HUMANTISSUEDr Robert Sharpe

A Neglected Experimental Resource

Introduction

The use of animals in medical research presentsdoctors with a serious problem: are the results validfor their human patients? The difficulties arisebecause people and animals are different in the waytheir bodies work and in their reaction to drugs. Whileexperimenters search for the species that mostclosely mimics human responses, a more effectiveand humane approach would be to concentrateresources on methods of direct relevance to people.Such techniques include human population studies,clinical observation of patients, work with healthyvolunteers and test tube experiments with humantissues. Test tube, or in vitro studies enable cells to bekept alive outside the body and in some casescultured to allow continuous growth. At present, mostin vitro experiments utilize tissues from animals killedfor the purpose but with the constant risk ofmisleading predictions, more could be achieved usingmaterial of human origin. Tissue can be obtained fromhealthy volunteers, during therapeutic operations orfrom autopsy specimens, and can be kept in coldstorage until required. As the following examplesshow, it could save many animals in medical science,drug research, toxicity testing and in the production ofbiological products.

Medical Research

One area where there is certainly no shortage ofhuman tissue for study is cancer research. Thedifferences between artificially induced cancers inlaboratory animals and the naturally arising disorder inpeople are widely recognized and have led Britishcancer researchers Dendy and Meldrum to suggestthat investigation of tumor cell properties "mustconcentrate more on the diverse nature of humantumor cells recently removed from patients and lesson animal model systems."1 A specific examplereported by the Karolinska Institute in Stockholmdescribes how isolated tissue from human pituitarytumors continues to produce hormones just as it doesin the living person. The tissue also responds in thesame way when stimulated by chemicals found in thebody.2

Even the spread of tumor cells (metastasis) can bestudied without using animals: researchers at the USFood & Drug Administration have used human muscletissue, normally discarded after routine surgery, as atest bed for studying the growth and spread of humancancers. The system successfully mimics the situationin the body where tumor cells proliferate, spread andinvade the surrounding tissues, and also provides ameans of testing new anticancer treatments.3

Animal ‘model’ ofcancer: ”...whileconflicting animal testshave often delayed andhampered advances inthe war on cancer, theyhave never produced asingle substantialadvance either in theprevention or treatmentof human cancer.”Dr Irwin Bross,Roswell ParkMemorial Institute forCancer Resarch, 1981.

The link between smoking and lung cancer was firstrevealed through human population studies butattempts to duplicate the effect by forcing laboratoryanimals to inhale the smoke have generally failed.4 Infact the harmful effects of individual chemicals presentin tobacco smoke can be investigated without resortto animal experiments. In 1968 studies with humanbronchial tissue led Britain's Strangeway ResearchLaboratory in Cambridge to conclude that,"hydrocarbons in cigarette smoke play an essentialrole in the development of human lung cancer."5

Today, the Karolinska Institute uses human bronchialcells to study lung toxicity and cancer-inducingproperties of chemicals in tobacco smoke and carexhaust emissions.6

Biopsy samples frompatients withneuromuscular diseaseslike muscular dystrophyhave been suggested as ameans of studying thedefects of neuromusculartransmlsslon. Using thehuman tissue samplesresearchers at Britain'sNewcastle GeneralHospital have obtained aworking nerve-muscle

preparation allowing studies of the chemical andphysiological processes involved, and how they aredisrupted in disease.7

Osteoarthritis and low back pain are commonconditions that have led to much research into thestructure and function of articular cartilage and theintervertebral disc. Most investigations have relied onanimals or their tissues but there are speciesdifferences which could invalidate results.8 A differentapproach has been taken by Professor Bayliss andhis team at London's Kennedy Institute ofRheumatology. Using human articular cartilage andintervertebral disc from patients, Bayliss argues that,"such systems could be used to gather informationabout drug

Forcing animals toinhale tohacco smokefailed to induce lungcancer. This delayedhealth warnings,costing thousands oflives. Human tissuestudies avoid thesuffering as well asthe misleading results.

action or to study biochemical factors in early stagesof disease without resort to animal models."8

Nevertheless he notes that "very few attempts havebeen made to use human cartilage as an alternativeto animals."

Epilepsy is another area of research that has reliedheavily on animal experiments. While there arenumerous "animal models" of epilepsy, noneaccurately reproduces the clinical disorder, and resultsvary depending on the model chosen. A more relevantapproach is to supplement clinical observations ofepileptic patients with studies on brain tissuesobtained during therapeutic neurosurgery. Forinstance, researchers at the National Institutes ofHealth in Bethesda and the University of TennesseeCenter for the Health Sciences, have studied thechemical basis of seizures in patients using tissueremoved surgically during treatment for intractableepilepsy.9

Low back pain:Research into thiscommon and disablingproblem promisesmuch through workwith human tissues.

Not surprisingly,artificially-inducedepilepsy in animalsdoes not accuratelymimic the humancondition. Helping thesepatients demands thesophistication of human-based approaches.

Tissues from the same source are also being used toinvestigate how chemicals in the brain transmitsignals between nerve cells and thereby control theirfunction. Tissue from rodents has traditionally beenused for the purpose and it was assumed that resultswould be similar in the human brain. However,marked species differences have now come to light,10

prompting some researchers to explore the use ofhuman brain tissue. Thin slices of tissue are used toinvestigate the electrophysiological andpharmacological properties of human cerebral corticalneurons, and according to David McCormick of YaleUniversity’s School of Medicine, the advantages aremany:10

Research withhuman brain tissue.

The use of human brain tissue in the study ofneurological disease is likely to yield many newinsights and was the method by which the chemicalimbalance in Parkinson’s Disease was discovered. In1960 Ehringer and Hornykiewicz found that patientswith Parkinson’s Disease had depleted levels of achemical called dopamine in those regions of thebrain most affected by the illness. This led to thesuccessful use of L-dopa, a drug converted todopamine in the brain, thereby making up thedeficiency.11

"... it overcomes potential species differences; it allows direct study ofthe cellular basis of numerous neurological disorders; and it decreasesthe number of animals required."

Drug Research

A major change in the strategy by which the NationalCancer Institute (NCI) searches for new anticancerdrugs was recently announced. The NCI traditionallyrelied on mice, in which leukemia had been induced,to screen around I0,000 chemical substances a year.But it has been admitted that such an approach hasnot identified new drug candidates with particularlypromising activity against any of the major cancers,including lung, colorectal, breast and prostate.12 In thenew system, the animals have been replaced by testtube studies with human cancer cells, at least inpreliminary tests:13 drugs successful at this stage stillproceed to further animal experiments. Otherresearchers argue this could be misleading andbelieve only human cancer tissue should be used totest the effectiveness of new drugs. Dr SydneySalmon of the University of Arizona argues that thebest means of assessing drugs successful in humantissue tests is not to carry out potentially misleadingexperiments on animals ("... inactivity in the mousewould not mean that a drug would be inactive inman") but to submit them for clinical trial in cancerpatients.14 Although the NCl's initiative is to bewelcomed, it was over 30 years ago, in 1956, thatEagle and Foley first showed that human cancer cellscould be used to test new anticancer drugs.15

Apart from searching for new drugs, human cancertissue can also be used to identify which combinationof existing remedies is most effective for individualpatients. To do this, cancer cells are taken frompatients and their sensitivity to drugs and radiationtested in vitro. The technique ensures that patientsare less likely to be exposed to treatments that do notwork.

Because AIDS is a uniquely human disease, scientistshave been forced to rely on human cell tests toidentify new treatments. Clinical observation of AIDSpatients has shown how the HIV virus works, enablinga simple in vitro test to be developed.

The AIDS virus disrupts growth of the T4 Iymphocyte,a cell crucial in regulating the body's defensemechanism. The beneficial effects of new drugs aretherefore easily assessed by adding them to test tubecultures of the T-cells to see if they prevent damagecaused by the virus.16

Researchers argue that sufficient in vitro techniquesexist so that almost any useful drug effect can bepredicted without using living animals.17 Such testsutilize cells, tissues and enzymes from the body andwhile in many cases these originate from animals, thepotential exists for human material to be used instead.For instance, a variety of in vitro tests can be used todetect new immunosuppressive drugs to preventrejection of transplanted organs. But while some ofthese tests do indeed employ human cells (humanblood Iymphocytes in this case), others still rely ontissue from animals.18

A further aspect of drug research is pharmacologywhere scientists study exactly how drugs and

naturally occurring bodysubstances exert their effects onthe tissues. An understanding ofthe chemical processes involvedcan be valuable in providing amore rational basis for the designof new drug treatments.Traditionally, pharmacologistshave relied mainly on animalsdespite numerous contradictoryresults. Acetylcholine, a chemicalreleased by nerve endings,produces entirely the oppositeeffect in animals: according toexperiments with dogs,acetylcholine was widely believedto dilate coronary arteries, but inhuman coronary tissue it actuallycaused a narrowing of the vesselswhich is thought to result in heartspasm in a living person.19

Man’s best friend?Not when it comes toresearch. Dogexperiments oftenproduce data whichcontradicts humanfindings.

Considerable species differences also exist in theaction of naturally occurring body chemicals on bloodvessels in the brain:20 noradrenaline contracts humancerebral vessels but has no such effect on similarvessels from cows while human cerebral basilararteries are relaxed by bradykinin whereas dog basilararteries are contracted. Further species variationshave been reported with natural substances calledleukotrienes(LT). LTC4 and LTD4 constrict guinea pigskin blood vessels but dilate human and pig skinblood vessels.21 And the prostaglandins (PG), a familyof substances discovered over 50 years ago in humanseminal fluid, show considerable differences incardiovascular responses between the species: inheart tissue from cats and rabbits, PGE1 has noeffect on contractile force or in heart rate butincreases them in rats, guinea pigs and chickens.22

These examples highlight the dangers of animal-based research but as Else Muller-Schweinitzer of thepharmaceutical company Sandoz has explained,23Obtaining animal tissues

"Despite the limited relevance for human pharmacology of most of theanimal tissues, the use of human material in pharmacological studies isstill the exception rather than the rule."

Fortunately, some researchers are beginning to recognizethat animal experiments have serious limitations. In 1987the scientific journal Trends in Pharmacological Sciencesstated that "direct extrapolation from animals to humans isfrequently invalid" and noted that "recently much interesthas focused on use of human autopsy or biopsy tissue asa means of overcoming these limitations."24 An example isthe use of diseased human heart muscle preparationsfrom patients who have died. Researchers at Hamburg'sUniversitat-Krankenhaus Eppendorf and the Universit atMunchen argue that such tissue is useful in evaluatingcertain heart drugs and may also provide new insights intothe nature of heart disease.25 The preference for humancardiac tissue is shared by scientists at StanfordUniversity and the School of Medicine at the University ofUtah who have studied the chemical changes that occur incardiac tissue during heart failure. Only human materialcan provide accurate results because of speciesdifferences in the type and proportion of the all-importanttissue chemicals known as receptors.26

It has even proved possible to study beating human heartcells. Researchers from the Children's Hospital ofWinnipeg and the Department of Pediatrics at theUniversity of Manitoba state that "although numerous invitro studies have been done on beating cardiac tissueand cells from experimental animals, there has been asurprising paucity of similar work with human material."During chromosome studies with tissue from early humanspontaneous abortions, they found isolated heart cellsmaintaining a rhythmic beat in tissue culture. Pulsationcontinued for up to 88 days allowing heart drugs and bodychemicals to be tested for their effects. As expected fromtheir action in a living person, adrenaline increasedpulsation rate while addition of the heart drug propranololslowed the rate.27

Pharmacologists have used many other human tissues fortheir research. Professor Schror of the University ofDusseldorf and Raphaela Verheggen at the University ofGottingen argue that human cerebral blood vessels,obtained within 24 hours of death, provide a valuablemeans of studying cerebral vasospasm, a condition inwhich blood

vessels in the brain constrict, with fatal results forpatients with subarachnoid hemorrhage. Little is knownabout how to treat cerebral vasospasm because theunderlying chemical processes are poorly understood.The German researchers refer to considerable speciesvariations in animal models and conclude that muchneeded improvements in treatment can be expected fromhuman tissue studies.20 Another example is the use oflung tissue to investigate asthma and related conditions.The tissue is obtained from patients undergoing surgeryfor lung disease. When treated with the bronchodilatordrugs used to treat asthma, the tissue is "relaxed" aswould be expected in patients receiving treatment. Onthe other hand, bronchoconstrictor drugs make the tissueconstrict.28

Toxicity Tests

A former Director of the Wellcome Research Laboratorieshas stated that "the unsatisfactoriness of predictingadverse effects in humans from animal experiments hasbeen known for a long time"29 while the Lancet medicaljournal acknowledges that "animal tests are veryimperfect indicators of human toxicity."30 Most drug side-effects occurring in people undergoing treatment cannotbe correctly predicted by animal experiments so it is notsurprising that the great majority of drugs found safe andeffective on the basis of animal tests fail during clinicaltrials with volunteers and patients.31 While such trials arethe most reliable test of a new medicine, somepreliminary testing is essential to identify and reject themost toxic substances. It is here that in vitro studies withhuman cell promise better protection than experimentson animals.

The idea that a combination of in vitro tests would allowthe general toxicity of chemicals to be correctly predicted,is a basic assumption behind a multicenter trial initiatedduring 1987 by the Scandinavian Society for CellToxicology.32 The research aims to find exactly whichcombination of in vitro cell systems best predicts lethaldoses of chemicals in human beings. Although many ofthe cell systems derive from animals, a human-orientedapproach is possible. Indeed, while introducing aworkshop

Medical research usinghuman tissues: Manyapproaches could be utilized tobenefit human medicine andsave many animals fromneedless suffering and death.

1. Cerebral blood vessels2. Brain tissue 3. Bronchus 4. Lung5. Intervertebral discs6. Spleen7. Kidney8. Skin9. Lymph nodes, foundthroughout the body10.Placenta after childbirth11. Blood12. Nerve cells13. Human muscle tissue14. Varicose veins15. Bone marrow16. Articular cartilage17. Intestines18. Liver19. Coronary tissue Heartmuscles20. Breast & mammary cells21. Tonsils 22. Pituitary gland 23. Eyes24. Human cancer cellsthroughout the body

© Lorraine Kay/MM

on the application of tissue culture in toxicology, Dr. Zuccoof Italy's National Council of Research explained how theproblem of extrapolating data from animals to people couldbe bypassed with the use of human cell cultures, in effectallowing us "to carry out studies on our species directly."60

For instance, in tests carried out at Denmark's RoskildeUniversity Center, the lethal concentration of chemicals tocultures of human blood Iymphocytes showed "very goodcorrelation" with their reported lethal doses in people.33 TheIymphocytes were obtained from a volunteer's bloodsample.

Such in vitro studies are valuable in assessing overalltoxicity but a more sophisticated approach would be tocarry out additional tests with tissues from organs mostcommonly damaged during drug treatment, such as theliver, kidney, blood and skin. For instance, some drugsdamage the bone marrow producing fatal blood diseases;but scientists at Britain's Lister Hospital in Hertfordshirehave recommended the use of human bone marrowcultures to detect hazardous products before they reachclinical trials. 34 They conclude that,

"any in vitro method using human tissue gives a degree of reassurancenot provided ... by animal experiments".

The technique can detect chloramphenicol, an antibioticknown from clinical experience to cause the fatal blooddisorder aplastic anaemia. Chloramphenicol was thought tcbe safe after experiments on animals.35

In another example, researchers have proposed the use ofhuman kidney tissue to study the damaging effects ofaminoglycoside antibiotics.36 These drugs are known tocause kidney problems in a substantial number of patientsand tests with human tissue correctly identified theantibiotics that were most toxic in clinical practice. Theresults give confidence that human kidney tissue couldaccurately predict the harmful effects of entirely new drugsOther scientists have suggested human cell tests to identifydrugs which damage the fetus,37 while human bloodIymphocytes have been recommended as one way ofdetecting mutagens and cancer-causing chemicals.38

A recent initiative by Organogenesis Inc. ofCambridge Massachusetts, is the production of livingorgan equivalents from human cells. Known asTESTORGANS, they are intended to promoteextended organ-like function in vitro for use instudying the effects of pharmaceuticals, pesticides,cosmetics, detergents and other substances onhuman organ systems. By 1989 TESTORGANSincluded TESTSKIN, TESTLUNG, TESTINTESTINEand a living artery equivalent test system.Organogenesis believes that its test organ systemswill have applications not only in toxicity testing but inother areas such as investigating how drugs can bedelivered through the skin, wound healing researchand the study of specific diseases like psoriasis andatherosclerosis.37 The company's most developedproduct is TESTSKIN, a full-thickness skinreplacement consisting of two layers - a living dermallayer and a multi-layered epidermis. Unfortunately,part of the skin model is currently built up on collagenof bovine origin. TESTSKIN is already being used bysome cosmetic companies.

Another company, the La Jolla-based Marrow TechInc. in California, has recently developed completeculture systems for human bone marrow, liver, oralmucosa and skin for in vitro safety tests. In the caseof the human skin model, the different layers of cellswhich form normal skin are placed in layers on anylon mesh producing a full-thickness skin equivalent.Unlike the Organogenesis product, no collagenextracted from another species is used to formMarrow Tech's simulated skin product.

Growing skin in thelaboratory

© Lorraine Kay/MM

The company feels that its skin equivalent will be useful indetecting potential skin irritants.37 This would be aconsiderable advance over the traditional use of animalswho are widely acknowledged as poor models for humanskin tests.39

With their obvious advantage in overcoming speciesvariations, the potential of human tissue tests should havebeen appreciated long ago. Yet only a handful ofresearchers appear to have recognized their importance:for instance, in 1952 Britain's Industrial Medicine and BurnsResearch Unit at Birmingham's Accident Hospital wasusing cultures of human skin to assess the relative toxicityof antibiotics;40 in 1962 researchers using human bonemarrow cells predicted that griseofulvin, an antibiotic, mightdamage the blood,41 a finding subsequently confirmed byclinical experience; in 1966 scientists were comparing thetoxic effects of various anaesthetics on human liver cells42

and three years later they reported similar studies withkidney tissue;43 and in 1971 Lash and Saxen showed howhuman cells could be used to investigate the harmfuleffects of thalidomide.44

Today, the overwhelming emphasis is still on animalexperiments and even those using in vitro techniques rely

Laboratory rats:Intelligent,sensitive,relatively cheap,and known tometabolize mostsubstances quitedifferently thanhumans.

“.. in the assessment of risk to man there are obvious theoreticaladvantages in the use of [a liver cell mixture] prepared from humantissues, which may differ from tissues prepared from rats . . . in theirability to activate or detoxify chemicals.”

Nevertheless, a survey of papers published by the scientificjournal Mutagenesis during 1989 showed that in nearly everyin vitro test where liver cells had been added to metabolizetest chemicals, the tissue had originated from rats orhamsters.

Production of Biological Products

1) Antibodies and Monoclonal Antibodies.A healthy body deals with the threat of invading bacteria,

heavily on animal cells rather than human tissues: at the 7thScandinavian Society for Cell Toxicology Congress held inDenmark in 1989, only three of the 18 papers studying thetoxicity of chemicals to people actually employed human cells.Most of the remainder used tissues from rats and mice.

There is another area of toxicity testing where scientists havebeen equally reluctant to use human cells. Sometimeschemicals only become hazardous when metabolized, orbroken down, in the liver, so researchers often include livercells in their in vitro tests to mimic the body's main metabolicreactions. The Ames bacterial test, which is designed toidentify mutagens and cancer-causing chemicals, routinelyincludes cells from the rat's liver. Yet common sense woulddemand the use of human liver cells since differences inmetabolism between rats and people are known to be the rulerather than the exception.45 Differences even occur betweendifferent rodent species as discovered during an investigationof 74 chemicals by the Edinburgh-based contract laboratoryInveresk Research International. Each substance wasassessed for mutagenicity by in vitro bacterial testsincorporating liver cells from either rats, mice or hamsters."Marked differences" in metabolism between the species werefound,46 suggesting that reliance on animal tissues might failto identify some mutagens.

As long ago as 1982, Britain's Guidelines for the Testing ofChemicals for Toxicity stated that,

viruses and other foreign substances by producingantibodies. These essential body chemicals seek outand form a close bond with the invading organisms asa prerequisite to their ultimate elimination. Apart fromdefending the body against attack, antibodies havebeen much used for basic research into the immunesystem and as a means of measuring theconcentration of small amounts of substances. Forsuch analytical purposes antibodies have traditionallybeen produced by injecting animals with thesubstance under investigation. Blood samples arelater taken and contain antibodies that can be used toidentify and measure the substance originally injected.But occasional scientific reports show that antibodiescan be produced in vitro. In 1974, researchers atJapan's Osaka University Medical School describedhow human tonsil tissue could be used to produceantibodies in response to foreign substances.47 Thetissue is obtained from therapeutic tonsilectomy:

"Since it is very easy to obtain large numbers of human Iymphocytesfrom tonsils and they contain complete sets of cells necessary forantibody formation in vitro, tonsil Iymphocytes could be very useful forthe investigation of the immunologic phenomena in humans."

Recently there has been great interest in monoclonalantibodies. It is in the nature of cancer cells toreproduce themselves indefinitely but this can beturned to advantage by combining them with othercells which produce antibodies. The combined cellsystem is called a hybridoma and continues toproduce antibodies indefinitely. Since the antibodiesare of the same type and come from the same originalcell, they are called monoclonal antibodies.

Although the two cell types that form the hybridomaoften originate from animals, there are advantages inusing human tissues. This is because monoclonalantibodies may have therapeutic applications inaddition to their more familiar diagnostic role. Usedtherapeutically, monoclonal antibodies areadministered to people, and if derived from animals,present a high risk of allergic reactions. Symptomsinclude fever, rashes, vomiting, rapid heart beat anddifficulty breathing.48 Furthermore the human bodysees

them as "invaders" and acts to reduce theireffectiveness. The solution is to develop monoclonalantibodies entirely of human origin: in other wordshuman cancer cells would be linked to humanantibody forming cells.

The requirement for human antibody forrning cells hasgiven scientists the incentive to produce antibodies invitro because the traditional method of antibodyproduction - the deliberate injection of foreignsubstances into a living being - would be regarded asunethical in people. Tonsils, spleens and Iymphnodes, obtained surgically, are valuable sources ofIymphocytes which can be used to produce humanantibodies in vitro. But by far the most convenientsource of Iymphocytes is human blood.48

A possible therapeutic application of monoclonalantibodies is in cancer research where they may havevalue as a less toxic form of treatment. Researchersat Japan's Kyushu University and the National KyushuCancer Center Hospital have produced humanmonoclonal antibodies that lock onto breast cancercells in sick patients. In this case the hybridoma wasmade up of Iymphocytes from the Iymph nodes ofbreast cancer patients and from human cancer cells.49

2) Vaccine ProductionVaccines against diseases caused by viruses havetraditionally been made from animals or their tissuesbut this can be dangerous as contaminants fromanimal tissues have produced fatal results in people.50

Furthermore, cancer-causing viruses have been foundin cells from primates, dogs, chicks and ducks whichare used in the preparation of vaccines. The cancer-causing viruses such as SV40 which contaminatetissue from primates only become dangerous whenthey cross the species barrier,50 so the use of humancells to make human viral vaccines would seem thesafest approach. Today, vaccines for many viraldiseases such as polio, rubella, measles, mumps,smallpox, rabies and diseases caused by arbovirusessuch as yellow fever, can all be produced from testtube cultures of human cells.

Indeed, scientists suspect that monkeys may be theorigin of the human epidemic of AIDS. Writing in thescience journal Nature, Drs. Sergio Giunta andGiuseppe Groppa of the INRCA Clinical Laboratory inAncena, Italy, ask whether the transfer of a monkeyvirus to humans could be linked with the beginning inthe 1950s of a massive trade in primates from Africato Western countries for virus research and studiesinto the production and control of polio vaccines. Intheir view, such events inevitably involved morecontact between the human population and themonkeys they captured and transported.52

In Britain, polio vaccine is made from human diploidcells by the Wellcome Research Laboratories yetdespite the risks of contamination, primates are stillwidely used for the purpose in other countries.53

Source of Human Tissue

While most human tissues for research and testingcan be obtained from volunteers, biopsies, surgicaloperations and post mortem samples, a muchneglected source is the

Making vaccines fromanimal tissues leaveshuman recipientsvulnerable to hiddenviruses. SV40, apotential cancer-causingagent, was laterdiscovered in poliovaccine made frommonkey kidneys.

As long ago as 1970, P. B. Stone of thepharmaceutical company Pfizer's TherapeuticResearch Division warned that:

"There is always the prospect of a new or unknown virus which wouldnot be detected by the present battery of tests. The situation would beunsatisfactory in the case of a non-pathogenic organism, but disastrousif the undetected virus were pathogenic for man."51

normally discarded human placenta. Many studies ofplacental structure and function continue to useanimals but as Joseph Dancis of the New YorkUniversity School of Medicine has explained, "of allmammalian organs, the placenta shows the greatestvariation in structure among the species ... Onecannot be confident that an observation made withanimal placenta is pertinent to the human, unless it istested in the human."54 The placenta may have otherimportant applications. Since it comes from the samesingle fertilized human egg as the baby, it can almostbe seen as a scaled-down human being. Testing theaction of drugs on placental biochemistry couldtherefore eliminate many tests currently performed onanimals. Soli Contractor of London's Charing Crossand Westminster Medical School argues that:

Placenta: Not onlyvaluable as a source oftissue for research, buta viable alternative toanimals for practicingmicrosurgery.

"The human placenta has enormous potential for studying metabolicprocesses without recourse to animal experimentation. Its greatestadvantage lies in eliminating the necessity for extrapolating results fromanimal experiments and trying to interpret them in terms of the humansituation.”55

The placenta contains tiny vessels and has beensuggested by surgeons at Britain's Frenchay Hospitalin Bristol as an alternative to animals for practicingmicrosurgery.56

In many cases it is advantageous for human cells tobe cultured to allow their continuous growth. Such"tissue cultures" allow researchers to increase thenumber of cells available for study. It also enables theeffect of drugs on

cell growth to be monitored, providing scientists with ameasure of toxicity. To enable cells to grow effectively,they are kept in a nutrient medium usually derivedfrom fetal calf serum. But there may often beadvantages in using synthetic growth media wherethe exact composition of nutrients is known, or indeedhuman sera. Researchers at the University of BritishColumbia compared the growth of human breastcancer cells incubated with either human or fetal calfsera. As might be anticipated, they found that use ofhuman serum most closely resembled the clinicalsituation not only in the growth of cancer cells butalso their sensitivity to chemotherapeutic drugs.57 Theresults have important implications for thedevelopment of anticancer drugs.

Why is human tissue so little used?

Despite anticipated savings in the cost of animals andtheir housing, the use of human tissue is very much aneglected experimental resource. The reason usuallycited is difficulty in obtaining regular supplies ofhuman material.23 Furthermore some tissues must beused quickly if they are to produce useful results. Anexample is cerebral blood vessels which must beused with 24 hours of death. Placenta also need to becollected quickly after childbirth and Soli Contractor ofthe Charing Cross and Westminster Medical Schoolnotes that "one needs to establish a considerablerapport with the midwives and the clinical staff,without whose help and interest the work would notbe possible."55 Taking the time to develop goodworking contacts with surgeons and other hospitalstaff is surely worthwhile, bearing in mind the greaterrelevance of human tissue studies. By sacrificingaccuracy for the greater "convenience" of animalexperiments, scientists do medicine a disservice. Inany case many human tissues can be successfullypreserved by storage at very low temperatures.23

A greater willingness to leave parts of our bodies formedical research and a well organized system oftissue storage would leave experimenters little excusefor continued reliance on animals. Prof. CorwinHansch, an expert in drug design, has stated,

Conclusion

The astonishing neglect of human tissue for researchand testing reflects poorly on the scientific communityand illustrates a widespread disregard for thesuffering and death inseparable from animal research.The overwhelming advantage of human tissue studiesis their relevance: compared to this, the continued useof animals must be regarded as bad science. Ashuman tissue researcher Maurice Panigel of theUniversity of Paris has pointed out,

"No laboratory animal will ever be a completely satisfactory substitute forthe human system and the time will come when we shall stop wasting theenormously valuable enzymes and organelles of the dead and instead putthese to use to understand the living human being better." 58

"Whenever human material becomes available for research in satisfactorycondition and without danger to the patient, it should be preferred to anyanimal living material."59

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