Biodiveristy, Ethics, and Human Health

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A presentation on the impact of biodiversity loss on our ability to combat human disease.

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Biodiveristy, Ethics, and Human Health

  1. 1. Biodiversity, Ethics, and Human Health Matthew A. Butkus, PhD McNeese State University April 24, 2009
  2. 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. 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. 4. Basic Assumptions
  5. 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. 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. 7. Obligations to future people
  8. 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. 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. 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. 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. 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. 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. 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. 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. 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. 17. Current biodiversity loss
  18. 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. 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. 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. 21. Current medication development
  22. 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. 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. 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. 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. 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. 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. 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. 29. Biodiversity loss impacts antimicrobial medications
  30. 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. 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. 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. 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. 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. 35. Biodiversity loss impacts anticancer medications
  36. 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. 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. 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. 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. 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. 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. 42. Ethical and Policy Implications
  43. 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. 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. 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. 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. 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
  48. 48. References Print Sources Altmann, Karl-Heinz and Gertsch, Jürg. “Anticancer drugs from nature – natural products as a unique source of new microtubule-stabilizing agents.” Natural Products Reports, 2007, 24:327-357. Appelbaum, P.C. “The emergence of vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus.”, Clinical Microbiology and Infection, 2006, 12(Suppl.1):16-23. Barker, John J. “Antibacterial drug discovery and structure-based design.” Drug Discovery Today, 2006, 11:391- 404. Bateman, Chris Living Bateman Chris. “Living the TB Resistance Nightmare”, South African Medical Journal 2006 96:1014-1016 Nightmare Journal, 2006, 96:1014 1016 Bonten, Marc J.M., Willems, Rob, and Weinstein, Robert A. “Vancomycin-resistant enterococci: why are they here, and where do they come from?” The Lancet Infectious Diseases, 2001, 1:314-325. Chivian, Eric. “Global Environmental Degradation and Biodiversity Loss: Implications for Human Health”, Biodiversity and Human Health (ed. Francesca Grifo and Joshua Rosenthal), Washington, D.C.: Island Press, 1997, pp. 7-38.
  49. 49. References Cragg, Gordon M., and Newman, David J.”Natural Product Drug Discovery in the Next Millennium”, Pharmaceutical Biology, 2001, 39(Suppl.): 8-17. Darvas, Ferenc, Dorman, Gyorgy, Urge, Laszlo, Sazbo, Istvan, Ronai, Zsolt, and Sasvari-Szekely, Maria. “Combinatorial chemistry. Facing the challenge of chemical genomics.” Pure and Applied Chemistry, 2001, 73:1487-1498. DesJardins, J D J di Joseph R. E i h R Environmentall Ethics: An Introduction t Environmentall Philosophy. B l t Ethi A I t d ti to E i t Phil ph Belmont: W d t Wadsworth, th 2006, p. 75. Dobson, Andrew, Campbell, Mary S., and Bell, Jensa. “Fatal Synergism: Interactions between Infectious Diseases, Human Population Growth, and Loss of Biodiversity”, Biodiversity and Human Health (ed. Francesca Grifo and Joshua Rosenthal), Washington, D.C.: Island Press, 1997, pp.87-110. Rosenthal) Washington D C : Press 1997 pp 87 110 Ducati, Rodrigo Gay, Ruffino-Netto, Antonio, Basso, Luiz Augusto, and Santos, Diógenes Santiago, “The resumption of consumption – A review on tuberculosis.” Memórias do Instituto Oswaldo Cruz, 2006, 101:697-714. Ernst, Joel D., Trevejo-Nuñez, Giraldine, and Banaiee, Niaz. “Genomics and the evolution, pathogenesis, and diagnosis of tuberculosis.” The Journal of Clinical Investigation, 2007, 117:1738-1745.
  50. 50. References Ganesan, A. “Natural products as a hunting ground for combinatorial chemistry.” Current Opinion in Biotechnology, 2004, 15:584-590. Grifo, Francesca, Newman, David, Fairfield, Alexandra S., Bhattacharya, Bhaswati, and Grupenhoff, John T. “The Origins of Prescription Drugs”, Biodiversity and Human Health (ed. Francesca Grifo and Joshua Rosenthal), Washington, D.C.: Island Press, 1997, pp.131-163. Huc, Ivan, and Nguyen, Ré i “D HI dN Régis. “Dynamic Combinatorial Ch i t ” C bi t i l Ch i t & Hi h i C bi t i l Chemistry.” Combinatorial Chemistry High Throughput Screening, 2001, 4: 109-130. Ireland, Chris M., Aalbersberg, William, Anderson, Raymond J., Ayral-Kaloustian, Semiramis, Berlinck, Roberto G.S., Bernan,Valerie, Carter, Guy, Churchill, Alice C.L., Clardy, Jon, Concepcion, Gisela P., De Silva, E. Dilip, Discafani, Carolyn, Fojo, Tito, Frost Philip Gibson, Donna, Greenberger, Discafani Carolyn Fojo Tito Frost, Philip, Gibson Donna Greenberger Lee M Greenstein Michael, M., Greenstein, Michael Harper, Mary Kay, Mallon, Robert, Lodise, Jr., Thomas P., and McKinnon, Peggy S. “Burden of Methicillin- Resistant Staphylococcus aureus: Focus on Clinical and Economic Outcomes.” Pharmacotherapy, 2007, 27:1001-1012. Jones, Ronald N “Resistance Patterns Among Nosocomial Pathogens”, Chest, 2001, 119:397S-404S N. Resistance Pathogens , 119:397S 404S. Jones, William P., Chin,Young-Won, and Kinghorn, A. Douglas. “The Role of Pharmacognosy in Modern Medicine and Pharmacy.” Current Drug Targets, 2006, 7:247-264.
  51. 51. References Knight,V., Sanglier, J.-J., DiTullio, D., Braccili, S., Bonner, P., Waters, J., Hughes, D., and Zhang, L. “Diversifying microbial natural products for drug discovery.” Applied Microbiology and Biotechnology, 2003, 62: 446-458. Koehn, Frank E., and Carter, Guy T. “The Evolving Role of Natural Products in Drug Discovery.” Nature Reviews Drug Discovery, 2005, 4: 206-220. Lazo, John S., and Wipf, Peter. “Combinatorial Chemistry and Contemporary Pharmacology.” The Journal of Pharmacology and Experimental Therapeutics, 2000, 293:705-709. Loganzo, Frank, Nunes, Maria, Poruchynsky, Marianne S., and Zask, Arie. “Anticancer Agents from Unique g yy g q Natural Products Sources.” Pharmaceutical Biology, 2003, 41(Suppl.):15-38. Miertus, Stanislav, Fassina, Giorgio, and Seneci, P.F. “Concepts of Combinatorial Chemistry and Combinatorial Technologies.” Chem. Listy, 2000, 94:1104-1110. Modzelewska, Aneta, Sur, Surojit, Kumar, Srinivas K., and Khan, Saeed R. “Sesquiterpenes: Natural Products that Decrease Cancer Growth.” Current Medicinal Chemistry, 2005, 5:477-499.
  52. 52. References Newman, David J., Cragg, Gordon M., Holbeck, Susan, and Sausville, Edward A. “Natural Products and Derivatives as Leads to Cell Cycle Pathway Targets in Cancer Chemotherapy.” Current Cancer Drug Targets, 2002 2:279-308. T 2002, 2 279 308 Ortholand, Jean-Yves, and Ganesan, A. “Natural products and combinatorial chemistry: back to the future.” Current Opinions in Chemical Biology, 2004, 8:271-280. Palmer, Clare. “An Overview of Environmental Ethics”, Environmental Ethics (ed. Andrew Light and Holmes Rolston III), Malden: Blackwell Publishing Ltd, 2003, pp. 1-11. Pojman, Louis P. and Pojman, Paul. “Obligations to Future Generations.” Environmental Ethics: Readings in Theory and Application. Belmont: Wadsworth, 2008, p. 346. Potterat, O. and Hamburger, M. “Natural Products in Drug Discovery.” Current Organic Chemistry, 2006, 10:899-920. Rice, Louis B. “Emergence of Vancomycin-Resistant Enterococci.” Emerging Infectious Diseases, 2001, 7:183- 187.
  53. 53. References Rishton, Gilbert M. “Natural products as a robust source of new drugs and drug leads: past successes and present day issues.” American Journal of Cardiology, 2008, 101(suppl.):43D-49D. Sharma, Surendra K., and Mohan, Alladi. “Multidrug-Resistant Tuberculosis: A Menace That Threatens to Destabilize Tuberculosis Control.”, Chest, 2006, 130:261-272. Singh, Sheo B., and Barrett, John F. “Empirical antibacterial drug discovery – Foundation in natural products.” Biochemical Pharmacology, 2006, 71:1006-1015. Tan, G., Gyllenhaal, C., and Soejarto, D.D. “Biodiversity as a Source of Anticancer Drugs.” Current Drug Targets, y j y g gg 2006, 7:265-277. Tan, Lik Tong . “Bioactive natural products from marine cyanobacteria for drug discovery.” Phytochemistry, 2007, 68:954-979. Wells, Charles D., Cegielski, J. Peter, Nelson, Lisa J., Larerson, Kayla F., Holtz, Timothy H., Finlay, Alyssa, Castro, Kenneth G., and Weyer, Karin. “HIV Infection and Multidrug-Resistant Tuberculosis – The Perfect Storm.” Journal of Infectious Diseases, 2007, 196:S86-107.
  54. 54. References Wijaya, Limin, Hsu, Li-Yang, and Kurup, Asok, “Community-associated Methicillin-resistant Staphylococcus aureus: Overview and Local Situation.”, Annals of the Academy of Medicine, Singapore, 2006, 35:479-486. y gp Winograd, Nicholas, and Braun, Robert M. “Imaging Mass Spectrometry and Combinatorial Chemistry.” Spectroscopy, 2001, 16:14-27. Electronic Sources El t iS Conservation International. Hotspots are tracked by Conservation International (http://www.conservation.org); more information can be found at http://www.conservation.org/explore/priority_areas/hotspots/pages/hotspots_main.aspx (accessed April 22, 2009). 22 2009) International Union for the Conservation of Nature. Major taxonomy species losses by year are summarized at http://www.iucnredlist.org/documents/2008RL_stats_table_2_v1223294385.pdf (Accessed April 4th, 2009). Current data on endangered and at risk species can be found at the International Union for the Conservation of Nature at http://www.iucnredlist.org/static/stats (accessed April 22, 2009). United States Census Bureau. Global census data are according to the United States Census Bureau. The population estimates can be accessed at http://www.census.gov/main/www/popclock.html ( (Accessed April 22, 2009). p )

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