Should We Replace Animals with Humans in Research?

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Should we Replace Animals with Humans in Research?
Gary Comstock Professor of Philosophy, NC State
University 2007-08 ASC Fellow, National
Humanities Center
AUTONOMY SINGULARITY CREATIVITY
Duke University 17 March 2008
2
Overview

• Abstract
• Definitions
• Assumptions
• Human Pesticide Toxicity Testing (HPTT)
• Arguments against HPTT
• Arguments for HPTT
• Objections
• Conclusions

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Abstract

• I argue for three claims
• Our intuitive rejection of human pesticide
  toxicity testing (HPTT) is not justified
• 2. In large part, this is because cost-benefit
  analyses of HPTT have not adequately weighed the
  costs to research animals and
• 3. As we seek to replace, reduce, and refine the
  numbers of animals used in research we ought to
  consider using more humans.

4
Definitions

• Pesticides Naturally derived or synthetically
  produced substances designed to kill, suppress or
  alter the life cycle of unwanted organisms.
• Modern industrial agriculture A
  capital-intensive global system of hybrid seeds,
  high chemical fertilizer and irrigation inputs to
  produce high volumes of commodity crops fed to
  animals killed for meat.

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Definitions

• Two-level utilitarianism Always choose the
  course of action that results in the best
  consequences.
• At the level of critical thinking, we ought to
  function as act-utilitarians.
• In everyday life, however, we ought to function
  as deontological thinkers.

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Assumptions

• Most developing countries have agricultural
  policies aimed at accommodating increased demands
  for meat.
• Crop yield increases are not keeping pace with
  global food demands.
• It is unlikely modern agriculture will be soon
  replaced by a post-modern agriculture (e.g.,
  small scale, family-owned and operated units
  using low-chemical inputs, renewable organic
  methods to produce regionally transported
  vegetables, soy, fruits, and other non-meat based
  products, etc.)

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Assumptions

• Global demand for food could easily double. Of
  particular concern are Asia and Africa over the
  next 50 years
• Many of the genetic resources required for the
  development of such improved crops are being
  destroyed.
• A number of the ecosystem services underpinning
  productivity are under increasing threat.
• The environmental and human health consequences
  of fertilizer and pesticide application in
  intensive production systems are of growing
  concern.
• Extreme climatic events accompanying global
  climate change may be expected to present an
  additional threat to food security for example,
  to pest control and crop yields.
• Gretchen Daily and Partha Dasgupta, Food
  production, population growth, and the
  environment. Science 281 (August 28, 1998) p.
  1291.

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Assumptions

• Scientific research policies are supported by the
  sanctity of life ethic.
• Extensive rights for humans to freedom, food, and
  opting-out of experiments that might save others
  lives.
• Minimal rights for animals to minimally painful
  invasive procedures and humane deaths.

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Assumptions

• Two-level utilitarianism is the best available
  ethical theory.
• Make routine daily decisions on the basis of
  Intuitive Level System (ILS) rules rights and
  deontological considerations.
• Overturn ILS rules only when Critical Thinking
  demands it.

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Human Pesticide Toxicity Testing
(HPTT)Historical background

• Prior to 1960s, safe levels of pesticide exposure
  are determined by
• Intentional dosing of experimental animals
• Animals of different species and sexes exposed to
  various levels of pesticides.
• The reference dose is the maximum amount of daily
  exposure that can occur with reasonable
  certainty of no harm.
• The tolerance level is the amount of pesticide
  expected to be in or on the food at harvest.

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From The English Patients
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Human Pesticide Toxicity Testing

• Prior to 1960s, safe levels of pesticide exposure
  are determined by
• Intentional dosing of experimental animals
• One million animals of different species and
  sexes exposed to various levels of pesticides
  then killed.
• The reference dose is the maximum amount of daily
  exposure that can occur with reasonable
  certainty of no harm.
• The tolerance level is the amount of pesticide
  expected to be in or on the food at harvest.
• 2. Epidemiological studies of normally exposed
  humans

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Epidemiological studies of people who work with
pesticides (normally exposed) Jaga K, Dharmani
C. Sources of exposure to and public health
implications of organophosphate pesticides. Rev
Panam Salud Publica. 200314(3)171-85 Accessed
3/15/2008 at journal.paho.org/uploads/Vol14N3/a04f
ig02.gif
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• Epidemiological meta-analyses of literature to
  test hypotheses of correlations

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Historical background of HPTT

• More accurate data on pesticide safety could lead
  to relaxed regulations on certain pesticides
  leading to increased crop production.
• In 1960s, to obtain more accurate data, private
  companies begin a third method of testing HPTT.
• Food Quality Protection Act (FQPA) in 1996 adds
  an additional 10x safety factor to existing
  pesticide tolerances to protect children.

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From The English Patients
17
HPTT

• Pesticide industry response to FQPA
• Test pesticides directly on humans.
• Eliminate the interspecies 10x safety factor.

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From The English Patients
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The proposal

• Test pesticides directly on humans rather than
  rely on extrapolations from animals.
• Animal tests may establish that a toxicant causes
  malignant tumors when the animal is exposed to
  high doses for prolonged periods.
• These animal results do not establish safe levels
  for humans exposed to low doses intermittently.
• The safety factor used to translate animal
  results to humans to account for the fact that
  humans may be more sensitive to the compound
  being tested is arbitrary (in the context of
  FIFRA, the EPA uses a factor of 10x. But why not
  9x or 11x? Or 100x? 100,000x?)
• To establish more accurate safe levels
• for humans, test directly on humans.

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Results

• Between 1996 and 2001, EPA received approximately
  4 HPTT test results per year measuring minor,
  reversible systemic toxic effects (trembling,
  nausea, or headaches resulting from chemical
  changes in the nervous system).
• Protections for Subjects in Human Research
• Federal Register February 6, 2006 (Volume 71,
  Number 24) Rules and Regulations Page
  6137-6176. Accessed 3/14/2008 at
  http//www.epa.gov/EPA-GENERAL/2006/February/Day-0
  6/g1045.htm

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5. Arguments Against HPTT

• EPA's Latest Human Pesticide Testing Rule Called
  Illegal, Immoral
• WASHINGTON, DC, January 25, 2006 (ENS) - Three
  U.S. legislators are asking the U.S.
  Environmental Protection Agency (EPA) to withdraw
  a planned rule to permit pesticide
  experimentation on humans, including pregnant and
  nursing mothers and children. . California
  legislators Senator Barbara Boxer, and
  Representatives Henry Waxman and Hilda Solis
  released details of the rule and called on EPA
  Administrator Stephen Johnson to withdraw the
  rule, calling it a "profound moral and ethical
  breach.

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Environmental Working Group, The English
Patients Human Experiments and Pesticide Policy
1998
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(No Transcript)
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Intuitive level system (ILS) rule Do no
harm. Implication No-test We should not
test pesticides on people.
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• Critical Thinking arguments for No-test
• 1. We do not need pesticides alternative
  agriculture.
• Pesticides damage nontarget organisms,
  including workers.
• Workers often are disempowered migrants.
• Pesticides can harm consumers who eat the
  foods.
• Test on animals, not people.
• Direct dosing can harm humans long-term.
• HPTT does not benefit the research subjects
  enrolled in the tests.

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• Arguments against No-test
• Pesticides lower food costs to the nation's
  poorest and neediest children.
• Industrial agriculture will not soon be
  replaced.
• Developing pesticides is costly, risky, and
  time-consuming.
• Food costs will rise if pesticides become more
  expensive.
• Pesticide testing harms animals the interests
  of sentient animals count.
• All humans used have have given informed
  consent.
• Self-interest is not a source of self-deception
  in this case
• We have substantial knowledge benefits are
  significant, risks are minimal.

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Mice and rats seem to have episodic
memory. Rats seem to lead biographical lives.
Episodic-like memory Rats prefer items on the
basis of recollections of what they have
previously seen, where they saw it and when it
saw it (Kart-Teke et al, 2006). Rats can
remember without any cueing influences what they
saw and where depending on which past situation
they are being asked to remember. (Eacott et al,
2005)
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Mice and rats seem to have metacognition.
Rats have metacognition, the ability to reflect
on ones own beliefs. Rats given a choice to
take a test they are likely to fail or refuse to
take it can base their decisions on their own
assessment of the state of their knowledge and
the likelihood they will pass. ------------- The
rats were more likely to decline these difficult
tests, as would be expected if the rats knew that
they did not know the correct duration-discriminat
ion response. Allison L. Foote and Jonathon D.
Crystal, Metacognition in the Rat, Current
Biology 17 (20 March 2007), pp. 551-555.
Accessed 3/10/2008 at http//www.sciencedirect.co
m/science?_obGatewayURL_methodcitationSearch_u
oikeyB6VRT-4N97NYR-N_originSDEMFRASCII_version
1md501a05b98c9f393f8360e2fa2807df88b
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• The regulatory process does not take into account
  the following
• that natural chemicals make up the vast bulk of
  chemicals to which humans are exposed
• that the toxicology of synthetic and natural
  toxins is not fundamentally different
• that about half of the chemicals tested, whether
  natural or synthetic, are carcinogens when tested
  using current experimental protocols
• (4) that testing for carcinogenicity at
  near-toxic doses in rodents does not provide
  enough information to predict the excess number
  of human cancers that might occur at low-dose
  exposures
• (5) that testing at the maximum tolerated dose
  (MTD) frequently can cause chronic cell killing
  and consequent cell replacement (a risk factor
  for cancer that can be limited to high doses),
  and that ignoring this effect in risk assessment
  greatly exaggerates risks.

Lois Swirsky Gold, T. Slone, B. Ames, What do
animal cancer tests tell us about human cancer
risk? Overview of analyses of the Carcinogenic
Potency Database, Drug Metabolism Reviews, 30(2),
359-404 (1998). Accessed 3/15/2008 at
http//potency.berkeley.edu/pdfs/DrugMetabolismRev
iews.pdf
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The human diet is full of chemicals. We dont
know which are dangerous. E.g., there are 1000
natural chemicals in roasted coffee. Only 28
have been tested for carcinogenicity in rodents.
19 were positive. Lois Swirsky Gold, T. Slone,
B. Ames, What do animal cancer tests tell us
about human cancer risk? Overview of analyses
of the Carcinogenic Potency Database, Drug
Metabolism Reviews, 30(2), 359-404 (1998).
Accessed 3/15/2008 at http//potency.berkeley.edu/
pdfs/DrugMetabolismReviews.pdf
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• Definition and scope of costs considered in
  assessment by the Home Office
• 1. Costs are defined as the adverse effects, i.e.
  pain, suffering, distress or lasting harm, likely
  to be experienced by the animals used during the
  course of a study.
• 2. This includes any material disturbance to the
  normal health, i.e. to the physical, mental and
  social well-being, of the animal, and covers
  disease, injury and physiological or
  psychological discomfort.
• 3. Both immediate effects, e.g. transient
  discomfort from injections, and longer-term
  effects, e.g. the subsequent toxic effects of
  test materials, are included.
• 4. Costs arising from both regulated scientific
  procedures and husbandry and care systems are
  considered, and all of the interventions applied
  to an animal or group of animals from the time
  they are issued from stock until they are killed
  or discharged from the controls of the Act are
  covered.
• 5. Regulation of scientific procedures starts at
  the level of adverse effect cause by skilled
  insertion of a hypodermic needle, or equivalent,
  depending on the procedure. It is noted that the
  following procedures are covered
• minor procedures with adverse effects below the
  above threshold, if they are part of a series or
  combination whose cumulative adverse effects are
  above the threshold for regulation
• procedures performed wholly under general
  anaesthesia
• procedures for generation and breeding of animals
  likely to suffer adverse effects, i.e.
• breeding animals with harmful genetic defects
• manipulation of germ cells or embryos to alter
  the genetic constitution of the resulting animal
  and
• subsequent breeding of such genetically modified
  animals.
• 6. Any expected adverse phenotypic expression in
  harmful mutant or genetically modified animals is
  included.
• 7. Costs arising from both acts of commission,
  e.g. dosing or sampling, and omission, e.g.
  withholding food or water, are considered.
• 8. Costs are assessed with reference to the
  biology, behaviour and life-style of the species
  concerned for example, although partial facial
  weakness may be a relatively minor adverse effect
  in humans, it has serious consequences for
  cud-chewing animals.
• The Animal Procedures Committee, Review of
  cost-benefit assessment in the use of animals in
  research, June 2003. Accessed 3/15/2008 at
  http//www.apc.gov.uk/reference/costbenefit.pdf

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Conclusion

• I have argued for three claims
• The ILS rule against intentionally dosing humans
  with pesticides is not justified at the level of
  critical thinking
• Cost-benefit analyses of the subject have not
  adequately weighed the costs to animals and
• As we seek to replace, reduce, and refine the
  numbers of animals used in research we ought to
  consider increased use of humans as a means to
  this objective.