NS Magazine 2012

8
shown that the drug can provide transient improvement in the condition of patients, which was repeated when the drug was readministered. The work at Aston involved MRI and MRS scans of the patient, designed to characterize both the anatomical and chemical damage caused by the stroke. Changes in brain circulation and activity were identified and administration of the drug showed improved circulation in the affected half of the brain. In the field of neurodevelopment, studies were carried out involving two children with rare neurological disorders related to epilepsy. One child’s brain was studied as she conducted certain tasks requiring her to move her fingers whilst being scanned for a recording period of 1 hour. The data from this girl was compared to results from her twin sister. In a second study, EEG and fMRI were used simultaneously on a patient with the epilepsy related disorder, to determine whether the areas of the brain that showed EEG spikes in between seizures also had signal changes due to the blood in that area. Results suggest that certain areas of the brain are connected, but that the Primates are frequently used in brain research and they suffer enormously. There are also fundamental differences between species, so adoption of new techniques in neuroscience is vital. For a decade, we have been funding the neuroimaging group at the Aston Brain Centre (ABC), headed by Professor Paul Furlong, which engages in a wide range of research activities studying human behaviour and brain function. The group works to establish how new techniques may be used to replace animal experiments. Projects include vision, neurodevelopment and clinical research, cognition and pharmacokinetics (drug characteristics). This has put us at the forefront of the drive away from horrific animal experiments in neuroscience. The team examined the effect of a drug, Zolpidem, on a stroke patient. This drug is typically used to treat insomnia and belongs to a class of drugs called sedative- hypnotics. It slows brain activity, allowing the patient to sleep 1 . Zolpidem has previously been reported to have an awakening effect in patients in a persistent vegetative state. It was amongst a few treatments that were shown to “improve the level of consciousness in certain cases” 2 . Several studies have NEW SCIENCE Lord Dowding Fund for Humane Research ADVANCED TECHNIQUES: News from the world of research without animals ISSN: 2042-9576 connectivity patterns from these areas suggest that the functions leading to the condition extend beyond these particular areas of the brain. One particularly intriguing study, another that could not possibly be conducted in animals with any reliability in animals, involves the differences in the brain when participants are critical or reassuring towards themselves. Self criticism has been strongly correlated with a range of conditions such as depression, anxiety and eating disorders, and “self-reassurance” is inversely associated with the same conditions. As little is known about the neurophysiology of these internal processes, the group used a new fMRI task to investigate. Results indicated self criticism was linked to activity in the areas of the brain which are connected to error processing and resolution, and behavioural inhibition. Self- reassurance was linked to the brain areas responsible for compassion and empathy towards others. This work is useful for showing the neural basis for certain mood disorders. This is the type of work that cannot be carried out on animals, and shows the elegance and real scientific relevance of these cutting edge technologies. 1. (http://www.nlm.nih.gov/medlineplus/druginfo/meds/ a693025.html - accessed 27/10/10); 2. Georgiopoulos, M. et al (2010) “Vegetative state and minimally conscious state: A review of the Therapeutic Interventions”, Stereotactic and Functional Neurosurgery, vol.88, pp.199-207 Human brain studies AP P E AL: We n eed to r a ise £50, 000 to s u s tain this projec t in 20 12

description

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Transcript of NS Magazine 2012

Page 1: NS Magazine 2012

shown that the drug can provide transientimprovement in the condition of patients,which was repeated when the drug wasreadministered.

The work at Aston involved MRI and MRSscans of the patient, designed tocharacterize both the anatomical andchemical damage caused by the stroke.Changes in brain circulation and activitywere identified and administration of thedrug showed improved circulation in theaffected half of the brain.

In the field of neurodevelopment, studieswere carried out involving two children withrare neurological disorders related toepilepsy. One child’s brain was studiedas she conducted certain tasksrequiring her to move her fingers whilstbeing scanned for a recording periodof 1 hour. The data from this girl wascompared to results from her twinsister.

In a second study, EEG and fMRI wereused simultaneously on a patient withthe epilepsy related disorder, todetermine whether the areas of thebrain that showed EEG spikes inbetween seizures also had signalchanges due to the blood in that area.Results suggest that certain areas ofthe brain are connected, but that the

Primates are frequently used in brainresearch and they suffer enormously.There are also fundamental differencesbetween species, so adoption of newtechniques in neuroscience is vital.

For a decade, we have been funding theneuroimaging group at the Aston BrainCentre (ABC), headed by Professor PaulFurlong, which engages in a wide range ofresearch activities studying humanbehaviour and brain function. The groupworks to establish how new techniquesmay be used to replace animalexperiments. Projects include vision,neurodevelopment and clinical research,cognition and pharmacokinetics (drugcharacteristics). This has put us at theforefront of the drive away from horrificanimal experiments in neuroscience.

The team examined the effect of a drug,Zolpidem, on a stroke patient. This drug istypically used to treat insomnia and belongsto a class of drugs called sedative-hypnotics. It slows brain activity, allowingthe patient to sleep1.

Zolpidem has previously been reported tohave an awakening effect in patients in apersistent vegetative state. It was amongsta few treatments that were shown to“improve the level of consciousness incertain cases” 2. Several studies have

NEW SCIENCELord Dowding Fund for Humane Research

ADVANCED TECHNIQUES: News from the world of research without animals

ISSN: 2042-9576

connectivity patterns from these areassuggest that the functions leading to thecondition extend beyond these particularareas of the brain.

One particularly intriguing study, anotherthat could not possibly be conducted inanimals with any reliability in animals,involves the differences in the brain whenparticipants are critical or reassuringtowards themselves. Self criticism has beenstrongly correlated with a range ofconditions such as depression, anxiety andeating disorders, and “self-reassurance” isinversely associated with the sameconditions. As little is known about theneurophysiology of these internalprocesses, the group used a new fMRI taskto investigate.

Results indicated self criticism was linked toactivity in the areas of the brain which areconnected to error processing andresolution, and behavioural inhibition. Self-reassurance was linked to the brain areasresponsible for compassion and empathytowards others. This work is useful forshowing the neural basis for certain mooddisorders.

This is the type of work that cannot becarried out on animals, and shows theelegance and real scientific relevance ofthese cutting edge technologies.1. (http://www.nlm.nih.gov/medlineplus/druginfo/meds/a693025.html - accessed 27/10/10); 2. Georgiopoulos, M. et al (2010)“Vegetative state and minimally conscious state: A review of theTherapeutic Interventions”, Stereotactic and Functional Neurosurgery,vol.88, pp.199-207

Human brainstudies

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ject in 2012

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New Science l 20122

or language) to the implementation ofalternative methods, if available.

� To identify, where necessary, the

cause of gaps in the provision ofalternatives.

Countries were selected for the survey inorder to give a good mix of geography,developing vs. developed countries andlanguages. Those chosen were the UK,France, Germany, Spain, Italy, Poland,Holland, Slovenia, Czech Republic andthe Republic of Macedonia.

A search was then conducted to identifycourses that contained components ofphysiology or pharmacology, especiallyvia practical laboratory classes. Thenumber of institutions contacted in eachcountry ranged from 3 to 52, with a totalof 294 contacted. Each was invited tocomplete the questionnaire, which hadbeen translated into their language inorder to maximise the response rate andensure clarity. Follow-up emails andtelephone calls were made.

The main findings

The average number of animals usedper institution was calculated, althoughthe low number of responses from theEastern European countries made validcomparisons difficult. However,Romania was found to have the highestaverage of 110.8 animals, followed byFrance with 68.6 andSpain with 48.2.

Of the westernEuropean

For almost thirty years, the LDF hassupported and promoted thereplacement of the use of animals inlife science education. We believethat in order to change the culture ofanimal use in industry, sciencegraduates need to learn usingadvanced techniques, rather thananimals.

As part of this ongoing work, wecommissioned a survey of the use ofanimals in higher education in Europe,which was carried out by Dr AkikoHemmi and Professor David Dewhurst,of the University of Edinburgh.

Aims and objectives;

� To establish the level and extent of

animal use in higher education inuniversities in ten European states.

� To ascertain the level of awareness of

alternatives to animals and theimplementation of these alternatives.

� To identify those courses in which

animals are used and to correlate thisto the available alternatives, thusidentify any gaps in provision.

� To identify any barriers (such as cost

Survey on animal use and alternativesin higher education in Europe

HELPING LDF

YOU CAN

HELP end

animalresearch

In these hardeconomic times,it is moreimportant thanever, that wecontinue thework of the LordDowding Fund.

The Fund issaving animalsfrom researchwhile it alsoprovides theworld withadvancedscientific

techniques – good for bothanimals and people.

Countless animals have beensaved, and more can be done.

By next year, our work with theEuropean and UK parliaments willhave produced new rules to ensurethat non-animal scientifictechniques are given more weightin the research decision-makingprocess.

So it is important to redouble ourefforts. The replacement of the useof animals in research with moresophisticated methods isundoubtedly the proposition thathas been the most effective inpersuading the scientific communityto end animal use.

Our steady progress over the pasttwenty nine years must continue.

YOUR DONATION CAN HELP US

We urgently need donations tocontinue our current researchprojects, as well as to expand

our work, bringing closer the daywhen animal research issomething of the past.

Please support the work of theLord Dowding Fund

www.ldf.org.uk

New ScienceISSN: 2042-9576 published by The Lord Dowding FundMillbank Tower, Millbank, LONDON, SW1P 4QPTel: +44 (0)20 7630 3340 e-mail: [email protected] web: www.ldf.org.uk

©2012 LDF. All rights reserved. No part of this publication maybe reproduced for commercial purposes by any meanswhatsoever without the written permission of the LDF.

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Human mirror neuronsrecorded for first timeResearchers at the Ronald Regan UCLAMedical Centre in the US have recordedthe neurons in the brain that fire whenwe perform an action, or see othersdoing the same. The “mirror neurons”were recorded directly for the first time inhumans during research involving 21consenting patients undergoing treatmentfor epilepsy1. Single cell recordings areusually taken in animals, often primates.The current research discovered “twoneural systems where mirroring responsesat the single-cell level had not beenrecorded previously, not even inmonkeys”1.

EU super computerThe Partnership for AdvancedComputing in Europe (PRACE) is aninternational non-profit association,enabling European researchers toaccess super fast computers located inother countries2. The PRACEinfrastructure will allow the investigation ofthe way drugs interact with the humanbody and protein folding, for example. Itcould also help to gain knowledge abouthow to increase blood flow in cardiacdisease, potentially predicting heart attacksand preventing deaths3.

Inhalation testsScientists are working to createtechnologically advanced alternativesto replace animals in inhalation studies.The results will be useful in drugdevelopment for humans.

Biological engineers at Harvard Universityhave created a “microsystem” whichmimics activity between the alveoli sacs ofthe lungs and their connected capillaryblood vessels. the scientists haveconstructed the model in such a way that itis possible to apply a “cyclic mechanicalstrain” to the cells which mimics breathingin the whole lung4.

The researchers believe the new “lung-on-a-chip” model and other micro-devicesmay “expand the capabilities of cell culturemodels and provide low-cost alternativesto animal and clinical studies for drugscreening and toxicology applications”.

1. http://www.sciencedaily.com/releases/2010/04/100412162112.htm accessed 5/11/10; 2. http://www.ehealthnews.eu/research/2110-european-commission-welcomes-launch-of-supercomputing-infrastructure-for-european-researchers accessed 4/11/10; 3.http://europa.eu/rapid/pressReleasesAction.do?reference=IP/10/706&format=HTML&aged=0&language=EN&guiLanguage=en accessed4/11/10; 4. Huh, D et al (2010) “Reconstituting Organ-Level LungFunctions on a Chip” Science, vol. 328, pp: 1662 - 1668;

New Science l 2012Lord Dowding Fund for Humane Research 3

ANIMAL USE IN EDUCATION

universities the UK had the third highestaverage levels after France and Spain.Underlying these figures is the fact thatSpain uses the highest number ofmammals, and the UK the highestnumber of amphibians.

The UK showed a staggeringly high useof guinea pigs relative to other countries,with an estimate of over 400. The nexthighest figure for guinea pigs wasFrance, with 11. According to ProfessorDewhurst “this fits with the guinea pigileum preparation being the mostfrequently used in teachingundergraduate pharmacology” in the UK.

The top three reasons why institutionsdid not use computer-based resourceswere identified as:

1. Difficulty in finding resources.

2. Lack of money.

3. Available resources did not meet specific learning objectives.

In Germany and Spain, the “lack ofcapacity to create resources in-house”was reported as an issue and in Italy thebarrier was cited as “the lack of supportfrom their institutions and/or colleagues”.Three of the four Eastern Europeancountries found that the cost of theprogrammes was a barrier to use.

Positively, a number of factors thatwould persuade academic staff tointroduce alternatives were identified.These included “published evidence

of effectiveness” and“recommendation from acolleague”.

Interestingly, in the WesternEuropean institutions the students’objections to animal use was “aserious driver”, whereas in theEastern European countries thiswas a lower priority than savingmoney. Thus in some countries,

moral objections may not besufficient to reduce animal use if it isperceived that the alternatives are moreexpensive.

It was noticeable that some institutionschose to remain anonymous, making itdifficult to obtain accurate data andcalculate response rates. This may have

been because the questionnaire wasperceived as being the “thin end of thewedge” to abolishing animal use ineducation. However, the authors believethat “the study has made a significantfirst step in this area and possiblyrepresents the most comprehensivesurvey carried out to date”.

As expected, mice and rats were themost common mammalian species usedfor teaching, although Macedonia andSpain were the only countries to reportthe use of dogs. Of the non-mammalianspecies, amphibians were most used;possibly to teach nerve and musclephysiology.

Language was reported by somerespondents to be a barrier. This showsthe importance of making foreignlanguage versions of these programmesavailable, especially if they are free orlow cost and there is published evidenceof their effectiveness.

It is hoped that eventually no animals willbe used in teaching. Alternatives arecertainly available and were reported asbeing used to replace animals at highlevels in Spain and at low levels inFrance and Italy. The authors concludedthat the “reported use of alternatives inUK universities (35%) is disappointing”.

This study shows that despite successesthere remains much to do to ensure thatalternatives to animals in education areactually implemented. Step one isdeveloping the alternatives but it is vitalto maintain the pressure to ensure theiruse. This study has provided vitalinformation for our drive to end the useof animals in education.

Survey on animal use and alternativesin higher education in Europe

Above: Dr Akiko Hemmi, of the University of Edinburgh

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This is not the case when using animaltissue.

Another programme is the “LangendorffHeart”. This is interactive and simulatesexperiments that may be performed onthe isolated perfused mammalian heart.The program covers the effects ofvarious different classes of drugs and theeffect of ions. The simulated data arederived from actual experimental data.

An independent review of theLangendorff heart programme stated that“The handling of the program is easyand its appearance attractive…Thisresource is suitable for the totalreplacement of an animal lab, thusoffering a solution to the difficultiesinvolved in running the animal lab.”

In order to make these excitingalternatives to animal use available tostudents across the world many topicshave been translated into languagesincluding Chinese, Spanish, Ukrainian,Romanian and Lithuanian.

work and the unnecessarysuffering caused by theexperiments which thissoftware seeks to replace.

The guinea pig ileumprogram simulates an isolatedpreparation of the guinea pig ileum. In

the animal model, this is tissuethat has been removed fromthe guinea pig prior to itsdeath. The aim of this practicalis to explore the effect ofdrugs and electricalstimulation on the release of,and response to,neurotransmitters in thenervous system in theintestine.

The computer simulationenables a range of

drugs to be used, alone or incombination and over arange of doses. In additionthe effects of electricalstimulation can bedetermined. A “magic” washfacility allows the model tobe instantly cleaned of allprior traces of drugs, andfurther experiments to beconducted, thereby speedingup the learning process.

For a quarter of a century, LDF hasfunded David Dewhurst in his work todevelop and refine software packagesto replace animal use on physiologyand pharmacology courses.

Not only does this ensure that thestudents’ learning experience is humane,

teaching them to use advancedtechniques rather than animals, but italso allows the students more flexibility.If a mistake is made when using ahumane method, or the student wishesto change a variable, they can simplystart the procedure again.

Professor Dewhurst’s work replacesseveral experiments and procedures inteaching. It is useful to look at these inorder to appreciate the magnitude of this

25 years of replacinganimals in education

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The RECAL guinea pig ileum simulation.

Transducer

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Stimulation Off

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Synapse

pre-synaptic post-synaptic

Diagram detailing the experimentapparatus in the RECAL guinea pigileum simulation.

Inset: RECAL 3D cross section ofguinea pig ileum.

Alternatives havebeen implementedin about a third ofUK Universities.But, despite aquarter of centuryof effective use,two thirds ofuniversities in theUK continue touse animals suchas guinea pigs. Itis vital thatpressure beincreased toensure thatalternatives areused.

Right: Diagram of aneuron showing aclose-up of thesynapse.

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Ileum Cross-section 3D Serous Coat

Longitudinal Muscle

Circular Muscle

Mucous Coat

MuscularisMucosae

Submucous Coat

Meissner’s Plexus

Auerbach’s Plexus

New Science l 2012 Lord Dowding Fund for Humane Research4

LDF PROJECT: EDUCATION

APPEAL: We need to raise £ 20,250 in 2012

to continue this important cancer research

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EXPERT OPINION

representative of the original tumour. Theteam have obtained samples of bothnormal and tumour containing breasttissue, and successfully cultured thesamples for up to 7 days. These havebeen treated with different doses of twocommon breast cancer drugs.

The models will be validated againstpublished data, to show that they providedata comparable with those observed inanimal experiments, and thus are viablereplacements.

New Science (NS): Describe a “typicalday” at the Aston Neuroimaging suite.

The work is varied but is roughly dividedbetween fundamental research,(exploring brain responses in healthyvolunteers) and our clinical researchwork (studying brain function in patientsreferred to us by NHS consultants). Twodifferent brain scans are performed forboth fundamental and clinical research;MRI or MEG based scans.

At the Aston MRI Centre we scan firstlyto obtain a high resolution brain imagewhich we can reconstruct in threedimensions, but also to then obtain vitalinformation about how the brainprocesses information. This is oftenachieved by projecting information orstimuli to human volunteers whilst theyare in the scanner.

Another type of scan we perform isMEG, where we detect brain waves,generated by brain cells. We can create‘virtual electrode’ data, which canreplace some types of invasivelyimplanted brain electrodes.

By merging MRI and MEG scans, wegather a tremendous amount of valuableinformation about how the brain isworking, helping us understand brainfunction in healthy volunteers as theyprocess information.

NS: Outline one use of animals thatcould be replaced today with non-animal methods.

In the field of behavioural neuroscience,primates are trained to respond to astimulus in order to study brain cellchanges associated with their responseand behaviour. In many cases I believethat the questions could more effectivelybe studied non-invasively usingneuroimaging techniques, especially withpain research, where human cognition isa vital factor in understanding theresponse to pain and analgesia.

NS: What are the advantages of usingnon-animal methods inneuroimaging?

Most importantly, human studies inhealth and disease are directlytranslatable to the human condition. Thisis vital if we are to truly understand theunderlying causes of mental illness andmany conditions that do not naturallyoccur in animals and are often artificiallyinduced to mimic symptoms and signs.

NS: Can you envisage a time whenanimals will not be used in medicalresearch? What, if anything, iscurrently preventing this happening?

I believe that eventually animals will notbe used in medical research because

alternatives will offer the most effectiveand productive data for treatment ofhuman illness and disease. There arealready compelling alternatives which willbe refined and improved over time.

Seeking alternatives needs to be astrategic priority, with appropriateresources in place. Establishment of theNC3R in the UK was a step in the rightdirection, although resourcing and scopeof action are relatively modest.

Government strategy and policy needs toput pressure on our commercial partnersin the pharmaceutical and cosmeticsindustries to make animal alternativestrategies viable and ultimatelyfinancially attractive. Financialconsiderations remain the greatestobstacle to progress in my view.

NS: What do you think neuro-imagingwill be like in 25 years time?

It would be wonderful to think that ourtechniques will be in the forefront ofscreening for developmental disordersand brain disease. Together with genescreening and gene therapy, that infantsand young children could be scanned toaid profiling for the likelihood of diseasesin later life, and preventative therapiesused to eradicate many of the braindisorders and mental health issues thataffect so many people today.

Paul Furlong, Professor of Clinical Neuroimaging atAston University, in conversation with New Science. Professor Paul Furlong, MPhil., PhD. and his group have published 36 high impactinternational peer reviewed journal articles and presented work at over 25 Internationalneuroscience conferences during their preceding 5 year funding period. LDF has nowgranted Professor Furlong funding until 2015.

In 2010, we awarded a grant to DrDebbie Holliday and her team at theLeeds Institute of Molecular Medicine tovalidate and test therapeutics in a novel,all human, model of breast cancer.

Breast cancer is a complex disease withseveral different molecular alterationsinvolved in its development andprogression. A comprehensive approach,taking this into account, is required toimprove the efficacy of target-basedtherapy in breast cancer. None of theabove can be easily or accuratelyreplicated in animal models.

The primary aim of the project is tovalidate two novel in vitro models of

breast cancer; a 3D

cell culture model and a tissue slicemodel.

The 3D cell culture breast cancer modelis the first to contain the 3 majorepithelial (lining) and stromal (connectiveand supporting) components of thebreast. The group have now extendedtheir model, to include human ductalbreast epithelial tumour cells, which formspheroid structures in culture similar tostructures seen in breast tissue. Dataproduced so far is encouraging, andconfirms that the 3D model is a goodrepresentation of living breast tissue.

The tissue slice model allows thevalidation of the 3D culture model,ensuring that it retains characteristics

Human model for cancer research

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Lord Dowding Fund for Humane Research6

The LDF is funding Professor GeoffPilkington at the University ofPortsmouth for his brain tumourresearch. We recently asked ProfPilkington about the difficulties hehas faced in obtaining tissue forstudy.

Prof Pilkington has been researchingbrain tumours for over 35 years and inhis view, in order to progress scienceand research at a sufficient pace to savelives, the system for tissue donationneeds to change.

Firstly, there are strict regulations on theuse of human tissue. The Human TissueAuthority (HTA) is an independentstatutory regulator, sponsored by theDepartment of Health. The HTA licencesorganisations that store and use humantissue for research, teaching, postmortems or treating patients andapproves the use of organs and bonemarrow for transplants1.

The Human Tissue Act 2004 (HT Act),which covers England, Wales andNorthern Ireland, is the regulation thatgoverns the removal, use and storage ofhuman tissue. Scotland is covered by the

Human Tissue (Scotland) Act 2006.

The HT Act also makes it unlawful tohave human tissue with the intention ofanalysing the DNA without the donor’sconsent.

The red tape

The HTA code of practice relates directlyand solely to research, and licencesorganisations that store human tissue forresearch.

There are different rules regarding tissuefrom the living and the deceased. Tissuetaken from a patient for diagnosis, andthen stored in a diagnostic archive canbe valuable in research, but can only bereleased when the following conditionshave been met:

� The patient has given consent for use

of their tissue in research; or

� The tissue will be released to the

researcher in a non-identifiable form;and

� The tissue will be used in a project

that has been approved by arecognised ethics committee (REC).

The guidance also states that “Ethicalapproval can only be given by arecognised research ethics committee”.This being either an REC operating tostandards issued by the UK Healthdepartment, or an ethics committeerecognised by the United KingdomEthics Committee Authority (UKECA) toreview clinical trials of certain products .

If the researcher intending to use thetissue is a university researcher, thesituation is slightly different in that “Auniversity ethics committee is not, for thepurpose of consent exception consideredto be a recognised research ethicscommittee. Therefore consent is stillrequired for tissue to be used in aresearch project approved by auniversity ethics committee, even if ituses tissue from the living and theresearcher is not in possession, and isnot likely to come into possession, ofinformation identifying the participant” 2.

Professor Pilkington comments that thesystem of applying for ethical clearanceto use tissue is cumbersome and, ratherthan increasing the availability of tissueand thereby the amount of research thatcould be conducted with it, it actuallyhampers such research. This leads tofrustration, not only to researchers butalso to those who wish to donate tissuefor research, and their clinicians.

Professor Pilkington explained to NewScience the complexity of the on-lineforms and the periodic reviews of ethicalclearance which take up time. He isregularly contacted by patients whowould like their tissue to be used inresearch to save lives, but he has toinform them that this is unlikely - he musthave separate ethics clearance for eachhospital from which he is to receivetissue. If that ethics clearance is not inplace, even if the patient wishes todonate their tissue, Professor Pilkingtonwould be unable to accept it.

In his words, this is leading to "around99% of all brain tumour tissue, whichcould be used in research, beingdiscarded". He also points out that "Thissystem is not helping patients, cliniciansor researchers, and it isultimately wasting time andhampering our research".He would like to see "thesystem being replaced withan opt-out, where tissue,which is removed duringsurgery and will bediscarded, wouldautomatically go toresearchers who could useit in their research. Ifpatients were unhappy withthis, they could opt out ofthe system".

Professor Pilkington wouldalso like to see theanonymisation of samplesremoved, giving researchers

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The metastasis of a cancer cell (green) into a donated human brain cell (red).

One of the best ways to research human disease is to use human tissue and cells. This can beeither in living subjects or donated tissue, which might be given after removal during surgery, ifsurplus to requirements. In legal terms human tissue is defined as “material that has come from ahuman body and consists of, or includes, human cells”.

Above: A capsularocular bag, from ahuman donor, withan intraocular lensimplanted as usedin project carriedout by Dr. MichaelWormstone at theUniversity of EastAnglia.

Right: Brain cells,from a humandonor, used in Prof.Geoff Pilkington’sproject at theUniversity ofPortsmouth.

TISSUE DONATION

Tissue banks and ethical clearanceTissue banks and ethical clearance

APPEAL: We need to raise £37,739 to sustain

our brain tumour research project in 2012

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New Science l 2012Lord Dowding Fund for Humane Research 7

access to patient information that mayhelp with research. This would also allowpatients to follow the progress of theirtissue in the laboratory.

How to donate tissue

The HTA advise that “If you want yourtissue to be used for any medicalresearch, or you may want it to be usedonly for specific types of research, it isimportant that you make these wishesclear to the healthcare professional whoseeks your consent, and that they arestated in writing on a consent form.However, you should be aware thatsome tissue establishments may not beable to use your tissue at all if youimpose very specific requirements for itsuse” 3.

Tissue and Brain Banks

The HTA also note that people who areon the NHS organ donor register havenot consented to their tissue being usedafter their death for research, although itmay be possible for someone to do both,should they wish to3.1. http://www.hta.gov.uk/aboutus.cfm - accessed 12/11/10; 2. HTA Code of Practice 9 – Research http://www.hta.gov.uk/legislationpoliciesandcodesofpractice/codesofpractice/code9research.cfm - accessed 02/11/10; 3. http://www.hta.gov.uk/donations/howtodonateyourtissueforresearch.cfm - accessed 11/11/10

Below: Threealginate constructs,seeded with humancells, prior toultrasoundexperiments.

Tissue banks and ethical clearanceTissue banks and ethical clearanceLDF PROJECT: CARTILAGE REPAIR

In the UK, around 10,000 people ayear suffer with cartilage damagesignificant enough to requiretreatment. The treatment for cartilagedamage currently includes supportivebraces, physiotherapy, painkillers andpossibly surgical intervention.However, due to a lack of bloodsupply to cartilage, it can take aconsiderable amount of time to healand regain normal function1.

Recent studies have examined the useof therapeutic ultrasound, involving highfrequency mechanical vibrations, as apotential tool for repairing cartilagedamage. The healing properties of thismethod have been beneficial in treatingbone fractures, repairing themsignificantly faster than normal.Ultrasound has therefore recently beeninvestigated as a possible treatment forthe enhanced cartilage regeneration.

Unacceptable animal studies have beencarried out in order to prove the efficacyof ultrasound therapy as a healing

method. These have included dropping a500g weight, from a height of 35cm, ontothe legs of rats, themselves weighingonly 300-500g. In another study this timeto assess the effects of low-intensitypulsed ultrasound on cartilage repair,106 rabbits had their legs damaged. Theanimals underwent surgery involving theopening up of both their hind limbs andthe drilling of the femurs, throughcartilage and bone, creating a 3.2mmdiameter and 5mm deep defect.

Drs Vehid Salih and Jamie Harle, ofthe Eastman Dental Institute and theUniversity of Liverpool respectively,have completed their LDF fundedproject, which aimed to advanceknowledge regarding the healingeffects of ultrasound on damagedcartilage without the unethical andunnecessary use of animals in thesepainful experiments.

The innovative, multi-disciplinary projectestablished a three dimensional cellculture model for cartilage, free fromanimal-derived products, in which toinvestigate the therapeutic effects of

ultrasound. By combining the expertiseof the scientists in biomaterial science,cell biology and ultrasound technology,they optimised the tissue constructcomponent of the project while perfectingthe ultrasound equipment for the study.

This project has established analternative to animal experiments forinvestigating the effects of ultrasoundtherapy on cartilage. The model wasdesigned to be simple to manufacture,with good biocompatibility andmechanical integrity. The early workconducted in this project was presentedat an International Biomaterialsconference in September 2009 (SeeNew Science 2009).

Looking to the future, and encouragingyoung scientists to adopt humanemethods of research, Dr Harle is also aScience, Technology, Engineering andMathematics Network (STEMNET)ambassador for the North West ofEngland. In this role, Dr. Harle discussedthe LDF work in the context of the

replacement of animals with school andcollege students interested in careers inscience, medicine or related subjects. Inaddition, the postgraduate students whoassisted with the project using non-animal derived products, will go on tocarry out PhD and MSc work which it isexpected to include these materials andmethods, helping to establish a newgeneration of humane scientists.

Cartilage repair

1. http://www.nhs.uk/Pages/Preview.aspx?site=Cartilage-damage&print=634248319918443869&JScript=1 - accessed08/11/10

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