Following is the transcription of a discussion held Tuesday, January 15, 1985, in the Woody Room ofVan Pelt Library under the auspices ofthe Office of the Vice Provost for Research. The original tapehas been preserved in case of questions arisingfrom editing to convert spoken word to printas described on page II.

Dialogue on Animal Research

Introduction and GroundrulesDr. Cooperman: Thank you all for coming

here. I think this promises to be a very interestingand informative dialogue. What I thought I'd doin beginning is tell you why we're here, reviewthe events that led to our being here, then justmake an announcement or two having to do withprocedures. Then we'll get right into the agendawhich you all have received a copy of.The immediate reason we're here, really, is a

letter from members of the Law School to theProvost and President requesting a dialogueabout experiments done in the Medical School onthe study of head trauma. I'm sure we're allaware of the facts, but I thought it would be use-ful to go very briefly into the background thatwas behind that letter.

Over the Memorial Day weekend there was abreak-in into Dr. Gennarelli's laboratory by agroup calling itself the Animal Liberation Front,at which time the laboratory was vandalized andsixty hours or so of tapes recording the experi-ments done in that laboratory over about athree-year period were stolen. These tapes wereprovided by some mechanism to an organizationknown as PETA, People for the Ethical Treat-ment of Animals. PETA then, over some period,prepared an edited version which they entitled'Unnecessary Fuss," at least allegedly drawnfrom these tapes, which they have distributedwidely throughout the United States and also inEurope. Acopy of this edited tape was shown tomembers of the Law School. These individualswere quite disturbed by what they saw and in theletter to President Hackney and Provost Ehrlich,they said that seeing the tape disturbed them,raised in their minds moral and legal issues, andalso raised in their minds the question of whetherexperiments done at the University were in con-formance with scientific norms. They, becauseof being disturbed, then called for this dialogue.The Administration felt that, as this was a re-

quest from colleagues at the University, we, theUniversity, from a collegial point of view, had anobligation to respond to this group in ways thatwe don't necessarily feel we have toward othergroups. We also felt that, given the attention thatthis experiment, or series of experiments, hasaroused, the concerns raised were not limited tomembers of the Law School. As a result, we re-quested Faculty Senate to see if there were otherpeople from other faculties who would like toparticipate in the dialogue. We also thought that,in responding, we would like to have a discus-sion of the type that we can have in a group ofthis size, that is to say, a meaningful discussionwith a small group. On the other hand, we felt itimportant, given the interest the case hasaroused, to make the information available to theUniversity community at large. The format thatwe've established, and your presence here, re-flect those two considerations.

In just a moment I'm going to introduce peoplehere, and if you'd raise your hand when I sayyour name everybody then will know whoevery-one is. Let me begin with Drs. Gennarelli andLangfitt, as the principals involved in the experi-ments. Then Professors Francione and Watson,from the LawSchool, who are two of the originalsigners of the letter, then four members from theSenate who were chosen as a representativegroup of the faculty: Gary Cohen from the De-partment of Microbiology in the Dental School;Abraham Edel from the Department of Philos-ophy; unfortunately Renee Fox is unable to behere because of the inclement weather, which isreally quite unfortunate-Dr. Fox is from the De-partment of Sociology-and finally, Paul Fussellfrom the Department of English.My own feeling was that there were two other

individuals on the faculty who should be presentin a more or less ex-officio capacity. One is AronFisher, who was the Chair of the Medical SchoolAnimal Care Committee at the time that Dr.Gennarelli's proposal was reviewed within theMedical School. The other is Helen Davies fromthe Microbiology Department in the School ofMedicine who chairs the University CouncilCommittee on Research. Finally we have fourrepresentatives of the University of Pennsylvaniapress: Ann Bailey from The Penn Paper: KarenGaines from Almanac: Jeff Goldberg from TheD.P.: and Marshall Ledger from The Gazette.

I would like to just add a personal note aboutthis meeting before we begin. I see this dialogueas a component of the University response to thegeneral question about the use of animals for ex-perimental purposes in research. I think the ma-jor issue is the inherent conflict, as I see it, be-tween what many of us in the Universitycommunity feel to be the necessity for medicaland scientific progress, and the kind of experi-mentation that is needed for such progress, ver-sus the ethical problem of inflicting pain on sen-tient beings-for although they are animals theyare sentient beings. I think that within the Uni-versity as a whole, and within American society,there is a consensus on the necessity for such ex-perimentation, so the question becomes, Whatnorms should govern the use of animals in labo-ratory experiments? I think a big portion of thisdialogue and, in fact, the continuing discussionof this issue within the University will center onwhat those norms should be, how the Universityshould meet those norms, and how Universityexperimenters should meet those norms. In thisdiscussion I expect us to place a lot of attentionon whether these norms are, in fact, met withinthe Head Trauma Center in particular.

That's really all I have to say by way of intro-duction. I do want to review for you the situationabout disseminating the proceedings of this dia-logue. I sent to you, in a letter dated December10, a notification as to howthe transcripts of the

tapes would be handled. At that time I told youthat Karen Gaines would be taping this conversa-tion, so I won't go through that because I con-sider our stated procedures still operative. Sev-eral people have requested that they be allowed,in addition to having the transcripts, to actuallyhaving copies of the tape itself. I've agreed tothat and so Karen Gaines will be copying thistape very shortly after this discussion has con-cluded. These copies will be available to anyonewho wants one with certain conditions attached.The thrust ofthose conditions is basically that thetapes be for personal use. I will have copies inmy office of both the release form and the tapesavailable, I think by early this afternoon. And so,I think anyone who wants to have a copy of thetape can have one very soon. That's really all Ihave to say. Are there other questions at thispoint? If not, I'd like to turn to the second part ofthe agenda, which is the presentation of theexperiments.Professor Francione: I have a question

here.Dr. Cooperman: Sure, Gary.Professor Francione: I have here a copy of

this release form. Is it necessary that you signthis release form before you get a copy of thetape?

Dr. Cooperman: That's my intent.Professor Francione: Participants will not

get a copy of the tape if they do not agree not togive it to the "broadcast media" or "to use it inany way to damage the reputation of the Univer-sity of Pennsylvania"? We have to agree to this?

Dr. Cooperman: That's right.Professor Francione: Do you see any prob-

lem with restricting how your faculty membersdisseminate information?

Dr. Cooperman: No. There are no restric-tions with regard to the transcripts. The tran-scripts themselves are going to be provided,really, without condition. Since we hadn'treached agreement among the participants aboutthe tapes and this issue came up rather late, Ithought the way to distribute them was to put thatrestriction on it. I mean I can't believe that any-body present here wants to damage the reputationof the University by using the tapes, and so Ididn't see that as a problem. Is it a problem?

Professor Francione: It depends on howyou define "damage the reputation of theUniversity."

Dr, Cooperman: I guess it does.

Professor Francione: Some people havedifferent thresholds for evaluating.

Dr. Cooperman: Well, it's really intent. I'mnot sure what the legal content of the releaseform is. It really is basically to give people com-fort that no one is trying to use the tapes in a way

ALMANAC SUPPLEMENT Februart' /9, 1985 1

that has a purpose damaging the reputation of theUniversity or of the participants in this discus-sion, and that's really the reason for saying that.

Professor Watson: I would rather not re-ceive a tape under these conditions, but I wouldlike to be assured that the transcripts would beavailable soon as well.(Discussion of typing and distribution schedule,deletedfor space. In whatfollows, speakers haveeliminated false starts and repetitious phrasing,adjusted syntax for clarity, and in a fewcases-with the knowledge of other participantsconcerned-improved word choicesfor accuracyof meaning intended. Elision marks (. . .) indi-cate interruptions and resumptions, and clarifi-cations by addition are in brackets.-KCG]

Dr. Cooperman: O.K. If we can now pro-ceed to the second item of the agenda. As Dr.Gennarelli goes through this description of re-search, if there are technical terms that come upwith which you aren't familiar, I think it wouldbe perfectly appropriate to raise your hand to berecognized for an explanation. Dr. Gennarelli

Description of the Research

Dr. Gennarelli: In preparing these remarksit became clear that I could go on for hours de-scribing, in various levels of detail, the re-search and its background and its productivity.I thought, since this is intended to be a dia-logue among us, that the bettter approachwould be to give a rather thumbnail sketch ofwhat this is all about so that we can leave am-ple time for questions and discussion. If thegroup would instead prefer a longer diatribefrom me, I'd be happy to give that, but Ithought I'd try to confine it to a very basicview.

I think, obviously, when trying to analyzeresearch, one of the first questions that comesto mind is "Is the question being studied ofany significance or importance?" and I hopethat many of you have had the chance to readtheAlmanac article that I wrote regarding this.I think it amply documents that brain injuriesare, in fact, a major problem-not only to doc-tors such as Dr. Langfitt and myself who treatbrain-injured patients-but is a substantialpublic health problem in the United States.The numbers are listed in the Almanac article,gained from several sources, but the bottomline is that there are in the range of two millionhead and brain injuries per year, of whichroughly fifty thousand of them are fatal and, ofthe survivors, a substantial number never re-turn to full productivity as useful members ofsociety. So this is a substantial problem and,we feel, worthy of investigation. The questionthen, is how to investigate such a problem.The problem has been around for millenia andit hasn't gone away with the kinds of investi-gations that have been present, that have beenundertaken to the present.

Historically, the patient, ofcourse, has beenthe first line of investigation, with clinicalstudies of various levels of complexity, study-ing both individual patients in greater or lesserdegrees of detail, and then studying groups of

patients in an epidemiological manner. Thosestudies, historically, have provided a greatamount of information. They've been able to

characterize the types of injuries that occur.Suffice it to say, that there are many, manydifferent kinds of brain injuries; depending onhow you classify them, there are anywherefrom ten to thirty or forty separate differentkinds of brain injuries. Some are clearly moreimportant than others. Some are clearly lessimportant than others in terms of the degree ofdifficulty of treatment, in terms of the mortal-ity (the deaths that they cause), in terms of thedisabling lives they leave the survivors and interms of the frequency.We ourselves have undertaken a study as

part of our head injury center activities to de-termine what are the bad injuries and what arethe not-so-bad injuries. We'll come back tohow those influence the animal research in amoment. So we feel that head injury is an im-portant problem.There have been a lot of clinical investiga-

tions that have shed a lot of light on the prob-lem, but the fact remains that the mortality ratefor serious brain injuries remains in the fortyto fifty percent range. This has been generallytrue over the last fifty years and, despite ad-vances in medications, advances in emergencymedical services, advances in surgical tech-niques, intensive care unit treatment, all ofthese things have not appreciably diminishedthe mortality rate from major brain injuries. Sothere's a lot of room to improve the roughlyfifty percent mortality rate that exists in seri-ous brain injuries. That gets us to how do weinvestigate brain injuries other than in an epi-demiological sense, that is studying popula-tions of patients or studying single patients in-tensely. There are simply data that cannot beobtained, that are felt important to be ob-tained, from human beings. And this relates toa number of matters, not the least of which, isthat patients, from a scientific point of view,become injured in very messy fashions. Thatis, they have circumstances that compoundtheir injuries, multiple injuries, and the spe-cific circumstances that cause their injuries arenever to be known. All one may know is thatthe patient was in a car crash, he may knowsome greater detail about the circumstances ofthe car crash, but the critical variables arenever known in a clinical situation. And thosevariables relate to whether the head strikessomething, how fast the head moves when itstrikes something, the direction that it moves,and some of the other biomechanical variablesthat are the things that cause the brain injuries.Now, to divert for a minute about what

brain injuries are, I think it's important for thegroup to understand, because it does relate di-rectly to the research, what brain injuries areall about. There are generally two kinds ofbrain injuries: focal brain injuries, and diffusebrain injuries. Focal brain injuries generallyresult from something striking the head orfrom the head striking something, that is, animpact with an object, and that impact causeslocalized deformations, localized forces to ex-ist on the skull and the brain, and causes dam-age that is generally in one area. It may be avery large area, a very small area, but thedamage is relatively localized. That is a funda-mentally different kind of brain injury than thesecond category-diffuse brain injuries. Dif-

fuse brain injuries result from the manner inwhich the head moves during an accident, thatis, the direction that it moves, how fast itmoves, and whether it's accelerated or decel-erated during an injury, and that group of inju-ries (the diffuse brain injuries) causes funda-mentally different kinds of brain damage thanthe focal injuries. It causes damage that, untilthese experiments, was exceedingly poorlyunderstood, to the point that some thirty orforty different names were given to these inju-ries that are clearly part of a spectrum of inju-ries that go from injuries that are more or lesspurely recoverable to injuries with a mortalityrate in the sixty percent range. The diffusebrain injuries, in terms of their cause, havenothing to do with an object striking the head.They have to do with the way the head movesafter it is struck or, in the case of deceleration,how the head moves as it's slowing down.These are the category of injuries that we havebeen most interested in-the diffuse brain in-juries. The reason for that is because they arethe least understood: Their therapy is entirelynonspecific. If one considers what we do asdoctors to take care of patients with diffusebrain injuries: It can be summed up to say,"We have no specific treatment for this largegroup of injuries. We provide supportive careto the patients and that's about it." This is de-spite all that has gone on in clinical medicinein trying to care for these patients historicallyover centuries. So the thrust of our researchhas been aimed at trying to understand the dif-fuse brain injuries.

It's common practice that when these pa-tients come into the hospital we explain totheir relatives that their relative has sufferedbrain damage. We teach that to our residents.Until very recently, and as a product of theseexperiments, we really didn't know what wewere talking about, in specific, when we said"brain damage." Now we have a very preciseidea of what this brain damage is, and are en-gaging upon a better understanding of it withhopes of providing specific therapy for thiskind of injury. This injury, by the way, com-prises between 40 and 50 percent of all seriousbrain injuries, so it's not an uncommon injury.This type of injury is one of the two largestcauses of death and disability in humans.

So it became clear that, for a number of rea-sons, we needed to develop model systemsthat would help us study this particular kind ofinjury. These were originally developed-let me backtrack a moment to say that pioneer-ing work in experimental head injury has beendone for a long period of time-but a signalstudy was done in the 1940s by Denny Brownand Richie Russell who demonstrated that ac-celeration of the head could produce cerebralconcussion. Those studies in the 1940s wereexcellent studies and were the predicate uponwhich many subsequent studies in experimen-tal head injury were done. They were done, Ishould mention for this group, under deepgeneral anesthesia and, partly as a product ofthat, many misconceptions arose from theirwork. As a product of their work, many gov-ernmental agencies, directly or indirectly, ormany investigators began to study head injuryin experimental situations.. Many species were

II ALMANAC SUPPLEMENT Februart /9. 1985

used, many preparations were used, almost allof which involved some type of impact to the

head where some type of striking device was

thrust against the head of various species and

the physiological results and sometimes the

pathology was observed. These led to a gen-eral understanding of what kinds of events

were necessary to produce brain injury. Astime went on, those initial studies from theforties and fifties became the groundwork forwhich most of the protective standards aimedat preventing injuries were designed. Theseare principally, transportation agencies in the

governments of many countries who have de-

signed standards that say, for example, a car

environment should not allow the head to do

such and such-should not allow it to exceed a

certain acceleration level in a certain period oftime, for example. Despite the implementationof those standards, as you all well know, carcrashes, for example, still cause many, manyhead injuries. Something in the range of25,000 head injury deaths a year are caused in

car crashes. So rather clearly, the preliminarywork that was done in the forties and fifties

had a lot of room for expansion just on the ba-

sis of the preventative aspects, not to mention

the fact that people's treatments were still be-

ing provided nonspecifically.We first began experimental head injury in

the early the 1970s with a paradigm that is

roughly similar to what we're using now. Thisinvolved a small-brained monkey, a squirrelmonkey, that has a brain of roughly 20 or 25

grams in size. The experiments were intended,as our current experiments are, to separatewhat we feel are the critical injury-producingvariables, namely, impact force from headmovement or acceleration. The experimentswere carefully designed by others as well as

ourselves to, as best as possible in an experi-mental situation, deliver a non-impact accel-eration force to the heads ofanimals. To do sois no mean feat considering the levels of accel-eration that are necessary to produce brain in-

jury. Therefore, a large developmental effortwas originally undertaken and the paradigmthat was used is similar to what we use now.

The basic gist of it being that an acceleratingdevice develops a force that is transmitted

through a metallic helmet, a metal helmet, tothe head of an animal. The head of the animaland the metal helmet must be tightly coupledtogether so that what is precisely delivered is

precisely received by the head. What this also

accomplishes is a distribution of the injuryforce evenly and widely over the head so thatthere's no focal loading or impact of a ball

pene-hammer-like effect, but rather, the effectof the force is as if you would grab the headand move it very rapidly in whichever direc-tion and amount you choose to do.

Those initial experiments were performed atthe NIH, under NIH review, in house, andwhen I came to the University ofPennsylvaniain 1976, the experimental head injury labora-

tory was just beginning to engage in thesesame general types of experiments. From

roughly 1976 through 1980, a different helmetsituation was recommended by our mechanical

engineering colleagues, and this was a thermo-

plastic helmet. Thermoplastic material was

warmed in a pan of warm water. When it be-comes very pliable, then the material was

molded to the animal's head so that a

form-fitting helmet was created. Then that hel-met was attached to the accelerating device in

the same manner as the metallic helmet.

What we found in those initial experiments-with what is now called the PENN-l device,

as opposed to the subsequent PENN-2 de-

vice-what we found in that group of experi-ments were several things. Number one, we

found that at low levels of acceleration physio-

logical changes occurred, often very dramaticin nature, that were not associated with loss ofbehaviorial consciousness or coma. This wasan important observation because in the1940s, those physiological observations wereused as an index of cerebral concussion or

coma. The blood pressure would change, the

heart rate would go down to perhaps one-third

of its control values. These were the kind of

things previously used as indices of coma, and

in the lightly anesthetized animal-as opposedto the deeply anesthetized animal-it was veryclear that these events occurred before coma

occurred.This, of course, brings into question a lot of

the other previous work and a lot of the safetystandards that were predicated on that previouswork. At higher levels of acceleration to thehead, cerebral concussion could be produced,

reproducively. That was not particularly a

striking finding, since other investigators hadbeen able to produce that using different ani-

mal models, or in different experimental

paridigms. What we were after, was to createthe severe form of the diffuse brain injury, theone that has a mortality rate of fifty to sixtypercent and that is so commonly seen by us inthe clinic. We felt that this injury was simply amore severe variety of injury than the cerebralconcussion, and that all we had to do was tocontinue to increase the levels of accelerationto the brain, and we would go from the shortcoma of cerebral concussion to the prolongedcoma of the major diffuse brain injury. This,

however, did not turn out to be the case, andwhat we found was that instead of producingprolonged coma of the diffuse brain injurytype, what we produced were animals thatwere dying within, or would die without sup-port, several minutes of an injury from anacute subdural hematoma. An acute subduralhematoma is a collection ofblood between thesurface ofthe brain and the inner surface of theskull. And this was a bit of a distraction fromone point of view, in that it was not our in-tended endpoint. We were intending toproduce the diffuse brain injury, but insteadproduced the acute subdural hematoma. Itturns out that that model to produce acutesubdural hematoma was very reproducible andit also turns out that the subdural hematoma isthe most frequent cause of death in humans.So we had inadvertently found a reliable ex-perimental model for studying the most impor-tant cause of death in humans. We did, how-ever, still want to study diffuse brain injury.

About this time, the late part of 1980, our

laboratory was moved from the Hospital build-

ing to its current location in the Ana-

tomy/Chemistry building. This was simply a

necessity because Hospital reconstruction wastaking over the space. Just a word about thelaboratory. The laboratory has an absolute re-quirement of being in a ground-level locationbecause the accelerating device requires asix-by-six-by-six foot cube of reinforced con-crete to attach the accelerating device to, sothat it obviously is unsafe to put it anywhereother than on a ground level. The only spaceavailable to us from the Medical School wasthe current location which is in the basement,or the subbasement of the lowest level of theAnatomy/Chemistry building.At this time, or very shortly before that, Dr.

Thibault, whom I had previously worked withat the NIH, was attracted to the University ofPennsylvania and came on to the faculty. Wewent back to our original paradigm of control-ling the head, that is, no longer using the ther-moplastic helmet, but going back to a situationwhere we used a metallic helmet and we fittedthe animal into that with a plaster-of-paris-likematerial of dental-stone.

During the early part, the early few monthsofthe new laboratory, many procedural changeswere going on and, because of these, we wereable to produce our intended goal of the dif-fuse, the severe form of the diffuse brain inju-ry in the spring of 1981. This became a veryexciting time in the laboratory because thiswas an absolutely unique finding. No one hadever produced-and to this day still has not-produced prolonged coma in any kind of ananimal preparation in the absence of largemass lesions within the head. So no one hadbeen able to duplicate the common clinical en-tity of the severe form of diffuse brain injuryuntil the spring of 1981. We were obviouslyvery excited about that and, in addition to theproduction of this, it also dispelled many,many questions about experimental head inju-ry. It had been, for instance, argued that thisinjury could not be produced in experimentalanimals either because it was unique to humanbeings, or because it was so rare in human be-ings that the events that cause it couldn't beduplicated, or simply because the brain size ofnon-humans is too small to produce such aninjury. So the mere production of this impor-tant type of clinical brain injury was extremelyimportant.The thrust of the laboratory since that period

has been to better understand the pathologyand the physiology, as well as the bio-mechanics, of this kind of injury. This has ledus to a somewhat revolutionary, I guess theword might be, understanding of this particu-lar kind of injury. We now feel quite strongly,the evidence is quite strong now, that these in-juries are caused by primary damage that ac-celeration induces on the axons of the brain,the nerve fibers of the brain. And hence,we've now named this injury "Diffuse AxonalInjury," or DAI for short, and this term hasnow become very widespread internationallyamongst the experts in head injury and iswidely used, especially by pathologists, andmore and more so by neurosurgeons. It pro-vides a very powerful explanation for the braindamage that occurs in these patients in whomwe didn't know exactly what we were talkingabout previously when we said "Your mother

ALMANAC SUPPLEMENT February 19, 1985 111

has 'brain damage.'" Now we know, rather

precisely, what we mean by that. We meanthat many, many nerve fibers, or axons in thebrain, have been damanged at the time of inju-ry, and the very intriguing thing that we've ap-preciated recently, is the precise location ofthat nerve damage. It's at what are called thenodes of Ranvier which, if you envision thenerve fiber as a chain of linked sausages orhotdogs together, the nodes of Ranvier are theuninsulated parts of the nerve that are verysmall, and that seems to be the precise locus ofthe influence of trauma on the brain underthese circumstances. I should say that coinci-dent with these primate experiments, we havedeveloped a rather extensive program of inves-tigation of trauma of the nervous system. Thisis reviewed, to some degree, in the Depart-ment of Surgery's annual research report and,included in the research report, if you are in-terested, are references to some recent publi-cations from the laboratory. I would just pointout, to say that the animal use, the animal ex-perimentation is only one portion of all our in-vestigative efforts involving brain injury. Theother kinds of things are listed there, and wecan go into them in more detail if you desire.

I think I'll stop at this point and open it forquestions unless there's something that youfeel we should cover specifically now.

Discussion PeriodDr. Fusseli: After these experiments in ac-

celeration are applied through this head de-vice, how is the animal behavior tested?

Dr. Gennareili: Well, there are variousmethods, depending on exactly the purpose ofthe experiment. There are some experiments,for example, designed by one of our investiga-tors, Eliot Stellar, who is interested in behav-ioral and memory deficits after brain injury.That group of animals is pretested for a periodof usually two, sometimes three, months be-fore the injury so that his new learning isquantitated, and then those same tasks are ap-plied after the injury to find the difference. Sothat's one behavioral aspect. The general be-havioral aspects are appreciated by those of usin the laboratory from our clinical experience.That is, neurological examinations are per-formed, observations of the animals are madeand recorded on a scale. We've developed aprimate injury scale that parallels the kind ofscale by which wejudge the severity of humaninjuries (it's called the Glasgow Coma Scale).Using that, we give numerical data insemi-quantitative fashion to be able to de-scribe the severity of the brain injury in oneanimal versus another.Professor Francione: Are we following the

schedule now?Dr. Cooperman:Yes, I think we're into part

three. If we are going to follow the agenda,and I think we should, that we should beginwith the questions on the general focus on theresearch. This list is not meant to be all-inclu-sive, but the kind ofquestions that were raisedin communications by this group to me priortothis meeting have to do with the control ofvariables, the use of animal models, the defi-

nition of head injury as opposed to treatmentand the like, and so I think if we could do partA, we could move right down this schedule.Professor Franclone: Can I first make a

statement about the dialogue? Is that accept-able to you?

Dr. Cooperman: Sure. You can say any-thing you want.

Professor Francione: Those of us whosigned the letter [requesting the dialogue]signed it in response to seeing a tape of ap-proximately twenty-four minutes called "Un-necessary Fuss." And we were upset by thatfilm. We wrote a letter to the Provost and tothe President indicating that we were upsetabout it and that we wanted to talk about theissues raised by this tape. We received a re-sponse saying that we would have this discus-sion about the issues raised by the tape. Istated to you in a letter and on the telephonethat I thought that it was crucial that we see theexcerpted tape. Your objection was that the tapemay contain excerpts taken out of context, andmay present some sort of unfair characterizationof the work done at the head injury lab. Drs.Gennarelli and Langfitt are here. Dr. Fisher ishere. I don't understand why.Dr. Cooperman: Gary, allow me to inter-

rupt. We have a limited time. I think it wouldbe more productive-I mean I consider that is-sue settled. I understand that you disagree withmy judgment, but I don't think we want tohave a long discussion about the rationale foror against showing the tape. If we do, we willsimply take away from your opportunity to askquestions that I thought you wanted to askabout the contents of the tape. If you want togo on, I can't prevent you, but it seems to methat that's going to take time away from what Ithought we were here for, which was to dis-cuss the questions raised in your minds aboutwhat was on the tape.Professor Francione: Fine.Dr. Fisher: May I ask Gary a question that

he may not be able to answer but, as he says,he is a member of PETA, maybe he doesknow. Why has PETA not given us a copy ofthe tapes so that we could see the whole

Professor Francione: I, along withtwenty-nine thousand, nine-hundred andninety-nine other people belong to People forthe Ethical Treatment of Animals. I also be-long to other organizations and I

Dr. Fisher: I'm not asking about your mem-bership. I'm asking if you have any insightinto why PETA will not give a copy of thecomplete sixty hours of tapes.

Professor Francione: I don't have any in-sight about that

Dr. Fisher: Sounds malicious.Dr. Cooperman:Well, we could have a dis-

cussion about the politics of the tapes, andProfessor Francione: We're sitting around

talking about the issues raised by the tapes butwe haven't seen them.

Dr. Cooperman: I understand that, but peo-ple have seen them, and I think you've exam-ined them and I think you're prepared to askquestions about them and, as I say, if we want

to spend an hour discussing the rationale ofhaving the tapes here or not, we can do that,but I think that would be unproductive. I thinkwe're here to discuss what questions wereraised, and I'd like to get to the crux of thematter.Professor Watson: I think we'd have gotten

to the crux of the matter if we had seen thetapes.

Dr. Cooperman: Well, I understand that.And I'm quite willing to let you have the lastword on thatProfessor Watson: Fine.Dr. Cooperman:. . . but could we now go

to the questions that are raised in your mindsabout the tapes?Professor Francione: Yes, but I just

wanted to make a couple of other observa-tions. The second observation I wanted tomake is I think it is unfortunate that Dr. JohnMcArdle from the Humane Society of theUnited States is being forced to sit in the hallbecause I was not allowed to bring a scienceadvisor into the room. I thought that was avery reasonable request, especially when Istressed to you that he would not participate inthe dialogue at all.

Dr. Cooperman: I think the record of thisconversation can have that.Professor Francione: Fine. The third thing

I wanted to say is that this committee was, inpart, convened by Dr. Jacob Abel

Dr. Cooperman: Yes.Professor Francione: . . . and I object to

the fact that Dr. Jacob Abel did not make pub-lic-he certainly didn't tell me-that he hasco-authored published research with Dr.Gennarelli having to do with head injury inprimates. I'm not questioning the integrity ofanybody who was selected by Dr. Abel. I'msaying that I'm surprised that the Administra-tion, which I believe knew that Dr. Abel hadpublished this research with Dr. Gennarelli,would tolerate such a clear conflict of interest.I'm sure that the reaction would have beenvery different if you appointed me to choosethe committee.

Dr. Cooperman: I will respond to that, butvery briefly. It was my judgment that JacobAbel could make those selections without aconflict of interest. And it was hisjudgment aswell. So, can we now return to the issue athand, which are the questions raised in yourmind by the tapes?

Dr. Cohen: Yes, I have two questions forDr. Gennarelli.

Dr. Cooperman: I believe ProfessorFrancione had the floor to ask these questions,and is there any reason why we can't proceedin that way?

Dr. Cohen: No. Not at all.Dr. Cooperman: Fine.Dr. Cohen: I thought you had finished.Professor Francione: Tom, you talked be-

fore about the statistics of head injury. Youtalked about the numbers of head injuries thatoccur every year. In those statistics that youtalked to us about this morning and in those

IV ALMANAC SUPPLEMENTFebruary 19, 1985

published in the Almanac, how many of thoseinjuries are consequential, survivable or notsurvivable under any circumstances, prevent-able by simple precautions, self-inflicted? Arewe making any sort of breakdown there?

Dr. Gennarelli: That's a mighty complexquestion. You've got six or eight differentquestions in there. Can you break them up oneby one?

Professor Franclone: Yes. How many ofthose injuries aren't survivable under anycircumstances?

Dr. Gennarelli: It's estimated that, of thosepatients who die, that there is probably an irre-trievable mortality of somewhere in the rangeof 15 to 20 percent depending on the kind ofinjury, the age of the victim, and so forth.What I'm saying is that the magnitude of theinjury itself is of such severity that survivalunder the most optimal circumstances is notcompatible with our current medical practices.

Professor Franclone: So those figures thatwe have, both in the Almanac and the oneswe've discussed this morning, don't break outinjuries that really you couldn't do anythingfor anyway, no matter how many primates youtested?

Dr. Langfitt: Could I respond to that, Barry?Dr. Cooperman: I think it's open to anyone,

but sure.Dr. Langfltt: First of all, if we take the fig-

ure of a million and one-half million individu-als who are at risk for head injury in this na-tion, the larger majority ofthose have minor tomoderate head injuries. They don't have thesevere head injuries with the very high mortal-ity rate. 1 don't know what the precise percent-age would be, but taking that number, thoseindividuals who could not survive, under anycircumstances that we understand today,would be a very, very, small percentage.A point that Tom did not mention, with re-

spect to the story of diffuse axonal injury, isthe evidence that it is important not only in se-vere head injury, but also in the field of minorhead injury. Just this past month, one of ourcolleagues published with Tom a paper in theJournal of Neurosurgery, in which they de-scribed what happens in primates who have aminor head injury; again, these were rhesusmonkeys accelerated in just the fashion that hedescribed. These animals were unconsciousfor no more than a few minutes, a sort of sim-ple concussion, or a little bit beyond concus-sion. The animals then awakened and wereperfectly all right, but when they were sacri-ficed in about two weeks, there was evidenceof diffuse axonal injury in the brains of thoseanimals that had been unconscious for no morethan two minutes. This is important because ithas only been in the past few years that wehave recognized the consequences of minorhead injury.Quite frankly, neurosurgeons of the past

used to sort of brush aside the complaints thatpeople had after having been knocked uncon-scious for brief periods of time, oftentimesthinking these were functional, or emotionaltypes of things, or goldbricking, whateverterm one wishes to use. Largely through theefforts of the group at the University of Vir-

ginia in a prospective study of some 500 pa-tients with minor head injuries, it was demon-strated that these patients were sufferingsignificant signs and symptoms suggestive oforganic brain damage after no more than just afew minutes of unconsciousness. In fact, athird of these patients were not back at workthree months after a minor head injury.Neuropsychological evaluation of some ofthese patients was done using very sophisti-cated tests, which indicated that many of thepatients had evidence of organic brain dam-age. We now think that we can draw a rela-tionship between that clinical story of minorhead injury producing devastating conse-quences in these patients and the evidence inthe animal studies that even with minor headinjury there is evidence of diffuse axonal inju-ry or organic brain damage.

Professor Franclone: Can anything bedone for axonal injury?

Dr. Gennarelli: We think so. And this is oneof the very, very exciting postulates

Professor Franclone: Axonal means nervedamage, correct?

Dr. Gennarelli: RightProfessor Francione: . . . as opposed to,

say, vascular damage?Dr. Gennarelli: That's right. Originally, we

felt that one thing happened in axonal damage,that is, that the nerve fiber-which in somecases is a couple of feet long-was transsectedat the moment of the head acceleration. Itturns out that our investigations have shownthat that's probably not the case, and the im-portance, of course, is germane to your ques-tion, because we felt that there would be verylittle to do from the therapeutic point of view ifthe nerve fiber was actually cut in two at theinstant of injury. If that were the case, thenone would have to rely on the regenerationmechanisms which are being intensely studiedby other neuroscientists, but are not known tobe particularly effective over long distances inthe adult mammalian brain. However, our evi-dence suggests that the nerve fibers, theaxons, are not transsected at the moment of in-jury. They're clearly damaged at the momentof injury and, subsequent to the injury, a chainof events is set into motion that by 12 or 24hours after injury begins to cause damage-axons that are damaged but not transsected dobecome transsected. This is what we call sec-ondary axotomy. That is, axons that aren'tbroken become broken by some process thatbegins at the time ofthe injury but does not be-come fulfilled for some to 12 to 24 hours. Soour efforts now, and this is very current, are totry to understand that process by which a dam-aged axon goes from being structurally intact,that is, damaged but still together, to the pointof being disrupted. And there's the therapeuticchallenge, in that if we can understand thatmechanism and develop strategies to prevent itthen there's a possibility now of a specifictreatment for brain damage-traumatic braindamage. And, as I mentioned, we now do nothave a specific treatment for brain damage.

Professor Franclone: These experimentshave been going on, at least with respect toyour participation, since 1975? Is that correct?

Dr. Gennarelli: I came to the University inJuly of 1976.

Professor Franclone: Were the experi-ments going on before then, here?

Dr. Gennarelli: In a very preliminary fash-ion. I believe for only a month or two.

Professor Francione: Can you sort of esti-mate the number of animals that have beensacrificed throughout the history of the headinjury clinical research lab at least going backas far as 1976?

Dr. Gennarelli: To date the number is justover 200, 1 think.

Professor Franclone: The protocol that iseffective, or purported to be effective, from1982 to 1987, talks about the use of 250babboons.

Dr. DavIes: 1987 did you say?Professor Francione: Yes.Dr. Gennarelli: You mean the currently run-

ning grant?Professor Francione: What I'm talking

about now, Grant Application NS08803-l3,principle investigator Thomas Langfitt. This isAugust I, 1982. through July 31, 1987. Ittalks about the use of 250 babboons, but todate there have only been two hundred animalsused in the

Dr. Gennarelli: Yes. On the average, thatbeing 24 a year.

Professor Franclone: I was reading re-cently an article that appeared in a Scottishnewspaper on December 1, 1983, involving aninterview with a man named Dr. Adams, whois listed on the protocol, Tom. Dr. Adamsmade the statement that, to date, the results are"academic" and that the team-and I believehe was referring to the team comprised of theUniversity of Glasgow and the University ofPennsylvania working on this-has not pro-vided any sort of preventive measures. Now isthis business with trying to figure out how toprevent the transsecting of axons going to bethe first treatment-related breakthrough thatthe laboratory will make?

Dr. Gennarelli: First off, let me make acomment about using quotations from newspa-per articles as biblical gospel. There havebeen, I can't tell you how many, mis-quotations. That particular citation is amisquotation of Dr. Adams.Professor Franclone: He didn't say that?Dr. Gennarelli: You may ask him if he said

that.Professor Watson: Well, you're saying he

didn't.Dr. Gennarelli: My understanding from him

is that that was a question to which he re-sponded and the response was misquoted incontext but, that aside, let me answer yourquestion. There exists no specific therapy forbrain injuries in clinical use today despite tri-als of innumerable therapies. One by onethey've been shown by at least some group tobe ineffective in one manner or another. Theonly specific therapy that exists at this momentis the removal of blood clots or what we callmass lesions, that is, damaged areas that aretaking up excessive space in the brain. All

ALMANAC SUPPLEMENT February 19, 1985 V

other treatments are currently aimed at eitherreducing swelling of the brain, reducing thewater content ofthe brain, the blood content ofthe brain, or other measures to treat what wecall epiphenomena of the injuries themselves.There is no specific treatment for the injuryitself. So we have not yet, as of this date, pro-duced a treatment for brain damage. We'reconfident that we're on the right road to beable to do that, and we're confident that thedata shows us that it's possible to have a spe-cific treatment.

These are all very new ideas, and whetherthey will become realities in the future, I can'ttell you. But I think we're further along than alot of other people in the area with regard tothis. There's no one else in the world who hasavailable to them this model of diffuse axonalinjury.

Dr. Langfitt: Tom, if I might make just acouple of comments in response to the ques-tion: It is not really possible to develop effec-tive diagnostic and therapeutic modalities for adisorder until the basic mechanisms responsi-ble for that disorder are understood-ranging,for example, from deficiency of insulin as acause of diabetes to causes and treatment ofcancer. One needs fundamental break-throughs. The more fundamental the informa-tion basic to the understanding ofthe the cellu-lar mechanism, and the abnormalities that leadto the disorder, the greater is the likelihoodthat one can develop an effective therapy.Cancer is a very good example: In the pastfour or five years, the discoveries of molecularbiology of genetics as they relate to cancerhave absolutely staggering implications, manyof which results from animal research. Whenthe cause of cancer, or of different kinds ofcancers, is determined, we're not going to stopat that point because we don't have the therapyto treat them. Rather, once we find the cause,we will try to develop the therapies. And itcould be that in given kinds of cancers it's go-ing to be a very long time, maybe a decade orlonger, before we find the therapy to treat thedisease. We don't stop once we've found thecause; we go forward to try to find the therapy.Now, as Tom described, we think we under-stand the fundamental basis of brain injury thatform a diffuse axonal injury. It may be a longtime before we derive the therapy that's goingto be effective in these patients, particularlyfor that twelve- to twenty-four-hour windowthat exists between the time of the injury andthe time of the secondary axotomy. However,if we succeed in so doing, then we're going tohave an enormous impact from this research.Professor Francione:A greater impact than

say, taking all of the money that has been usedover the years, and trying to develop safe-guards and precautions, trying to outlaw blowsto the head in such frivolous ways as boxing?

Dr. Fisher: I don't see any point to this one-way discussion about the merits of scientificresearch, and it seems to me a waste of timefor most of us here. Instead of discussing thephilosophy of research, we should bediscussing the use of animals in research.Professor Francione: Well I have specific

questions. If you want to hear them I'd behappy to ask them.

Dr. Fisher: I would rather do that. Other-wise, the dialogue is not relevant to whatwe're after.

Dr. Cooperman: Gary, you had a question.Dr. Cohen: Well, I don't think I'll interject

it at this moment. I think the decision as to thedirection of the discussion is more important.

Dr. Fussell: If I might ask Dr. Gennarellione question, which I think might move us offthis into something that is more precise. Thisis item "C" under Roman "3," the matter ofanesthesia. I think if these animals were anes-thetized, I think the objections of the PETApeople would disappear. I think, therefore, it'simportant that we ask the question, why arethey not anesthetized, to what degree are theyanesthetized, and so on. So could you shedlight on that?

Dr. Gennarelli: Sure. I'm not sure that Iwould agree with you that PETA would disap-pear on the basis of this one issue. It's obvi-ously the most crucial issue, I think. I guessthe best way to approach it is by what the par-ticular needs are for anesthesia in the particu-lar experiment that we're doing. Those needsare several-fold and they sort of run longitudi-nally with the experiment.The first need is to be able to get the animal

safely handled so that he is not a threat to per-sonnel and not a threat to himself while beingtaken from the animal care facility to thelaboratory.The second need for anesthesia is the need

to prevent pain during the time of the minor

surgery that's used for insertion of the various

monitoring lines. And, I should say at this

point, that those procedures are absolutelyidentical to the kinds of things that we do inthe intensive care unit or at the bedside. Thatis, we're not talking about major brain surgeryor major chest or abdominal surgery here.We're talking about minor surgical proceduressuch as we commonly use out of the operatingroom in patients.The third need for anesthesia, and perhaps

one that will be the most debated, is the actualtraumatic insult itself. Maybe if I just outlinethese first, then we can go back to specificareas.The fourth is the need for anesthesia while

removing the monitoring lines, the intra-veneous lines, the line to measure intracranial

pressure. And the last need for anesthesia is inthe general recovery phase, and again is onethat can be some point of debate, after thebrain injury has been achieved.Now to subserve all of those various needs,

and you can appreciate that they're a complexgroup of needs from being able to handle theanimal safely to absence of pain and so forth.It's fairly clear that a lot of thought must haveto go into this, in order to develop the agentsthat we feel are most appropriate. There areseveral considerations that we needed to con-sider when choosing the anesthetics, amongstwhich were the animal's inability to feel painand, the ability to be able to examine the ani-mal neurologically to determine if we've pro-duced a coma and, if we have, to be able toassess the depth of that coma, the severity ofthat coma, and any other neurological abnor-malities that may be present. One of the criti-

cal variables in this whole laboratory effort isthe correlation of those clinical events with theinput phenomena, the biomechanics, the shapeof the acceleration pulse, its height and widthand rate of onset, all of these variables corre-lated with the physiological observations cor-related with the structural observations fromthe pathology of these injuries and in some in-stances, with biochemical alterations in thebrain. So, we chose the particular anestheticparadigm that we did with those consider-ations in mind, and chose two agents to beused conjointly: a drug called phencyclidine,trade name Sernalyn, which is a drug given byinjection, and an inhalation drug, nitrousoxide

Professor Franclone: Where was it in-jected? How was it injected into the animal?

Dr. Gennarelli: With a needle.Professor Francione: Yes. I understand

that, but where? Intravenously or into the bodycavity?

Dr. Gennarelli: No. It was given, usually,intramuscularly-sometimes intraperitonially,but usually intramuscularly. The way that'sdone is that the animal is in a cage that has amovable back.

Professor Francione: A squeeze cage?Dr. Gennarelli: A squeeze cage type of af-

fair. If the rest of you are not familiar withthat, that's one of the common ways that theanimal's brought forward to the front of thecage and given the injection. One of the mostimportant points about this particular drug isthat the drug provides an adequate level of an-algesia, that is, absence of pain sensation,without producing depression of respiratoryfunction and cardiac function which is one ofits unique properties, in distinction to many ofthe other commonly used drugs such as narcot-ics or barbituates whose functions depress re-spiratory activity and cardiac activity in almostthe same linear fashion as they depress theability to appreciate pain. This is of particularadvantage, to use a drug like Sernalyn, be-cause the laboratory is not adjacent to the ani-mal care facility, so the animal has to be takenfrom where he lives to the laboratory. We feelthat a drug like Sernalyn can do that verysafely because we don't have to worry aboutwhether the animal is going to stop breathingor whether his heart's going to slow down ap-preciably because this drug does not have theproperty of depressing the heart and the bloodpressure.

Professor Francione: How far in advance,Tom, is this Sernalyn administered before theinjury is actually inflicted?

Dr. Gennarelli: Well, the answer is that it'svariable from several minutes before to anhour before

Professor Francione: Several minutes be-fore the actual injury?

Dr. Gennarelli: It's possible that that's inthe range-depends on how many doses ofSernalyn are used in any one particularanimal.

Professor Francione: The protocol saysthat the animals are given a single parenteraldose of phencyclidine, one milligram per kilo,on the morning of the experiment-that's atpage 192 of the protocol. The protocol later

VI ALMANAC SUPPLEMENTFebruar 19, 1985

says that it takes between two or three hours tointubate the animal, to get all the monitoringdevices placed, and to pot the animal's headinto the injury device using the dental-stone. Isthe protocol incorrect?

Dr. Gennarelli: It's incomplete, I think. Ithink maybe Dr. Langfitt could speak to thispoint of protocols in grants. Dr. Fisher and Ihad a little go-around about this and thereseems to be some concern-as this is an exam-ple of-of how detailed one's protocol shouldbe in a grant. The purpose for the protocol in agrant may be substantially different from thepurpose of the protocol, let's say to the Ani-mal Care Committee. Perhaps Dr. Langfittcould address that global point; he has moreexperience with grants.

Professor Francione: Before he does that,can I perhaps flesh out my questions so Dr.Langfitt could do it all at one time?

Dr. Cooperman: Sure. And it would begood to get the reason that you feel you wantto press this point.

Professor Francione: The discussion in Al-manac states that the animals were anesthe-tized at the time that the injury was inflicted.And, in looking over the protocol and in thepublished papers, it appears as though the fol-lowing regimen was used: On the morning ofthe experiment, approximately two to threehours before the injury was inflicted, one mil-ligram per kilogram of phencyclidine was ad-ministered to the animal. The animal sponta-neously ventilated seventy to eighty percentnitrous oxide until one hour before the injury,and I'm reading from the protocol,through the endotracheal tube, the animalspontaneously ventilates seventy to eightypercent nitrous oxide anesthesia until one hourbefore acceleration, after which it breathesroom air, infiltration anesthesia is utilized atall surgical sites." If you're using infiltrationanesthesia, there must be some need for it ifthe animal was anesthetized, and that if thephencyclidine and nitrous oxide combinationwas working all the way through up until thetime of the injury, there would be no need forinfiltration anesthesia.

But in any event, the protocol also says thatwithin the hour before the injury, the animals-at least some of the animals, it's unclear-are taught new memories. It's unclear to mehow you can be teaching new memories to ani-mals who are under the influence of a dissocia-tive. The excerpted tape itself shows the ani-mals moving around on the table. There arevery purposeful activities going on on that ta-ble. At one point a baboon twists the sameway five different times. I suspect one can saythat those could be characterized as randommovements, but what is the possibility thatthat sort of activity could be random? The ani-mals are grasping at the restraints.

Dr. Gennarelli: If we could respond to onepoint at a time, I think it would be easier.You're getting a lot of questions mixed up andit becomes hard for us to answer them in sucha global fashion.

Professor Francione: Were the animalsanesthetized at the time of the injury?

Dr. Langfltt: Let me try to add a bit to whatTom said in describing the characteristics of

dissociative anesthesia. We don't use Sernalynor phencyclidine but we do use dissociativeanesthesia in our neurosurgical procedures inthe operating room. Just as in the experiments,the whole objective in clinical anesthesiologytoday for neurosurgery is to try to keep the pa-tients as light as possible. We've learned overthe years that the deeper the anesthesia, thegreater the complications. Under dissociativeanesthesia, the patients appear or often looklike they are awake. For example, patients willopen their eyes and look around while on theoperating table when one is doing acraniotomy to remove a brain tumor or operateon the spine, and they'll move a bit from timeto time. It really takes the judgment of an ex-perienced anesthesiologist to know what isjustright. Any time an animal or a patient hasmovement, one has to make a judgment as towhether the animal or patient is experiencingpain. With experience derived mainly from theoperating room and transferred into the labora-tory, the investigators think they can do thatquite well. The reason for having the infiltra-tion anesthesia, however, is to do everythingpossible to relieve pain. Under some circum-stances it can be somewhat difficult to know.As I understand it, from the experience of thelaboratory, where I have spent some time butnot nearly as much as my colleagues, the sin-gle dose of phencyclidine generally suffices.

Professor Francione: Three hours beforethe injury?

Dr. Langfitt. Yes. Tom and I were reading avolume on phencyclidine in which two distin-guished anesthesiologists regarded it to beone of the best general anesthetics ever devel-oped

Professor Franclone: That's funny, be-cause the materials that I've been reading saySernalyn is

Dr. Langfitt: . . . May I finish? As a matterof fact, a single dose is ordinarily all that isneeded because it generally lasts for two tofour hours, and the acceleration occurs some-where around two hours after the initial dose.But, as Tom has indicated, when a seconddose is needed it is given; in the vast, numberof cases it is not needed.

Professor Francione: So then the protocolwould be inaccurate, or incomplete.

Dr. Langfitt: Yes; the other point is that oneis limited in the amount of space in which to

present this material. Proposals are very long,so ordinarily one puts down what the generaloperating methodology is. Exceptions to allthese things are not included, since one could

go on with pages of exceptions.Professor Franclone: How could you teach

a baboon a memory within an hour of the inju-ry if the animal is on phencyclidine with ni-trous oxide? I'm just curious as to how that'sdone as a practical matter. The protocol saysthat animals are taught memories within anhour before the injury. Now if you've admin-istered phencyclidine, which is a dissociative- I believe that it is used by some illegally asa recreational drug called PCP or Angel Dust-and if the animal is under the influence ofphencyclidine and nitrous oxide in the hourbefore the experiment, how do you teachbehaviors to the animal?

Dr. Gennarelil: I think you're getting your-self a little confused. The studies on memory-let me answer your question so that yourconfusion can be dispelled. The studies onmemory are performed by Dr. Stellar and hiscolleagues. The animals are trained, as I men-tioned, for some period of time, usually two tothree months beforehand. They are not trainedunder anesthesia. They are trained by Dr. Stel-lar or one of his associates working with theanimal on a one-to-one basis at the cage, usingthe techniques that he has developed to trainand ingrain memory and learning behaviorinto the animals. The morning

Professor Francione: But you said it takesthree hours.

Dr. Gennareili: Would you please allow meto finish the answer?

Professor Francione: You are doing mostof the talking.

Dr. Gennarelli: Well, you asked a ques-tion

Dr. Gennareili: The morning of the experi-ment on which Dr. Stellar wants to ingrain anew memory, that is done prior to the animal'sleaving his cage, before he is anesthetized, be-cause that's the way the old memories were in-grained. Some of these are called pattern re-versal changes, that is, there's a choice of twoobjects and the animal has learned that one isalways correct and he gets a food reward for it.On the morning of the experiment the investi-gator goes to the cage, and now what pre-viously was the correct object is now made tobe the incorrect object, and the animal has tolearn that prior to going down, prior to gettinghis anesthesia and going down to thelaboratory.

Professor Francione: But you say in theprotocol that it takes between two and threehours to get the animal prepared for the injuryand on page 201 of the protocol, it says withinthe hour before head injury the baboon istaught several new and therefore, recent,memories. What is the purpose of stopping thenitrous one hour before the injury earlier, asyou say, earlier in the protocol? What is thepurpose for that, and how do I understand thestatement on page 201?

Dr. Gennareili: Well, let me just make ageneral comment on protocols. Protocols areguidelines. They are not etched in stone, andthey are very mobile. That is, the protocol thatyou have before you has probably changed,not in large degree, but in specific detail, aswe've felt that better ways of.

Dr. Cooperman: I'm going to take a privi-lege of convener in this to talk about protocolsbecause I think we're getting off on anunproductive route. The purpose of a proposalis to tell people something of what you're go-ing to do. It's not at all to tell people in precisedetail exactly how each experiment is going tobe conducted, because the expectation is thatyou're going to find things out as you do theexperiments which will impinge upon howyou do the [next] experiments. I think it'sunproductive for you to persist in a line ofquestioning based on a protocol which mayhave many inconsistencies when comparedwith the actual procedure. What bothers meabout this is that I thought, and still believe,

ALMANAC SUPPLEMENT February 19. 1985 VII

that what you saw disturbed you, and I reallythink it makes sense for you to use the oppor-tunity presented by this dialogue, to tell uswhat you found disturbing that actually hap-pened rather than focusing on a written proto-col, in order to see whether there is a fault inthe experiment, which is one possibility, orwhether there isn't a fault and it's just some-thing that's disturbing but which has a veryclear rationale.

Professor Franclone: But, Barry, one ofthe things which is very disturbing about thetape is that the animals appear to beunanesthetized so I did read the protocol andpublished research.

Dr. Cooperman: I understand why you didit. I'm not saying that a reasonable personwould not act as you have. That's not mypoint. My point is that I think it's a mistake tobelieve that what is written in an NIH protocolwill be slavishly followed by the investigator.That is not the general practice within the sci-entific community. The purpose of the pro-posal is to outline the thrust of the research;the details change all the time. And so, if youhave questions about what you saw

Professor Watson: Were we that mistakenin what we saw, that the animals appeared tobe unanesthetized?

Dr. Cooperman: Let's talk about the state ofthe animals before the injury. I think that'swhat bothered you and that's what we shouldbe talking about.Professor Franclone: I have here the re-

search paper written by Dr. Genneralli called"Diffuse Axonal Injury and Traumatic Comain Primates." I have now stopped looking atthe protocol. The research paper reports that"behavioral, psychological, and neurologicalobservations were performed one hour afternitrous was stopped." Now, is one also not tobelieve what one reads in the

Dr. Cooperman: No. No. I think the paperis a betterProfessor Franclone: Could you please ex-

plain that to me then?Dr. GennarelH: Those behavioral observa-

tions were not the trained behavioral observa-tions that you've alluded to before. Thosewere observations of the animal's behavior,that I mentioned before, that we record in asemi-systematic fashion. Behavioral observa-tions being, "Is the animal awake? Is the ani-mal comatose? Is the animal apparently nor-mal? Is he apparently not normal?" Those areneurological behavioral observations.

Dr. Cooperman: Could you give us an indi-cation of what that would constitute so thatwe're clear about what you're talking about?What do you actually observe?

Dr. Gennareill: Well, the general state ofthemonkey and what he does either spontane-ously or by inducement or stimulation iswhat's observed. That's sort of a fundamentalclinical observation that one makes and is oneof the

Dr. Cooperman: Is it rate of blinking, is itreflexes, is it that kind of stuff?

Dr. Gennarefli: No, it's a general gestalt that

you get when you walk up to a patient and say"Is that patient comatose, or is that a patientwho is doing differential calculus? Does hehave the capability of doing differential calcu-lus with what I see and what I can observefrom that person or that animal?" Now, what Ithink you're really asking is "Does the anes-thesia last sufficiently long to be present insufficient quantities at the time of the injury."Is that what you're really asking?Professor Franclone: I have questions that

concern whether the animal was anesthetizedproperly before the injury, at the time of theinjury,

Dr. Gennarelli:Why don't you ask them oneat a time?Professor Franclone:. . . after injury, and

at euthenasia when the brains were frozen.Dr. Gennareill:Why don't you ask them one

at a time so thatProfessor Franclone: Well I've asked-

perhaps this indicates the need for a scienceadviser-I'm trying desperately to ask you thequestion concerning whether the nitrous wasstopped one hour before the injury, because ifthe nitrous was stopped one hour before the in-jury and there had only been a single adminis-tration of phencyclidine, at the dosage of onemilligram per kilogram on the morning of theexperiment two to three hours before the inju-ry was sustained, it seems to me that an argu-ment could be made, and it seems to me fromwhat I've read that the argument would be astrong one, that the animals were not anesthe-tized. In fact, part ofthe purpose of the experi-ment was to perform a neurological examina-tion immediately after the injury with whichany trace anesthesia would have interfered.Dr. Gennareill: O.K. Now you've got a

question that we can answer.Professor Franclone: But I had that before.Dr. Gennarelli: You have to distinguish be-

tween the absence of pain sensation, which iswhat we were after, and an animal being co-matose as a product of a drug. Those are twoareas that many times are related areas, but arenot necessarily always related. That's whatDr. Langfitt mentioned is what a dissociativeanesthesia compound does, what it does. Thatis, it allows the animal to be, or the human tobe, pain-free, that is, incapable offeeling painsensations, but still does not render the patientor the animal into a coma, which is our com-mon conception of what anesthesia is. Thecommon lay conception is you get a shot oryou get a gas and you fall asleep and you don'tfeel anything. That's deep anesthesia. Disas-sociative anesthesia has analgesia, which isthe absence of pain sensation with the pres-ence of varying amounts of cognitive or mo-tion function. It's a difficult concept, I agree.That's the kind of anesthetic that Sernalyn is.One can monitor the effective effect ofSernalyn in several ways. One can do it behav-iorally, that is, with experience with a particu-lar species, one can get an appreciation ofwhether they're feeling pain or not. That'ssomething that is a clinical judgment, and inour clinical judgment the animals were notfeeling pain. They were clearly moving. That

was one of the intentions because we wantedan agent that would allow us to perform a neu-rological examination but still enable the ani-mals to be pain-free.Professor Franclone: So the animals were

pain-free at the time of the injury?Dr. Gennareill: Yes. Now whether that took

one dose of Sernalyn or two doses or fourdoses was entirely dependent on the animalbecause there's a lot of variability, as with anydrug, in terms of its effectiveness, the durationof its action and so forth

Professor Franclone: In this paper.Dr. Gennarelli: Now let me finish the re-

sponse. I mentioned that one of the ways thatone can tell if an animal is having pain is bythese observations. There are other ways. Onecould draw drug levels and relate them to nor-mative data. We did not do that. One of theother things to do is to make observations ofthe kinds of physiological responses that arecharacteristic of pain. Those are fairly well de-tailed in all literature, they are very constant.When a human or an animal feels pain, itsheart rate goes up, its blood pressure goes up,its respiratory activity generally gets a little er-ratic and usually goes up. We've monitoredthose things in every experiment. We'vemonitored blood pressure, heart rate, respira-tory rate and brain wave activity. And in no in-stance immediately before the experimenthave we noticed alterations of those physio-logical parameters of the type that would beconsistent with pain.Professor Watson: On the film which has

not been shown, one of the researchers saysthat an animal which is about to have his headbashed, "It's off anesthesia." But you say thisdidn't occur.

Dr. Gennareill:You didn't ask-I didn't saythat didn't occur

Professor Watson: I thought you said thatyou never noticed that the animals were suffer-ing pain?

Dr. Gennarelli: That comment specificallyrefers to the disconnection of the nitrous oxidefrom the animal prior to the injury. That'swhat the local term "off-anesthesia" meant.And that's one trouble one gets into by extract-ing things out of context. That's specificallywhat that meant, that the animal-when thelaboratory workers speak of "off-anesthesia"they are talking about the inhalation agent, thenitrous oxide.

Dr. Cooperman: Gary?Dr. Cohen: I'd like to get your answer to

one of the questions that you raised. Was thereany time or is there any reason for you to sacri-fice an animal and study nervous tissue in theabsence of anesthesia-in the absence of anes-thesia within the brain?

Dr. Gennarelli: No.Dr. Cohen: O.K. because that was your

question at the moment as stated.Professor Francione: Although I now real-

ize that I'm not supposed to rely on the proto-col, but the protocol talks about how, in somecases, the animals have their brains frozen by

VIII ALMANAC SUPPLEMENT Februarv /9, 1985

having their skulls exposed and then liquid ni-trogen applied to the exposed skull. The proto-col does not mention, anywhere, the use of an-esthesia in that procedure.

Dr. Gennarelli: A reasonable person wouldassume that that's the case. I think that's whatBarry alluded to with regard to the NIH proto-cols. I think that's the-what is done is thoseanimals are re-anesthetized before any sacri-fice procedure if they're in any way capable offeeling pain: they are anesthetized.

Professor Franclone: Well let me ask youthis. Tom. In this paper on diffuse axonal inju-ries, you say that coma, or unconsciousness,following the injury can last as few as fifteenminutes. is that correct? I'm reading it now. Itsays "cerebral concussion coma of less thanfifteen minutes' duration"?

Dr. Gennarelli: Yes.Professor Franclone: It also says "uncon-

sciousness-coma-was defined as the ab-sence of any eye-opening (spontaneous or inresponse to noxious stimuli) in the absence ofoccular injury or occularmotor palsy." If theanimals are anesthetized and they are anesthe-tized before injury, at injury, and after injury,what is the purpose of applying noxious stim-uli to an animal that is properly anesthetizedwith phencyclidine?

Dr. Gennarelli: Well, you can't have it bothways. You can't have us test whether they'refeeling pain, and not test whether they're feel-ing pain at the same time. The purpose

Professor Francione: What are the noxiousstimuli that you use?

Dr. Gennarelli The purpose of applying anoxious stimulus, which is a pinch, is to see ifthey respond to pain.

Dr. Langfltt: This is exactly the same thingthat we do in the clinic every day. In otherwords, a patient comes in with a severe headinjury. The Glasgow Coma Scale has threeitems: verbal response, eye opening, and re-sponse to painful stimulation. Theneurosurgeon or neurologist

Dr. Gennarelll: Sure.Dr. Langfltt: Icontinuing] . . . has always

tried to determine whether or not a patient iscomatose and also to quantify the level of con-sciousness by the response of that patient to apinch. It's the same pinch that we use in theanimals.

Dr. Cohen: Well how would you know ifthe loss is due to the injury or due to theSernalyn?

Dr. Gennarelli: We may not know, on a sin-gle basis, but whether coma or not has beenproduced by the injury for us, with experi-ence, is relatively easy to determine. That is,the animal is unconscious. There's no questionabout it. The eyes are closed. They don't opento painful stimulation. The eyes are open un-der Sernalyn anesthesia. 1 mean, it's perhapsharder to describe than it is to show you or toappreciate it, but, look at an animal and lookat his eyes, examine him, and in your judg-ment, he's either unconscious or he's notunconscious.

Dr. Cooperman: In the interest of trying tocomplete. this agenda, if there's

Professor Franclone: I have hundreds ofquestions I'd like to

Dr. Cooperman: I'd like to move on. I'dlike to move to another area ifwe can, becauseI don't know how much more we're going toget out of this one.

Professor Franclone: I have many ques-tions on this area, additional questions on thisarea, as I do on the other areas. I do want tofinish up with one thing. Dr. Langfitt men-tioned before that he has consulted sourcesthat inform him that Sernalyn is a completelyproper and wonderful anesthetic agent. Iwould like to know, and I sincerely mean this,what sources he's talking about because theones I've looked at state the following:Sernalyn is a dissociative agent useful 'ratherfor its tranquilizing properties than for its use-fulness as anesthetic." (Veterinary Pharma-cology and Therapeutics' Fourth Edition.)Soma's textbook says that although immobi-lizing or sub-anesthetic doses are particular)'valuable in subhuman primates and other ani-mals which are difficult to handle, the use ofphencyclidine as a total anesthetic, "should bequestioned because of the tremors and poormuscle relaxation." I note that the nitrous ox-ide was removed an hour so its-an hour be-fore the injury-so the phencyclidine was theoperative agent and, so far as we know fromthe protocol it's only a single dose. And, fi-nally-and 1 have other sources as well, Idon't want to bore you with that, but, in a re-cent letter from Dr. Wall, who's director ofthe cerebral functions group at University Col-lege, London, Department of Anatomy, andEditor of the British journal, Pain, he stated-in a letter which I have- that "these animalswere not anesthetized at the time of the headinjury." And he bases that on the publishedwork of Dr. Gennarelli. I have that letter. Ifanyone wants to see it, he is welcome to see it.I also have other letters from other physiciansand scientists who have looked both at the pro-tocol, which I guess they put more credence inthan this group does, and in the published pa-pers that Dr. Gennarelli has produced. I wouldlike to go on to the

Dr. Gennarelli: Well, you have to give me achance to respond. I don't know the informa-tion upon which Dr. Wall makes his com-ments. If he has read either the protocol or thepublished works with the same sort of legalis-tic viewpoint that you have, it's not surprisingto me that he can make some conclusionslike-it's actually still surprising

Professor Francione: He's not a lawyer.Dr. Gennarelli: I understand. I think you ob-

viously have let a lot of things pass by that Imentioned. So I guess that means that I haveto stress them. There are several points in ourprocedure where anesthesia is critical and cer-tain points where it is not. What we feel is themost important points of the anesthesia is theinitial part of the animal handling, for the ani-mal's safety and the humans' safety who areworking with the animal, and the second pointis for the minor surgical procedures that areperformed to insert the monitoring devices. Inmy mind those are two critical points whereanesthesia has to be at its deepest level. Theactual injury itself is not painful, and a strongargument can be made, and has been made inthe past, to do that portion of the experiment

with no anesthesia, purposely. That's what wedid at the NIH, in-house at the NIH, in thoseearly experiments. Those experiments werereviewed. The laboratory was visited by oneof the directors, and those experiments wereapproved. The laboratory is much more so-phisticated now than it was 15 years ago. Thatargument could still be made, with extremevalidity, should we chose to make it. The factis, that we've provided an anesthesia, albeit alight anesthesia, but sufficient anesthesia atthe time of the injury to preclude the animalsfrom appreciating pain. The fact of the injuryis, that it occurs in a hundredth of a second.The coma is instantaneous. At the time of thecoma, the patient, the animals, are incapableof feeling pain because of the coma. And sim-ply, the duration of the insult which causes theinjury is too short for a pain impulse to be reg-istered by the brain.Professor Francione: What sort of pain do

they feel when they recover from the comawhich may be as few as 15 minutes after theinjury?.

Dr. Gennarelli: Can we handle one point at atime, please?Professor Franclone: Sure. There are just

so many of them.Dr. Gennareill: There are other issues in-

volving the anesthesia that I pointed out to Dr.Fussell's question. If you want to address thelong term effects, it's fairly characteristic ofpatients in the recovery phases of brain injurynot to complain of pain, to require virtually-virtually no-pain medication. This is almostan absolutely regular part of our clinical expe-rience in taking care of patients asneurosurgeons. Patients recovering from se-vere brain injury do not complain of pain.

Professor Franclone: Tom, how long arethese animals permitted to survive after theycome out of the coma?

Dr. Gennarelli: That depends on which ofthe many faculty investigators is performingthe experiment at that time, and what his goalsare for that experiment. So there's quite arange from instantaneous, virtually instanta-neous, termination, that is, within a few min-utes, to animals that we have kept purpose-fully for long-term pathological studies, whowe, with great effort, I must admit, with greateffort cared for in the severely brain damagedcircumstance. One in the case of three weeks,and one in the case of. I believe, seven weeks.That range is from a few minutes, to in twocases, more than a month.

Professor Franclone: According to docu-ments purporting to be notes made by you andyour researchers, baboon B-47 was injured onfive different occasions: July 28, 1983; Sep-tember 20, 1983; February 3, 1984; twice onApril 4, 1984. B-47 was killed approximatelyone month later on May 2, 1984. I am nowreading [my notes] from a document thatpurports to be a lab note. "B-47 was a trainedanimal whose injury was a little too severefrom him to be testable. Woke up first day,post-injury, unable to sit up, more or less re-mained in this state over the next month." Theprotocol itself states that the animals would bekept alive from ten minutes to two months.This goes back as far as 1975, Monkey-A,

ALMANAC SUPPLEMENT Februar 19, /985 IX

INSG #E245/75, Monkey B, INSG#E24775. These animals were injured andtested behaviorally over much longer periodsof time than seven weeks.

Dr. Gennarelli: The details of those we cango into. Animals A and B preceded my arrivalat the University and were studied early in1976, 1 think, or 1975. 1 don't know the de-tails of those animals, and can't speak for theinvestigators who performed those experi-ments. The other animal was under the directcontrol of one of the other investigators in ourgroup and perhaps it would be more appropri-ate for him to answer that question, althoughI'm not sure exactly what your question is.What is the duration of survival you felt wasinconsistent with something?Professor Francione: In the Almanac you

say that most of the animals are terminated,and that the animals are permitted to surviveonly for a few hours or days. And then I findout about B-47. I also read the protocolagain. I know I'm not supposed to put muchcredence in that, but it says that 80 of the 250animals are going to be used for behavioraltesting. That's more than just a few. It's cer-tainly more than the Society for Neurosciencesreported-fewer than 20.

Dr. Gennarelli: Yes. I'd be happy to discussthe current practices in the laboratory if that'swhat.Professor Francione: This is 1984 though

we're talking about, Tom.Dr. Gennarelli: Yes. I understand. As Dr.

Cooperman has mentioned, protocols arefluid. The experiments will go in different di-rections. If we say we're going to do one ani-mal that's chronic, it may change, dependingon the interest of the investigators in terms ofwhat may be most productive. What I can tellyou with regard to chronic animals is that inthe last four years there have been 35 chronicanimals with the mortality in those animals ofseven, that is a twenty-percent mortality rate,and we feel that's pretty darn good consideringthe virtual 40 to 50 percent mortality in.

Dr. Cooperman: The question I think.Dr. Gennarelli: . . . similar injuries in

humans.Dr. Cooperman: Ijust have to intervene, be-

cause I don't know how long everybody canstay and I would like to push the discussionalong. I think the point is "Is there a philo-sophical objection to multiple injury?" Thatwould be one of the points. That is, is thereanything in your protocol which would makemultiple injury on a single animal beyond thepale of your experiments or do you feelstrongly that that's perfectly o.k., an o.k.thing to do?

Professor Francione: Can I take a break forone second?Dr. Cooperman: Sure. We started a little

later than scheduled and so we'll probably goto about ten after, but that's about as much aswe can do.(Professor Francione goes to outer roomwhere Dr. McArdle is.]

Dr. Gennarelli: With regard to the multiply-injured animals, let me make it clear that theseare the exceptions in the laboratory, and

they're virtually only-there are only multipleinjuries under two circumstances. The uncom-mon circumstance is that there is some failureof the injury apparatus. For some reason itdoesn't deliver properly the dose of the traumaand then an animal is not injured at all or bare-ly injured at the time of the insult. That animalis then re-anesthetized and if the problem canbe fixed with the injury apparatus, the animalis given a second injury on the same date withthe intention of going on with the procedure asit was.The second circumstance of multiple in-juries are exclusively the animals with minorinjury that are being subjected to the detailedbehavioral and learning studies. In no instancehave we ever given a second injury to thosewhose first injury was already severe.

Dr. Cooperman: O.K. In the interest of timeI'm going to use the privilege of the convenerto go to Section 3D of the agenda which dealswith the attitude and comments of the experi-menters. I think certainly the attitudes andcomments of people handling the animals as,from things I've heard, were deeply disturbingto many people. Along with the issue ofanesthetics the other issue that some peoplewho have seen the edited tape have really fo-cused on has been what they have said to be acallous, uncaring, attitude on the part of theinvestigators as revealed in the tapes whichI've not seen, but the transcripts ofwhich I'veseen. So I'd like to get to that portion of thisdiscussion if we could, and then we'll go topart four ofthe agenda very quickly thereafter.quickly thereafter.

Dr. Cohen: Who is present at these experi-ments? Are senior investigators present?

Dr. Gennarelli: It varies during the timecourse. The people who are absolutely full-time in the laboratory are a technician, some-times more than one technician, and aneurosurgical fellow, sometimes more thanone neurosurgical fellow. Those fellows areeither fully trained neurosurgeons who cometo us for research exposure, or they are resi-dents of our own, and generally are in thethird, fourth, or sometimes, fifth year of theirneurosurgical training. They've already had aconsiderable amount of training before that. Inaddition to that, there are occasionally stu-dents involved in a particular project in thelaboratory. One of the senior investigators is,except for exceptional circumstances, in thelaboratory for, usually not for the entirety ofthe procedure, but for portions of theprocedure.(Professor Francione returns during exchangeabove.]

Dr. Cooperman: Were there any otherpoints that the people wish to raise on the issueof the attitude of the investigators?

Professor Francione: Yes. I would like toknow...

Dr. Gennarelli: What, about the attitude ofthe investigators, is objected, to?

Professor Francione: The excerpted tapehas a number of very disturbing scenes. Thereis one scene where the animal is strapped tothe operating table and one of the researchersgoes over and plays with his limbs, and thevoice narrating-not the overdubbed People

for the Ethical Treatment of Animals narrationvoice supplied by People for the Ethical Treat-ment of Animals, but what purports to be theresearcher's voice-says, "Well, the animalis down, ready for the injury," then the cam-era pans to an animal strapped in what appearsto be a highchair, sort of makingpeculiar-looking movements, and the voicesays "there is B - - -" whatever the numberis-let's just say BlO. "There's BlO. B10 ischeerleading in the corner. As you can see,BlO is still alive. BlO is hoping his counter-part has a good injury." There's a scene wherea young woman is holding a baboon that hassort of massive cranial sutures, and they aresaying, "Oh here is the baboon on the street,and Sir, what do you think about all of this?"And the baboon falls backward and looks atthe young woman, and the experimenter says"He's saying, you're going to rescue me fromthis aren't you?" And there are just a numberof scenes like that, that I don't really think youcan characterize as analogous to "gallows hu-mor." I spoke with some physicians, recently,about what "gallows humor" means, and Idon't think that you can really link that uphere. It's correct, Barry, I think to say thatpeople have been very distressed who haveseen it. They have just been awed by the cal-lousness and the lack of regard that those peo-ple have for the animals that they acknowledgeare suffering-that they explicitly acknowl-edge are suffering.

Dr. Langfltt: I would have to say that weclearly don't condone behavior like that, but Ithink it's a mistake to totally disregard thewhole issue of so-called "gallows humor" inrelationship to these experiments. It's verytense, during the course of these experimentsfor a wide variety of reasons, not the least ofwhich is that no one enjoys this kind of thing.No one enjoys delivering these injuries to theanimals. We're doing it for a very specificpurpose. It is quite analogous to what happensin the operating room, particularly under verytense situations. Anybody who ever saw theseries M*A*S*H* understands what we meanwhen we talk about "gallows humor" occur-ring in the operating room.

Professor Francione: Is it directed at thepatient?

Dr. Langfitt: I would state again, that no onecondones this kind of behavior. Also, experi-ence suggests that the vast majority of such re-marks that might have been made were madeby one person who was in the laboratory for avery brief period of time.

Dr. Cooperman: Aron?Professor Francione: Could IDr. Fisher: I can see how this would be dis-

concerting. It certainly would be to me. But Ibelieve that the bottom line is whether the jok-ing influenced their behavior. I see it as analo-gous to the difference between prejudice anddiscrimination, for example. Although wemay not like what they said, do you think itinfluenced the care and the treatment of theanimal?

Professor Francione: I most certainly do.Dr. Fisher: Why do you say that?

ALMANAC SUPPLEMENT February 19, 1985x

Professor Francione: I've not watched thatmany episodes of M*A*S*H, and I don't wantto debate with Tom Langfitt about what hap-pens in episodes of M*A*S*H, but it seems tome, that when we are talking about "gallowshumor" generally, what we are talking aboutis jokes made in the course of performingsome sort of, or involving, some sort of stress-ful situation, performing some sort of opera-tion, or whatnot. I don't recall there being inM*A*S*H comments made directly about thepatient, derogatory or mocking comments,made about the patient. But even assumingthat this were the case, it would seem to methat to the extent that that's morally justifiable,and I'm not saying it is, I'm saying to the ex-tent it is morally justifiable, some of that justi-fication has to derive from the fact that one isattempting to help that person on the tableabout whom one is making mocking or jokingcomments, assuming that that's what "gal-lows humor" means. However, if you look atthe excerpted tape, and I invite you to look atit any time it is convenient for you, I think youwill see that this sort of humor on the tape isnot telling off-color or obscene jokes in thecourse of doing this research, it ishumor-mocking-scorn directed at the animals.

Dr. Fisher: I won't say it's not, and I don'tsay that I personally would mock animals. Onthe other hand, I feel that telling a joke ormocking an animal is not necessarily a punish-able offense. I would be more interested inwhether they did not give the best possiblecare to the animals because of their attitude.Knowing what I know about the program andhow successful they've been in keeping theanimals alive, it seems that maybe they didgive the best possible care even though theytold animal jokes. I mean we all tell elephantjokes. Maybe we shouldn't do it, and theyshouldn't have done it in their situation. Butmore important to me is the result ofthejokingand whether it really influenced their actions.I'd like to see the whole tape before makingthat judgment .

Professor Francione: There is one scenewhere surgery is going on, these mockingcomments are being made, and one researchersay to the other "Stop it, it hurts him, forChrist's sake." And they're making jokesabout it. Now it certainly seems to me thattheir attitude most certainly influenced theiractions.

Dr. Fisher: It sounds possible that they weretrying to be protective of the animal.

Professor Franclone: They didn't adminis-ter any anesthesia that I could see.

Dr. Gennarelli: I assume they gave it. Withall the comments that have been made regardingwhether or not these attitudes should be preva-lent in the lab, I would submit to you that this isone of the most successful of PETA'spropagandas and maneuvers with this tape

Professor Francione: I object to thatcharacterization.

Dr. Gennarelli: . . . I don't care if you door not, but I'll tell you why

Professor Francione: I know you don't.Dr. Gennarelli: . . . The reason

Dr. Cooperman: Could we have decorum,please?

Dr. Gennarelli: . . . [The reason] beingthat, number one, these whatever you weregoing to call them, attitudes or comments, areattributable by the tape to the entire labora-tory, and all of its personnel are being charac-terized as having made these remarks whereas,in fact, the period oftime in the PETA tape ex-tractions comprises a three month period oftime out of some nine year history of the labo-ratory. That's less than three percent of thetime and, as Dr. Langfitt mentioned, are at-tributable in large part to one particular indi-vidual

Professor Francione: How do you knowthat if you haven't seen the tape? I'm justcurious. If you haven't seen the tape?

Dr. Gennareiii

ye been provided withexcerpts from the tape as well

Professor Franclone: But they don't iden-tify who the people are. How would you knowwhat voice belongs to whom from an excerpt?I'm just curious.

Dr. Gennareiii

m not going to be-labor the point of how I know who is on thetape. The tape has been described to me, Ihaven't physically seen the tape, it's been de-scribed to me in exquisite detail. Those com-ments are basically from one person during athree-month period of time. During that samethree-month period of time, several of thechronic animals were being investigated at thetime and that same person to whom these com-ments are attributed spent virtually every nightin that laboratory feeding, caring for the ani-mals that were chronic survivors. They couldnot eat or drink for themselves. They could nottake care of any bodily functions. And the per-son to whom these comments are attributeddid that for a seven-week period in that seven-week survivor. Feeding the animal three orfour times a day, with a tube going into hisstomach, making sure he didn't aspirate it intohis lungs, giving him physical therapy and anincredible amount of care-that's not men-tioned in all of these activities, of whether thelaboratory personnel are being appropriate.My view is that their verbal commentary is apersonal attribute, is not characteristic of thelaboratory, and I can document that to you bytapes that weren't stolen from the laboratory.Ifyou would like to characterize the laboratoryby comments such as these as being character-istic of the laboratory or the current practice ofthe laboratory, then you are wrong.

Dr. Cooperman: I'm going to stop this partof the session now. I think we can agree to fin-ish at about 11:15, given the fact that westarted a little later than scheduled, and I'd liketo turn now to the last full item on the agendawhich is

Professor Francione: Can I ask one morequestion, Barry? You told me that if I hadquestions to ask that I could ask them. Yousaid this to me the other day when we dis-cussed the format of the dialogue.

Dr. Cooperman. Yes, but not without re-gard to time, Gary.

Professor Francione: Just one more,

please?Dr. Cooperman: One more question.Professor Francione: Dr. Genarelli, in any

of the published works have you ever revealedhow the dental-stone helmets are removed?I'm focusing specifically on the fact that theexcerpted tape shows researchers using con-siderable force to knock off the dental-stonehelmet with a hammer and chisel. There issome concern that, given that you are trying todistinguish between contact injuries and accel-eration injuries, or trying to distinguish be-tween vascular damage and axonal damage,there is some concern about knocking off ahelmet, the dental-stone helmet, with a ham-mer and chisel. In one case, the baboon's earappears to come off on the dental-stone, andthat's in the excerpted tape. I'm curious as towhether that's ever revealed because I can'tfind it anywhere in the protocol, and I can'tfind it in the published works I've looked at,although I would admit to you that I have notread everything that you've ever written. Ihave read a considerable number of yourpieces. I'm curious as to whether the use ofthehammer and the chisel is revealed anywhere.

Dr. Gennarelli: No, and it wouldn't ever berevealed because it's not germane to the re-sults of the experiment. It's not common prac-tice in the laboratory, and it's certainly notcurrent practice in the laboratory.

Professor Francione: When did it cease?

Dr. Gennarelli: It ceased when we devel-oped better methods of removing the helmet,and only existed under - I wouldn't say ex-ceptional, but unusual circumstances. That is,there were a certain number of animals whoseskin simply stuck to the inner surface of thehelmet. That's one problem. And in evenfewer animals, the dental-stone stuck to the in-ner surface of the metallic helmet. What yousee as hammering is loosening the junction be-tween the helmet and the dental stone, not be-tween the dental stone and the head. Do youunderstand the difference?

Professor Francione: Oh, yes sir, I cer-tainly do.

Dr. Langfitt: If I could just make a com-ment. After having spent ten years of trying todevelop this methodology, with the enormousamount of effort and the expense and the per-sonal reputation involved, it is beyond reasonto me that anyone would think that we woulddeliver a very precise injury to the animal'shead and then bash the animal's head with ahammer in order to try to get the animal's headout of the dental-stone. That is absolutely be-yond comprehension to me.

Professor Francione: I agree. It's certainlysurprising, but the excerpted tape speaks foritself.

Dr. Gennarelli: It doesn't speak for itself,Mr. Francione. You've interpreted it in a fash-ion that you choose to interpret it. The factsare, and we don't have time to go into thetechnical details, that loosening thedental-stone between the helmet and thedental-stone has no effect on the head. Thereis no pathological evidence of damage.

ALMANAC SUPPLEMENT February 19, 1985 Xl

There's no physiological evidence of damage.And there's even no theoretical reason that itshould cause injury, because of the type of ac-celeration that that kind of hammer blow,away from the head, would cause to the brain.

Professor Francione: I respectfullydisagree.

Dr. Cooperman: O.K. Fine. I'd like now toturn to the last item on our agenda. Our discus-sion of this item will be abbreviated, which isunfortunate, since in many ways it is one ofthe more interesting parts and that is, to tryand put the experiments that we've been ex-haustively discussing into some type of per-spective and context. I know that Dr. Edel hasbeen patiently listening and has thought aboutthese issues quite a bit. I would be delighted,sir, if you would begin this part of thediscussion.

Some Ethical Questions

Dr. Edel: Very briefly. I'm not sure how rel-evant this is to our discussion because we'vebeen dealing with only one premise here;that's the premise of no pain and, therefore,everything has come within that. Now, allthese . . . [the questions listed on the agenda]are broader problems, but they are importantbecause problems of that sort will specify thekinds of reasons that are given for an ethicaljudgment, and when you have different rea-sons, then the scope of the ethical judgment isaffected thereby. If you say the reason is no in-fliction of pain, then you can handle it entirelyin terms of: 'We don't inflict pain." and thenkill the animals and that's all there is to that.But if the reason is that animals have rights,then you've got a quite different picture, andthe question of the right to induce death iswhat's involved. Perhaps all I can say aboutthe several questions is simply to amplify a lit-tle bit by reading from the original letter that Iwrote you. These are questions that try to putin order various kinds of reasons, and thenraise the question of what kinds of consistencyyou have to expect: what will be proof ofwhat, and how far is it possible to agree onpractical treatment from different bases andfor different reasons'? The answer to that lastquestion, of course, is that it is possible. Onecan have many different reasons for doing thesame thing, but the reasons are very importantbecause, quite formally, they'll tell you howfar you extend when you go beyond the range.The question "Who is to count?" is. of

course, a very central question since everymorality does contain a kind of picture of itscongregation, so to speak. And we all knowhow long it has taken, in the history ofmankind, for even the whole of mankind to beincluded within the moral community. The oldways of doing it were, at times, to exclude astranger who's fair game for anything. Andeven now, one cannot tell whether the wholeof mankind has really been included practi-cal/v. although it has, in our usual verbal re-sponses. Who is to count, then, as to be amember of the moral community? All humanbeings? All animals? All forms of life? Onlythe higher animals? Only human beings?

The second question, which wasn't in-cluded in the agenda, is "Is the ground for in-clusion the independent fact of being a specificform of life (for example, as in the claim thatanimals, as such, have rights) or the dependentfact of being associated with humans?" Forexample, pets are not to be experimental ani-mals. Is the ground for not hurting animals thefact that they are capable of pain, or that hurt-ing them intensifies propensity for crueltyamong humans? The second, of course, is amuch narrower ground, which used to be ofteninvoked. There has been some transition to thefirst one, as was evident in the discussiontoday."How far is the human use of animals for

experiments qualified morally by projectedhuman purposes?" For example, learningabout cancers as distinct from testing thesafety of cosmetics? One could see the reason-able argument about why you wouldn't wantto sacrifice animals for testing of cosmetics.Similarly, with respect to killing of animalsfor food, or for safeguarding health (extermi-nating rats) as distinct from hunting forsport-in the history of the ethics there hasbeen plenty of debate about hunting for sport."How far in a controversy over principles is itsound to use consistency as a criterion forcredibility? For example, does one advocatinganimal rights lose credibility if he or she is nota pacifist or vegetarian?" That is the episte-mological problem of trying to decide whetherto take seriously or not an argument that's pre-sented. I might say that the most sincere peo-ple I've ever met in this regard, in mychildhood in Western Canada, were the Dou-khobors. When they came to work on thequestion of preserving potatoes from potatobugs, they simply refused to spray any kind ofparis green, which was used at the time, oranything like that; they would just spend hourspicking the bugs up and carrying them away.Whatever you could say about them, theywere thoroughly consistent-vegetarians andliving in peace.Well, now, I think that's enough to suggest

about the comparison of the reasons and ethi-cal judgments. You can't simply reject givingreasons and say 'I intuit that this is so, this iswrong," at least in communication with oth-ers; you have to give your reasons. And so, inraising the questions, I thought we might findmany different reasons being employed in ourdiscussion today, and it would be importantpractically to distinguish which would operateat what particular points, and how far theystretched, and whether broader reasons or nar-rower ones were being offered.

But, as a matter of fact, this didn't happenin our discussion, which stayed with one sim-ple reason-a minimum of pain, or no pain.Can I just make one more remark? There's thekind of question Professor Francione raised:Should this money be spent, could this moneynot better be spent, instead of on these experi-ments, on greater safety devices againstcrashes, things of that sort? That, of course, isa general question of tremendous interest thatconcerns the whole of medicine in treating hu-man beings, not simply the question of the re-search done here. Are we spending too much

that will benefit only a few people? Shouldn'twe do more for general nutrition instead, andthe like? But that's another story.

Dr. Cooperman: Unfortunately, I don'tthink we're going to be able to discuss thesequestions at least at this session, althoughsome of the comments you've made are quiteprovocative. As the University goes forwardin consideration of this issue, which I think wehave the responsibility to do in many forms, Iam sure the points you address will be morefully discussed in other meetings. There is anopportunity for a last word from anyone or anypersons who wish to make it.

Dr. Fisher: To your knowledge, Tom, werethere instances that went beyond the ethicalstandards expected by the Animal Care Com-mittee at the Medical School?

Dr. Gennarelli: Not to my knowledge, no.Dr. Fisher: How extensive is your knowl-

edge of what goes on in the head injury labs?Do you know everything?

Dr. Gennarelli: No, I don't know every-thing. I direct the laboratory, but there areother faculty investigators involved with it. Ican't speak for all of them.

Dr. Fisher: If there had been a seriousbreach of what you consider humane stand-ards, what would have happened?

Dr. Gennareili: Well, I'm sure I would havefound out about it one way or another if Iwasn't directly in the laboratory at one time. Ifit were something that were, for one reason oranother, well, if it's something that could beremedied by speaking to the people working inthe laboratory, such as clarification of thedepth of anesthesia at certain points in the pro-cedure, now that could be done fairly easily. Ifit were something that I thought were lessclear, then I would discuss it first with Dr.Shalev, the veterinarian, and he would thenprobably get in touch with the Animal CareCommittee if he and I couldn't resolve theproblem.Professor Francione: Aron, would the min-

utes ofthe Animal Care Committee relevant tothe head injury laboratory be available to othercolleagues in this University to look at?

Dr. Fisher: I can't answer that as I'm nolonger chairman of the Animal Care Commit-tee. I guess that those minutes are not publicinformation. I don't know what the policywould be with respect to colleagues. I supposethat the present Animal Care Committeewould have to take that up. I don't know whatthe standard University policy is.

Dr. Cooperman: I'm going to, on that note,terminate this discussion in fairness to peoplewho have agreed t&come and who are verybusy .

Professor Francione: Could we have an-other meeting? I have many more questionsabout this research.

Dr. Cooperman: . . . Oh, I know you do,and the question of another meeting is on thetable as far as I can see.

I want to thank you all for participating, andI hope we've made at least a first step towardunderstanding some of these issues. Thankyou very much.

XII ALMANAC SLi'PPLEMENTFehruarv /9, 1985