Presidential Perspectives: Thoughts from Professor Sir John Tooke PMedSci

Talking to Dr Geoff Watts FMedSci, Professor Sir John Tooke PMedSci shares his views on biomedical careers, the medical

science ecosystem and the role of the Academy

Presidentialperspectives

The Academy of Medical Sciences

41 Portland Place

London W1B 1QH

+44 (0)20 3176 2150

For further information visit:

www.acmedsci.ac.uk

Registered Charity No. 1070618

Registered Company No. 3520281

Presidents of the Academy of Medical Sciencesspend only a small proportion of their time inthe organisation’s headquarters in London’sPortland Place. But when they are there theyoccupy a small room with floor-to-ceiling glasswalls on two sides offering full exposure toanyone passing along the corridor outside.Architectural metaphors can be overplayed –but besides bringing natural light to a roomthat would otherwise lack it, this literaltransparency signals something aboutcommunication and its importance within theAcademy. The President can see what’s goingon, and the staff know when he’s in thebuilding, what (to a degree) he’s doing, andwhen he can be approached.

To the present incumbent this exposure shouldpresent little problem. Several of the tasksProfessor Sir John Tooke has undertaken duringthe past decade or so will surely haveimmunised him against the glare of public andprofessional visibility. He’s been inaugural deanof the Peninsula Medical School, led the inquiryinto the ill-fated Modernising Medical Careersand, since 2010, served as Vice Provost (Health)at University College London (UCL) and head ofits School of Life and Medical Sciences and itsMedical School. And now, of course, there’s thePresidency as well. None of these jobs iscalculated to appeal to someone who can’t cope with occasional scrutiny.

The scale on which Tooke currently operates isin striking contrast to the literally microscopiclevel at which much of his research was pitchedback in the 1980s. An interest in his principaltopic, microvascular physiology, had originallybeen triggered during an eight week project carried out with an established research groupwhile he was still a student at Oxford. “Thiswas the most engaging part of myundergraduate career,” he recalls. It led to aMedical Research Council (MRC) researchtraining fellowship with scientists in that samegroup. “The work was particularly fascinatingbecause the microscopy techniques we usedallowed you not only to see this living system,but to interrogate it.” ▶

“They are the key resource, they are theAcademy. And they’re tremendously supportivewhen called on to contribute to our foresightand the formulation of our policy and reports.”The evidence of a recent survey, he adds, is that the Fellows are broadly content with thedirection in which the Academy is moving, and with its emphasis on supporting careersand influencing policy to getting the‘ecosystem’ right.

London or southeast domination is a familiarcharge in many areas of the UK’s cultural andeconomic life: one the Academy intends tocounter by increasing its regional activities. As aphysician scientist who spent many years basedin Exeter, Tooke is predictably keen to supportthis intention. “Despite the fact I now work inthe ‘golden triangle’,” he says, “I will notforget that world class talent is also veryevident in our smaller regional centres. It’s onereason I am so keen to see the Academyworking proactively with such centres. I startfrom the position that talent is pretty evenlydistributed across the country, and we need tobe sure we’re exploiting it all.”

This, he adds, is one reason why the Academyhas been keen to promote the concept ofregional academic health science networks.“And we already have a number of regionalAcademy champions to encourage the nextgeneration. We are holding more regionalevents. The tenth anniversary of the mentoringscheme, for example was launched inNewcastle this March.

1 Presidential perspectives Presidential perspectives 2

“I’m very keen that theAcademy doesn’t becometoo ‘establishment’. It has to remain fresh andfuture focussed if it’sgoing to continue making real contributions.”

On the Fellows of the Academy...

insight into the management of a sizeableorganisation. His more recent appointment as aVice Provost at UCL, an even bigger job, isadding still more to that experience. WithTooke at the helm, UCL’s School of Life andMedical Sciences will aim to use inter-institutionalcollaboration and interdisciplinarity as the keydrivers in shaping its future and continuing tomake an impact.

Returning to the Presidency, it’s self-evidentthat ambitions of this kind chime with the aimsand objectives of the Academy - which is whyTooke speaks of his two posts as meshingtogether. That said though, slotting a day ormore a week of Academy work into the UCLjob is not easy. But being based in London closeto Portland Place adds a helpful degree offlexibility. And in the nature of the two posts -they both involve attendance at a lot ofnetworking or representational events, forexample - there can be an overlap betweenthem. “Though I do have to look out forpossible conflicts” he adds.

Reflecting on what the Academy has achievedover the decade or so of its existence gives himencouragement for the future. “It’s donespectacularly well given its relative youth. It’sdeveloped a status and a capacity for influencefar greater than might have been expected inthat time. It’s produced a number ofauthoritative reports that have directlyinfluenced policy, particularly the regulationand governance of health research and hasbecome a respected voice on the developmentof sustainable training and career pathways foracademic medicine and the biomedicalsciences. This means the Academy is listenedto and valued.”

Tooke sees no reason for a radical change ofdirection. “We need to continue our supportfor the next generation of medical scientists,and be very careful that we’re meeting theneeds of the fundamental scientists, as well asthe clinical scientists. But I’m very keen that theAcademy doesn’t become too ‘establishment’. ▶

In 1999 Tooke lead the bid for what was tobecome Peninsula Medical School. “I rathernaively thought I’d do it for three months. We’dbe making the best stab at it we could, andprobably failing.” In fact the bid found favour.“Then we were invited to develop the fullbusiness case and the curriculum. At the time Iwas running a full clinical service and a lab, andI ended up devoting more than a year to thebid process. By that time I was sufficientlyseduced to apply for the job of Dean.” Which he got.

He has no regrets. “It was a fabulous opportunityto think afresh about what medical educationshould be trying to do. Our focus was on thefuture: how to devise something that would beright for the patients of tomorrow, and to startwith that brief rather than coming at it from atraditional educational standpoint.” He alsohad the excitement of building a researchstrategy from scratch.

“I think we met our major objectives in that ourmedical students were and are regarded inrecent surveys as the best prepared in thecountry. And I was pleased, given our standingstart, that we achieved a very respectableposition in the research assessment exercise,and showed we were capable of internationallevel work.”

“The organising principle was that everybodygot together behind two ideas: that the newschool should benefit the health of thepopulation of the south west, and the economyof the south west. To fulfil both of those meantresearch as well as education.”

“There’s still work to be done in ensuringsufficient flexibility in the career pathway toenable people with particular aptitudes to take time out to develop their research skills, and to go abroad and so on.”

Tooke led the independent inquirycommissioned by the Secretary of State forHealth into Modernising Medical Careers.Aspiring to Excellence, his 2008 report on its findings, was highly critical of the system he’d been asked to investigate.

It’s now going in the right direction, he says,“But things haven’t moved as fast as I wouldhave liked in terms of implementation.

There’s general agreement that the principleswe espoused in Aspiring to Excellence are stillrelevant. So why haven’t they been fully implemented?”

He also talks of the Academy’s emphasis onmentoring. “The Academy is renowned for thework it has done on the mentoring scheme.We’ve recently launched a booklet summarisingour experiences to encourage otherorganisations to support mentoring in theirinstitutions. The Academy will also be doingsome very exciting work supported by theWellcome Trust on engaging medical students in research.

Inspecting the fine detail of a capillary networkis far removed from shifting the blocks aroundas you design a new medical school orrestructure a major research institution: so farremoved that you might wonder how a mindattracted to a study of one could be at homegrappling with the other. But Tooke himselfsees no contradiction. While aware of thetransition he’s made, he regards what he doesnow as a natural progression. “What I mostenjoyed about science was the formulation ofstrategies, the generation of ideas, and theanalysis. And of course this is still my job. I’mdealing with uncertainties, identifyingopportunities and marshalling resources.” As Tooke points out, he’s predisposed to afascination with policy and strategy issues: bothkey elements of the Presidential task. “I could

see very quickly how the Presidency meshedwith what I was already doing. When you’reoperating at this level you’re involved in policyissues, concerned about the next generation ofscientists, and facing questions such as whetherwe’re building the right capacity. I learnedthrough my role in the Medical Schools’ Council[he chaired it from 2006 to 2009], and throughthe enquiry into postgraduate medicaleducation and training, about the importanceof establishing the right principles on which tomake policy.”

Tooke did indeed come well-prepared to takeon his role at the Academy. Setting up a newmedical school had concentrated his mind ontraining and research, two of the Academy’scentral preoccupations. It also gave him an

On the current career structure in medicine…

On launching a newmedical school...


encompass both groups should be seen as oneof the Academy’s strengths. “Translation ofbasic discoveries into health gain needs a closeworking relationship and a mutualunderstanding of challenges that those workingat either end encounter. I’m going to try andfuse the Fellowship rather than think of themas separate entities,” he says.

As Tooke sees it, part of the future success ofmedical science, and of the Academy, lies infinding answers to several broad questions thatencompass the way in which 21st Centuryresearch will be conducted. “We have to askhow to promote interdisciplinarity. What are thenew interfaces that we need to be exploring?How do we develop the concept of teamscience? How do we best equip the newgeneration of medical scientists to engage inthose new ways of working?”

To say that Tooke is posing questions about thefuture is not to suggest that he has no answers.Quite the contrary. For example he gives muchthought to what he describes - using the jargonof the topic - as the R&D “ecosystem” in whichnew drugs and devices are developed. “Muchof the focus at the moment is on how best toclose the proof-of-concept gap, the firsttranslational gap. We need a new model whichavoids the massive investment in time andmoney now required to get from a concept to anew therapy.”

To explain more of his thinking on how theAcademy should position itself Tooke outlinessome of the elements of his ecosystem. First,he’s a firm believer in the importance ofunderstanding clinical need as a starting pointfor research. Once a need has been identified ithas to be turned into a research question. Thenyou have to ask yourself whether the questionis tractable with the current state offundamental knowledge. “The cautionaryexample I use is Nixon’s War on Cancer,” hesays. “Vast sums of money were invested at atime when we simply didn’t know enoughabout how cells replicate.” ▶

“I do believe that medical science has to beinformed by patients’ perceptions of need. The example I use in relation to my owninterest, diabetes, is that in the 1920s, wheninsulin was developed, it was initially availableonly by injection at every meal. In the middle of the last century someone decided this wastough on patients, and why didn’t we devisesomething that delayed insulin’s absorption.The legacy of that was 30 years of poordiabetic control, with people having to eatto match the insulin dose they’d taken. Lots of hypoglycaemia.”

“What wasn’t recognised was that far moreirksome to patients than injecting themselveswas the loss of control leading to them fallingover and looking foolish because they’d got ahypo, or having to break off what they weredoing because they had to have something toeat. I was intrigued, as a clinician, when I firstrealised that many patients would much preferto take multiple injections if it enabled them tobehave more like everyone else.”

It has to remain fresh and future focussed if it’sgoing to continue making real contributions.”He adds that care has to be taken about wherethose contributions are made. He says thisbecause the very fact that the Academy hasachieved respect and acquired authority couldtempt it to start entering into too many areas,especially those less central to its main purpose.He offers the example of basic medicaleducation. Its importance in the creation ofnew generations of doctors who mayeventually wish to contribute to medical scienceis self-evident. So the Academy can and doesoffer opinions about how it might be improved.The danger, he says, would lie in trying to takeit on as a major project: in trying to stretchfinite resources further than they’ll comfortablyextend, and in producing a report or policydocument that proved to be insufficientlyconsidered. “We can better extend ourinfluence on such matters by working inpartnership with high calibre likemindedorganisations for which the issue is a morecentral concern”, he says.

Partnership is also the key word when it comesto the Academy’s relationship with industry.Relations between academics and industry havenot always been perfect. But Tooke is bullish.“Industry is now looking to forge closer and novel partnerships with academia,” he insists.“Industry’s changed because it’s acknowledged

that its old way of working was not productiveenough in terms of new drug development.And academia has got itself into a morerealistic space where it’s looking at its broadersocial responsibilities.” Stepped out of the ivorytower, you might say. “I suspect one of thecultural problems in the past was the businessmodel of pharma with the big emphasis onmarketing and blockbuster drugs.” Academics,he thinks, are more comfortable with thesmaller, more personalised approach tomedicines development that’s emerging. “Weneed to encourage people to move seamlesslybetween the academic preserve and thecommercial world. We need to valueentrepreneurial experience and achievement asmuch as we value high quality fundamentalscience qualifications.”

Tooke also believes it essential that theAcademy takes care to meet the needs of theFellowship’s fundamental scientists as well as itsclinical scientists. There is always the danger ofa tension within the Academy between clinicaland non-clinical Fellows. The latter may feelthat clinical issues - not least, at present, theNHS reforms and the attention that has to bepaid to them - tend to predominate. Tooke seesany separation between the two groups asunhelpful and divisive when what needs to bestressed is their interdependency. Indeed, theexistence of a body specifically intended to

On learning from patients…


We also have to become smarter than we arenow at estimating the potential value of a newdrug or device. “In developed nations we’re allaware of burgeoning health care costs. Themajor cost driver is the adoption of treatmentsof marginal incremental benefit. We’recurrently promoting an unsustainable position.So a number of drug companies now arelooking to see how they can identify value at anearlier stage, and feed that back into what theychoose to focus on.

“Commissioners are getting smarter. NICE isdetermining, on the basis of perceived value,what gets used. If we knew what was going tobe bought, investment at the developmentstage of a new drug or technology couldbecome more rational. You could also usedifferent models for getting drugs into society;earlier conditional licensing, for example.”Under arrangements of this kind, patients getnew drugs and devices earlier, and theirdevelopers don’t have to wait so long to see areturn on their investment.

The final element in this innovation ecosystemis implementation: ensuring that peopleactually use the new drug or whatever ithappens to be. For virtually all classes of drugs,he points out, adherence is no better thanabout 60 per cent. Some of this failure isattributable to side effects; more personalisedmedicine should help to overcome thisdeterrent factor. But it also raises the questionof whether the drug is hitting the target thatmatters most to the patient. Back, in otherwords, to where we began: the correctidentification of true clinical need.

So how does he see the Academy slotting intothis broad conception of the researchenterprise? For a start, he says, it can remind allconcerned with research and development inmedicine that this is what the processcomprises, how important it is, and how itneeds to operate. The Academy, he argues, hasthe authority and the perspective to sketch thisblueprint, and do so persuasively. Indeed the

Academy provided valuable input in advance ofthe Comprehensive Spending Review whichresulted in a favourable settlement for the lifesciences and was instrumental in influencingthe Government’s Life Science Strategypublished at the end of 2011. Key to repeatingthis funding success is an emphasis on the roleof the life sciences in the UK economy. “Wehave to promote medical research for thisreason as well,” Tooke argues. “It’s reality.” Thedays when learned bodies like the Academy feltthat worrying about the nation’s economy wasnot part of their mandate are long gone.

Tooke himself can’t say for certain why hechose to enter medicine. Nobody in his familyhad studied it. In retrospect though he thinkshe can pick out a couple of the factors whichshifted his focus from the humanities andtowards the sciences. “My mother had a braintumour when I was about 12 or 13. I was quiteappalled by the slowness of the diagnosis andwhat she had to go through in relationship tothat.” A further factor, at a slightly later stageof his career, may have been the experience ofanother close relative. “He was diagnosed withdiabetes at the age of 21. Again I was prettyappalled by the early management of hiscondition.” He doesn’t assert that these eventsdetermined his career choices; he merely citesthem a possible influences.

The seeds of Tooke’s lifetime preoccupationwith diabetes and its academic explorationbegan to germinate while he was still atOxford. When he eventually entered clinicalpractice and started to appreciate theoverwhelming impact of morbidity andmortality in vascular disease, he realised theextent of the unmet need. “In those days therewas no such specialty as vascular medicine andI began to think how my research interest in themicrocirculation might play into clinicalpractice. That’s how I settled on diabetes as aspecialty.” But it also had other attractions forhim. “I’d be dealing with patients of all agesand with prevention and health maintenance as well as therapy and the complications of disease.”

Tooke did his specialist training in Leeds, then spent a year at the Karolinska Institute inStockholm doing vascular studies on patientswith diabetes. It was very productive, he says.“I was working with vascular specialists -angiologists, as they were then called - in a verydifferent health system, which made mequestion the adequacy of our own. It’senlightening to compare and contrast.”

He returned to the UK in 1984, first as aWellcome Trust Senior Lecturer in Medicineand Physiology at Charing Cross, and then onto Exeter to develop a diabetes service and setup a clinical science division.

He opened a microvascular lab and developed a series of technologies for studying the humancirculation. “The best model for diabeticcomplications is man. There aren’t really goodmodels of these complications.” It was in 1998that the opportunity to bid for a new medicalschool came up, and Tooke began themovement away from hands on research and clinical practice and into academicmanagement, although he remained active inclinical practice until his move to UCL in 2010,and to this day retains research links with Exeter. ▶

Although initially bound to focus on domesticissues, the Academy had begun to developinternational contacts and policies well beforethe end of the first decade of its existence.Under Tooke’s Presidency, this emphasis willcontinue and grow. “At a European level,” hesays, “we must be sure that those policieswhich directly impact on medical science in theUK are favourably developed and interpreted,whether it be the EU clinical trials directive ordata protection legislation. We need to beworking with other European academies toensure that the policy environment is favourable.”

The Academy is in regular touch with itsEuropean counterparts through its ForeignSecretary, and through the Federation ofEuropean Academies of Medicine (FEAM). “Our Academy is relatively well developed and

structured, so inevitably plays quite a lead role.Statements of ours that have an influence bythis route help to determine the crafting of EUpolicy and legislation.”

“We also need to be very alert to how UKimmigration rules affect medical sciencebecause we want to attract talent fromwherever it’s found. Being able to accommodatepeople from overseas is very important toBritish science.”

“We also need to recognise the medical sciencechallenges that have a global dimension. Wemust be alert to issues of global proportion andto emergent threats such as climate change.Our historic links give us a point of contact withmany other countries.”

On international activities...


Work, he claims, is not all consuming. Heenjoys being in London, but admits that fewevenings are free. He still has his house inDevon, and gets there at weekends when hecan, claiming that that’s where he tries to putwork to one side.

Meanwhile, questions for the Academy keep oncoming. “It takes years to develop a skilledworkforce; what are the needs going to be in adecade’s time? Will we have, for example,enough bioinformatics people? Is there a careerpathway for the people who are going to drawall the new data together and synthesise it?What are we doing about regenerativemedicine? What is the future for researchinvolving animals? How are we going to get a good understanding of the potential of genetics?”

His experience at Peninsula Medical Schooland now at UCL, he says again, will stand himin good stead as he leads the Academy throughits second decade.

Although now fully at home in its splendid 18thCentury John Adam townhouse, the product ofa successful fundraising venture, the Academycannot afford to neglect the long termfinancing of its activities. The conference hirebusiness at 41 Portland Place supports the costsof the new premises and provides a modestincome, but any President must be concernedabout the future.

“We run a balanced budget, and a very tightone,” says Tooke. “Our base funding comesfrom a very welcome grant in aid by theDepartment of Health and from Fellowshipsubscriptions. And there’s also commissionedwork. But we have very little in the way offreedom to decide for ourselves to financework that we feel to be important.” Reportsand meetings generally require a sponsor.“I think we could do far more to influence policyin an inventive way were we to have a relativelymodest increase in our uncommitted income.”

On the funding challenge...


On diabetes...

The workloads of his post at UCL and thePresidency of the Academy have forced Tooke’sretreat from lab and clinic; but he’s notforgotten the condition that has dominatedhis career, diabetes.

“It’s rightly been described as the 21st Centuryepidemic. Globally the biggest causes ofmortality in the developing as well as thedeveloped world are now chronic conditions,with diabetes and associated vascular diseasesbeing major contributors.” The roots ofdiabetes, he points out, are multi-dimensionaland range from lifestyle to biology – or acombination of both. “My colleagues in Exeterwere contributors to the discovery of thevariant of the FTO gene that predisposes us to obesity, and that one sixth of us possess.Once the function of that gene is understood, it may turn out to be mediating its effectsthrough satiety.” Successful treatment will quite likely rely not only on drugs, but onbehaviour change.

“One problem with a condition like diabetes,”he adds, “is the tendency to group it alltogether because it’s all characterised by highblood sugar. We’re increasingly learning that it’sactually a heterogeneous disorder, and differentvariants respond differently to differenttherapies. So I see a future where carefulphenotyping and genotyping will provide moreprecise treatment for subsets of what iscurrently viewed as one condition. This offersexciting opportunities for medical science. Itcan draw on the current emphasis on findingtreatments for niche or rare diseases. What we learn here may turn out to be applicablemore broadly.”

He does believe that the scale of the problemposed by diabetes has now been recognised.Hence, for example, the growing emphasis onchildhood obesity. He suggests that theAcademy may have to devote some thought to the provision of more academic effort inpublic health in addition to other branches of medical science.


"Fellows are the key resource,they are the Academy. And they're tremendouslysupportive when called on tocontribute to our foresight andthe formulation of our policyand reports"

Our vision is to improvehealth through research.

Our mission is to promotemedical science and itstranslation into benefits for society.

Underpinning our strategy are six objectives:

• Promoting excellence • Influencing policy to improve health and wealth • Nurturing the next generation of medical researchers • Linking academia, industry and the NHS • Seizing international opportunities • Encouraging public and professional dialogue about

the medical sciences

The Academy's strategy for 2012-16 is available at www.acmedsci.ac.uk

About the Academy

Presidential perspectives 1413 Presidential perspectives

Founded in 1998, the Academy of Medical Sciences is the independent bodyin the UK representing the diversity of medical science. Our elected Fellows –over 1000 - are central to our success. They are drawn from the fundamentalbiological sciences, clinical academic medicine, public and population health,health technology implementation, veterinary science, dentistry, medical andnursing care and other professions allied to medical science as well as theessential underpinning disciplines including mathematics, chemistry, physics,engineering, ethics, social science and the law. It is their knowledge,influence and networks that are the Academy’s most powerful assets. We areone of the UK’s five National Academies and work closely with them and oursister Academies overseas. We are also an integral part of the UK’s strongbiomedical research community, working closely with funders, medicalresearch charities, the NHS and the private sector.

At its core the Academy is:

• A champion for excellent research and researchers • Independent, evidence-based and authoritative in its approach• Proactive in identifying and responding to developments in

health, society, science and policy• Expert and accessible in the information we provide• Committed to partnership and interdisciplinary engagement

Documents

Presidential Perspectives: Thoughts from Professor Sir John Tooke PMedSci