cell pathways and anticell pathways and anti--cancer cancer cell pathways and anticell pathways and anti cancer cancer medicationsmedications◦ Microtubule inhibitors (Altmann and Gertsch

2007)

Microtubules critical in cell membranes, organelle and vesicle transport and cellular divisionand vesicle transport, and cellular divisionTaxol increases microtubule polymerization, inducing cellular apoptosisMany novel cytotoxic compounds have been identified of varying efficacy

Biodiversity impacts research on Biodiversity impacts research on cell pathways and anticell pathways and anti--cancer cancer cell pathways and anticell pathways and anti cancer cancer medicationsmedications◦ Cyanobacteria derivatives (Tan 2007)

100+ marine alkaloids have been identified and are being exploredAdditional research occurring in hectochlorins Additional research occurring in hectochlorins, lyngbyabellins, apratoxins, and aurilides

Ethical and Policy ImplicationsEthical and Policy ImplicationsEthical and Policy ImplicationsEthical and Policy Implications

Ethical and policy implicationsEthical and policy implicationsEthical and policy implicationsEthical and policy implicationsPreserve existent biodiversity

◦ Failure to preserve biodiversity generates future health problemshealth problems

◦ Empirical basis: Global Seed Vault established by p ca bas s: G oba S au t stab s by NORDGEN (Denmark, Finland, Iceland, Norway, and Sweden) at Svalbard

◦ Goal is to minimize loss; complete avoidance of biodiversity loss is unlikelyy y

Ethical and policy implicationsEthical and policy implicationsEthical and policy implicationsEthical and policy implicationsDevelop economic and agriculture alternatives to development in ecosystem ‘hospots’

◦ Use market forces to incentivize environmental responsibility and biodiversity environmental responsibility and biodiversity maintenance

◦ Aid programs to reduce incentive to develop diverse areas for agriculture

Ethical and policy implicationsEthical and policy implicationsEthical and policy implicationsEthical and policy implications

Revision of chemical research techniques and economic incentives

◦ Improve efficiency of natural product researchScreening processes already more efficientScreening processes already more efficientManipulate biosynthetic pathwaysUse NP’s as the building blocks of other moleculesUse NP fra ments f r rec mbinati nUse NP fragments for recombinationComplete synthesis of NP analoguesUse NP scaffolds to develop new chemical entitiesDevelop NP libraries

Ethical and policy implicationsEthical and policy implicationsEthical and policy implicationsEthical and policy implications

R i i f h i l h t h i Revision of chemical research techniques and economic incentives

◦ Use market forces to increase incentives to develop natural products

Tax incentivesTax incentivesExtension of drug patentsRegulation to protect intellectual property and research regionsregionsIncentives to explore biologically active leadsState and federal assistance in refitting laboratories and databases

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 religious or pagan conviction, is a far 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

h i i ieach time a species goes extinct.

G if l 1997- Grifo et al. 1997

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El t i SElectronic Sources

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Biodiveristy, Ethics, and Human Health