3 2 DVM NEWSMAGAZINE January 2006

INTERVIEWS IN POLITICS. MEDICINE & PRACTICE

DVM NEWSMAGAZINE february 2006

newsmakersIRTERVIFIVS IN POLITICS. MEDICINE t PHACTICE

ROLLIN UNCENSOREDContinued from page 32

Dr. Bernard E. Roliin, considered oneof the foremost experts in animal ethicsand distinguished professor of philoso-phy at Colorado State University's De-partments of Philosophy and BiomedicalSdences, talked with DVM Newsmagazineabout the ethical questions faced by vet-erinarians on issues like euthanasia, con-trol of pain and distress, and animal wel-fare.

Roliin won the Henry Spira Awardlast fall, one of only three recipients inthe world to achieve such an honor fromthe Johns Hopkins Center for Alterna-tives to Animal Testing. And while theflamboyant, sometimes outspoken Roliinattests that advancements in all three areasare transparent, there's still plenty of roomto improve.

"I think that an animal can't value lifein itself. If you and 1, God forbid, werestricken with cancer, we can say, 'Well, Iwill go through six months of chemo hellbecause it might buy me five or 10 moreyears. An animal doesn't seem to havethe intellectual apparatus to form thatnotion. It cannot postpone future bene-fits for its current pain." But humans do.

W t^h it comes the inherent responsi-bOity of choosing the risk/benefits of treat-ment versus quality of life, Roliin says.

"When an animal is subjected to lotsof surgeries, radiation and chemother-apy, it isn't because the animal wants tolive longer," he says. "So, there is an issue

of how much you are doing it for the an-imal and how much you are doing it forthe owner's own selfish needs."

A doctor takes an oath to save and ex-tend life. It's the ethical dilemma thatevery veterinarian and pet owner mustface when treating a sick or injured ani-mal. How far do you go with medicaltreatment?

While Roliin dubs it an ethical judg-ment call in each case, the dilemma shouldbe focused on alleviating pain and suf-fering and improving the patient's qual-ity of life no matter which option is pur-sued.

Roliin recalls an example. "A fiiend ofmine came up to me and said, 'My dogwas just diagnosed with cancer.' He asked'How do I know when to pull the plug?I am willing to spend the money on treat-ment.' I told him to go and talk it overwith his wife and family and write downas many things that you can about whenthe dog is happy. Then, I told them toput it away. As treatment progresses, pullit out and use it as a measure of whetheror not that animal has a decent life."

His friend later thanked him becausethe test made him and his family realizethat even though the animal's quality oflife had diminished so greatly, they heldon to the emotions that they couldn'tbear to lose the dog.

And yet another segment of sodety isfar too quick to shed it ownership re-sponsibilities.

Why are we, as a sodety, still killing mil-lions of healthy animals a year? Roliin asks.

NADA lJI-210, Appio.od b, FDA

GenesisTOPICAL SPRAY

FOR TOPICAL USE \H DOGS ONVf

Caution Federal Law [USA| ra^tricls Fhps drug lo USA by or on ihe oidei

INDICATIONS: Genesis Topical Spray ,i ixdicaiBd for the control o

W M R N I N V S I U^ e< 5*nnpplying ifieproduct Soro^

AMMAL SArwm Ch

induce ihe fi'H itage of parturition if u$l during iha losF tiimetier ofp'flgnor^ and may precipitate pf emoturB parfuiihon bllowed by dy4ixia,tetal doalh, ralairted placenta, ond meirilit Additionolly, cortico&tQroidsodminiiiBred ID dogs, tobbils, and Todenh durrng pregnancy hovn rmijted

PKECAl/TTONS: The ^aleiy oF ihii producr br doQi lea rhan eighipounds Or f dofli leis fhon orw yearof oge hoi "Of baen ovaiuaFed. The^lety of mii product in breeding, pr^gnont or loctahng dogs ha^ nor been9*aluowd |w9 WABNfNGS) The safely ol Jcmg rcnn c* rpaFed use ofFhiE product (greater ihan 2B days} hai IKII baan evaluated Prok>nged J H I ovBTooH]^ of any cortico^lsroid fay produce adverw attects. &ecouHabsofpticm (^ WionKincioro oatfonida tirougli top^ol oppJ^iolian or tha skinand by lickfrtg may occvi, dogs receiwirtg IriaFrKinolono acotonhde Phwapyshould ba abwrved ctosflly fo< avidonfe of hyptllhlarnlC-plhJltary^ldrnal[HPA^ ax\i hjpprfluion WSan ihe product was upplivd GI oppioxiinalely

ol hvo dag& lor rive days, plasma carliuH levett were docraated afterihe Uiv iraatrnflni and reipansA to ACTH woi reduced. If ac^eiia cdnFColsigns ara ob^srvvd, trsonnent should be di^onhjiued Onca Fhe iignshavft diHippeoTBd, Freotmenl can be rsmrrted al o lowsr doK or FraquervTyof application W hyperMtnsitivity to the produd ctccurs, trealmeni shouldb* driCQnhnued and opproprloie iharapy instituted Ir* ihe preKnce of

ogenF ahculd ba inihluted I' a favorable reipoms dom not occur prompily,Ifni corhco^teiaid E hoy Id bfl diiconlinued until tn* mfecHan hoi been

ACnONSi In a fiakJ ^ludy wiih Gv^vi Topical Spray.polyuna wat rpo(tQd in 3 d 57 dogi (5 1%\ and polyphogia tn I of57dag i j ] 8%] Mild Iwithin rofvence rar^e) decrea^^ m total leukocyte,lymphocylQ and eaiinophil counti were al^o rsporled. The followingloraI reactions luflW repocled in K 3 6% of 1 10 rlog^ Irwted wp|h Genii^TopKal Sprrry of itw ptodwcl vehitle' avarsion/ditcainfoil, meezirtg andwatery ayat.

For lachnpcol inforrr>affon or lo repor'F adverse reaciions please callI 800338 3659

Bernard Roliin, philosopher and ethicist, wantsveterinarians and lawmakers to "re-appropriatecommon sense" when it comes to animal welfare.

"Spay/neuter hasn't worked. What isour next approach? What is the answer?

"I think people should be forced todemonstrate that they know what theyare getting into before they purchase oradopt an animal. You know damn wellthat someone sees Turner and Hoochand they dedde they want a Tibetan Mas-tiff or whatever breed it was. They go tothe store and buy it, and they discoverthat this is a high-maintenance aimal...They just take it to the pound and hopeit gets a good home."

And while veterinarians might nothave made the decision to purchase theanimal, they can certainly help stave offrelinquishment in other ways, such as of-fering behavioral training or client coun-seling on the realities of pet ownership,yet another philosophical consideration.

"There are plenty of ethical issues inveterinary medicine, and the teachingand discussion has not kept up with theproliferation of issues," he adds.

Take animal welfare, for example. Inrecent years, concerns about tradition-ally accepted agriculture practices arebeing challenged, and it puts veterinarymedicine squarely in the middle. "Thephrase I used in front of Congress once:I just want to re-appropriate commonsense."

Roliin adamantly believes that veteri-nary medicine must unite in its message,even if it alienates traditionally strong al-lied groups, like agriculture or even thebiomedical research community.

Foie gras production, which faces aworldwide assault from animal rightsgroups, sow housing and use of gestationcrates are all symptomatic of where thewelfare debate has transcended. It startedon animal pain. The buzzword is now dis-tress.

What is occurring is the divergencebetween traditional husbandry practicesand a "retum to feirer treatment," he says.

Continued on page 36

3 6

ROLLIN UNCENSOREDContinued from page 34

"Husbandry was being practiced be-fore the 20th Century. You wanted youranimals to be productive, you put in thebest possible environment, augment theirability to survive and thrive by prevent-ing food during famine, water duringdrought, medical intervention duringbirthing and protection from predation.Those were the basics. We developed these

technological standards like antibiotics,vaccines and air-handling systems thatreally allow us to force square pegs inround holes. The animals might be pro-ductive, but they aren't really that welloff. 1 think societies around the world aredemanding a return to fairer treatment.It is a huge issue."

Rollin adds that organized veterinarymedicine needs to step up to the plate.

"And not enough of organized veteri-nary medicine is taking strong ethical po-

sitions on issues that sodety expects themto lead in. They are trying to satisfy every-body. When you do that, you satisfy no-body. They are not alone. The human med-ical community has been delinquent inaddressing medical ethics in the same ways."

While attitudes are changing, he says,it's not fast enough. "Now, there is a lotmore ethics being taught in veterinaryschools than what used to be. But still,it's not enough."

Consider, how we view pain, Rollin says.

NADA 141-213 and NAOA 141-219, Approved by FDA

Metacam*imeloiicam) 1.5 mg/mL Oral Suspension {equmalent to 0 05 mg per drop] and 5 mg/mL Solution lor InjectionNon-steroidal anti-tnflammatpry drug fof oral or injeciable use in dogs onlyCaution: Federal law restncls Bus drug to use by or on tde order of a licensed velernarian.Description; Meloxicam is a Non-Steroidal Anti-Inflammatory (NSAID) drug of the oxicam class. Eacb milliliter of Metacam*Oral Suspension coniains meloicam equivalent lo 1 5 milligrams and sodium Mnzoate (1.5 milligrams) as a preservative.Each mLot tbis sterile product for injection codfainsmekwicam 5.0 mg, alcohol 15%, glycofurol 10%, poloxamer 188 5%,sodium chloride 0 6%, glycine 0.5% and meglumine 0.3%, in waler for in]eclii, pH adjusted with sodium hydroxide andbydrochloric acidThe chemical name for Meloiicam is 4-Hydroy-2-metbyl-N-(5-metbyl-2-fJiia2ulyl|-2H-l ,2-ben;othiazine-3-carboxaini(te-1.1-dioiide. Ttie suspension lormulafion is a yellowish viscous suspension with ttie odor of honey.

Clinical PtarTTiaco(ogy:Melo ontntiK tap of the bottle

lam tfte fvtlUsynnge upsideflown Pull Vie plunger outuntil ttie tilack line on Itieplunge' conesponds to thedog's body weight tn pounOs

Pvsh the plunger lo emetyIfte contents at the syringe.

Contraindications: Dogs with known hypersensitivity to meloxicam sbould not receive Metacam* Oral Suspension orMetacam'' 5 mg/mL Solution for Injection, Do not use Metacam* Oral Suspension In cats.Warnings: Not for use m humans Keep this and all medications out of reach ot children. Consult a physician in case ofaccidentai ingestion or iniection by bumans For oral or injectable use in dogs only.As with any NSAID all dogs stiould undergo a tfiorr)ugh history and pbysical examination before the initiation of NSAIDtnerapy ApDiopriate laboratory testing to establish hematological and serum biochemical baseiine data is recommendedprior ID and periodically during administration of any NSAID. Owners snould be advised to observe their dogs for signs ofpotenfial drug toxicity. Owners should be advised to observe their dogs for signs ol potentiai drug toxicity and be given aclient information sheet about Metacam "^For technical assistance or to reoort suspected adverse reactions, call 1 -flSB-METACAM |638-2Z26|,Precautions: Ttie safe use of Metacam' Oral Suspension or Mefacam'' 5 mg/mL Solution tor Injection in dogs younger than6 months ot age, dogs used tor breeding, or in pregnant or lactating dogs has not been evaluated.Safety has not been establisfied tor intramuscular (IM) administration.As a class, cycio-cxygenase inhibitory NSAIOs may be associated witb gastrointestinal and renal toxicity. Sensitivity to drug-associated adverse events vanes with the individual patienL Patients at greatest risk for renal toxicity are those ttiat aredehydrated, on concomitant diuretic tfierapy, or those wrth existing renai, cardiovascuiar,and/or hepatic dysfunction. Concurrentadministration ot potentially nephrotoxic drugs stiould be carefully approached NSAIDs may intiitiit the prostaglandins thatmaintain normal homeostatic tunction Such antiprostaglandin effects may result in clinically significant disease in patientswith underlying or pre-existing disease that has not been previously diagnosed. Since many NSAIDs possess ttie potentiai toproduce gastrointestinal ulceration, concomitant use of Metacam' Oral Suspension or Metacam'" 5 my/mL Solution (orinjection witb other anti-mtlammatorv drugs, sucb as NSAIDs or corticosteroids, should be avoided or closely monitored Ttieuse of concomitantly profeio-bound drugs with Metacam'' Oral Suspension or Metacam* 5 mg/mL Solution for Iniection hasnot been studied in dogs. Commonly used protem-bound drugs include cardiac, anticonvulsant and behavioral medications.The influence ot concomitant drugs that may inhibit metabolism of Metacam' Oral Suspension or Metacam* 5 mg/mLSolution tor Injection has nol tieen evaluated. Drug compatibiiity should be monitnred in patients requiring adjunctive therapy.Adverse Reactions: Field safety was evaluated in 306 dogs. Based on the results of two studies, Gl atinormalities (vomiting,soft stools, diarrtiea, and inappetancei were tfie most common adverse reactions associated with the administration otmeloxicam.

Ouring two field studies,cer1ain adverse reactions were oteerved.Ot the dogs that took meloxicam (n=i57), forty experiencedvomiting, nineteen experienced diarrhea/soti stool, tive experienced inappetance, and one eacfi experienced bloody stool,bleeding gums after dental procedure, lethargy/swollen carpus, and epipnora. Of the dogs that took the placebo (n=i49).twenty-three experienced vomiting, eleven experienced diarrhea/soft stool, and one experienced mappetance.In foreign suspected adverse drug reaction (SADR) reporting over a 9 year period, incidences ot adverse reactions related tomeloxicam administration inciuded: autc-immune hemoiytic anemia (1 dog), thrombocytopenia (1 dog), polyarthritis (I dog),nursing puppy lethargy (1 dog), and pyoderma (1 dog).

Post Approval Experience: The tollowng adverse reactions are based on voluntary post-api^oval reporting. The categoriesare Iisted in decreasing order of frequency by body systemGasirointestinal vomiting, anorexia, diarrhea, melena, gastrointestnai ulceration.Unnaiy Azotemia, elevated creatinine, renal failureNemological/Behavioiat/Special Sense: lethargy, depressionHepatic elevated liver enzymes.Dermatological/lmmunological- fVuritus.Effectiveness;Metacam" (melnxicam) 1,5 mg/mL Oral Suspension: The effectiveness ot melomcam was demonstrated in two field studiesinvolving a total of ?77 flogs represenfing varinus breeds, between six months and sixteen years of age, all diagnosed withosteoarthrtis. Both of the placebo-contn]iled, masked studies were conducted tor 14 days. All dogs received 0.3 mg/kg onday 1. All dogs were maintained on 01 mg/kg oral melonicam trom days 2 through 14 of both studies Parameters evaluatedby veterinarians inciuded lameness, weight-bearing, pain on palpation, and overall improvement. Parameters assessed byowners included mobility, ability to rise, limping, and overall impmvement.In the tirst field study (n=109), dogs showed clinical improvement with statistical significance after 14 days ot meloxicamtreatmeni tor all parameters In the second field stufly (n=48), dogs receiving meloxicam showed a clinical impmvementafter 14 days ot therapy tor all parameters: however, statistical significance was demonstrated only for the overall investigatorevaluationonday 7, and tor the owner evaluation on day 14.Metacam" (meloxicam) 5 mg/mL Solution for Iniection. The effectiveness of meloxicam was demonstrated in a field studyinvolving a total of ?24 dogs representing various breeds, all diagnosed with osteoarthritis. This placebocontrolled, maskedstudy was conducted for 14 days. Dogs received a subcutaneous iniection ot 0 2 mg/kg meloKicam on day 1 The dogs weremaintained on 0.1 mg/i^ g oral metoxicamfrom days 2 through 14, Parameters evaluated by veterinarians included lameness,weigbt-beanng, pain on palpation, and overall improvement. Parameters assessed by owners included mobility, ability torise, iimping, and overall improvement. In this field study, dogs showed improvement with statistical significance after 14days ot meloxicam treatment for ail parameters,Palattbility: Metacam" Oral Suspension was accepted by 100% ot the dogs when vetennarians administered the initialdose into tbe mouth Metacam' Oral Suspension was accepted by 90% of the dogs (123/136) when administered by ownersProtJiems associated with administration included refusal ot tood, resistance to swallowing and salivation.Safety;Six Week StudyIn a six week target animal satety study, mekwkam was administered orally at 1,3, and 5X the recommended dose with nosignificant ciinicai adverse reactions. Animals in all dose groups (control, 1, 3 and 5X the recommended dose) exhibitedsome gastrointestinal distress (diarrhea and vomitmgl. No treatment-related changes were observed in hematological,blood chemistry, urinalysis, clotting trme, or buccal mucosal bleeding times,Necnjpsy results included stomach mucosal petechiae in one contml dog, two dogs at the 3X and one dog at the 5X dose.Other macroscopic changes inciuded areas of congestion or depression ot the mucosa of ttie jeiuoum of ileum in three dogsat ttie 1X dose and in tvro dogs at ttie 5X dose. Similar changes were also seen in two dogs in the control group. There wereno macroscopic small intestinal lesions observed in dogs receiving the 3X dose. Renal enlargement was reported during thenecropsy of two dogs receiving the 3X arnl two receiving the 5X dose.Microscopic examination of the kidneys revealed minimal degeneration or slight necrosis at the tip ot the papiila in threedogs at the 5X dose. Microscopic examination ot the stomach showed inflammatory mucosal lesions, epithelial regenerativehyperplasia or atrophy, and submucosal gland inflammation in two dogs at the recommended dose, tbree dogs at ttie 3X andtour dogs at the 5X dose Small intestinal microscopic changes included minimal focal mucosal erosion affectiryg the villi,and were sometimes associated with mucosal congestion. These lesions were ot)served In the ileum of one control dog andin the jeiunum of one dog at the recommended dose and two dogs at the 5X doseSix Month StudyIn a SIX month target animai safety stinty, meloiicam was administered oraliy at 1,3. a/id 5X the recommended dose with nosignificant clinical adverse reactions. All animals in all dose groups (controls, 1,3, and 5X the recommended dose) exhibitedsome gastrointestinal distress Idiarrhea and vomiting). Treatment-related changes seen in hematology and chemistry includeddecreased red blood cell counts in seven of 24 dogs (four 3X and three 5X dogs), decreased hematocnt in 16 of 24 dogs(including three control dogs), dose-related neutrophilia in one IX, two 3X and three 5X dogs, evidence of regenerativeanemia in two 3X and one 5X dog. Also noted were increased BUN in two 5X dogs and decreased albumin in one 5X dog.Endoscopic changes consisted of reddening of the gastric mucosal surface covering less than 25% ot the surface area. Tfiiswas seen in three dogs at the recommended dirae, three dogs at the 3X dose and hivo dogs at the 5X dose. Two control dogsexhibited reddening in conjunction witfi ulceration of fhe mucosa covering less ttian 25% of the surface area.Gross gastrointestinal necropsy results observed included mild discoloration o' the stomach or duodenum in one dog at the3X and in one dog at the 5X dise. Multifocal pinpoint red foci were observed in tbe gastric tundic mucosa in one dog at therecommended dose, and in one dog at the 5X doseHo macroscopic or microscopic renai changes were observed in any flogs receiving meloxicam in this six month study.Microscopic gastrointestinal findings were limited to one dog at the recommended dose, and two dogs at tbe 3X dose. Mildinflammatory mucosal infiltrate was Wiserved in the duodenum ot one dog at the recommended dose. Mild congestion of thefundic mucosa and mild myositis ot the outer mural musculature of the stomach were observed in two dogs receiving ttie3Xdose3 Day Target Animal Safety StjjdyIn a three day satety study, meloxicam was administered intravenously to beagle dogs al 1, 3, and 5X the recommendeddose (0 2, 0.6 and 1.0 mg/kg) for ttiree consecutive days. Renal compromise with associated protein loss was ttie mostsignificant clinical tinding during the study. This occurred in the 5X group Two dogs in the 5X group developed acute renalfailure by the end ot the study. Overall decreases in the means for total protein in ttie 3X and 5X groups were not clinicallysigniticant, ranging from 5.4 mg/dL and 5 5 mg/dl. baseline, respectively, to 5.3 mg/dL for both groups at the study's endAssociated decreases in mean albumin values were seen in tbe 5X group, whose baseline mean of 2.9 mg/dL decreased to2,5 mg/dL by Day 4.Mean blood urea nitrogen (BUN) and creatinine values were increased only in the 5X group THe BUN increased from abaseline value of 14 mg/dL to 26 mg/dL by Day 4, wtiile the creatinine increased from 0.9 mg/dL (baseiine) to 1,1 mg/dL byDay 4. Increased mean urinary pnjtein excretion was found to be both clinically and statistically signiticant in ttie 5X group,where mean values increased fmm 10 mg/dL Ibaseline) to 50 mg/dL by Day 4,Vomiting occurred in one of six dogs in the 5X group. Fecal occult blood was also detected in ttiree of six dogs in the5X groupHistologic examination revealed several renal changes, including dilated medullary and cortical tubules, interstitialintlammation, and renalpapillarynecrosis. This wasseenintwoof sixdogsinbottithe 1Xand3Xgroupsandintour of sixdogs in the 5X group. Gastrointestinal lesions observed inciuded superticiai mucosal hemorrhages, congestion, and enjsions.Mesenteric lymphadenopattiy was identified in two ol six dogs in ttie 1X group, four of six dogs in the 3X group, and five ofSIX dogs in the 5X group.Injection Site ToleranceMeloxicam was administered once subcutaneously to beagie dogs at the recommended dose ot 0.2 mgAg and was well-toleratefl by Ihe dogs. Pain upon injection was observed in one ot eighl dcgs treated with meloxicam. No pain or inflammationwere observed post-injection Long term use ot Metacam'5 mg/mL Solution tor Injection in dogs has not been evaluated.Effect on Buccai Mucosal Bleedino Time (BMBDMeloxicam (0 2 mg/kg) and placebo (0.4 mLAg) were administered as single intravenous injections to B female and 16male beagle dogs. There was no statistically significant dltference (p>0.05) in ttie average BMBT between the two groups.How Supplied;Metacam' Oral Suspension 1.5 mg/mL: 10, 32 and 100 mL dropper botDes wih measuring syringe Metacam' 5 mg/mLSolution for Injection; 10 mL vialStorage; Store Metacam' Oral Suspension at controlled room temperature 59-B6F (15-30Cj. Store Metacam* 5 mg/mLSolution tor Injection at controlled room temperature, 68-77'F (20-Z5"C),Manufactured byBoehringer Ingelheim Vetmedica, Inc,St. Joseph, MO 64506 U.S.A.US Patent 6,184,220METACAM'' is a registered trademark of Boehringer Ingelheim Vetmedica GmbH, Iicensed to Boehringer IngeiheimVetmedica, Inc.Metacam'' Oral Suspension6015161L-00-0301Code601511,601521,601531Revised 04/2005

Metacam* 5 m^mL Solution for Injecton6D1307L-00-0307Code 601311Revised 04/2005

DVM NEWSMAGAZINE ftbrHary 2006

"One issue is the undertreatment ofpain in human medicine. Back in the'80s, they were doing open-heart surgeryon infants without anesthetic, just para-lytic drugs. We have come a long w^y, butit has taken public pressure. Right now,you have the medical community con-demning morphine use for terminally illpatients on the grounds they might beclinically addicted. That's stupid. And itsho\\^ inadequate ethics, especially if peo-ple are actually suffering. It also showsthey don't understand addiction."

Rollin adds that the discussion aboutanimal pain and strategies to controlpain are very healthy. Ethics discussions,according to Rollin, should not simplyaddress intraprofessional etiquette. In-stead it should take on meaningful sci-entific and moral questions that are im-portant to veterinary medicine and itsrole in society.

A closerlookIn the mid-1970s, Rollin began his stud-ies at the University of Edinburgh andColumbia University in ethical issuesraised by animal use in research. To date,

he has published 14 books and more than300 research papers on general philosophy,genetic engineering, farm animal welfareand animal pain, tn 1985, in collaborationwith a number of CSU veterinarians, Rollinhelped devise legislation that became fed-eral law to regulate the veterinary and sci-entific treatment of animals. He has alsobeen credited as the first to pioneer collegecourses for scientists and veterinarians re-lated to animal bioethics,

CSU Provost Tony Frank says, "Dr Rollinhas been at the leading edge of quite liter-ally changing the way the world views thesubject of animal ethics. Dr, Rollin's globe-spanning work has had, and continues tohave, a major impact on the thinking of sci-entists, attorneys, ranchers, psychologistsand numerous other professionals who in-teract with animals."

The criteria used to select Rollin werebased on 10 points: a person of absolutecredibility, be open to dialogue from vari-ous audiences, understand public opinion,balance action amid varied opinions, vec-tor in the intensity of animal suffering andseize upon opportunities for change. "Theaward recipient also must be willing to workwith all interested parties to make progresswithout dividing or polarizing groups, aswell as focus on practical realities involvedin change along with ethical and moral im-peratives."