animal research and human medicine booklet

8/3/2019 Animal Research and Human Medicine Booklet

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Animal research andhuman medicineA resource for schools


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This booklet is designed to support teachers working with pupils on the issues

surrounding the use of animals in medicines research. Whether used in the contextof Citizenship, PSE, Science, English or RE, it aims to provide a useful resource forboth teachers and pupils across the UK.

The ABPI wishes to thank Understanding Animal Research, the Science PhotoLibrary, Wellcome Images, the University of Newcastle upon Tyne, Corbis, theInstitute of Animal Technology and GlaxoSmithKline.

Teachers Notes and Pupil Worksheets for Animal Research and Human Medicinecan be found on our websitehttp://www.abpischools.org.uk/page/animal_research.cfm

Association of the British Pharmaceutical Industry7th Floor, Southside, 105 Victoria Street, London SW1E 6QT

t +44 (0)20 7930 3477

Introduction 1

Why we need medicines 2

Bringing medicines to patients 4

Following up an idea 5

Research and testing 6

Epilepsy the quest for control 9

Using animals in research 10

Developing alternatives 12

The law, compassion & respect 14

What the law says 15

Penicillin the wonder drug 16

Cystic fibrosis 18

Glossary* 19

Food for thought 20

*Please note that pharmaceutical terms and phrases placed in bold are explained in the Glossary.

Contents


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People have always used animals for food, warmclothing, transport and all kinds of work, such as

pulling ploughs and carrying loads. How do we feelabout the other ways in which they are used? Is itacceptable to eat meat? What about wearing leatherand wool? Should we have new medicines if thisinvolves using animals in research? The rights andwrongs of such use of animals have been debated forhundreds of years and the debate continues in the21st century.

Today, most of us are concerned about the protectionof our natural world and have respect for the needs ofother creatures as well as human beings. At the same

time, our rapidly growing knowledge of science andtechnology presents us with increasingly complicatedmoral issues. To try to make sure that science is usedin an ethical way, society needs to discuss these issues.

Unfortunately, sometimes there are no easy answersand difficult choices have to be made.

This book looks at the use of animals by people whocarry out research into new and better medicines.

All new medicines are studied in animals beforeresearchers are permitted to test and use them

in people.

Many people accept the use of animals in this waybecause of the benefits to human health and well-

being it helps to bring about, but some of us may feelthat animal research is simply wrong, whatever itsimportance to medical progress.

Some feel that the morality of using animals dependson the aims and achievements of the experiments,whether the animals are treated humanely, or on theseriousness of the illness involved maybe they canaccept the use of animals in trying to develop a curefor cancer but not for migraine, even though theseheadaches can be very painful and, for some unluckypeople, occur frequently.

The use of animals in medical research is an issue onwhich there are many differing views, and opinionscan change with knowledge and experience. In orderto make up your own mind it is important tounderstand all aspects of the debate. This booklet setsout to explore the discovery, development and safetytesting of new medicines using real case studies asexamples and presenting the current laws relating toanimal experiments. We hope that this informationwill help you to think through your own viewpoint.

Introduction I 01

Medicines successfully prevent or treat many commondiseases, helping millions of people to live longer and have agood quality of life.


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The state of our health is important to us mostpeople want to be as healthy as possible. Thats

why How are you? is the most common greeting inmany languages!

Being ill can be very unpleasant, limit what we areable to do and even shorten our lives. And illnessaffects the whole of society, not just individuals andthe people who care for them, because our absencefrom school, work and family responsibilities is adrain on the community, and we all pay for theNational Health Service.

What causes illness?

Infectious illnesses like colds and tonsillitis are causedwhen micro-organisms such as bacteria and virusesinvade our bodies. Other diseases like cystic fibrosisare the result of the genes we inherit from our parentsand grandparents. Many diseases are the result of acombination of bad luck and genetics.

Our lifestyle also affects our well-being. Eating abalanced diet, not smoking, drinking alcohol only in

moderation, taking plenty of exercise and gettingenough rest all help to protect our health. But lifestyle

factors alone may not prevent us getting ill, nor causedisease. Some people with unhealthy habits stay well(though they are unlikely to be full of vitality). Butyour lifestyle can seriously tip the balance one way orthe other.

Whats more, even after recovery, disease cansometimes have knock-on effects on overall health.Measles, for instance, could leave children with alegacy of blindness or brain damage, while someteenage boys and men are left infertile by mumps.

Dealing with new diseaseMany of the diseases that affect us have been aroundfor thousands of years, but new diseases still appear.AIDS and swine flu (H1N1) are just two remindersthat we need to be constantly on our guard againstnew infections. We need to know what causes newdiseases, how they are spread and what healtheducation programmes, medicines and vaccines mighthelp to control them.

Why we need medicines

Having a healthy lifestyle gives us a better chance of staying fit and well.


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Modern medicines have made it possible for almost everyonewith asthma to lead active lives.

Preventing illnessPersuading people to make healthy lifestyle choices

means they are less likely to develop heart disease andsome cancers. Even more importantly, good hygiene,proper sewage disposal and clean drinking water arevital in preventing disease. Prevention can also involvethe use of medicines. Vaccinations have almosteliminated killer diseases like diphtheria and polio andhave wiped out smallpox worldwide. And preventingone disease can remove the risk of other, linked healthproblems that can arise later.

The more we know about a disease, the easier it is toprevent or treat.

Treatment or cureThere are many different types of medicines availableto us today, some of which treat and cure diseases,while others simply make us feel better and thereforeable to get on with our lives. They include:

Medicines that destroy infectious organisms e.g. antibiotics

Medicines that destroy cancer cells e.g. cytotoxins

Medicines that replace missing chemicals in thebody e.g. insulin

Medicines that relieve inflammation or pain e.g. ibuprofen, morphine

Why we need medicines I 03

Asthma is becoming increasingly common. Aboutone in eight children is affected, although manyoutgrow the problem later. It often runs in families.Asthma causes bouts of wheezing, breathlessness,coughing and tightness of the chest.

Asthma usually starts with mild allergies whichoften pass completely unnoticed. The most commonallergies are to house dust mites, cat and dog fur andpollen. For some people, regularly breathing in theseallergens irritates the cells that line the airways to thelungs, so they are always slightly inflamed and over-sensitive. These over-sensitive airways then react totriggers like cold air or exercise to cause an asthma

attack. The airways swell up and narrow, so breathingbecomes difficult, which can be very frightening.

In the past, most people with asthma did no exercise,to avoid making their airways work too hard. Today,most people with asthma learn how to manage theirillness so they can lead active lives. This is donelargely by gaining a good understanding of theircondition and the proper use of two different typesof asthma medicines. Some of the medicines areused regularly to keep the background inflammationof the airways under control. This makes asthmaattacks much less likely to occur. Other medicinesare used at the first signs of a problem, to open upthe airways and make breathing easier. Today, wehave Olympic athletes with asthma, something thatwould have been unthinkable in the past.

Tackling asthma

Many of the medicines we already have work well but there is still a need for them to be improved.Medicines work better for some people than forothers and some people will experience side effectswhen others dont. For example, there are severalpowerful and effective medicines used to helppeople with epilepsy live active lives. But for somepeople, the medicines simply dont work wellenough so more new epilepsy medicines arebadly needed. Scientists and doctors are constantlytrying to improve existing medicines as well asdiscover new ones.

Improving medicines


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All of us take medicines at some time, for example,childhood vaccinations, medicines to control long-term conditions like asthma and epilepsy orantibiotics to clear up a bacterial infection. We are soused to having these benefits that we take them forgranted. But every medicine is the end result of a long,expensive process to discover or identify a potentiallyuseful compound and then develop it to be as safe andeffective as possible. Only a tiny number ofcompounds make it through this long process.

New medicines what really mattersThe starting point for developing new medicines is anunderstanding of how the human body works andhow it is affected by a particular disease. A usefulmedicine may treat many thousands or even millionsof patients. For any medicine to be allowed to beprescribed, an enormous amount of information must

be collected to demonstrate that it is:

Effective it must prevent or cure the illness, orrelieve the symptoms for the patient. For instance,a compound might be seem to be useful in theearly stages of research but it must also be able tobe absorbed into the body. It wont help the patientif it cant reach its target or it is destroyed by thebody before it has a chance to work.

Safe it has to deal with the problem withoutcausing unacceptable side effects, taking intoaccount the seriousness of the illness themedicine is designed to treat. For instance,will it affect blood pressure or maybe collectin the bone (storing up trouble for the future),rather than being passed out of the body once ithas done its work?

High Quality the medicine must be able to bemanufactured to a high standard every time and itneeds to remain stable so it can be stored withoutdeteriorating for a given period of time.

Research into a new medicine has to make sure thatall these conditions are met. This is why it takes a verylong time up to 12 years and around 1,000 million

to bring a new medicine into the doctors surgery.

When people consider medicines research, they mayalso think about the use of animals in testing. Animaltesting is a small but crucial part of the researchprocess for all new prescription medicines.

Bringing medicines to patients

The NHS would be unable to function effectively were it not for

the availability of medicines and treatments that have beendeveloped or validated through research using animals

Department of Health

Information from animal tests are required by law

In the UK, the law known as the Animals (Scientific Procedures) Act 1986 (explained later in this booklet),controls the use of animals in research.

At the same time governments around the world have to do their best to see that new treatments can be usedsafely. As a result, there are laws that demand animals are used in medicines testing. Below is a quote from theEuropean legislation about the testing of new medicines. The UK must abide by these rules.

Clinical trials must always be preceded by adequatepharmacological and toxicological tests, carried out on

animals in accordance with the requirements..(This is from European Directive 2001/83/EC, Annex 1 Part 4)


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In the 1920s an American veterinary surgeon wascalled out to a number of cases of uncontrolled

bleeding (haemorrhage) in some cattle. At first he waspuzzled as to the cause, but eventually began to thinkthat the outbreak might be connected to some spoiledclover which the cows had eaten. The food had beenstored and had begun to go bad, so perhaps a naturalchemical in the fresh clover had changed, becomingharmful in the spoiled clover.

To test his theory, the vet designed the followingexperiment: he fed spoiled clover stalks to one rabbitand fresh stalks to a second rabbit, the control. Thefirst rabbit haemorrhaged and died, but the second

thrived, confirming his idea that something in thespoiled clover caused the bleeding. Obviously, thecattle would not be given the clover again but, evenmore importantly, the vets observation was to have amajor impact on medicine.

The story of the haemorrhaging cows attracted lots ofinterest, because scientists wondered if the substancein the plant that caused bleeding in cattle and rabbitsmight also prevent blood clotting in people.

Blood clotting is essential, as it seals a wound.However, it is dangerous if the blood clots too much.A clot in an artery can block the circulation of blood,causing a heart attack or stroke. If something in theclover could prevent clotting, the scientists thoughtthat it might be used (in a safe concentration) toprevent blood clots.

To test this hypothesis, scientists had to find out whichof the many naturally occurring chemicals in the cloverwas causing the bleeding, and identify its properties. In1939, using a test developed with specially bred rabbits,the chemical was discovered to be a form of coumarin.When they tested the compound they found it did

indeed prevent blood clotting.

Further research with animals was needed to findout how coumarin caused the bleeding and as aresult of the research a range of medicines calledanticoagulants based on coumarin wasdeveloped. Both the vet and the scientists followedan experimental process which is the basis for allinvestigative work in science.

Although the original problem was observed in cattle, theresearch which followed used rabbits which are much smallerand easier to manage.

Following up an idea I 05

The experimental process

Observation

Hypothesis (possible explanation)

What do you think should happen if youridea is correct?

What information (data) will you look for

and how will you collect it?

What will you vary and what will you keepthe same?

Experiment

Analysing the results

Do they support your hypothesis? If so

Further experiments To refine your ideas


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Clinical trials (human testing)Testing in people usually begins in healthyvolunteers. They are given very small doses of thenew medicine over short periods. The way theirbodies react to, or have an effect on, the medicine ismonitored and compared with the animal data.Scientists are always aware of possible speciesdifferences and check for them as they go along.Also, some side effects can be difficult to see inanimals, such as headaches or mood swings. If allgoes well, the dose is slowly increased to realisticlevels. Doctors must find out how effective themedicine is in the patients it is meant to help andlook for any unexpected side effects.

Scientists must get permission from a specialgovernment agency, theMedicines andHealthcare products Regulatory Agency(MHRA), to begin tests in people. People are onlyincluded in these trials if they agree to take part

and the trial itself has been approved by specialethical committees. At first, the number ofpatients will be small. Later, the studies canbroaden until there is enough information todecide if, for what type of patient and in whatdosage the medicine should be licensed.

The role of computers

When scientists understand a disease process andthe structure of a molecule that might help, theycan use computers to design new molecules thatmay help deal with the problem. Sometimes theyfind active chemicals in plants and other livingorganisms and then computers can design similarcompounds that can do the same job.

Computers are also used alongside high-techrobotic in vitro systems to check rapidly throughtens of thousands of known compounds atenormous speed to pick out ones with a usefulcharacteristic. That doesnt mean those compoundswill work in the body, but it is a good start.

Animal research and testingWhen body systems work together, they create newconditions which do not exist in tissue cultures. Forexample, the digestive system may destroy amedicine before it reaches its target, the potentialmedicine may be converted into something entirelydifferent which is useless or harmful. It may bepassed out of the body before it has time to work,or the medicine may affect other systems, indirectlycausing problems like raised blood pressure ororgan damage. Animal testing enables scientists toidentify most of these problems before a medicineis given to people.

The first stages of animal studies are used to showthat a medicine is likely to have the desired effect.If a compound looks promising in animals, thenmore extensive safety testing will be carried out.Potential medicines that seem to have a reasonablechance of being effective and safe from animal tests

will then be tested in small groups of humanvolunteers, while further animal testing continuesat the same time to look at the effects when amedicine has to be taken for a long time.

Animal testing is required by law. See page 15

In Vitro screening

Specalised cells, tissues and simple organisms likeyeast can be grown in the laboratory. Potential newmedicines are tested using these systems. Thesetests give scientists a valuable guide to compoundswhich might be useful as medicines. Big advancesin the methods for growing cells in culture andkeeping them alive have made this type of researchincreasingly valuable. However, the conditions in alaboratory culture, isolated from the influences ofother organs and cells, are very different from thosein the body, so it would not be safe or ethical to takecompounds straight from this stage of testing andgive them to people.

Research and testing


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Research into new medicines is made up of threemain areas: non-animal research (computer andin vitro work), animal research and clinical researchin people. The three types of investigations are allneeded at different stages of the research. This

flow chart gives a simple explanation of thedevelopment of a new medicine.

Search for possible therapeutic compounds thisincludes computer design of new virtual moleculesand screening of many thousands of existingmolecules. These have been synthesised or foundin micro-organisms, animals or plants.

New compounds synthesised in the lab.

First, ideas are developed and the disease targeted,

then:

In vitro screening testing the potential medicines

on cell cultures, tissue cultures and lowerorganisms, like yeast. Most compounds are rejectedat this stage.

Animal research & testing the small number ofmolecules that have made it through the first stagesare now studied in animals so that researchers canget a better understanding of their possibleeffectiveness and then their safety both in the shortand long term. This gives researchers and doctorsthe information they need to decide whether, and ifso at what dose, the medicine can begin to be tested

in people.

Clinical testing on people begins with humanPhase Itrials on a small number of healthyvolunteers, to start investigating the safety of themedicine and consider the best dosage. Data ischecked with the results from the animal studies tolook for any species differences that might berelevant, before going onto the next stage.

Phase 2 trials run with a small number of patientswho have the target disease.

Phase 3 trials continue this with a larger number

of patients.

If the medicine has passed all the trials, thecompany sends all the data to the MHRA. If,after rigorous evaluation of the data, the MHRAis satisfied with the research, it will recommendthe medicine be granted a licence, along withconditions on its use. The medicine will continueto be monitored after it becomes available.

You can see an animated flow chart with more

details of the different stages atwww.atworkwithscience.com/Flash/rnd.html

Research and testing I 07


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Thalidomide is a medicine which was developed

in the 1950s, before there were agreed standardsfor studying the effects of new medicines. The

specific animal tests which we now know to be

essential were not carried out. Because

thalidomide seemed very safe for adults, it was

assumed that it was also safe for unborn children

and it was given to pregnant women to help

relieve the symptoms of morning sickness. This

assumption was wrong, and many babies were

born with malformations as a result.

The thalidomide tragedy led to a new law which

set standards for the testing of all new medicines.

Since the Medicines Act 1968, all new medicines

must be tested in animals for their potential toharm an unborn child.

In Vitro tests can

Tell whether a newcompound has the desiredeffect on isolated cells ortissues

Show certain hazards causedby direct effects on the cells

Suggest the most promisingchemical leads to follow

In Vitro tests cannot

Tell whether the desiredeffect will occur in acomplete living system

Tell whether the compoundwill have a harmful effect ina complete living system

Animal tests can

Show what happens to thecompound in completeliving systems

Suggest which compoundsare likely to be effective inhumans

Help to determine whether acompound can begin to bestudied safely in people andat what starting dose

Animal tests cannot

Predict with absolutecertainty what will happenin people

Human tests can

Show that a medicine iseffective in people and atwhat dose

Confirm side effects thatwere anticipated from theearlier stages but judged to

be acceptable

Identify any potentialhazards that were not seenin the earlier research

Human tests cannot

Prove that a medicine willwork for every person whomay ultimately take it

Identify every possible riskfor every patient who maytake a medicine, as peoplesgenetic make-up andmedical histories vary

Here you can see some of the particular benefits gained from in vitro testing, animal

and human testing and some of the limitations of which human scientists anddoctors have to be aware.

Bringing medicines to patients

The stakes are high


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In an ideal world, no animals would be used inmedicines research, but at the moment animals have

to be used if we want to develop new medicines tohelp us tackle more diseases successfully. Only a smallproportion of all the research carried out to develop anew medicine involves using animals, but thatproportion is vitally important for scientists to find outhow potential new treatments work in a livingorganism, before they are tested and used in people.So what are the facts about the animals used inmedical research?

When are animals used?The use of animals in medicines research is very

closely controlled by law through the Animals(Scientific Procedures) Act 1986. It is only allowed ifthe potential benefits of the research are judged to beimportant enough to justify the use of animals, and ifthe research cannot be done in any other way (see p14).

Which animals are used in research?From the outside, rodents like rats and mice mayseem very different to us but, as our DNA clearlyshows, the biological differences between us are verysmall indeed. Most of the effects of medicines in

people can be seen in well-designed animal tests,most of which can be carried out on rodents, mainly

rats and mice, so these are the animals which aremost commonly used in research. Rodents also havethe advantages that they are relatively small and easyto keep healthy in well-designed laboratories. And astheir natural lifespan is short, information on theirlong-term health can be obtained quickly. Largeranimals are used in research too. The law demandsthat new medicines are tested on two different typesof animals, one a non-rodent such as a rabbit, dog orprimate. As the figures show, 80% of all researchinvolving animals is done in rodents. Less than 0.3%involve dogs, cats or primates.

Where do animals come from?Virtually all animals used for research into newhuman medicines are specially bred. Any exception tothis would be rare and need special permission. It isvery important that the scientists know their animalsexact state of health, the conditions they have beenkept in, what theyve eaten and how they have beencared for all through their lives. Pets are never used not only would it be illegal and morally wrong butthey havent all been reared in the same way.

Using animals in research

Scientific procedures involving animals

Total approx. 3.72 million procedures in 2010.This figure includes breeding to produce genetically modifiedanimals (total 1.6million procedures)

Pharmaceutical research and development accounted for7% of the total; a decrease of 56,700 procedures since 2009

%

Mouse 71.68

Rat 8.19

Other rodents 0.53

Reptile/amphibian 0.41

Fish 13.18Bird 3.81

Other mammals 1.9


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How are the animals kept?Healthy animals are vital for successful research. They

are kept in clean, airy surroundings and those thatnaturally live in groups are also housed in groupswhere possible. The animals are provided with aninteresting environment in their enclosures and cages,unless this would interfere with the research.Specially trained and qualified animal technicianslook after the animals and make sure they are fed,watered and healthy every day. A vet is on call 24hours a day.

How are the animals used?The majority of procedures carried out using animals

are mild, such as injections and blood sampling. Forexample, after a new medicine is given, blood samplesmay be taken to see what is happening to the chemicalin the body. But some research does cause distress and

researchers must explain to the Home Office, inadvance of obtaining a licence, how distress will be

minimised. At the end of an experiment, most animalsare painlessly killed so that scientists can carry outpost mortems. They need to find out the effect of newmedicines on the body organs, looking for the earlysigns of problems which could develop later.

Scientists prefer not to use animals in their research,both for humane reasons and because other methodslike tissue culture can give results more quickly andcheaply. Animal tests often take months rather thandays. They need stocks of specially bred animalslooked after to very high standards and this is

expensive the costs of keeping one experimental dogcan run into many thousands of pounds.

Using animals in research I 11

Social animals like rodents are kept in groups with plenty of opportunity to explore, play and retreat from others if they want to.


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Developing alternatives

Scientists are continually looking for ways toreduce the numbers of animals used in medicines

research, and for alternative methods which can givethem the information they need to develop safe,effective medicines.

Cell and tissue cultures These tests are used tothe full. In fact, modern pharmaceutical industryresearch would not be possible without them.These in vitro methods allow research in animalsto begin at a later stage than used to be possible,saving many animal lives, millions of pounds andmonths of time. However, cell culture work givesonly a very limited picture of what happens in the

living body.

Computer models Scientists can use computersto model how a medicine will work in the body aswell as to help them discover and design possiblemedicines. Essential though they are, computerscan only use the information they are given, so thebig gaps in our biological knowledge limit whatthey can help researchers to achieve.

Good experimental design Scientists around theworld are refining existing tests and designing new

ones which give more high quality information andneed fewer animals.

Scientific advances Shared scientific expertiseand an ever-growing pool of biological knowledge

about the human body in health and disease, newtechnologies such as state of the art scannerswhich enable us to see what happens inside livingbodies, added to the ever improvingin vitro testsall help to reduce the need for animals.

Research in other organisms Our increasingunderstanding of biology shows us that we sharemany genes, body mechanisms and reactions withorganisms such as bacteria, yeast, fruit flies andfrogs eggs. This means scientists are able toreplace some of the testing done on mammals

with work on biochemical pathways in thesesmaller organisms.

Harmonising regulations Some animal testshave to be done because they are required by lawin another country where the medicine will besold. Government departments of health alongwith the pharmaceutical industries in the US,European Union and Japan are working togetherto agree the tests that pharmaceutical companieshave to carry out. These international agreementsallow fewer animals to be used in the UK and

around the world.


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Developing alternatives I 13

Animals need medicines too

The 3Rs are accepted as the basic principles for working towards good laboratory

animal welfare and a steady reduction in the need for animal testing

REPLACETHE USE OFANIMALS

WHENEVERPOSSIBLE

REFINETESTS TO CAUSEANIMALS THE

LEAST POSSIBLEDISTRESS

REDUCETHE NUMBEROF ANIMALS

NEEDED TO AMINIMUM

Animals benefit too. Our pets are very important tous. Unfortunately, they are just as likely to get ill aswe are, and a sick animal often means a visit to thevet, who has a wide range of medicines with whichto treat animal patients. Some of these medicines such as the vaccines for distemper in dogs orenteritis in cats were developed specially for

animals.

Vets also use many medicines which are exactly thesame as, or very similar to, treatments developed forhumans. Like human medicines, potential newanimal treatments are studied in laboratory animalsbefore they are tested in animal patients. Medicinesresearch in animals doesnt only help people, ithelps other animals as well. See if you can find some

examples of animals having similar health problemsto people and needing similar treatment.

Developing alternatives to animal testing in medicinesresearch is a long and difficult process. At the

moment, there is always a point in the medicinesresearch process where we meet barriers to ourknowledge that computers and in vitro methodscannot yet help us to cross. As our biological,

medical and technological knowledge grows, we lookforward to a time when animal research may not be

necessary. Until then, the priority remains to developsafe and effective medicines involving the consideredand compassionate use of animals when necessary.


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The law, compassion and respect

Some people seem to think that scientists cansimply decide that they want to use animals in

their research and then go ahead. Nothing couldbe further from the truth. In the UK, researchinvolving the use of laboratory animals is controlledby the most comprehensive legislation in the world.In fact, Britain was the first country ever to pass alaw specifically controlling research with laboratoryanimals and that was in 1876!

What is the law for?Animal tests on human medicines are a legalrequirement in almost every country in the world. Nonew prescription medicine can be developed without

the use of animal testing. These laws come under theresponsibilities of UK Department of Health and theEuropean Union. However, we have further lawswhich set out to make sure that animal research iscarried out humanely and only when necessary.

The Animals (Scientific Procedures) Act, passed byParliament in 1986, is overseen by the Home Office.

For animal research to be conducted, three separatedetailed Home Office licences are required. Scientists

and the organisations they work for aim for highstandards of animal welfare by ensuring that theresearch is conducted within a culture of care.

The law also aims to protect animals fromunnecessary distress. Most animals experience littleor only momentary pain during research procedures for example, when a blood sample is taken. Butsome procedures are stressful and researchers mustexplain, before they start, how they will minimisethis. Painkillers or anaesthetics must be usedwherever appropriate, although the majority of

procedures are too minor to require this givinganaesthesia would be more troubling to the animalsthan the procedure itself. If any animal is in severedistress which cannot be relieved, the law states thatit must be painlessly killed immediately, whether ornot the experiment is complete.

The Animals (Scientific Procedures)

Act 1986 balances the needs ofresearch with the welfare of

laboratory animals.

The use of animals must be kept to

a minimum and only the smallest

number of animals necessary for

the research may be used.

Non-animal methods must be used

wherever they can realistically

supply the required information.

The welfare of animals must be

protected: any distress an animal is

likely to experience must be justified

by the potential benefit of the

research and kept to a minimum

before, during and after experiments.


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What the law says I 15

The Animals (Scientific Procedures) Act 1986 requiresthree types of Home Office licences. A laboratory and

the research team must obtain all three licencesbefore they can work with animals.

Inspecting laboratoriesUK law is clear animals used in research must betreated with care and respect. A team of Home Officeinspectors all qualified vets or doctors check upregularly on the laboratories where animal research iscarried out. They often arrive unannounced, so nospecial preparations can be made, and they have to begiven free access to the whole area.

Around 2,000 Home Office visits are made each year.Most of these are to check that research involvinganimals is carried out in a proper, legal and humaneway. Most of this type of visit is made unannounced.Other visits are made to give advice, for instance, andmake assessments about changes to licences.

We have a moral

obligation to make surethat the animals used in

research are healthy andcomfortable. But good

welfare is also goodscience, because the way

we house and handleanimals can affect

research results.

Dr Vicky RobinsonHead of the National Centre for the

Replacement, Refinement and Reduction

of Animals in Research.

The Certificate of Designation

This authorises the premises where the animalsare kept. The Home Office will only grant acertificate to a scientific establishment which isequipped and properly staffed to look after theanimals before, during and after the research. Theanimal houses, laboratories and all the animal careprocedures must meet very high standards. Eachestablishment must appoint someone to be incharge of the day-to-day care of the animals and aveterinary surgeon to advise on their health andwelfare. There must be an internal ethical reviewprocess to foster high standards.

The Project Licence

This is granted to the scientist who takesresponsibility for the whole research project. Fulldetails of the project must be provided, including:

The likely benefits of the research

What non-animal methods are being used andwhy they cannot be used for everything.

The procedures that will be used that involveanimals

The likely effects on the animals

What types of animals and how many animalswill be used

What steps will be taken to minimise any painor distress the animal may feel

The Home Office considers whether the likelybenefits of the research to humans or animals (for

veterinary medicine) justify any possible distress tothe research animals. If so, a licence is granted.

The Personal Licence

This gives permission to a person to performcertain types of experiments on certain types ofanimals and only on approved research projects.It is only given to people who have the necessaryeducation and training. If they decide they need todo extra or different experiments during the

research, they have to apply for change to theirlicence and may have to undergo further training.


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Extracting penicillin

Original petri dish showing the penicillin at work

Penicillin the wonder drug

Before the days of antibiotics, infections lasted longerand were much more serious than today. Illnesses like

pneumonia were greatly feared, and even smallwounds could be life-threatening if they becameinfected. Amputation of an injured limb wassometimes the only hope of stopping an infectionfrom spreading through the body. Everyone, even infamilies with access to the best available health care,could expect to lose family members from bacterialinfections that can now be cured.

In 1928, Alexander Fleming made one of the mostimportant observations in medical history whileworking as a scientist studying bacteria at St Marys

Hospital in London. He returned to his rathercluttered laboratory after a break to find mouldgrowing in a Petri dish containing a bacterial culture.What intrigued him was the fact that bacteria close tothe mould had not grown as he would have expected.The further away from the mould he looked, the morebacteria there were, and he realised that somehow themould was damaging or killing the bacteria close to it.This chance observation was not just luck, as only atrained and alert mind would have made theconnection. If the mould could do this in the Petridish maybe it would do so in the body!

To test his idea, Fleming first needed to know howlong penicillin would stay active in the body, so hegave it to a number of healthy animals and found thatin all of them it disappeared quickly from the blood.This told him that the drug would not have much timeto work.

Then, using Petri dishes, he set up experiments to tryto understand how the mould harmed the bacteria,but the way the mould seemed to work was so slowthat he was convinced it would not work inside thebody. He ended the experiment and wrote a paperon this interesting but seemingly disappointingdiscovery. We now know that Flemings originalhypothesis was correct, but that he came to thewrong conclusion after misinterpreting the resultsof his Petri dish experiments.


19/24

Penicillin the wonder drug I 17

Ten years later Howard Florey, an Oxford professor,and his assistant, Ernst Chain, read Flemings paper

on penicillin during their own search for naturalsubstances to fight bacterial infections. Thankfully,they disagreed with Flemings conclusion and decidedto test penicillin for themselves. The research teamcarried out a critical experiment.

Eight mice were artificially infected with a lethal doseof bacterium called streptococcus. Half of the micewere then given penicillin. At the end of theexperiment all four mice treated with penicillin werealive and well, but the four mice that had not beentreated were dead. Penicillin worked against bacterial

infection in mice!

Soon it was time to try the medicine in humanpatients, but this was to prove difficult, as the mouldwas difficult to grow and the result was very impure.And because it disappeared so quickly from the blood,a lot of it was needed. The first patient was adesperately ill policeman who began to make adramatic recovery when given penicillin. Thescientists struggled to produce sufficient quantities ofthe medicine even recycling the excreted penicillinfrom his urine but unfortunately their efforts werein vain and the man relapsed and died.

In fact, it took a hundred litres of penicillin broth tomake enough of the medicine to treat one patient forone day! As the team became more skilled in makingthe medicine, more patients were treated, but still thenumbers were small and it finally took a massiveinternational effort to make penicillin widely available.One breakthrough came when a different strain ofpenicillin mould was discovered growing on a mouldymelon in America. The new strain was easier togrow and gave a higher yield of the precious penicillin.

Since those early days scientists have continued tosearch for more antibiotics. They have had a numberof successes with chemicals which are often producedby bacteria themselves or by fungi (like penicillin).Doctors now have a range of antibiotics available fortreating different types of infections. These includeerythromycin, streptomycin, cephalosporin,tetracycline and when all else fails vancomycin.

Most antibiotics work either by interfering with theway bacteria build their cell walls, or by stopping the

process of protein synthesis. Human cells dont havecell walls, and the way our cells make proteins isdifferent from the process in bacteria. This meansantibiotics can safely interfere in the working of thebacterial cells without damaging the patient at thesame time.

The number of compounds that stay in the body safelyAND destroy bacteria are few and far between. Andunfortunately, bacteria become resistant to theantibiotics. This is why doctors have to prescribeantibiotics carefully.

Flu, for instance, is caused by a virus, so antibioticsdont work. However, flu can leave a person open tobacterial chest infection. Then, antibiotics may beneeded to clear up the infection and avoid thepermanent damage infections can sometimes leavebehind.

The search goes on for new medicines to help keepbacterial infections at bay.

Fleming in his laboratory


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Cystic fibrosis

Cystic fibrosis and gene therapyResearch into human disease progresses slowly in

areas where there is no equivalent illness in animals. Agood example is cystic fibrosis (CF), a genetic diseasewhich affects about 8,500 people in this countryalone. Existing treatments help patients lead longer,healthier lives average life expectancy has gone upfrom 25 to 38 in the last 15 years or so but as Laurasstory shows, more options are needed.

Cystic fibrosis is an inherited disease that affects anumber of organs, particularly the lungs, and thedigestive system by clogging them with stickymucus. Until recently, the search for treatments was

severely hampered, because scientists were unable tostudy CF in animals. In 1989 the faulty gene thatcauses CF in people was discovered, followed by theequivalent gene in mice. By artificially creating thedisease in mice, researchers could experiment withnew ways in which to override the faulty gene.Scientists have already learnt how to make workingcopies of the CF gene.

Medicines research is a slow process and it has takenyears of work to find a way to get a working gene intothe body cells where it is needed. Gene therapyoffersus the chance of treating genetic diseases, and aclinical trial is planned to test if gene therapy canimprove lung function in people with cystic fibrosis.Development of this potential treatment has relied onstudies in animals.

Laura Cowell was diagnosed with cysticfibrosis when she was three months old. In2002 Laura decided to speak out to explainthe benefits of animal experiments to peoplelike her.

To control my cystic fibrosis, I takearound 30 tablets and an inhaled medicineevery day. I also have developed diabetesnow, like many people with CF, so I alsoneed two insulin injections a day. Those

medicines have all been tested on animalsso Im very grateful to the people and theanimals. Without them, Id be dead.

Sadly Laura died, aged 25, in June 2011


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Glossary I 19

Allergens substances which trigger an allergicresponse in the body e.g. pollen, dust mites

Antibiotics chemicals which destroy micro-organisms such as bacteria and fungi

Anticoagulants chemicals which prevent the bloodfrom clotting

Cystic fibrosis a genetic disease which causes thick,sticky mucus to build up, mainly in the lungs anddigestive system

Cytotoxins substances harmful to cells, (which can

be used to kill cancer cells)

DNA deoxyribonucleic acid, the molecule whichcarries the genetic information in our cells

Epilepsy a disorder caused by abnormal electricaldischarges in the brain which lead to seizures

Ethical having to do with right or wrong

Ethical review process a system for determiningwhether research is ethical

Gene therapy treating a disease by correcting faultygenes in a patients cells

Haemorrhage an uncontrolled loss of blood

Humanely with kindness

Hypothesis an idea which could explain the knownfacts and which can be tested by experiment to see ifit is accurate or not

Ibuprofen a painkiller and anti-inflammatory

medicine

in vitro literally in glass

Insulin a hormone involved in the regulation ofblood sugar

MHRA the Medicines and Healthcare productsRegulatory Agency, an agency of the Department ofHealth protecting and promoting patient health andpatient safety

Morphine (or alternative) a strong painkiller whichcan only be prescribed by doctors

Pharmaceutical company a company whichmanufactures medicines and carries out research intonew medicines

Pharmacological relating to the study of effects ofmedicines in the body

Post mortem an examination of the body afterdeath

Stroke a sudden reduction in the blood supply to

the brain, usually because of either ahaemorrhage or a clot forming, often causing loss offunctions such as speech and movement on one sideof the body

Synthesised produced using chemical methods

Therapeutic helpful in treating illness

Toxicological relating to harmful substances

Vaccination giving someone a vaccine, a substancewhich stimulates the immune system to recognise andattack specific disease-causing organisms


22/24

Food for thought

Is it right or wrong to use animals to help findtreatments for human illnesses? Would it be right to

deny sick people the chance of a long and productivelife? Should we have vaccines when they have beenresearched and developed in animals? What about

conditions like migraine which are not medicallyserious but can be very distressing? There are many

rights and wrongs to consider in the complex issue ofanimal research, and it is only natural to considerdifferent opinions before forming our own.

FORAnimal research has been and

continues to be essential for

the development of new

medicines

AGAINST

Animal research is not neededto make new medicines

FORNobody wants to use animals for

research but it would be much

worse to let people be ill, in pain

or die unnecessarily

AGAINSTRegardless of the benefits,

animal research is morally

wrong, there is no

justification

FORMost scientists care a great deal

about the animals they use and

animal research is strictly

controlled by law

AGAINSTAnimals are cruelly treated in UK

laboratories. Scientists only care about

their research, not the

animals

FORAnimals and peoples bodies are not exactly

the same but the similarities are enormous

compared to the differences. Provided the

research is well designed and conducted,

animals give essential guidance about

the effects of medicines in people

AGAINSTAnimal research does not help in the

development of medicines for people. Animals

are too biologically dissimilar to give useful

information about the effects of medicines in

people. Whatever your moral position,

animals are not needed...


23/24

Food for thought I 21

Do you believe researchers when they explain thatanimal research is necessary to develop new

medicines? Can we condemn the people who do thiswork on the one hand, and applaud the results of

their work on the other? All of us who have benefitedfrom modern medicine should question every side of

the argument.

FORPrevention is always better

than cure. We should prevent

illness where we can, and treat

it where we cannot...

AGAINSTWe would not need research if

people took better care of

themselves. Prevention is

better than cure...

FORAnimal research gives scientists a good

indication of what to expect in patients, so

that the human studies can be conducted

safely. But even years of these studies

involving thousands of patients cannotguarantee that a medicine is safe

for everyone

AGAINSTAnimal research gives misleading

information, making medicines

look safe when they are not. This is

why medicines have unexpected

side effects

FORWherever non-animal methods give the

necessary information, they are used. The

contribution of these methods is increasing all

the time but it will be a long time, if ever, beforeit will be possible to mimic all the functions

of a complete living body by computer

or in the test-tube

AGAINSTIf scientists really cared about

using alternatives, they would have

already replaced all animal

experiments

AGAINSTWe can find out all we need to know

from careful observation of patients and the

identification of factors which lead to illness,

along with increased use of computers

and cell culture tests....

FORObservation in patients provides

ideas, not answers. Computer and test-

tube research provides some of the necessary

information. In addition, scientists need to

study the effects of a medicine in carefully

designed animal studies. Only then

could doctors justify testingmedicines in people


24/24

Association of the British Pharmaceutical Industry

7th Floor, Southside, 105 Victoria Street, London SW1E 6QTt +44 (0)870 890 4333 [email protected]

ABPI ScotlandCrichton House, 4 Crichtons Close, Edinburgh EH8 8DTt +44 (0)870 890 4333 [email protected]

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2 Caspian Point, Pierhead Street, Cardiff Bay CF10 4DQt +44 (0)870 890 4333 [email protected]

abpi org uk

animal research and human medicine booklet

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