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BIOLOGY AND MEDICINR ETHICAL CONSIDERATIONS IN HUMAN EXPERIMENTATION of the 12th Annual. held at Gatlinburg, Tennessee
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JUN 22 '94 14:W INEL TECH LIBRRRY During the past three or four years soiattfic journals aad ppollar rmzgazines have contained an idcreasednumber of articlee about the ethias of human experimentation, Most of the wriera '"point Wsul d a m t 1expresshg concern that hvestigators, in their sed, are being oarelees of the rmta of the patient who serves as EUL ea~~rimtntalsubject. This coneem has been pmcipitaEed publidtg g i v a to oertain research activities. The Cangmssioaal investigator8 of the drug Must ry revealed s o w serfdue abuser;. wbeh &e experimental 5.Qjectfollof cauter cells into aged patient13in a New York charity hoapital received widespread aondemnatiop in prfnt, organhed medicine felt the e to go on record as disapproving the method greatly 8cCmtded by Dr. enry K. Beeoher, of Harvard M e d i d School, who ha6 iu an intenrrely e otion-laden miasion, baa on occasion made misleading d exaggerh WhiOEr tihe B t u d g was uarried out.9. The attention given to tbis problevr has been Although there is recent empbasie on this problem, it ia quitLt erroneou~to suggest, 88 bo- lay eoience writere have, that it wa8 largely neglected in tbe psst and that mtiI recently investigators have given little thought to tha ethicsrl aspects of human experimentalSon. Furthermom, it is incorrect to assume that, because a pubiicaaoa of soientif5rz data makes no reference ta cansent from experimental subjects. such Coas ~ twas not obtained. Nevertheless, it is widely recognhed that a serious probi6m doe6 Iw#r'exiSt aad we may wen eeek the regsOns for it. One is, obviously, the great increase in mearch ob aI1 Qvpes that ie now be* done and the corresponding inarewe in possible abuseo. With this bsa come the growth of irrstikrtiozu~and, in some projsats statfed ?qr a large group of physidsaa, a reduction in personal coatact8 between the iadividual physicianavestigatur and the patient. With the progress of medicine away from aimple trials af therapy toward a search for basic knowledge, we find that a larger share of the irrve~tigationsare concerned with studles not airectly related to a practical trial of therapy: thus the subject may have Little to gab directly- There is, or is believed to be, a growing irrterrsity of aoxnpetition among fnvest;tgatOrs, a desire for recog- *tion, and a desire for academic posts that are filled 0x1the basis of reeearcb achievememt. Thus we have the opportunity for the investigator to let aelfieh interests *From the Medical Division, Oak Ridge Associated Wvereities, Inc., Oak Ridge, Temeseee. operating under contraut with the United .Stabs Atomic Energy Commission.
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predominate over his concern for the experimental subject. Whether or not such a b n d exists, there i8 no doubt that the public has decreaeing faith in the nobslSty of their phyaiciana for malpractice, real or alleged. (Incidentally, except Sn connection wlfk the trials of new drugs, there have been few if any lawsuits against physicians on the basis af acta performed in the course of clinical ewerimentation.) Quite different from the unduly ambitious investigator i s the one who with completely uneeUish xnoffve8 becomes 80 fervid inhis desire to help mftnldnd that he uses poor judgement Sa relation to the risk to the individual patient-subject. I motives o# physicians, and that paaente are showing an increasing tendency to sue Whatever the reasoas and explanation8 may be, there is no doubt that some experimeztts not ethicdly Justifiablebave been performed iP recent years. Yet, an unresolved question Is, How extensive is this problem? It i s a truism that in all large fields a€human endeavor one could, with careful search, find some examples of unsavory conduct. There is alwsyo the danger that a worthwhile activity w i l l be discredited or destroyed became some publicity seeker dramatizes the ex~eptioaal, evil cawe~and @res the impression that the practices represented are typical. A b l a n d assessment of the whole field - "...OD the one hand this is good, while on the other band the weaknesses are.. .'?- never attracts the attention that the muckraking approach om yield. . No one real$ knows bow much of experimental medicine is open to challenge on ethical g r o d a ; osrtainly fMs Cannot be clearly evaluated withoat more intimate howledge .of what goes OD than c80 be obtained from the published scientific Iitera- . m, Furthermore, to put the ffndings in perspective one might need to compare them with mme~other aotivities; for example, the etbics of behavior toward patients of physicians not engaged tn research. Lacking the hope of any such inforrrred appraisal we must rely upon opinione. My o m is that we are not facing 8.n appalling sltuatioll but that we have a clear need for impmvemat. la considering: codes of ethics for investigators we need to be c o f i 8 ~ i 0 U 8 of the various relationships that may &st between the investigator and the person who i s the .subjectof the expelriment. Subjects of experimeats may fall in the following categories (and possibly others): 1. Mependent normal volunteer @aid or donating service), 2. Volunteer'' who is in employ of laboratory, in military service, or in prison, a) Research directed toward dtagnosis or therapy needed by subject, b) Research directed toward advances in diagnostic or therapeutic methods in general, or toward baBic scientific advapcemmt. unlikely ta be helpful to the volunteer, c) Subjects serving as controls, 5. Healthy person taking new prevent3ve material (i.e, , vaccine) that may be potentially useful to him, 6. Tiseue donor; research directed toward direct benefit to another peraan, related or unrelated. '1 This liet clearly shows that ethical aspects of research vary greatly from experiment t0 experiment. No simple set of rules can deal specifically with all possible situations, but some rather general codes have been presented that give
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useful guidelines. For background, the mdent Hippocratic Oath, and the intereating writings of Claude Bernard, in the mlddle ob the last oentuTy, may prove ueeiul. Rel tively reatmt, amfully elaborated statements include the Nwp ~ berg the statement by the British Medical Researah Counail, 1964. Beems to me the most useful because it attempts to cope in Borne detail with the mbtleties involved. Beecher* bas also stated general principles. Code (194nf the Declaration of Belsinld (World Health 0rgytb.n) 1964, and Of these, the last Among the considemtiona that are imporkt in these o d e s and in our thinMng about the subjeot are the following: Wormed Consent - Great emphads ie placed on the effort to have th8 subject tmzly understand the miwing of &e experimental procedure in whlcih he is to p8rbioipate. Those who have dealt with this problem in practice realize that it is an ideal to be aimed at rather than an objeotive that can be achieved. Even a rela#vely simple expedmaat may be qutte beyond the ability of the average patient to evaluate. Risk# are never known with great accuracy, and the patient often decides on the basiis of some intentional or unintentional signal from the physician he trusts, even sxperiment i s being done by another phgtitieiatl. it documented. Whether it will often be really informed consent is aaotber matter. NeverthelessP,copsent can be cleady given or refused, and it is important to have it9 and Conmetence of the Researah -L The more hazardous the pMCedUS& the ~ $ o r t a n tit i e that adeqpate preliminarg work (i.e., animal experiments) be dorm, that relevant previous pu~icationeare known agd aonsided, and that suitab16 precautions are laken. The potential value of the research must be thomu@y evaluated, oftea .the.particfpatidnof a group of inveetigatora ie needed, as is the evaluatioh by independent physicians hviug no direot interest in the rebearch and ealisted specfbUy as the proteabra of the patient's welfare. la our culture the su'premac~of the rights of the individual is much stressed. T b we am remiadeh that we must not take the responsfbiliQr of sacriftclng, even to a amall extent, one p~rmd6rights for the aake of' help- maqy people even to a great extent. I am in agreement with this pzlrhcipe; I do not always fW it easy to interpret ia relation to specific reeeiUTcb situations. improper mearch praotices need ta be on guard against xnaldng a i r judgementa and impairbg research progress. They should remember that hindsight is a dangerous thing, For example, five years ago one could say, with s good deal of experimentaJ data in support, that when cancer cells were take33 from one per3On and duce clinical malignaacy in the recipient, Now there are reports uf rare but definite exceptiuns tu this Mile. Thiol new information may tempt us to change our evaluation of the e t h i d ~oundnessof some previous research. It has been quite rightly pointed out, however, that research ie either ethical or not at ita inception. they do not wieh or intend to restrict pductivity. It should be clear, however, that denial of intest to restrict researoh accampliehments does not indeed prevent the While '&forming 8 vriluable service, b e e who have sounded the alarm about Those who establish contools on'anyhumaa activifq aften assert repeatedly that
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impairment in productivity that m y result when the fears engendered in administrators lead to new regulations. One might concede that some restriction on aahievemeat is a fair prim to pay for inoreased pratectioa to experimental subjects; if so we should gay i t kpowingly. I have not attempted to even suggest the positive benefits that may accrue to the Person who volunteers as an experimentat eubjeot. This i s a topic that deserves mUoh more attention thaa it bas received in recent publications. It is worthwhile that wt have hrrd our attention directed to the ethics of human experimentation. The main responsibility for dealing with it s W d be in the hands of the investigators, and future sbdardsl will depend largely on their integrity d canecientiousnese. Scientifio jour ~ a l scan perform a useful service by requirha& ' that manuscripts indicate the mure d oonaent obtained from experimmtsl subjects. It i s to be hoped that if scientific admbistrators feel impelled to rgsot to woBIlt criticism with iqoreased restriotions, the new rules will be carefully plannd SO as not to unduly inhibit good, deeirable, 8 t h r C d researah. Kettering stir Publlo Debate on Medioal Ethics, Science, 143: 551-553 (1964). (Tbisindudes the Nuremberg Code.) Ib. E. E. Mandel, Experimental Cancer Cell Implasts in Patients, 2. E. Langer, Human Experimentation: New York Verdict Affirms 3. H. K. BeeCher, Experimentation in Man, Americaa Lecture Series, A Dtfonograpb in American Lectures in Medicine, Publioation No. $92, Charles C Thomas, Spriagfield, Illinois, 1959. 4. EI. K. Beecher, Some Guiding Principles for Clinfcal Investigation,
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6. Claude Bernard, An Introduction to Study of Experimental Medicine, M+Millan Company, New York, 1927, pp. 101-102. 7. Human ExperimemhUon, Code of Ethics ob the World Medical Aseaciation (Dedaration d Helsinki), Brit. Abed. J., 2, 177 (1964). 8. Responsibility in hvestigatiom on Human Subjects, Brit. Med. J.,