Prognosis issue 7

The periodical of the Harley Street Medical Area Issue 07 / 2020

Good pharma How the role of the pharmacist is changing to meet current needs HIV positivity The significant changes seen in recent years in approaches to HIV CAR T cell therapy A new form of immunotherapy that could revolutionise cancer treatment Intelligence community The potential of AI to improve drug development and diagnostics

The Harley Street Medical Area (HSMA) is located in Marylebone, in the heart of central London. It is a collective of world class healthcare providers with a reputation for medical excellence.

It benefits from a central London location that attracts millions of London, UK and international visitors every year, but it also has the additional benefit of being part of the desirable local neighbourhood of Marylebone Village.

@HarleyStMedArea #HSMA

HSMA’s reputation for medical excellence, innovation and patient experience has grown significantly over recent years, as has its contribution to the UK medical sector and the wider economy. This is a prestigious location for any healthcare provider or medical practice.

The Howard de Walden Estate is the landlord for a large proportion of the medical properties that sit within the Harley Street Medical Area.

To find out more about this acclaimed medical area please visit harleystreetmedicalarea.com

Harley Street Medical Area

harleystreetmedicalarea.com

Prognosis is owned by The Howard de Walden Estate 27 Baker Street London W1U 8EQ 020 7580 3163 hdwe.co.uk

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34 HIV positivity Recent developments in the treatment of HIV have been cause for much hope, but there is still work to be done in the fight against the disease

Estate contact Annette Shiel annette.shiel@hdwe.co.uk Publisher LSC Publishing 13.2.1 The Leathermarket Weston Street London SE1 3ER lscpublishing.com Editor Mark Riddaway mark@lscpublishing.com Deputy editor Viel Richardson viel@lscpublishing.com Assistant editor Clare Finney clare@lscpublishing.com Managing editor Ellie Costigan ellie@lscpublishing.com Editorial desk 020 7401 7297 Advertising sales Donna Earrey 020 7401 2772 donna@lscpublishing.com Contributers Jean-Paul Aubin-Parvu, Jessica Brown, Sasha Garwood, Orlando Gili, Christopher L Proctor Design and art direction Em-Project Limited 01892 614 346 mike@em-project.com Printing Warwick

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With an algorithm, there are so many areas where things can go wrong, fatally compromising the accuracy of the predictions. If you train the algorithms with faulty data, or choose data that reflects your own cultural or scientific biases, you can build in biases which can end up being amplified

04 Collective strength Simon Baynham of The Howard de Walden Estate on how the depth and quality of the Harley Street Medical Area’s offering has reached new heights 09 News New arrivals, developments and events 10 Crystal ball The evolution of the treatment of mitral prolapse 11 Harley Street hero Thomas Richard Allinson 12 How does it work?

DEXA scan 14 Thinking aloud The thoughts of Dr Ian Nnatu, consultant psychiatrist at The Priory Group 16 Profile of a pathogen Cytomegalovirus 18 How to...

Treat floaters 20 A day in the life Elisa Pirotti, physiotherapist at Isokinetic London 24 Beaming in Advanced Oncotherapy comes to Harley Street 26 Second opinion Has the growth of the medical ‘direct to consumer’ genetic testing industry been a positive development?

28 The big interview Professor Jackie Hunter on the vast potential of artificial intelligence 34 HIV positivity What are the current priorities for medics working on the frontline of HIV treatment, and where do we go from here?

42 Good pharma The changing role of the pharmacist 48 Q&A Professor John Gribben on CAR T cell therapy 52 Patient experience A woman whose life was changed by a foot operation she’d spent decades avoiding 56 Delivery driver The life and legacy of Grantly Dick-Read

60 My Marylebone Sandra Price of Price’s Back Clinic 62 What’s on Cultural events near the Harley Street Medical Area 63 Five Places in Marylebone to enjoy a bowl of soup 64 The guide Marylebone memorial sculptures

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At a time when many women wanted more access to painkilling drugs in childbirth, Dr Dick-Read was decrying the ‘interventionist’ practices of modern medicine and suggesting they should have none at all

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COLLECTIVE STRENGTH Simon Baynham, property director of The Howard de Walden Estate, on how the depth and quality of the Harley Street Medical Area’s offering have expanded thanks to an influx of impressive providers

If, today, a group of forward-thinking experts started planning a modern medical campus from scratch—and right now, around the world, that is exactly what many governments and wellfunded private institutions are doing—it is highly unlikely that it would end up looking much like the Harley Street Medical Area (HSMA), from the outside at least. The usual starting point would probably be a large expanse of unused space—empty fields or barren desert— from which could emerge vast blocks of medical accommodation, associated hotels and a multitude of parking spaces.

There is very little chance that anyone would instead choose as their location a tight grid of inner city streets, lined with period buildings. But despite the challenges caused by its picturesque and highly regulated central London setting,

the HSMA is managing not just to keep up with the glass towers and open spaces of the world’s new generation of out-of-town medical mega-complexes; it is, certainly in the depth and quality of its medical offering, beginning to lead the way.

For well over a decade, in our role as the landlord and steward of the HSMA, The Howard de Walden Estate has been focussed on slowly improving the area’s buildings and infrastructure, creating a strong and widely recognised HSMA brand and shaping a cohesive community of providers. In recent years, the hard work that was done to maximise the area’s appeal to world class operators, while actively seeking out the very best specialists to fill any gaps in the overall offering, has led to a dramatic step-

change in the HSMA’s global profile. There have long been world class hospitals here—The London Clinic, King Edward VII’s Hospital and HCA among them—but the flow of new arrivals in the past few years means that these stalwarts now find themselves part of an increasingly impressive collective, unmatched anywhere else in the UK and far beyond.

Not long ago, it would have seemed ambitious beyond reason for us to presume that the HSMA could be home to both the Mayo Clinic and Cleveland Clinic—the USA’s two highest performing and most forward-thinking non-profit academic medical centres—yet here they are. As part of a wider collaboration with the University of Oxford, Mayo Clinic has opened a screening and diagnostics centre on Portland Place, and Cleveland Clinic has chosen to locate its diagnostic

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Nobody planning a modern medical campus from scratch would come up with anything that looks quite like the HSMA, but they would definitely hope to emulate the professionalism, resourcefulness and expertise found in the parts of it that really matter: the parts where patients and medical professionals come face to face

and outpatient facility, where most patients begin and end their treatment journeys, on the same wide Georgian street—the latter is due to open in October 2020. Similarly, one of Germany’s most respected hospital groups, Schoen Clinic, chose the HSMA as the site for the first clinic it has built outside of its home country, which opened last year.

From closer to home, some of the biggest and most respected names in British medicine have either arrived recently or are on their way. Royal Brompton & Harefield Hospitals and Moorfields Eye Hospital have both set up private facilities here, and they will be joined in 2020 by the private arm of The Royal Marsden NHS Foundation Trust— one of the UK’s leading cancer hospitals.

Located within a mansion block dating from 1907, the Royal Marsden’s new unit will primarily be used as a state-of-theart diagnostics centre. The Priory has joined our impressive rollcall of mental health experts. Advanced Oncotherapy, a pioneer in the field of proton beam therapy, is on its way. The list goes on and on.

After years of prompting from Howard de Walden, this flow of expertise into the area has now developed a momentum all of its own—as the collective grows in strength and its profile rises accordingly, its appeal becomes further enhanced, and the cycle continues. The HSMA has so much going for it at a logistical level—located in the middle of one of the world’s best-connected cities, surrounded by universities, research institutions and royal societies, with access to highly trained staff and a large population of

potential patients—and clinics know that the nature of the collective means that they can collaborate with each other and explore their mutual interests without having to compromise their own individual identities. Thanks to the recent creation of the Harley Street Medical Area Partnership, the board of which includes nine of the HSMA’s larger occupiers, these medical providers are now able to play a role in directly shaping the future of the area, and if, as we hope, this partnership is formally confirmed as a Business Improvement District in 2021, the collective voice of the medical community will soon be even stronger still. As a result of all this, the challenge for the HSMA now isn’t finding world class providers to join the collective, it is finding the space to accommodate them.

The growth of the Harley Street Medical Area could not be better timed, as competition in the private medical sector becomes increasingly fierce. Medicine is a big and increasingly globalised business: the medical travel resource Patients Beyond Borders estimates the global market for medical tourism to be worth US$65-87.5 billion per annum, with approximately 20-24 million patients seeking treatment outside their home country each year, and the market is growing at a staggering annual rate of 15-25%. This extraordinary growth in patient numbers has caused—and in part been fuelled by—an equally spectacular surge in the number and scale of the medical destinations competing for their patronage. As well as the traditional private medical heartlands of the USA and Germany, other parts of the world are now pouring resources into building and promoting their capacity. Singapore

is home to a highly sophisticated network of healthcare providers. Other Asian countries, including India, South Korea, Malaysia and Thailand, have also joined the race, creating medical facilities that offer high levels of care at a lower cost than can usually be found in Europe or the USA. Mexico and Costa Rica are attracting large numbers of American patients. The Middle East, a region that has long been one of the main sources of patients for London’s hospitals, is also building world class facilities of its own.

As the market changes, standing still is simply not an option.

Against this backdrop of intense competition, it is thanks to the impressive pulling power of its collective that the Harley Street Medical Area is able to thrive: proven providers that cover a vast array of specialisms, employ some of the most respected practitioners in their fields, invest in cutting-edge equipment, contribute to game-changing research, provide a truly exceptional patient experience, and focus relentlessly on tracking, analysing and improving the quality of their outcomes. Nobody planning a modern medical campus from scratch would come up with anything that looks quite like the HSMA, but they would definitely hope to emulate the professionalism, resourcefulness and expertise found in the parts of it that really matter: the parts where patients and medical professionals come face to face.

The Howard de Walden Estate 27 Baker Street London W1U 8EQ 020 7580 3163 hdwe.co.uk

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NEWS

Harley Street Medical Centre, part of the international UME Group, has increased its presence in the Harley Street Medical Area by leasing 17 Harley Street from The Howard de Walden Estate. It has agreed a 20-year lease and will relocate from 27 Harley Street to the Grade II-listed building once fit-out works are complete in early 2020.

Howard de Walden’s development works on the on the 7,940 sq ft space included the restoration of an ornate ‘spider’s web’ design stucco ceiling on the first floor, which is thought to date from the building’s construction around 1750.

Phoenix Hospital Group has launched a state-of-the-art memory clinic at its outpatient centre at 25 Harley Street. The new memory clinic helps to support the early diagnosis of dementia and other memory-related conditions. Patients experiencing memory loss are able to undergo in-depth consultation and comprehensive assessments, both cognitive and physical, with the ability to be seen and examined in a single visit.

25harleystreet.co.uk/memory-clinic

harleystreet-medicalcentre.com

Cleveland Clinic London, the British outpost of the highly regarded American non-profit multispecialty academic medical centre, is on track to open a new clinic at 24 Portland Place in autumn 2020. Set over six floors, totalling 28,000 square feet, this facility will offer outpatient appointments, diagnostics and general practice consultations. Its launch will be followed in 2021 with the opening of a 185-bed Cleveland Clinic hospital in Belgravia. Mayo Clinic, another of the leading names in American medicine, opened its new preventative medicine and diagnostics centre, a joint venture with Oxford University Clinic, on the same street in September 2019. clevelandclinic.org mch-ouc.co.uk Cleveland Clinic London

King Edward VII’s Hospital has recently introduced the latest da Vinci surgical system, the da Vinci Xi robot. As well as offering increased flexibility and versatility, the system provides multi-quadrant anatomical access, which increases the range in which surgeons can operate and creates room for more complex and challenging procedures. The hospital can now offer a new range of diagnostics and treatments for a variety of conditions and urological disorders, including pelvic reconstruction, erectile dysfunction, female urology, urinary incontinence, female functional urological reconstruction, kidney stones, male infertility, and prostate, bladder and kidney cancer.

Phoenix Hospital Group

King Edward VII Hospital

kingedwardvii.co.uk The Howard de Walden Estate is planning to convert one of its Harley Street Medical Area buildings into a sessionable space for doctors. With rooms available to rent by the half-day, this high quality facility will be designd to provide a more affordable route into private medicine for young doctors and allow older doctors and working mothers to continue to practice on an affordable part time basis. harleystreetmedicalarea.co.uk

In autumn 2020, The Royal Marsden Private Care is opening a dedicated diagnostics and treatment centre on Cavendish Square, in the Harley Street Medical Area.

Part of the private arm of The Royal Marsden NHS Foundation Trust—one of the UK’s leading cancer hospitals —it will offer access to eminent cancer specialists in a state-of-the-art building. royalmarsden.nhs.uk/cavendish

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I expect that beating-heart mitral valve repair will eventually be rolled out across the UK. Rather than being the norm, using the heart-lung bypass machine might become the exception

CRYSTAL BALL

Mitral valve prolapse Ms Rashmi Yadav, consultant cardiac surgeon at Royal Brompton Hospital, on how the treatment of mitral prolapse is set to evolve Interview: Jessica Brown State of play Of the heart’s four valves, the mitral valve is arguably the most complex—and certainly the most challenging to repair.

It has two flaps, which have chords that attach it to the wall of the heart, and these chords can break or elongate, resulting in prolapse of the mitral valve.

With each heartbeat, the blood leaks backwards into the upper chamber of the heart and towards the lungs, which can cause serious complications.

To repair a mitral valve, the patient has until recently needed to be connected to a heart-lung bypass machine, which performs their heart and lung function for them. The heart is then stopped temporarily while the surgeon works on the valve. The stakes can be high, particularly in patients with weak heart pump function. Such a heart may not

be able to resume sufficient function after being separated from the bypass machine and the patient may develop multi-organ failure as a result. When bypass technology was invented, it was lifesaving, but it brings with it some risks.

It is these challenges that have made the development of an option for mitral valve repair on the beating heart so welcome. The NeoChord procedure allows the surgeon to make a small hole in the left chest wall and repair the mitral valve without first stopping the heart.

On the horizon The team at Royal Brompton Hospital has already carried out 18 cases of beating heart mitral valve repair in high-risk patients who could not otherwise have been treated using the conventional bypass procedure. The NeoChord procedure requires careful pre-operative imaging and planning, and it is not suitable for every patient, but for those with mitral valve prolapse and a suitable anatomy, it can be highly effective. In the future, I expect to move towards using it to treat low-risk patients as well, carefully selecting those who are predicted to get the best results with this new technology.

A randomised trial in the USA involving young, fit patients with mitral valve regurgitation is currently comparing the NeoChord procedure with the standard operation. The results will tell us if NeoChord is equal to conventional surgery over a fiveyear period in terms of effectiveness, and superior in terms of side effects and surgical complications. Three-year results of NeoChord treatment are also due to be published soon by an experienced centre in Italy, and these will

shed more light on long-term outcomes.

In their experience of treating low-risk patients with NeoChord, researchers have learnt that even if the beating heart repair may not last a lifetime, reducing or eliminating the mitral leak may arrest progression of the disease sufficiently to postpone open heart surgery by several years. Additionally, because of the way NeoChord works, it doesn’t damage the mitral valve and preserves future options of surgical mitral valve repair.

In the distance I expect that beating-heart mitral valve repair will eventually be rolled out across the UK and other European centres. Rather than being the norm, using the heart-lung bypass machine might become the exception. My hope is when we have enough data and we feel safe enough to use this technology on lowrisk patients on a regular basis, surgeons will be able to repair a mitral valve as soon as it starts to leak. This would prevent the downstream effects, when the heart becomes enlarged and weak and the valve is much harder or impossible to repair.

The NeoChord procedure will certainly become a strong tool in any expert mitral surgeon’s toolbox, but I don’t believe it will replace everything we do. There will always be patients who can’t be treated by this technique. But we may be able to treat the majority of patients with mitral valve prolapse using this safer, less invasive procedure.

RB&HH Specialist Care Outpatients & Diagnostics 77 Wimpole Street, London W1G 9RU 020 3553 9648 rbhh-specialistcare.co.uk

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MUSEUM PIECE Intubation nasal tubes The endotracheal intubation nasal tube was developed early in his career by Sir Ivan Magill, one of the driving forces behind the creation of the Association of Anaesthetists, in whose Heritage Centre this resides.

At the time, the best available method for delivering general anaesthesia for facial surgery was by endotracheal insufflation through the mouth or nose. This involved a flexible catheter being fed into the pharynx, through which air and vaporised ether were driven by a motorised pump.

When the patient exhaled, their breath—still laden with ether—went straight into the surgeon’s face, as did any blood that had entered the pharynx. In 1922, while working on a soldier with a deformed jaw who found it hard to exhale, Magill passed a second tube through the patient’s nose and into the trachea alongside the catheter.

This helped the patient to breathe but also carried his exhalation away from the surgeon’s face. This was recognised as a major step forward and widely adopted in the field.

HARLEY STREET HERO Thomas Richard Allinson 1858-1918

On Saturday, 12th September 1891, Dr Thomas Richard Allinson wearily trudged the last few paces to his home and surgery at 4 Spanish Place, Marylebone. Starting in Edinburgh on 29th August, it had taken him just a fortnight to walk the 426 miles to London. His goal was to prove what a persevering Englishman could accomplish “without beef or beer”—the kind of one-off publicity stunt that made the then 33-year-old Dr Allinson infamous within the Harley Street medical set. This was a man whose commitment to whatwould now be called ‘preventative medicine’ was then deeply divisive, even though much of it (although by no means all) sounds quite sensible. He would spend most of the last 30 years of his life in professional exile, all the while gleefully tilting at the “great temples of medical priestcraft”.

Allinson was born in Grange-overSands, Lancashire and trained as a doctor in Edinburgh. After moving to London, he opened his surgery in Spanish Place in 1884, close to the medics who lined nearby Harley Street and Wimpole Street, but in other ways a world apart. In 1886, he published a book entitled The System of Hygienic Medicine, which set out the idea that, living in close confinement, modern man did not have the diet, exercise, pure air or clean skin needed to maintain a healthy body. Allinson decreed: no meat, no alcohol, no tobacco, no coffee, no tea and—above all—no white bread. Instead, he touted a vegetarian regimen of brown bread, nuts, fruits and vegetables. He was ridiculed in the general medical press for suggesting that people return to eating like “beasts of the field”. It was said that the Allinson diet would leave its adherents

too weak for any serious labour for Queen and Empire. Hence, his great walk from Edinburgh to Marylebone was an effort “to prove the fallacy of these people”.

To modern readers, none of this sounds particularly radical, but, in the 1890s world of High Victorian medicine, such attention-seeking was frowned upon. Even more troubling to the profession was his belief that most surgeries were unnecessary and most prescribed drugs were poisons.

In 1893, Allinson founded the Natural Food Company, with a bakery in Bethnal Green producing ‘Dr Allinson’s Brown Bread’, sold under the slogan ‘Health without Medicine’. Among other benefits, it was promised that a slice or two per day would fend off the “menace of constipation”. The upshot of such marketing was that in 1894 the General Medical Council voted to strike Allinson’s name from the physician’s register, accusing him of “infamous conduct in a professional sense”. Specifically, he was found to have violated the medical canon precluding “advertising, canvassing or touting for patients”. In response, he hung a new plaque outside the doorway at Spanish Place—‘Ex-Doctor TR Allinson’— and informed the public that, while he may have lost a title, it was really no matter after all. “The orthodox member of the medical trades union would like it to be otherwise, and does his best to spread this false conception; but it is not so … my practice goes on the same and my patients are as numerous as ever.”

Allison later became active in a litany of causes, including birth control, in support of which he privately published A Book for Married Women. It declared: “The information contained in this book ought to be known by every married woman, and it will not harm the unmarried to read.” The most controversial section dealt with contraception, or as he phrased it, “Mishaps and how to avoid them”. He defended the frankness of the material: “Some may think too much is told, such can scarcely be the case, for knowledge is power and the means of attaining happiness.” Those women, married or otherwise, who wished to have “the knowledge” were instructed to send 1s, 2d to 4 Spanish Place. Allinson was soon again hauled before the courts and fined for sending indecent material through the mail.

Allinson died of tuberculosis in Spanish Place late in November 1918. His name endures as that of a bread brand.

His thoughts on diet and birth control endure in quite a lot of current public health advice.

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HOW DOES IT WORK?

DEXA scan Dr Shirley Bradbrooke, consultant radiologist at The Princess Grace Hospital, on a low-dose scanning technique that plays a key role in the fight against osteoporosis Interview: Viel Richardson

The Princess Grace Hospital 42-52 Nottingham Place London W1U 5NY 020 3131 2549 hcahealthcare.co.uk

I have been a consultant radiologist at The Princess Grace Hospital for 35 years and for the majority of that time have concentrated on breast disease diagnosis using mammography, ultrasound and DEXA scanning, which is a tool for measuring the bone strength.

This type of scan complements women’s breast health checks very well—when they come for a mammography, I can suggest that they also undergo a DEXA scan, as reduced bone strength is a common issue for women, particularly after the menopause.

DEXA stands for ‘dual energy x-ray absorption’. The machine generates x-rays and fires them at the body. As the generator moves along above the patient, travelling across the area to be scanned, the sensor that receives the x-rays travels along beneath.

Depending on what they encounter as they pass through the body, the x-rays will be absorbed in varying degrees, from losing a small amount of energy to being completely blocked. What you end up with is a series of ‘slices’ that can be assembled to create the final image.

When scanning for bone density, what we are measuring is the amount of trabecular bone the patient has in specific areas. Trabecular bone is a porous, spongy material made up of hard and soft tissue and is found at the end of long bones and vertebrae. It looks a bit like a net, and when healthy appears as a denselooking matrix. If it degrades, you see fewer strands and bigger holes between them. As the density of the network gets thinner, the bone gets weaker.

When checking for bone density, we always scan the lower lumbar spine and the left hip. In order to build strength,

bone has to undergo minor stress, which is generated by the muscles connected to the bone during daily activity. The reason the lumber vertebrae are a good place for the bone density scan is because this type of stress happens much less there than in some other places, giving a good indication of bone production and replacement.

When taking this scan, it is crucial to get the patient positioned so the lower back is flat. DEXA scanners have a specially designed box, upon which the patient lays their legs. This raises the thighs, causing the lumbar region to flatten out. We also scan the left hip as part of the process. In order to obtain the position to get the best reading, the legs are shaped into a position where the feet turn inwards.

This is a quick, pain free procedure during which the patient is exposed to a very low radiation dose. In fact, the radiographer doesn’t even need to wear radiation protection or stand behind a protective shield while the scan is being taken. The dose you get is equivalent to three hours of walking along a London street. For comparison, a mammogram will deliver the equivalent of seven weeks of background radiation, while a CT abdomen and pelvis contrast scan delivers seven years’ worth. So, you can see how safe DEXA scanning is for the patient. While these low levels of radiation mean that DEXA scans do not have the diagnostic power of other scanning methods, they have an important role to play.

The scans can show degenerative changes to the bone. Occasionally, we need to do an instant vertebral

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DEXA scan

What to expect during a DEXA scan 1. Lie on your back on table below x-ray generator 2. Legs are positioned on a padded box 3. The generator and the receiver below the table move along in tandem, gathering images of the spine and hip

assessment, which involves looking at the whole of the spine. You can also check for vertebral body collapse—a type of compression fracture of the vertebra—or vertebral body wedging, which is a compression of the front part of a vertebra.

The main reason we are checking bone density, especially in women, is to find osteoporosis. This is important because of the risk of fracture. For some people, especially the elderly, fractures can be extremely serious, even life threatening. There is a formula called the fracture risk assessment tool (FRAX) which assesses a person’s risk of fracturing or breaking a bone. The formula calculates the patient’s level of risk based on results from the DEXA scan and additional information such as their sex, weight, age and medication intake.

Normal trabecular bone: dense matrix with smaller holes

It is also important to assess the trend in a patient’s bone density and response to any treatment they are undergoing, which means performing several DEXA scans over a period of time. This is where the low radiation dose really helps, as it means that a patient can have a scan once a year for several years with no ill effects. Comparing these scans allows us to see if a patient is maintaining a healthy bone density, losing it at a normal rate or losing it at an disproportionate rate, which would be the real concern. You particularly want to target those who are postmenopausal, have low bodyweight or who are taking certain medications.

DEXA is a safe, quick, painless and important tool in the diagnosis of bone thinning, which can potentially be highly debilitating.

Osteoporotic trabecular bone: larger holes, less material

Trabecular bone One of the two types of bone tissue. It is very porous and contains red bone marrow, where blood cells are made.

Morquio-Brailsford One of a group of mucopolysaccharidoses—metabolic diseases caused by the absence or malfunctioning of enzymes needed to break down molecules called glycosaminoglycans.

Compression fracture A type of fracture or break in the vertebrae. Compression fractures can cause the vertebrae to collapse, making them shorter in height.

Osteoporosis A condition that weakens bones through reduced bone density.

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THINKING ALOUD

Dr Ian Nnatu Consultant psychiatrist at The Priory Group Interview: Ellie Costigan Portrait: Christopher L Proctor

Medicine is not for everyone.

Nothing quite prepares you for the responsibility of it—making decisions that can have such an effect on people’s lives. But what comes with that is how incredibly rewarding it can be. You see very quickly and very directly the impact of your work on people, on families.

It’s incredibly fulfilling.

Electroconvulsive therapy in the 1950s was really the first treatment that led to demonstrable benefits to patients.

Before, we just locked them away in asylums. Then came the development of antidepressants, which are increasingly tolerable and effective, and there has also been a significant evolution in psychological therapies. There are now treatments that really work for patients.

In the future, medication will become more personalised. Already, we are able to identify which patients are more likely to respond well to particular types of medication. New drugs are being developed all the time, and new uses for existing drugs are being explored.

Ketamine is now being developed as a treatment for depression. A few years ago, who would’ve thought that?

I trained many years ago in cognitive behavioural therapy (CBT) because I saw it was the future. I think the difficulty now is how to make something like CBT, which is an excellent evidence-based treatment, available to a wider range of people.

As a psychiatrist, you’re dealing with the whole person. The amount of time you spend with a patient means you really get to know them.

Adjustment disorders are common. It is an extreme reaction to a stressful life event, such as going to university, starting a new job, moving house, getting married, or suffering a bereavement. Patients can develop a range of emotional and behavioural symptoms that affect their day to day function. Change is inevitable: it’s about building resilience, finding ways of coping with those challenges.

For a lot of mental disorders there is a genetic predisposition. If you have a parent who has schizophrenia, you’re more likely to develop it. If you have two parents with the illness, your risk goes up 50% or so. It’s the same with bipolar disorders, Asperger’s syndrome, even depression. But it’s not just about the genes: it’s the interplay between your genes and the environment.

This is a really exciting time in mental health, because there is so much more awareness. A lot of people feel a sense of failure in seeking treatment—there’s still a sense of shame attached to it—but because we’ve had a lot more public figures come out and talk about their own personal struggles, I think it has emboldened people to seek help.

Looking to the future, I can see patients becoming more centre-stage in making decisions about their treatment; more of an equal relationship between doctors and patients. But to be able to make those decisions, patients need more information about their condition.

Of course, there has to be a reputable source of information—not ‘Dr Google’.

Every patient is different: I’ve perhaps seen thousands of patients and it’s never ceased to fascinate me, because every case is unique. We try very much to individualise the treatment that we give to patients—it’s not a one size fits all and I think that is the beauty of the work we do: it forces you to think creatively.

Some cultures are more resistant than others to talking openly about mental health. For example, people in Caribbean and African communities in the UK still find it difficult to seek help, particularly if they worry about being unfairly treated, or not properly understood. Often things get to a crisis point before they seek medical help. That is a big issue. There’s still a lot of work to be done.

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Priory Wellbeing Centre Harley Street 41 Harley Street London W1G 8QH 080 8159 2776 priorygroup.com Prognosis—15

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PROFILE OF A PATHOGEN

Cytomegalovirus While the name cytomegalovirus (CMV) might call to mind a lesser-known species of dinosaur, it is actually one of a family of eight herpes viruses. These viruses are everywhere in nature, infecting everything from humans to oysters. Human CMV was first observed in the late 1800s and was finally isolated and identified in 1956-7 by Prof Margaret Smith and Prof Wallace Rowe, with the name cytomegalovirus being proposed

by Dr Thomas Weller and his team in 1960. It has taken time, but we have come to realise that this is a virus about which we should be very concerned.

CMV is easy to contract—it can be transmitted through saliva, urine, blood, tears, semen and breast milk, through sexual contact as well as blood transfusions. By the age of 40, over half of any population tested will show signs of infection. While the vast majority of people suffer little or no ill effect, a CMV infection should not be taken lightly. In healthy people, it can cause fever, sore throat, fatigue and swollen glands, and very occasionally it can develop into Epstein-Barr syndrome or hepatitis.

However, for people whose immune systems have been compromised by

auto-immune diseases such as HIV, CMV is a much more serious proposition. The virus base can been found in significant concentrations in the brain, eyes, lungs, liver, oesophagus, stomach and intestines, and if your immune system is compromised it can cause disease in any or several of these organs. CMV infections can also be dangerous for those with cardiovascular disease and patients who are on medication to reduce the chances of rejection after a transplant. For these three sets of patients, an infection can lead to serious illness and even death.

Another area of real concern is pregnant women. This is because the infection, which tends to remain in the system in a dormant state long after infection and without causing any symptoms, can easily be passed by a mother to her unborn child, a condition called congenital CMV. It is in fact the most common congenital viral infection in the developed world. Only about 10% of babies with congenital CMV infection show signs of the infection at birth, making it hard to catch early, and catching it early gives the best chance of effective treatment. These signs can include rash, jaundice, microcephaly,

Microcephaly A condition in which the circumference of the head is smaller than normal.

Retinitis Inflammation of the retina in the eye, which can cause permanent damage and even lead to blindness.

CMV glycoprotein B (gB) An envelope protein of human vytomegalovirus (HCMV), which acts as a receptor for entry of the virus into host cells.

low birth weight, hepatosplenomegaly (enlarged liver and spleen), seizures and retinitis. While for the majority of children these will pass—either by themselves or with some treatment— about one in five babies with the virus will develop long-term health problems.

The most common is hearing loss, but brain, liver, spleen and lung disease are not uncommon.

Certain anti-viral therapies have been effective in some cases of congenital CMV, especially in reducing the severity of hearing loss, but developing a vaccine remains the best hope for establishing real control over the disease. The problem is that CMV viruses are extremely species specific— more so than most. This means that the usual routes to drug development are less applicable. For example, to test the effect of the CMV virus on a guinea pig, you have to use guinea pig cytomegalovirus—any other CMV won’t work. This makes translation of results to humans extremely tricky. Even so, there has been some success with a vaccine based on the CMV glycoprotein B (gB), which stimulates vigorous antibody production and has prevented infection in some young women.

However, as with influenza, a patient can later be re-infected by another strain of human CMV. There is still much that is not known about the virus, such as the mechanism through which it can survive in a dormant state undetected by the immune system. A great deal more research is needed. So sadly, despite some progress, any road to a general vaccine is going to be a long and winding one.

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HOW TO...

Treat floaters Miss Louisa Wickham, chief surgeon at Moorfields Private Eye Hospital

Floaters

What are floaters?

Floaters occur when collagen condenses in the vitreous jelly that sits at the back of your eye. When you’re born, this jelly is very firm, but as you get older it becomes more liquid. The collagen begins to change in nature, becoming thicker and forming into clumps, which then begin to move around. It’s a bit like when you shake a snow globe and the little snowflakes move around—as your eye moves, these clumps of collagen are agitated, and as they move around they catch the light and disturb your vision.

How common are floaters?

Very common. Around 75% of patients will say that they’ve had them at some point. Certainly, floaters become much more prevalent with age. They can also get much worse quite suddenly. For example, vitreous detachment—where the vitreous jelly changes its position in the eye—is a common condition among patients in their fifties and sixties, and this can suddenly cause the appearance of floaters to increase considerably in a short period of time before settling back down again.

What does someone with floaters actually see?

You might see little black dots moving across your eye—I’ve heard floaters described as being like little flies. Other people might see them as a big clump.

They might notice, for example, that when they’re reading, a large floater will gradually drift into their central vision, causing them problems. They can seem worse in certain lighting conditions, so if your job requires you to look at lots of white screens, for example, you might notice floaters more commonly.

The same is true if you live in a very sunny country. There is also evidence to suggest that people who are either very short-sighted or long-sighted tend to notice floaters more than those who aren’t. The symptoms are usually transient, so floaters are not always experienced in the same way or in the same place. And if you went to an optician for an eye test, it would often come back as normal, because although the quality of vision is affected, your ability to see letters on a chart is likely to be entirely normal.

Can they become a serious problem?

Floaters can be very annoying and can significantly affect your quality of life, but in the vast majority of cases they don’t indicate any disease of the eye.

But if there’s a sudden increase in the number of floaters—as happens with vitreous detachment—then that could be indicative of a wider issue that needs to be checked out by an optician or ophthalmologist.

Are there treatments available?

In the vast majority of cases, floaters will only be visible for a while before settling down. That’s not because the floaters have gone away—they don’t get broken down or absorbed in some way—but because your perception of them changes. After a while, the brain understands that the floaters are insignificant and will begin to fade them from your vision, except in particular lighting conditions where they might become visible again.

Where floaters are causing a significant issue with a patient’s quality of life or preventing them from doing their

job effectively, there are treatments available.

What are these treatments?

The one that I would strongly discourage patients from pursuing is the YAG Floater Lysis laser treatment, which targets and disperses floaters.

Very often, the floaters are dispersed into smaller ones, making those patients more symptomatic than they were beforehand. Also, you’re introducing a lot of energy into the eye in a fairly unregulated fashion, and this can cause retinal injuries. To my mind, this treatment is neither regulated nor controlled enough to deal with the issue.

The second treatment is called a vitrectomy. This keyhole surgery is a very effective and controlled way of removing the floaters, but it is not entirely risk-free. There’s around a 3-5% risk of complications that could cause permanent visual reduction not correctible with glasses.

What should we do if floaters become a problem?

In the first instance, you should see your optician, so they can check whether there’s anything untoward going on.

Once you know your eyes are healthy, the floaters will often settle down. But if they don’t, then your next course of action would be going to see your GP and asking them to refer you to a consultant for an expert opinion.

Moorfields Private Eye Hospital 8 Upper Wimpole Street London W1G 6LH 0800 328 3421 moorfields-private.co.uk

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A DAY IN THE LIFE

Elisa Pirotti, physiotherapist at Isokinetic London Interview: Jean-Paul Aubin-Parvu Portraits: Orlando Gili

At Isokinetic, I look after a wide range of patients who are recovering from surgery or musculoskeletal injuries. They range from world class professional athletes from a wide variety of disciplines through to people who aren’t used to exercising at all.

And based here in London, my work has an international feel, because our patients come from all over the world.

With our multidisciplinary team of doctors, osteopaths, physiotherapists, hydrotherapists, movement coaches, onfield rehabilitators and clinical administrators, we welcome patients from the time of their actual injury all the way through to their full recovery.

My day starts quite early. I wake up at six in order to be ready to begin work at 7:30am. My shift is divided into two. During the morning I work

in our hydrotherapy pool and then in the afternoon I switch to our exercise therapy gym. I feel very lucky to be able to work in two completely different environments, as this allows me to follow a wider range of patients through every stage of their rehab process.

Our rehabilitation environments are open spaces for therapeutic exercise, which means I provide one-to-one care in a group setting. This allows for a wonderful atmosphere for the patients.

Each patient has their own specific programme and so at the start of the day I go carefully through the notes from their previous appointment to ensure that I offer them the very best treatment during this session.

Our hydrotherapy pool is a unique environment. It has multiple floor levels and descends to a maximum depth of

Musculoskeletal conditions Injuries or diseases pertaining to the musculoskeletal system. This includes the joints, ligaments, muscles, nerves, tendons, and other structures that support the limbs, neck and back.

Hydrotherapy The use of water, usually based around a pool, in the treatment of different injuries and conditions.

Plyometrics Exercises in which muscles exert maximum force in short intervals of time, with the goal of increasing power.

Biomechanics The application of mechanical principles to the structure, function and motion of biological systems such as the human body.

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My job is never repetitive.

Even if the injury or the surgery is exactly the same, every single person reacts to the recovery process in a slightly different way, both physically and mentally.

I find myself perpetually learning and growing, both as a physiotherapist and as a person, and that is the most fascinating aspect of my work here

two metres. This is actually one of the few places in the UK that uses a pool as part of the rehab process. Many of my patients don’t really know what to expect from these sessions and usually have lots of questions about it, but having worked here for seven years I can guarantee them that the benefits are widely recognised.

Hydrotherapy sessions are hugely beneficial in the early stages of rehabilitation because they help to reduce pain and swelling, increase the range of motion in a joint and restore movement and function. Essentially, patients can move more and with less discomfort in water compared to what they can do on land, and this allows me to introduce certain movements and exercises earlier than I could do otherwise. Patients experience a decrease in mobility, strength and function following an injury or surgery and my primary aim in the pool is the early restoration of all three.

I also use hydrotherapy sessions to treat patients who are at a later stage of rehab with the different goal of introducing landing, jumping and plyometric exercises. Sometimes these are the very movements that caused the injury, so the patient can be understandably scared of performing them again. It helps them psychologically to attempt them in a facilitating environment, and that also allows me to correct any biomechanical issue before the patient performs them on land using their full body weight.

The second part of my working day takes place in our gym. Patients start their sessions here during the acute phase, focusing on the management of

swelling and pain and the recovery of range of motion. After that, the main focus in the gym is on restoring full strength. This is essential before the patient can progress to more dynamic movements. We need to ensure there’s no overload of the site of injury, to prevent re-injury.

I like to challenge my patients to make the most out of each session.

I assist them by making sure they perform exercises and movements correctly, and that there’s a constant yet safe progression throughout their rehabilitation process.

The most challenging aspect of my job is the fact that rehab is almost never a linear process. There are the inevitable ups and downs that occur along the way, and when those downs happen it can lead to some challenging situations. I see patients during a particularly difficult

time in their life, perhaps after surgery or when they’re in acute pain, so my job isn’t just about my technical ability to treat the patient. It’s also about being able to maintain a positive environment where the patient feels constantly supported, encouraged and motivated. One key example is when I’m required to treat professional athletes who are dealing with the recurrence of an injury or with a surgery that could potentially end their career. To enable them to achieve a full recovery and get their careers back on track, it is crucial that I help these patients maintain a positive mindset throughout the course of the rehabilitation.

Some injuries take many months to recover from. In every case, it is important that I clearly define the ultimate goal that my patient needs to achieve, but this goal can sometimes seem a long way away, which can demoralise the patient and hinder their progress. That’s why I always try to set and agree a constant flow of short-term goals with them. This helps the patient to stay motivated and maintain a positive attitude. When I treat a patient I always keep in mind the ultimate goal that they want to achieve, but every single session marks a small but important step towards it.

My job is never repetitive. Even if the injury or the surgery is exactly the same, every single person reacts to the recovery process in a slightly different way, both physically and mentally. I find myself perpetually learning and growing, both as a physiotherapist and as a person, and that is the most fascinating aspect of my work here.

Having competed as a rhythmic gymnast for 13 years, I ended up seeing a physio from time to time and it was these sessions that sparked my interest in physiotherapy. I have always loved helping others and being a physiotherapist is a very practical way of doing that. It is hugely satisfying to see my patients reach milestones along their rehab journey, like being able to walk without crutches, going through their daily activities without suffering pain, or getting back to the sport they adore. Ultimately, I love to see a smile returning to their face. I feel very proud of them for everything they’ve been able to achieve.

Isokinetic London 11 Harley Street London W1G 9PF 020 7486 5733 isokinetic.com

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BEAMING IN Michael Sinclair, executive chairman of Advanced Oncotherapy, on bringing proton beam therapy, a revolutionary new cancer treatment, to Harley Street Interview: Viel Richardson

When I was young, I trained as a physician and went on to specialise in psychiatry and neurology, but it has been many years since I have been a practicing doctor. The contribution I am trying to make to the medical world now is a very different one: helping to build a facility that will bring proton beam therapy to the wider public.

Proton beam therapy will, I believe, revolutionise the way we treat cancer.

The key point of difference between this and other forms of radiology is our ability to target cancers while avoiding causing damage to healthy tissue. In other types of radiotherapy, the radio waves continue to travel through the body once they have passed through the tumour, causing harm to healthy tissue as they go. In proton beam therapy, the energy carried by the protons peaks as it reaches the target. This allows us to give higher dosages to the tumours but cause less damage to healthy surrounding tissues in the process.

In 2013, Advanced Oncotherapy acquired the first medical spin-off from the European Organisation for Nuclear Research (CERN). Many of the world’s best physicists, mechanical engineers and computer engineers are developing cutting edge technologies at CERN, and

working with them has been a once-ina-career privilege. The technologies we have access to are known collectively as ADAM, which stands for ‘accelerators and detectors as applied to medicine’. These have been used to develop the particle accelerators which are the basis of the particle beam therapy we are using.

As executive chairman, I’m involved in developing the strategy of Advanced Oncotherapy. I spend my time anticipating what the next steps will be, both in processes and technology: what will version 2.0 or 3.0 of this therapy look like, and how do we prepare for their arrival? I work closely with the CEO, Nicolas Serandour, and his team in financing the company and I also spend time liaising with academics from all over the world. This is a key part of the role, because it helps us to develop relationships and embeds us within the thinking and planning of institutions that might seek to harness our technology in the future.

Rather than going to a hospital or a big medical institution and saying: “I’ve got this wonderful piece of kit, please buy it”, the relationships we are building mean that the conversations are more like: “We are involved in developing this new type

of particle accelerator and we’d like to collaborate with you in doing research on its therapeutic uses, either in real life or simulation.” The expectation is that over a period of time the very significant technical and clinical advantages of our technology over anything else available in the oncology field will become so compelling that they decide to include it in their offering.

We decided to come to the Harley Street Medical Area partly because it is such an iconic medical location, and partly because The Howard de Walden Estate has been incredibly helpful. Of course, people often wonder why we would be doing this here in central London when there are plenty of green field sites outside the city. Traditional circular accelerators used in radiology are large machines that need huge amounts of land and shielding, but our proton beam accelerator is much more compact than you might expect. We took the view that if we could put our machine into the basement of two terraced houses in the middle of a global city, people will realise that we can put one just about anywhere.

Everybody in the medical world knows the Harley Street Medical Area brand and they are going to be impressed when they arrive at a terraced house a few minutes’ walk from Oxford Circus.

At a conference about four years ago Dr Jay Loeffler of the Harvard Medical School said that if the cost of proton beam therapy comes down to the same cost as x-ray therapy, then within 10 years, 100% of cancer patients having radiotherapy will have it delivered by protons. This is why much of our focus is on bringing the costs down—not only the capital cost of installation but also the cost per treatment.

There are currently only about 80 centres offering proton beam therapy, which means about 200 treatment rooms worldwide. With the estimated need being about 9,000 rooms, you can see that we are barely scratching the surface.

We believe that this is a technology that has the capability in the future to reach many more people—people for whom traditional radiotherapy has been out of reach, both financially and geographically. This is one of the main reasons the team and I are so committed to this project.

Advanced Oncotherapy avoplc.com

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Our proton beam accelerator is much more compact than you might expect and we took the view that if we could put our machine into the basement of two terraced houses in the middle of a global city, people will realise that we can put one just about anywhere

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1 DTC tests allow people to be more informed about their health risks and more proactive in managing them Christian Holland A ‘direct to consumer’ genetic test is one that the public can access without being referred by a clinician. Offered by a growing number of companies, a DTC test will generally provide ancestry information or assess your risk factors for certain diseases. We are at the very beginning of this journey, but I can foresee a future in which patients are more empowered to make choices about their own health. DTC tests have the potential to allow people to be more informed about their health risks and more proactive in managing them.

It is important to begin with a caveat about accuracy. These services will only be a net positive if they are accurate.

I am not talking only about clinically accurate descriptions of the gene, but ensuring enough information has been

SECOND OPINION

Has the growth of the medical ‘direct to consumer’ (DTC) genetic testing industry been a positive development?

gathered to make a robust prediction.

We are offering people probabilities, so you need to sample enough of the gene for any results to be reliable.

However, if run well, these tests hold the promise of a future where doctors don’t act as gatekeepers, but as partners; where patients have a much greater understanding of their health status.

For example, if someone discovered they had increased risk of diabetes, they could approach their doctor to discuss specific actions that could mitigate that risk. While more research is needed, there is evidence that when people are given this kind of information in the right way, they are much more likely to take proactive steps to mitigate any risk factors in a way they simply would not have done before. This has the potential to be a far more effective driver of lifestyle change than blanket public health messaging about food and exercise.

A far-reaching effect could be a switch to a more proactive and preventative approach to medicine, as opposed to the reactive, treatmentbased approach that dominates at the moment. Another area of real potential is the facilitation of early disease diagnosis through increased awareness.

If someone knows they have an increased risk of a disease and what the early symptoms look like, it increases their chances of recognising them if they arise and then taking action.

For many serious conditions, early diagnosis hugely improves the chances of effective treatment, so the impact of this could be huge.

I am hopeful that the DTC companies will come to embrace what I’m sure will be an increasing amount of regulation about their accuracy and reporting protocols. Initially, I would probably limit tests to conditions where you have a chance of taking steps to mitigate your risks, but that would be for society as a whole to decide. My optimism derives from the fact that these technologies clearly have massive positive benefits, to which the potential harms are not inextricably linked. With well thought out, robust legislation and legally enforceable protocols, I can conceive of a world where you can get the benefits of DTC testing without the harms.

Christian Holland is a medical student at Oxford University.

In November 2019, he led one of the teams in a varsity debate on DTC genetic testing at the Royal Society of Medicine.

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2 These are data companies whose business model is completely uncoupled from the health of their customers Edward Arbe-Barnes My main argument against DTC testing is that it simply isn’t very effective. Most use a process called ‘snip genotyping’, which looks for single letter mutations in the DNA code taken from sections of a gene sample. There are other techniques, but at the moment this is the only one cheap enough to make the process commercially viable.

One of the larger companies that offers tests to assess a woman’s risk of breast cancer only looks at just two snips across the whole gene. The international oncological consensus recommends looking at the whole gene. In fact, 80% of women with the BRCA mutation, which can increase the risk of breast cancer, would not have it picked up by this level of testing. These tests simply do not look at the gene in the depth required for

clinical decision-making and would never be used in our conventional healthcare system. Why then should the consumer be making possibly life-altering decisions based on the results?

Another issue is the fact that medical genetics has never been merely about the testing. When conducting a test in a medical setting, the most important part is often the counselling that patients get both before and after. Genetics is a complex science, with nuanced concepts like penetrance, relative risk and absolute risk. No matter how wellworded the results documentation is, it will never be as effective as a trained clinician who is able to put the results in context. Counselling is the hardest, and most expensive, part of the genetic testing process. You need great clinical acumen and empathy and there are consequences for getting it wrong.

One paper showed cases of heightened anxiety and decreased mood in people who were told they were at an increased risk of Alzheimer’s—just a risk, remember—when there was nothing wrong with them at the time of testing.

While not providing counselling, these companies do suggest that their customers visit a clinician, such as a clinical geneticist or a GP. This is

a gross misuse of time and money.

Clinical geneticists are few and far between, while GPs already have an incredibly difficult and time-pressured job. To expect them to interpret results generated by the DTC industry is simply not tenable. These services also play into the ‘inverse care law’, in which those with the greatest need often have the least access to care. There is a danger that those more able to pay, more neurotic or simply more curious will swamp the system at the expense of those who need the testing most.

My biggest issue is with the nature of the businesses themselves. These are not healthcare companies; they are data companies, whose business model is completely uncoupled from the health of their customers. To them, the real value of the test is not the price you pay, it is the fact that your most intimate and personal information, your genetic code, can then be sold on.

Their data—your data—is being turned into a commodity. I think this is a deeply warped model on which to base our genetic testing system.

Edward Arbe-Barnes is a medical student at Oxford University. He led the other team in the varsity debate on DTC genetic testing at the RSM. Prognosis—27

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THE BIG INTERVIEW Intelligence community Professor Jackie Hunter, a director of the biological innovation company BenevolentAI, on the vast potential of artificial intelligence to improve drug development and diagnostics, and the cultural changes that need to take place for this potential to be fully realised Words: Viel Richardson Images: Orlando Gili

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The concept of AI—artificial intelligence—is not a new one. As far back as 1950, the great mathematician and computer scientist Alan Turing developed his eponymous test to determine whether a machine could exhibit intelligent behaviour equivalent to or indistinguishable from a human being. Six years later, it was computer scientist John McCarthy who coined the term that has now become fully embedded in our language when he organised the Dartmouth Summer Research Project on Artificial Intelligence in Dartmouth College, New Hampshire. However cutting-edge it may feel, the idea of the ‘smart machine’ has been around for a very long time.

“In some ways, working in AI feels like going back to my roots,” says Professor Jackie Hunter, director of strategic partnerships and clinical research at the biological innovation company BenevolentAI. “When I was doing my undergraduate degree I went to a lecture

by Donald Hebb which covered, among other things, the uses of technology in medicine. AI is a field of computer science that uses machines to solve the kind of cognitive problems that would normally be the preserve of a human— tasks like pattern recognition, visual discrimination and data analytics.”

While the concept is far from new, the potential of artificial intelligence has been accelerating in recent decades as the power of computers has grown exponentially. AI is based upon the concept of machine learning: the ‘training’ of computer algorithms to assess a situation and make predictions as to their probable outcomes. This

is done by feeding in data from situations where both the progress and outcomes are known, and then tweaking the algorithms until their predictions match the reality. “You do this an enormous number of times using vast amounts of data,” Prof Hunter explains. “The algorithms ‘learn’ to make predictions. The idea is that eventually you can give them data from live patients to make predictions about the likely progress of the condition and the efficacy of potential treatments.”

AI is now moving beyond human capabilities, doing things that would be impossible for humans, and this can be transformational in a medical context. “Everything from supporting clinical decision-making, being able to triage patients earlier and more rapidly, to streamlining predictions of hospital bed availability, the list goes on. It holds out the promise of allowing clinicians to focus more on their patients and less on administrative tasks.”

These transformational possibilities are rooted in the mindboggling capabilities of modern computers.

The current record for calculations per second stands at 200 quadrillion— a two followed by 17 zeros—while ‘normal’ supercomputers routinely perform billions of calculations per second. Such computational power allows algorithms to simultaneously assess and integrate the data from several modalities, such as genomic, ethnic and image information, and critically, develop new ways of displaying the results.

“Here at BenevolentAI, we generate new hypotheses about diseases: new ideas about the mechanisms that

cause a disease, how it works and new approaches for tackling it,” Prof Hunter explains. “For us, a successful project is when we validate a hypothesis which advances knowledge about a disease and suggests actionable ideas for fighting it. We have already achieved this in some quite difficult diseases like motor neurone disease and glioblastoma.

Those hypotheses about specific targets within a disease are then progressed by developing chemical compounds aimed at modulating these targets. These compounds can then be used to create new and highly targeted drugs.”

“Developing computer algorithms that allow us to interrogate clinical data is key,” she continues. “Being able to predict things like a disease’s trajectory or which subset of patients might respond best to a particular

Computer algorithm A set of unambiguous instructions that allow a computer to solve a specific problem.

Machine learning A method of data analysis based on the idea that by repeatedly analysing and identifying patterns in a type of data, computers ‘learn’ how to make predictions with minimal human intervention.

Hypothesis A proposed explanation of an event, situation or idea, made on the basis of limited evidence but proposed as a starting point for further investigation.

Phase three clinical trial A trial to evaluate how a new medication works on human patients in comparison to existing medications for the same condition.

Data scientist A professional who uses computer algorithms to analyse raw data and extract meaningful information.

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drug is hugely useful to clinicians and researchers. We have our own research programmes, which tend to be for diseases where we can get evidence of efficacy without running large clinical trials. For larger projects, we collaborate with companies like AstraZeneca.”

An algorithm’s ability to ingest data from hundreds of millions of documents makes possible the creation of a visual systems biology map of a disease, through which clinicians can trace the simulated progression of disease pathways and the effect of a particular drug upon those pathways.

This allows them to pose questions that they simply could not have asked before. “Let’s take multiple sclerosis, as an example. If we build a map of the process of autophagy [the body’s way of cleaning out damaged cells, in order to regenerate newer, healthier ones] and overlay it on a map describing MS, it gives us an incredibly complex and nuanced way to approach the study of the disease,” Prof Hunter explains.

“You can move the map around in 3D space, move forwards and backwards in time. All this can reveal interconnections and possible pathways that would have been impossible to see before. You can simulate the effect of different drugs, different processes, and see how they interact with the disease map, and you can gain some real insights from this technique. This is hugely important for drug development. We can also use the technology to make inferences about potential new target proteins for fighting the disease.”

I am passionate about making clinical trials more effective and I see the potential of technological platforms to make a real difference.

It is the only way we are going to solve one of the major problems facing the pharmaceutical industry

Almost every healthcare system in the world is under severe pressure, either because of an ageing population or a lack of infrastructure. Where AI can help is by doing a lot of the heavy lifting, augmenting the expertise and experience of the scientists: “You have this enormous haystack of facts and what the technology does is to pull out some really promising needles.”

Far from the high-tech environments of biological science labs, AI algorithms are having an impact on frontline medicine.

One company called MobileODT has developed the technology to carry out accurate cervical screening with a handheld device, which takes a photo and analyses it on the spot.

“In poor or remote places without the facilities to otherwise do this type of analysis, it is literally a life-saver,” Prof Hunter reveals. In Botswana, triage examinations of children’s eyes are w Prognosis—31

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Academy of Medical Sciences Professor Jackie Hunter is a fellow of the Academy of Medical Sciences. The academy, based on Portland Place in the Harley Street Medical Area, is an elected fellowship of medical researchers.

It has over 1,200 fellows, about half of whom are clinically qualified, the other half being laboratory scientists in a range of disciplines. It is not a major funding agency; it instead seeks to promote excellence in research, influence policy to improve health, promote careers in medical research, and foster links between academia, industry and government. Its reports tend to review a specific topic related to biomedical science, identify where the gaps are in the research environment, and make practical recommendations for how progress might be made. Funding comes from a combination of subscriptions, donations and government grants. To support the academy’s work, visit: acmedsci.ac.uk/support

being done using a mobile phone app.

Only those needing treatment are then referred to local clinics, reducing the pressure on resources. Another company, Zipline, uses technology to guide pilotless medical delivery drones in places with poor road infrastructure.

In one case, an eight-hour trip has been reduced to 20 minutes. Another, perhaps surprising, area in which AI is making a difference is that of mental health, in which AI-based programmes have shown real promise by providing predictions about the type of therapy that would be most effective for specific patients.

“The algorithms underpinning all of these examples are based on artificial intelligence and I can see this happening across healthcare. For example, it takes a radiographer around two hours to analyse MRI scan images and give the surgeon the coordinates for a tumour removal. Using artificial intelligence to analyse the same images, you can get very precise results in three minutes. With diagnosis, there is some evidence from Canada that the improved quality of the results seen in AI-based tumour diagnosis was a result of algorithms reading information from cells in the scan that the pathologist was not aware of.”

It was in Prof Hunter’s previous roles as chief executive of Biotechnology and Biological Sciences Research Council (BBSRC), the largest UK public funder of non-medical bioscience, that the potential of AI really began to strike home for her. Visits to facilities like the High Performance Computing Center at Stanford University and the Sanger Institute in Cambridge

showed her the scale of the ongoing development of computational power and analytical sophistication. “It was really eye-opening,” she says. It was also exactly what she had been waiting for. The professor easily recalls her past frustrations, working within the pharmaceuticals industry, when a clinical trial might produce 26,000 pages of data which could then only be analysed within the narrow parameters of the trial itself. Here were huge quantities of high quality raw data, but it was impossible to access most of the information contained within the dataset. It felt to her that opportunities to gain valuable insights were being wasted. She saw this as a failure of innovation, a failure of the industry to exploit the available technology to get the most out of the information they were gathering, and in doing so bring down the cost of clinical trials and drug development and, therefore, the cost of the final medications.

“That was one of the reasons why I wanted to come to BenevolentAI,” she says. “I am passionate about making clinical trials more effective and I saw the potential here for making use of our technological platforms to make a real difference. From my perspective, it is the only way we are going to solve one of the major problems facing the pharmaceutical industry. New drug development will simply not be sustainable unless we really embrace this technology. Around 97% of the work the industry does fails to produce viable medication. You can be in a phase three clinical trial having spent several hundred million pounds on a drug compound and it will still fail 50%

of the time. This is very complex work and failures are inevitable, but we have to drastically cut both the amount and the cost of those failures. It can be done.

Using algorithms to help guide research, we have cut the leadtime to candidate drug phase from three years to one year in some cases. We have also been able to significantly reduce the amount of the biological compounds we need to make in the early stages, significantly reducing costs. These are steps in the right direction, but more needs to be done.”

Given that the necessary computing power has been around for a while, AI could already be much more fully integrated into the medical world, but the reality on the ground lags far behind the potential of the technology. The issue is that medicine and computer science are very different worlds, and getting them to synchronise has been a challenge. “When I arrived, we had to spend a lot of time creating a culture where people spoke the same language,” Prof Hunter remembers.

“Teams had different views about what the technology could and should do. The tech teams would work on a problem for six weeks and come back saying: ‘Here you are, we have solved it.’ It will have been excellent work, but not a precise fit for what the biologists and chemists needed. In turn, the biological scientists were not asking for what they really needed because they did not think the data scientists could deliver it.”

It is a pattern that is still found in the industry: medicine and computing may both be empirical, data-driven fields, but they have different worldviews and speak different

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As soon as we started building teams where data scientists and bio-scientists worked together, they challenged each other’s assumptions by simply asking: ‘Why do you do it this way?’

languages. Prof Hunter’s solution was to create cross-functional teams with members from both fields. “We have people we call translators who bridge the gap between the deep data scientists and the drug discovery scientists, and they are hugely important people. It has been transformational, significantly shortening the time between the technological output of the computer scientists and its use by the biologist or chemists. But it did take about two years,” she adds with a wry smile. “Not everybody needs to know how to code, but they need to understand what the output of that coding looks like, what it can tell you and what is needed for the best quality input. About 80% of the work in any machine learning project is cleaning up the data and getting it into a format that allows the technology to usefully use

it. You need to understand the language at least through a kind of phrase book, so that you can ask realistic questions.”

One major barrier to the uptake of AI in medicine is trust, from both clinicians and public alike. Auditing and monitoring the performance of algorithms can be very difficult. A veil of mystery can cloak these processes, leading to a propensity to distrust the outcomes. This has spawned a growing industry of ‘forensic AI’, which seeks to understand how these algorithms were built, how they are run and how neutral they are, while looking out for any inbuilt biases, either technical or cultural. “Transparency is extremely important if we are to make the best use of the power of AI,” says Prof Hunter.

“With an algorithm, there are so many areas where things can go wrong, fatally

compromising the accuracy of the predictions. If you train the algorithms with faulty data, or choose data that reflects your own cultural or scientific biases, you can build in biases which can end up being amplified if they are not spotted early. It is hugely important to pay attention to this.”

One effective guard against these unconscious biases is having access to a wide range of cultural and technical perspectives. Unfortunately, the diversity of the workforce in this area is very low, a problem the professor says needs to be urgently addressed.

To develop technologies aimed at the wider public, you need to be aware of the different ways that different groups relate to and use things. For example, the colour white represents purity and health in the west, but death in some parts of China, so something as simple as making a healthcare device the wrong colour can be a barrier to some communities using it.

“We saw this as soon as we started building teams where data scientists and bio-scientists worked together. They challenged each other’s assumptions by simply asking: ‘Why do you do it this way?’ This led to some really innovative solutions. There is lots of literature showing that diverse teams are more innovative,” Prof Hunter insists.

She also points out that on a very prosaic level, as AI moves into even more areas of our lives, Britain is going to need an enormous number of data scientists in the future. If the county wants to stay relevant in the field, the traditional white male workforce simply won’t be capable of meeting the demand. Diversity is, therefore, crucial on many levels.

“Overall I am very optimistic about the field—this is an incredibly exciting area to work in,” Prof Hunter says, with a genuine smile. “It is also important work. I also don’t see how we are going to meet some of the serious medical challenges we have without this technology. For me, the real excitement is in changing how drug discovery and development is done, making it quicker and cheaper. I’m bringing the tool in to the hands of the scientists so that they can ask new types of questions and find new types of answers. I find that very fulfilling, as well as exciting.”

BenevolentAI benevolent.ai

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Since the 1980s, when AIDS first swept into the public consciousness, advances in the treatment of HIV have transformed the potential outlook for those who contract it.

So, what are the current priorities for medics working on the frontline of HIV treatment, and where do we go from here?

Words: Clare Finney

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HIV Human immunodeficiency viruses. Relates to two species of lentivirus, the presence of which can lead to the development of acquired immunodeficiency syndrome (AIDS).

AZT Zidovudine: the first antiretroviral medication used to prevent and treat HIV/AIDS Highly mutable virus A virus that changes its gene make-up quickly through changes in its DNA when reproducing. These rapid genetic changes makes it difficult to develop drugs to fight it.

Combination therapy A disease treatment that uses two or more drugs to achieve efficacy.

PrEP Pre-exposure prophylaxis: a drug taken by HIV-negative people before and after sex that reduces the risk of getting HIV. CCR5 coreceptor A protein on the surface of certain immune system cells that can act as a receptor for HIV when the virus enters a host cell Antiretroviral A combination of drugs that work by stopping a virus replicating in the body.

In 1985 a little known teenager and an internationally recognised megastar struck up a friendship. The reason?

13-year-old Ryan White had contracted HIV from a blood transfusion and, when he was diagnosed with AIDS, the local community turned on him, slashing the tyres of his mother’s car, sending his family to the back of the church and preventing him from attending school. Upon reading of his plight, Elton John invited White and his family to one of his concerts, then arranged a private tour of Disneyland.

Calls, visits and gifts quickly followed, and in 1990 when Ryan’s health took a turn for the worse, Elton flew to be by his bedside when he died. They were, recalls infectious disease specialist Dr Kristin Englund of Cleveland Clinic, who started her medical training the same year that Ryan passed away, just weeks before his own graduation was meant to take place, “very dark days for people with HIV”.

“There was a lot of misinformation, a lot of fear, very little knowledge about how HIV was transmitted. A lot of irrational decisions were made,” Dr Englund continues. The plight of Ryan White was a classic example of the terror and ignorance that plagued

the start of the disease’s time in the limelight: “They tried to prevent him from going to school because they thought he would spread HIV.” That a 13-year-old boy would have to fight for his right to attend class seems unthinkable now, but when Ryan fell sick, the virus had only just been discovered; indeed the disease itself had only really come to light in 1981, when growing numbers of previously healthy gay men started presenting with immune deficiency problems.

It was known as GRID initially—gayrelated immune deficiency—“because it was thought to be limited to gay men.

Then it became clear that it was not limited, that it could easily to spread to the rest of the population.” The decision of Ronald Reagan to mention AIDS in his Special Message to the Congress in 1986 was a landmark event, in part because it took him so long, says Dr Englund. “This epidemic went on for a number of years without a mention from the highest in government. Speaking about it more freely meant more people understood that the virus was spreading—then the public demanded more attention be paid to the disease.”

By this point, the number of fatalities from AIDS in the USA

alone was around 16,300—including film star Rock Hudson, the most high-profile death to date. Across the country—across the world— people were presenting with similar symptoms: not just gay men, but haemophiliacs, women and even children. “It was an epidemic,” says Dr Taha Huda, consultant physician at City of Coventry Health Centre and president of the sexuality and sexual health section of the Royal Society of Medicine. And because of the stigma and judgement around the gay community—“all the politics around it”—the medics were taking a while to catch up. 1987 saw their first breakthrough, in the form of AZT—zidovudine, the world’s first antiretroviral drug—which “was better than nothing, but still inadequate,” says Dr Huda. “It was a monotherapy,” Dr Englund adds, “and HIV is a highly mutable virus. It would see AZT and mutate around it. Just a single mutation would be enough to make the virus resistant to the medication.”

Only in the 1990s did doctors come to understand that if they wanted to get the viral ‘load’—the amount of virus present—down to an undetectable level, they needed a combination

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TARO YAMASAKI / GETTY IMAGES

18-year-old AIDS patient Ryan White, accompanied by his mother Jeanne, is examined by his doctor in early 1990

This is a rich country.

We’re a long way off seeing such success in parts of Africa, where they still take cheap medication with serious side effects; where they don’t even have the facility to measure viral load

therapy, “so the virus would need multiple mutations to survive”.

“We figured out using two or even three drugs at a time was far more effective, and caused fewer side effects than applying single medications,” Dr Englund continues. For one thing, the virus mutated so quickly, patients were constantly being shifted from one medication to the next “until we were out of drugs to treat them with”. For another, the levels of monotherapy needed to have any material impact were almost toxic, says Dr Huda. “The side effects and complications were huge.”

Developments in HIV medication continued along these lines over the decades until the present day, which sees HIV carriers prescribed with three different medications contained in a single pill, with few or no side effects.

What was six tablets a day—three in the morning, three in the evening—is now just one, which can even be tailored to individual patients according to age, lifestyle, gender and underlying conditions. In the near future, there’s potential for “injectable medications— so instead of taking a pill once a day they can take a shot per month,” says Dr Englund, a “far more convenient” form of medication and “a great

deal easier for those who struggle to remember to take their pills”.

One of the upshots of the new medication was that it enabled, for the first time, couples who carried HIV to conceive naturally, and to breastfeed their children. “Previously, if a couple wanted a biological child, the father would have to have gone through the complex and expensive process of removing HIV from his sperm— a process not available on the NHS— or else gone down the route of sperm donation or adoption,” says Dr Huda.

If the biological mother was carrying the virus, the possibility of breast feeding was non-existent. To have medication that can “reduce the viral load to the point whereby it’s undetectable and untransmissible” makes it possible for those with HIV not only to survive but to build a fulfilling family life that would previously have been inconceivable.

So far, so much progress. But when Dr Huda was asked to take part in a debate in which the motion was ‘Is this the end of HIV?’ she successfully argued against it. “We won the argument that this is not the end. Yes, in the UK we’ve hit the UN’s target of 90% of people with w Prognosis—37

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HIV IN THE UK IS NOW A TREATABLE CHRONIC CONDITION THAT IS ENTIRELY MANAGEABLE AS LONG AS YOU ARE TAKING YOUR MEDICATION

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If people don’t know they are infected, they are able to pass it on to other people. We need to do a better job of identifying them, and at protecting at-risk people to keep them HIV negative

HIV being aware of their status and on antiretroviral therapy—but this is a rich country. We’re a long way off seeing such success in parts of Africa, where they still take cheap medication with serious side effects; where they don’t even have the facility to measure viral load.” Even in wealthy countries like the US and the UK where medications are effective and readily available, addressing the social and psychological issues surrounding HIV remains a serious challenge.

“Issues like poverty, addiction, stigma, lack of housing or transport and—in the US—lack of adequate insurance,” Dr Englund lists. “We have the right medications, but there are reasons why we haven’t been able to reach everyone who has HIV.” An estimated 10-15% of Americans who have contracted HIV don’t know they have it; that number falls to 7% on this side of the pond, but it is still a high enough number to be deeply concerning. “If people don’t know they are infected, they are able to pass it on to other people. We need to do a better job of identifying them, and at protecting at-risk people to keep them HIV negative.”

Education and outreach aside, one very tangible means of achieving that is PrEP: a drug taken by HIV negative

people before and after sex that reduces the risk of contracting HIV. Containing tenofovir and emtricitabine (drugs commonly used to treat HIV), taking PrEP before being exposed to HIV means there’s enough drug inside you to block the virus should it enter your body, Dr Englund explains.

Ensuring this medication is available to at-risk groups such as those with HIV positive partners, or intravenous drug users, is one practical way of stemming it’s spread. Nonetheless, the biggest challenge is the stigma that pursues HIV even to this day, says Dr Huda, “because the hardest hit by HIV demographically are the black African and gay populations. From clinical practice I would observe that the gay population today are more open about their sexuality and we notice less stigma and more transparency, whereas some of the black African population is still affected by this stigma. They cannot acknowledge the possibility they may have HIV, so they just don’t come.”

Worse still is when those who are affected seek help not from clinicians, but from the church. “They’ll come to us saying the church has cleared me, please test me,” and of course they haven’t.

They aren’t. And by that time their viral load numbers millions. We still see people die from advanced stage HIV [the more common term these days for AIDS]”, which is shocking given how effective treatment is today. The second biggest challenge is that even when an undetectable viral load has been achieved—that is, the virus is at such a level it cannot be passed on—it can still affect certain organs through “heightened systemic inflammation and persistent immune activation”, explains Dr Huda. “It is evident that people with HIV have a higher risk of heart disease and kidney problems such as HIV-associated nephropathy (HIVAN) where the kidneys become enlarged.”

In short, while these effects are by no means a given, they affect certain demographics more than others.

Dr Huda cautions strongly against complacency, and considers HIV in the UK as “a treatable, chronic condition that is entirely manageable as long as you’re taking your medication, as well as medication for any other conditions you need treatment for.”

Earlier this year there was talk of a cure, after the story broke of a man with HIV who had developed Hodgkin’s lymphoma. When his cancer responded to neither chemotherapy

nor immune therapy, the doctors found him a matched bone marrow donor— and, as it happened, these donor stem cells included a naturally occurring genetic mutation affecting the CCR5 coreceptor: the point on a cell that the HIV virus uses to lock on and infect it with HIV. If a co-receptor has this specific mutation, HIV cannot infect the cell by this route. After the bone marrow transplant in 2016, the man continued to take the antiretroviral drugs he’d been taking since his HIV diagnosis, while receiving intense treatment to suppress his own bone marrow.

Sixteen months after that treatment, he stopped taking antiretroviral drugs and had weekly blood tests to check his level of HIV. He was pronounced clear in spring this year. The press went wild—the Sun proclaimed a “miracle cure”—but the headlines were red herrings, in so for as their heralding an HIV solution.

“This is a man who has had leukaemia, and required a bone marrow transplant, along with strong drugs to supress his own bone marrow. That is a very severe and potentially deadly treatment,” Dr Englund points out. It’s an interesting development, of course, but bone marrow transplantation “is not the answer for the vast majority of people with HIV”. Nonetheless, to Dr Englund, a cure does seem tentatively possible. The case of ‘the London patient’ (as he is referred to, to protect his privacy; doctors in Berlin saw a similar outcome with ‘the Berlin patient’) has “given us some ideas of what might be effective”. The trick— and technical difficulty—will be “designing it in such a way that it proves useful to people who aren’t as deathly ill as those with leukaemia; using gene modification techniques to try and get rid of CCR5 in a patient’s immune cells”—CCR5 being a somewhat unnecessary feature, it seems.

“There are high powered gene researchers in UCL, Seattle and all over the world working together looking at this,” Dr Englund continues. “We have funding from the Bill and Melinda Gates Foundation and more and more interest. It is not easy. It will take time.

But in terms of potential for a cure, there is more hope on the horizon than ever before.”

Cleveland Clinic clevelandcliniclondon.uk Royal Society of Medicine rsm.ac.uk

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GOOD PHARMA The pharmacy is a familiar sight on high streets across the land. However, pressures on our healthcare system bring with them new challenges. Claudio del Duca of John Bell & Croyden explains the role of the pharmacist and how this is changing to meet modern needs Words: Viel Richardson

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Asclepius, the Greek god of the healing arts, delegated the duty of making up the remedies he dispensed to his daughter Hygieia. The physicianpriests of Egypt were divided into those who visited the sick and those who prepared the remedies back in the temple. Whether they have been called apothecaries, alchemists or herbalists, pharmacists have been around for a very long time, in one form or another.

For almost as long as we have had healers, there have been people whose skill was in preparing the medicines that would be dispensed. But however deep its roots, the role of the pharmacist continues to evolve.

As superintendent pharmacist for John Bell & Croyden on Wigmore Street, it is Claudio del Duca’s job to remain up to date with the everchanging legal and clinical regulations governing his field. “The modern pharmacy has evolved into something very different from the ancient practices.” he says. “In the same way that a division of duties developed between the physician and the pharmacist, the duties of the modern pharmacist have also now been divided.

In modern pharmacies, you now have both a dispenser and a pharmacist.”

The dispenser, often seen scurrying around behind the pharmacist in a world of bottles, boxes and packages, has been trained to package and label the medication before it is dispensed to the patient by the pharmacist.

This might sound like a simple task, but getting it wrong can have dire consequences: people have become seriously ill after receiving the wrong medication or the wrong dosage.

Labels on all medicines have to conform to strict legal standards and contain the dosage, usage instructions and any other information the patient needs in order to take it safely and effectively. Accuracy is absolutely key.

“When the pharmacist receives the medication from the dispenser, it has to be ready to be handed to the member of the public. The pharmacist then does a clinical check on the prescription. This is a very important step. There can be some interactions between different medications that may not be beneficial to the patient, and the pharmacist has to check for this if more than one medication is being prescribed,” Claudio explains. “If the pharmacist sees some contraindications, they will contact the customer’s doctor and talk through the case. In some cases, this can

lead to a change in the prescription and in others the doctor will know about the contraindications but believe that they are necessary in order to take care of a bigger problem.”

Among other things, the pharmacist also checks that the labelling is correct, the correct medication is in the box, the name of the patient is correct and that any instructions are the appropriate ones. Mistakes can happen either in writing the initial prescriptions or in the dispensing and the pharmacist is the very last line of defence before the patient wanders off with the medication. After that, then they take the most important step of all.

“They talk to the patient,” Claudio says.

One of the good things that has happened over time is that pharmacies have become less clinical in feel. While this has had the benefit of making them less intimidating and more accessible to the public, it also means that people dropping in to pick up their prescriptions can sometimes underestimate the clinical importance of any conversation that takes place between them and the pharmacist.

“When the pharmacist asks if you are taking any other medication it is a very

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Some aspects of our training are the same, but at a certain point the pharmacists go on to study more pharmacology than the doctors. This means we understand the relationship between drugs to a higher degree

important question. The patient may mention something they take regularly that they have not told their doctor about, such as natural supplements or probiotics—but these are still forms of medication, and we need to know about them. A pharmacist may spot that they will react poorly with the medication and suggest stopping them for the duration of the prescription,” he explains. “This is why it is important to tell your doctor whatever you are taking, and also to be completely open with your pharmacist. While this might lead to a delay in your prescription, that would be better than suffering unpleasant side-effects of incompatible medication that could so easily have been avoided.”

This last point speaks to a real point of difference between the doctor and the pharmacist—one of training. “Pharmacists know much more about drugs used in medications because of their training,” Claudio explains. “Some aspects of their training are the same, but at a certain point the doctors go on to study more anatomy, pathology and clinical conditions,and pharmacists study more pharmacology. This means we understand the relationship between

drugs to a higher degree. I have always strived to have good relationships with doctors we work with, because we are all part of the same team. We know more about the medications and they know more about the conditions, so working together we have the skills to do the best for the patient.”

It was probably this emphasis on the science that attracted Claudio to the world of pharmacy in the first place. He worked as a neuroscience researcher in Rome for 17 years before training as a pharmacist. Because of his background—several of his family worked as doctors when he was growing up—he has always understood that medication needs to be treated with respect. “Looking back at my life, it was quite rare that I took antibiotics. I have always taken another medication if possible,” he explains. “So when I moved to this country one of the things that struck me very quickly was that doctors here were prescribing a lot more antibiotics than I was used to. Perhaps that was because of my background, as well as cultural differences between Italy and the United Kingdom, but it did seem w strange to me.”

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In this increasingly complex medical world, we have a responsibility to help educate people about the best way of interacting with medications to preserve their long-term health

Strange, and also problematic.

Those levels of prescriptions were symptomatic of a worldwide problem of over-prescription of antibiotics, a problem that has led to the extremely serious issue of antimicrobial resistance (AMR). Simply put, this means that an increasing number of disease-causing bacteria are no longer being killed by the drugs we have used to control them for decades, leaving parts of the world with no defence against several lifethreatening diseases.

In 2019, the UK government released a plan that sets out a 20-year vision for tackling AMR. It focuses on three key aims: reducing the need for and unintentional exposure to antimicrobials; optimising use of present antimicrobials; and investing in new ways to supply and improve access. The aim is to contain and control the rise of drug-resistant bacteria. Claudio thinks that because of the pace and busy nature of our lives, there is a tendency, especially in the west, to feel the need to be at our best all the time. This translates into a desire to be given medication whenever we are feeling a bit less than 100%, and antibiotics, because they

in scale. Under the auspices of the government’s NHS 10-year plan, released in 2019, it pledged to make greater use of community pharmacists’ skills and their ability to engage patients.

have been so effective, tend to be our first port of call. This has led to real pressure on frontline clinicians to prescribe ever more antibiotics.

“This is where the pharmacist can play a crucial role,” Claudio explains.

“When someone comes in with a cough or sore throat, the pharmacist can advise products that are not antibiotics.

There are a range of medications that can provide the relief of symptoms— it does not just have to be a case of going home and waiting it out. The good thing is that the message is definitely getting across. I remember being asked for some advice by a customer recently and when I suggested another type of medication, she said to me: ‘I’m so glad you said that; the reason I came to you was I was hoping to get advice on some medication that was not antibiotic.’ That was really good to hear. Antibiotics are a fantastic tool, but they are a tool that needs to be used wisely. Our ancestors did very well for thousands of years without antibiotics, and there are parts of the world today without common antibiotics use, where people are living long and healthy lives.”

With GPs and hospitals under increasing pressure, the role of the pharmacist is about to increase

Under these plans, thousands more clinical pharmacy professionals will be employed in multidisciplinary teams as part of primary care networks (PCNs) throughout the country. PCNs are structured teams in which mental health, social care, pharmacy, hospital and voluntary services work together at a local level to provide a more joinedup and comprehensive healthcare service. Under the new plan, instead of simply being the place where you pick up your prescriptions, pharmacies will be an increasingly vital part of the multidisciplinary team that treats patients’ conditions. It is envisaged that, more and more, there will be times when the patient won’t need to see a GP at all. According to the plan, participating pharmacists will be expected to undertake a range of medicine reviews, educate patients on the correct use of medical devices such as inhalers, and find and treat people with common, high-risk conditions such as high blood pressure.

Last year, health secretary Matt Hancock promised to increase investment in community pharmacies. Many pharmacists hope, like Claudio, that this decision means that the new NHS plan will not simply be about hiring a few more pharmacists, but instead making more use of local pharmacies and the network of relationships that they have built up over many years. However, details remain hazy at the moment.

“I believe that in this increasingly complex medical world, we have a responsibility to help educate people about the best way of interacting with medications to preserve their long-term health,” Claudio says with real feeling.

“I also believe that pharmacies like ours are very well placed to do so because of our position in local communities. For me, this is a responsibility on a very personal level, between you and the person across the counter, as well as on a wider societal level.”

John Bell & Croyden 50-54 Wigmore Street London W1U 2AU 020 7935 5555 johnbellcroyden.co.uk

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Q+A CAR T cell therapy Professor John Gribben, consultant haematologist at The London Clinic, on CAR T cell therapy, a form of immunotherapy that has the potential to revolutionise cancer treatment Interview: Viel Richardson Portrait: Christopher L Proctor

Where does CAR T therapy sit within the field of cancer treatment?

CAR T therapy is a recently developed form of immunotherapy. The concept was born out of the question, why do T cells—which our immune system uses to identify and fight infections—not recognise and kill cancer cells?

It turns out that some cancers can be pretty much invisible to the immune system, or switch off the T cells that attack them. With CAR T cell therapy, you genetically introduce chimeric antigen receptors (CAR) into the patient’s own T cells. What’s new about it is the way we are combining the fields of gene therapy and immunotherapy.

What is a CAR and what does it do?

Antibodies are one of the body’s ways of fighting foreign and diseased cells. We have known for some time that we can use these antibodies to treat cancer. We have also developed the ability to make in the laboratory antibodies that attack cancer cells. There is a protein in the surface of lymphomas called CD19, for which there is an antibody. The CAR has two distinct parts, each with a different task. The outside of the receptor is the CD19 antibody: this recognises and latches onto the CD19 protein, attaching the T cell to the tumour cell. The other part is inside the CAR T cell, and this sends a signal for it to activate and kill the tumour cell. What the gene we introduce does is ensure that the CD19 antibody expresses on the surface of the CAR T cell and that the T cell is fully activated.

So, you then re-introduce the modified cells?

Yes. The cell now recognises the CD19 protein on the surface of the lymphoma cell and attaches to it. As well as switching on the CAR T cell, another signal instructs the cell to send out a signal for any CAR T cells that receives it to multiply. You then get an extremely rapid expansion of the number of these cells, which attack other lymphoma cells and, if all goes well, eradicate the cancer.

Is it difficult to introduce the genetic material?

It is quite difficult and there are also several things you need to be very sure of, as with any gene therapy. Once you genetically modify a cell, you have to make sure it does precisely what you want and nothing else. The whole field of gene therapy was put back when a gene therapy treatment

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We are now talking essentially about a pharmaceutical product that is attached to your cells. This product has come out of the world of research and into the realm of proven pharmaceuticals. Having the ability to adapt the immune system to fight cancers is exhilarating

designed for children with immune deficiency syndrome went wrong. One of the children developed leukaemia and died, because the gene they introduced switched on processes it was not designed to affect. A lot of work is needed to fully understand what the new gene is doing to the rest of the cellular machinery. We are always looking at safer and better ways to introduce new genes.

Have CAR T cells advanced since their introduction?

Yes they have, and real progress is being made. In fact, the product we are using now is second-generation CAR cells.

The first CARs recognised and attached to the tumour cells, but activation performance was not what we wanted. This is why we added what we call a ‘co-stimulation’ modification— the part that sends the signal to activate the CAR T cell.

There are now third generation CAR T cells on the way.

As it is quite new, is access to the treatment limited?

Yes, it is operating under a limited licence at the moment.

The CAR T cell we are using at The London Clinic is supplied by a company called Gilead Sciences and is licensed to treat two conditions: diffuse large B-cell lymphoma and primary mediastinal lymphoma, two subtypes of non-Hodgkin’s lymphoma. There is another CAR T cell that has been licensed to treat acute lymphoblastic leukaemia, but we are not using that treatment here as yet. The license also places limitations on the patients we can treat. At the moment, it is for people for whom chemotherapy and stem cell transplant therapy have failed, or for people who were not fit enough to have a stem cell transplant. These are cases where the prognosis is very poor. One very large study suggested that 95% of these patients would otherwise die within a year.

Are these cancers particularly suited to this treatment?

This was the logical area to start, certainly. Lymphomas and the acute leukaemias are diseases seated in the immune system. Therefore, T cells can find their way into lymphoma and leukaemia cells because that is what they are designed to do. Lymphoma was also a very good place to start because we knew all about the CD 19 antibody and understood the impact of targeting it on other areas of the body. When you start to look at other organs like the pancreas, lung and brain, we have to figure out how to get the modified T cells to the

cancer as this would not normally occur. We also have to understand the wider implications of targeting the antibodies, so there is a lot of work still to do.

Some people have concerns about genetically modifying cells. How safe is this procedure?

Everyone is very focussed on making this as safe as it can be. The geneticists are working very hard to ensure that the introduced gene does not integrate into the normal part of the genome in ways that cause unintended genetic switching within the cell. Also, the way this gene is delivered into the T cells means it should never migrate to other cells, and so far no one has found any evidence of the gene migrating elsewhere. In fact, the gene modification remains restricted just to the CAR T cells and has not been found in any other T cells in the immune system.

How effective is this therapy?

After this treatment, the condition of around 50% of patients stops deteriorating, then plateaus. This is a real advance, but we still have much to learn. As the treatment is relatively new, we do not have long-term follow-up data on a large cohort of patients. However, we know that these can be aggressive diseases that tend to return quite quickly, so having patients who have been on that plateau for several years is hugely encouraging. We cannot say they are ‘cured’, because we do not know what will happen 10 or 20 years in the future, but at the moment the data from the test results is stable. This is especially encouraging because if the patient responds as we hope, we are unlikely to see a very late return of the cancer.

There are no guarantees, but the fact that there is some uncertainty about the future is still a vastly better scenario than we have ever been able to offer these patients before.

Are there side effects?

When we give the CAR T cells to a patient, there is a manythousand-fold increase in the number of cells. The cells trigger this expansion through chemical signalling using proteins called cytokines. The scale of this chemical release can lead to something called cytokine release syndrome, as this flood of chemicals enters the patient’s system. Patients can get high spiking fevers, feel very flu-like and extremely unwell. In some individuals, the effects can be serious enough

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The London Clinic 20 Devonshire Place London W1G 6BW 020 3613 4413 thelondonclinic.co.uk

for them to need careful monitoring in an intensive care unit. There is also a second potential problem: a neurological toxicity that significantly impairs the patient’s ability to think clearly. What seems to happen is that the brain swells.

Medication is needed to combat this, requiring time in an ICU. You need a neurologist involved in monitoring patients during treatment as part of a multi-disciplinary team.

With the right support they are fully reversible.

A longer-term side effect is caused by the fact that the CD19 protein we are targeting is also expressed on your normal B cells—a type of white blood cell that is part of the immune system. This treatment can deplete the patient’s healthy B cells and some will need to have immunoglobulin replacement therapy until their B cell levels recover.

It seems extended multi-disciplinary support is vital?

Absolutely key. The treatment would not work without it.

In fact, in order to get approval to offer this treatment, the company that produces the CAR T cells has to visit and evaluate your facility. A very rigorous inspection process takes place to ensure that you have all the clinical and technical resources in place to offer the necessary support.

Gilead Sciences inspected The London Clinic as part of our approval process.

How often do you give the modified cells to the patient?

You only plan to give it just once. This is because the cells multiply enough to eradicate even large amounts of tumour.

T cells are very long-lived and ideally will be around long enough to kill all the cancer cells. After this, they either disappear or fall back to very low background levels and become part of the normal immune surveillance system.

The huge advantage over chemotherapy is that while chemotherapy kills the cancer cells, it only lasts a day or so, leading to repeat treatments being needed. However, the patient can reject the modified cells because our bodies can make antibodies against the chimeric part of the modified cell. We have found that the second time you introduce the modified cells they tend to be less effective, therefore you really would like the treatment to work the first time.

Is this treatment chemotherapy-free?

No, and it is extremely important for potential patients

to realise this. We have to use chemotherapy to kill some cells and create room for the implanted CAR T cells to expand into. If we don’t, they die out, so a small dose of chemotherapy at the beginning is a vital part of the process.

It also reduces the patient’s own immune system, so it doesn’t fight the new cells. Another factor is that these can be very aggressive cancers and the patient may need chemotherapy to keep their situation stable while their T cells have been sent away to be modified, which can take several weeks.

What else is coming from the clinical trials?

People are now asking: if this works so well in the very end stages of treatment would it be better used earlier on? There is a big clinical trial going on at the moment which is looking at whether, if someone has had a cancer relapse, they should go to the standard treatment of high-dose chemotherapy with a stem cell transplant, or straight to CAR T cells. If these trials show that is a successful way to go, can we use the cells as frontline treatment after the initial diagnosis? The thing is, some patients can be cured with chemotherapy alone. There are ways that we can identify people who are more likely to respond well to chemotherapy and those who will not, so I can see a time where if you identify a high-risk patient for whom chemotherapy is unlikely to work, they might be offered this type of treatment much earlier.

What excites you about this treatment?

We are now talking essentially about a pharmaceutical product that is attached to your cells. This product has come out of the world of research and into the realm of proven pharmaceuticals. Having the ability to adapt the immune system to fight cancers is exhilarating. CAR T cell therapy is one of a group of therapies called adoptive cellular therapies, where we make targeted modifications to the patient’s immune system to fight specific cancers. We are in the very early days, but this could be transformative for cancer treatments. It will be a long and difficult road to get there, but I can see a time when we will look back at the use of toxic chemotherapy chemicals in treating cancer in the same way as the concept that leeches were once considered good medicine—now we wonder how anyone could have ever have thought that.

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Patient experience How Mari Carmen had her life changed by a foot operation she’d spent decades avoiding Interviews: Clare Finney

I’ve had bunions since I was 12 years old—at least, that’s the first time I remember being aware of them. I grew up in Spain, and I remember my mother taking me to the doctors there, but they said I was too young for them to do anything. I didn’t think about them again for years. I’d always heard that it’s very painful to operate, and that it takes ages to recover. It was only when my cousin went to get hers checked (my dad and all my cousins on that side of the family have bunions) that I thought to go and get them checked, by which time I was 37, and living in London.

I went to see Mr Kaser Nazir. I told him they were quite painful when I was doing exercise, when I was wearing heels, and sometimes even when I was just wearing trainers, and I thought

he’d tell me not to worry about it. I thought he’d say, “Unless they’re super painful, it isn’t worth operating.” But he didn’t. He said the pain would only get worse over the years. When he said I could have both feet operated on at the same time, and that I would recover after a few weeks at home, I agreed to come back for surgery. The way Mr Nazir explained it all was so simple and reassuring, so I booked my surgery in for just a few weeks later.

I did feel a bit anxious in the run up to surgery, thinking about everything that could go wrong. What if I lose my foot? What if it’s really painful?

I emailed the practice manager, Anjelica, to say I was feeling a bit scared and she reassured me that Mr Nazir was a very good surgeon who had

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Scarf-Akin osteotomy correction for hallux valgus: short-term results from a district general hospital HL Kerr et al (Journal of Foot and Ankle Surgeons, 2010) Hallux valgus osteotomy technique VK Panchbhavi (Medscape, 2018) Outcomes after scarf osteotomy with and without Akin osteotomy a retrospective comparative study G Kaufmann et al (Journal of Orthopaedic Surgery and Research, 2019)

done this procedure hundreds of time, but that he would happily give me a call to talk through my concerns. I felt a lot better after that. My mum flew over from Spain so she could stay with me while I was recovering, and she was very supportive too!

On the day of the operation itself I couldn’t eat from 8am. I couldn’t even have water. Mum and I went for a walk, because I knew it would be the last time I’d be walking for a few weeks, then we went to the hospital. The nurse took my blood pressure, then Mr Nazir joined us and took me to the theatre.

I fell asleep in seconds after they administered the general anaesthetic.

The next thing I knew, I was waking up two hours later—the time was 4:20pm—and looking at my feet.

Apart from a bit of nausea from the anaesthetic, which cleared as soon as I had some drugs and some food, I couldn’t feel anything. The recovery was super-easy. The biggest challenge was showering actually, because of the bandages. I worked from home for a month—I had the operation on a Wednesday, and was working from home on the following Monday—and was in trainers for three months before I could wear ballet flats and then venture into heels. The first time I wore heels was quite painful, but the fact I had to replace those (they had moulded to the shape of my bunion!) was a good excuse to buy some quality shoes and look after my feet.

I was really scared. But I look back, and have a good memory of the experience. I am super happy with how my feet look, and I feel absolutely fine.

WHAT ARE BUNIONS?

Mr Kaser Nazir, consultant podiatric surgeon at Podogo

Bunions are a deformity in which the big toe deviates toward the second toe.

A bump develops as the first metatarsal bone of the foot then turns outward, causing the joint to jut out painfully.

As it progresses, it can give an eviction notice to the second toe, which gets pushed out into the air, and the ensuing de-arrangement of toes causes more pain in the ball of the foot. Bunions are painful, troublesome, and very common: about one in three women in the western world is affected. Though they don’t affect every generation in a family, the underlying cause is genetic: it has nothing to do with how you look after your feet. You find bunions in cultures that don’t wear high heels. You find bunions in cultures that don’t wear shoes at all. That your choice of shoes can cause bunions is a myth that needs busting.

The other big myths around bunions are that surgery is very painful, that the recovery is very long, and that it might not work. These are not true in our current times. Techniques have changed hugely over the past 100 years: even as recently as 20 or 30 years ago, surgery was being carried out by doctors who weren’t specialist foot surgeons; hip, knee and ankle specialists would offer foot surgery too, as an afterthought. But surgery today is a very straightforward procedure, carried out by experts.

With a greater understanding of the mechanics of the foot, we now have a much better idea of what we’re trying to achieve—by which I mean, restoring normal function to the foot and re-establishing the big toe’s natural position—and how to get there. We fully correct the deformity, not just partly, and we address the underlying causes of the bunion—the position of the joint and ligament instability—by releasing them on one side where they are too tight, and tightening them on the other side of the foot. Specialised screws are used to ensure the position is perfect, and we check the precision on x-rays before we close. It is a largely predictable operation, which can be done under local or general anaesthetic, and takes six weeks to recover from fully. Mari came to me about a year and a half ago with quite bad bunions, and had both done at the same time, and she has had perfect results.

Podogo 79 Wimpole Street London W1G 9RY 020 7412 8882 podogo.com

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KEYSTONE PRESS / ALAMY

Dr Grantly Dick-Read

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DELIVERY DRIVER How the radical, minimally-interventionist childbirth techniques promoted in the early-20th century by Grantly Dick-Read came to prove profoundly influential, despite the problematic nature of some of his beliefs Words: Sasha Garwood

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From his clinic at 25 Harley Street, the splendidly and implausibly named ‘natural childbirth’ advocate Dr Grantly Dick-Read changed the way a generation of women and medical practitioners thought about giving birth. Although to 21st century eyes his assertion that birth, as a natural process, would surely be painless if women would only stop worrying about it might raise a few eyebrows, his minimally-interventionist techniques (including such modern essentials as relaxation, present fathers, and permitting mothers to keep hold of their infants after birth) were profoundly influential. His archive, comprising lecture notes, papers, autobiographical fragments, news clippings, letters, and other unpublished ephemera, is now housed by the Wellcome Institute, and offers a fascinating insight into the life and work of this strange, problematic, but compelling figure.

It was hardly obvious that DickRead would go into medicine, let alone obstetrics. He was born around 1889 or early 1890, the sixth of seven sons of a Norfolk miller, and educated at Bishop’s Stortford Grammar School and St John’s College, Cambridge. At both institutions he excelled in sport and music, alongside a sustained interest in the natural world.

He undertook his medical training at the London Hospital, qualifying in 1914 and promptly dropping everything to join the Royal Army Medical Corps, with which he served in Gallipoli and France and was severely injured at least once. Surviving the war, he returned to the London Hospital for a year before completing an MD in Cambridge in 1920.

In 1921, he married Dorothea Cannon, and proceeded to have four children with her: two boys and two girls.

At first, Dr Dick-Read went into general practice. It’s unclear to what extent his marriage and impending fatherhood affected his developing professional preoccupations, but by the early 1920s he was working in a clinic in Woking and recording voluminous case histories on childbirth and antenatal and post-natal care. From this point on, he had some astonishingly sensible ideas about practical approaches to childbirth, alongside a slightly strange and of-its-time (or possibly 50 years earlier) idealisation of maternity. He claimed in Childbirth Without Fear (1944) that a woman “is adapted primarily for the perfection of womanhood which is, according to the law of Nature, reproduction,” adding in

his book Motherhood in the Post-War World (1944) that “woman fails when she ceases to desire the children for which she was primarily made. Her true emancipation lies in freedom to fulfil her biological purposes.”

As far as Dr Dick-Read was concerned, feminine reproductive capacity reached its apotheosis in the childbirth practices of so-called “primitive” women, who were “rarely troubled by anxiety states or toxic manifestations”. He attributed this apparent lack of birth trauma partly to their hard physical labour, but also to a supposed confident ignorance of possible medical complications. He claimed in Natural Childbirth (1933) that “the primitive knows that she will have little trouble when her child is born. She knows that it will be small and healthy, and she has no knowledge of bones misshapen by rickets disease and faulty habits during childhood.

Natural birth is all that she looks for; there are no fears in her mind; no midwives spoiling the natural process; she has no knowledge of the tragedies of sepsis, infection and haemorrhage. To have conceived is her joy; the ultimate result of her conception is her ambition …There is unquestionably a sense of satisfaction when she… receives the impatiently awaited indications that her child is about to arrive… [she] isolates herself, and, in a thicket, quietly and undisturbed she patiently waits.”

He added that when these women die in childbirth, they do so “without any sadness… realising if they were not competent to produce children for the spirits of their fathers and for the tribe, they had no place in the tribe.”

Explicit devaluing of women’s lives and autonomy aside, there are some problems here: not only did Dr DickRead form these ideas early in his career when working in the distinctly un-primitive Woking, but he also never explicitly defined what he meant by “primitive” women. He included in that category women from “the South Sea Islands, Hindustan, China, India and Japan”. Many of these had highly sophisticated civilisations at the time.

He would also go on in South Africa to praise not women’s isolation, but the fact that older and more experienced women never “left them alone” during labour.

For Dr Dick-Read, modern western practices of education and socialisation alienated women from their bodies. “From the earliest childhood, the modern cultured girl

is brought up protected from the hard facts of life, rarely called upon to use her natural instincts … parturition is almost invariably the first primitive, fundamental physical act which she is called upon to perform.” (He does not, apparently, include conception as a “fundamental physical act”, which rather begs the question of how he thinks it takes place, but this is perhaps another issue.) This alienation is exacerbated by secrecy around the process of childbirth, inaccurate information passed onto mothers through social networks, and religious teachings which constructed the pain of childbirth as a punishment for original sin, all of which made women fear labour, and thus contract their wombs in damaging and painful ways.

“Anything that disturbs the confidence and peacefulness of the mother disrupts the neuromuscular harmony of her labour ... In childbirth, fear and the anticipation of pain give rise to natural protective tensions in the body.

Unfortunately, the natural muscular tension produced by fear also influences the muscles that close the womb and thus delay the progress of the labour and create pain.”

In 1934, a year after the publication of Natural Childbirth, Dr Dick-Read set up his private clinic at 25 Harley Street, and established a practice along these lines. He was blessed with significant personal charisma, and while his passionate declarations often alienated fellow practitioners, he was popular and appealing to many patients. An obituary in the BMJ praises him as “delightful company”, a doctor who “enjoyed the good things in life” and “a man of striking appearance and an enthusiastic and brilliant speaker”.

In some ways, it was just as well Dr Dick-Read had his charm and conviction to fall back on. In 1938, his partnership in Woking was dissolved amid accusations of false advertising. Ironically, at a time when many women were campaigning to have access to painkilling drugs in childbirth, particularly for those lower down the social scale, Dr Dick-Read was decrying the ‘interventionist’ practices of modern medicine and suggesting they should have none at all. He communicated these ideas to the public through writing books, chapters, pamphlets and lectures, and corresponding endlessly with patients, doctors and newspaper editors. He declared that birth should be “carried out by natural processes from beginning

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At a time when many women wanted more access to painkilling drugs in childbirth, Dr Dick-Read was decrying ‘interventionist’ practices and suggesting they should have no drugs at all

to end, influenced by natural emotions and perfected by the harmony of the mechanism, [with the woman] conscious throughout the progress of her baby’s birth, so that she can truly fulfil herself emotionally when she sees and welcomes the child emerging from her womb into the world.” Because of the supreme emotional dominance of this “motherlove”, an emotion he believed would prompt men and women to “shape the course of history” and banish “poverty, distress and misery”, Dr DickRead declared that “the safest and most effective way to minimise the discomforts of childbirth is to enable a woman, by preparation for, and understanding attention at labour to have her baby naturally...”

Some of the implications of these ideas, however, were surprisingly practical. Certainly, hefty doses of multiple drugs were often administered in childbirth at the time, and these were not always needed.

Some obstetricians recommended compulsory episiotomies—a surgical cut made at the opening of the vagina during childbirth to aid a difficult delivery—and manual exploration of the uterus, and in 1920 American gynaecologist Joseph DeLee addressed the American Gynecological Society on “prophylactic” use of forceps. Under Dr Dick-Read’s care, on the other hand, these interventions were minimised.

He had learnt relaxation techniques from an Indian subaltern in the war, and saw them as an easy way to reduce labour pains. In his clinics, babies should not be removed from their mothers, fathers should be present at

births, and mothers should exercise and educate themselves in preparation for the big day. Moreover, in some ways Dr Dick-Read’s ideas—despite his combative means of expressing them—were not actually all that revolutionary. As early as 1812, America physician Samuel Bard suggested that state of mind had a significant effect on the experience of mothers, and in 1832 these ideas were expanded upon by Thomas Denham. Perhaps the hostility he encountered from the medical establishment—and bewailed throughout his life—was as much a response to his manner as his message.

In 1948, the newly established National Health Service refused Dr Dick-Read a consultancy. With his second wife, ex-patient Jessica Bennett, Dr Dick-Read moved to South Africa and established a practice in Johannesburg, there bemoaning the way in which his urbanised patients of colour had abandoned their “primitive” practices in favour of demanding “the needle”. After five years, he went on a tour around Africa, investigating “primitive” women’s childbirth experiences, and revised or contradicted some of his earlier contentions.

Dr Dick-Read died in 1959, in Norfolk, having distributed his ideas impressively widely with neither an emphasis on scientific evidence nor the wholehearted support of the medical profession. He claimed extraordinarily and dubiously high success rates, and notably failed to provide the data to back up his claims. Repeatedly, during his life, fellow doctors challenged his ideas and he reacted with anger and disdain, most notably to the extensive rebuttal of his fear-tensionpain theory by D Reid and ME Cohen in their ‘Trends in obstetrics’ in the Journal of the American Medical Association (1950). Nevertheless, for many women, his was a powerful and revolutionary approach, and doubtless some experienced his focus on their divine capacity for maternity and the transformational capacity of ‘motherlove’ as validating. The charisma and charm that led to such emotional, flamboyant and openly contentious work was perhaps a doubleedged sword, bringing widespread public attention just as it alienated the professional medical support that Dr Dick-Read so craved. Regardless, his non-interventionist and emotionallyfocused approach to childbirth still resonates profoundly to this day.

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MY MARYLEBONE

of me, and always goes the extra mile.

Sandra Price, Price’s Back Clinic

Caffe Caldesi

Work I followed in my grandfather Frederick Price’s footsteps by working in the osteopathic clinic he had established in Croydon in the 1920s. I was also lucky enough to work alongside my father, Dr John Price, an orthopaedic consultant physician in private hospitals and clinics in London, Sussex and Harley Street, to where he had expanded Price’s Back Clinic.

It wasn’t a given that I’d go into osteopathy, but you are influenced by what you see at an early age.

As a child, I was inspired by the transformation in wellbeing I saw in my father’s patients while I helped out at his clinic’s reception on Saturdays. After 30 years working at 142-146 Harley Street, which incorporated the rooms where Lionel Logue once worked as a speech therapist, I am now located at 20 Harley Street, which has less Victorian architectural grandeur but

benefits from overlooking a lovely garden with tweeting birds and a goldfish pond.

I think it adds to the healing power of my osteopathic treatments—there’s a sense of peace and calm that is restorative in itself. I still love my job. I am still passionate about it. I still love helping people and effecting that transformation.

Shop I’ve now been on Harley Street for more than 30 years, so I’ve seen an awful lot of changes in the area.

Marylebone has picked up hugely in the past 12 or 15 years. I like an occasional wander into The Conran Shop, or Daunt’s bookshop— it’s not often you get to explore a bookshop of that standard. I don’t usually interact with the area until later in the day—I’m not a breakfast person, and the moment I get in to the office I am straight away seeing patients—but when I do have

some time, I like to walk up to the rose gardens in Regent’s Park. I think they are stunning—absolutely amazing. I’ve actually taken quite a few pictures of them over the years, and a wander around there really clears your head.

Culture If I have too much time on my hands, I will head over to The Wallace Collection.

You can drift into another era walking around that amazing house. I dabble in art myself—watercolours, pastels, pencil—and I find the art there to be inspiring and very uplifting. Usually, if I am distracting myself to avoid the reports I should be writing in Harley Street, I feel guilty, but in The Wallace Collection my mind is completely absorbed.

Incidentally, very near the gallery is an excellent travel agent called Tecno Travel. The guy there, Ash, is amazing: he really takes care

Eat I don’t often go out to eat at lunchtime—I tend to just have fruit in the office—but every so often on a Friday my friends will insist that we’re having lunch, and they’ll take me to The Golden Hind or Caffe Caldesi. The steamed plaice in The Golden Hind is just to die for—and, of course, the chips are exceptional. Otherwise, I’m more of an evening person when it comes to eating out.

I quite like to meet friends at Fischer’s for dinner. It’s a bit different, and I love the smoked salmon with lemon creme fraiche, or the goulash, which I enjoyed the other day. My favourite pub is The Wigmore, and for a special occasion I like Artesian Bar in The Langham hotel—but I most often choose 108 Brasserie & Bar for a coffee in the afternoon and a drink in the evening. I was in 31 Below the other day with a group, though, and was amazed at how busy and lively it could be on a Tuesday.

I’ve basically been to almost all of the restaurants and bars, because I’ve been here so long—I’m a bit like the Wigmore Hall!

Community Being in medicine, an important place in the area for me is John Bell & Croyden: they supply everything I need surgically as well as all sorts of lotions and potions.

If I order in the morning, they deliver in the afternoon, and you can’t say fairer than that.

One place that has been in Marylebone a similar length of time to me is Harley Medic International: a very efficient visa agent and medical service on Harley Street headed by Michaelle, who is a fountain of knowledge on the area too. They do medicals for different companies and privately, whether it’s going abroad on work visas or for a thorough health check-up.

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The Wigmore

My favourite pub is The Wigmore, and for a special occasion I like Artesian Bar in The Langham, London

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WHAT’S ON EXHIBITION

EXHIBITION

EXHIBITION

THEATRE

BEYOND BAUHAUS: MODERNISM IN BRITAIN 1933 TO 1966 Until 1st February RIBA 66 Portland Place London W1B 1AD architecture.com

LIFE Until 1st February Atlas Gallery 49 Dorset Street London W1U 7NF atlasgallery.com

TONY CRAGG: STACKS Until 29th February Lisson Gallery 27 Bell Street London NW1 5BY lissongallery.com

SHAPING DUST 11th—15th February The Cockpit Gateforth Street London NW8 8EH thecockpit.org.uk

Following its relaunch in 1936, Life magazine would become a repository for some of the greatest photography of the 20th century. Andreas Feininger, Joe Rosenthal, Margaret Bourke-White and Alfred Eisenstaedt, among many others, documented some of the most important events and memorable lives of the recent past, creating a canon of photojournalism unmatched by any other publication. This exhibition commemorates the magazine’s golden age, including portraits of the Kennedy brothers, the Beatles and Frank Sinatra, as well as iconic images from the 1945 VJ Day celebration and the 1968 Olympics.

For his 15th Lisson Gallery show, Tony Cragg presents a selection of complex polymorphic sculptures, rendered in bronze, wood and steel, many of which offer insights into the sculptor’s repeated and ever-evolving use of ‘stacking’ methods—the creation of solid, cohesive forms out of small, disparate parts. Across five decades of work, starting in the 1970s, Cragg has stacked, gathered and layered a variety of materials, deploying various acts of stratification, compilation, accrual and accumulation and drawing upon his fascination with geology, archaeology, biology, chemistry, natural history, psychology and anthropology.

Emma has mid to late stage Alzheimer’s disease. Beginning in her childhood home, Shaping Dust leads us through Emma’s life, recounting memories that both delight and terrify, in an exploration of the “darkness and absurdity” of living with this debilitating disease. Produced and presented by Fancy Another? theatre company with the support of the Alzheimer’s Society, a dementia awareness talk will take place following each show.

Marking the centenary of the creation of the Bauhaus, the German design school that would become a crucible of modernist design, this exhibition looks afresh at its influence on Britain, particularly the impact of three notable Bauhaus émigrés, Walter Gropius, Marcel Breuer and László Moholy-Nagy, all of whom were uprooted to the UK after the Nazis came to power. Drawing on RIBA’s world-class collections, rarely shown works by the three ex-Bauhaus tutors will be displayed alongside those of the young British architects they inspired.

Beyond Bauhaus: Modernism in Britain 1933 to 1966

Tony Cragg: Stacks

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PAUL ROTHE AND SONS 35 Marylebone Lane London W1U 2NN

Forgotten Masters showcases the work of a series of extraordinary Indian artists, each with their own style and tastes and agency

EXHIBITION FORGOTTEN MASTERS: INDIAN PAINTING FOR THE EAST INDIA COMPANY Until 19th April The Wallace Collection Manchester Square London W1U 3BN wallacecollection.org Curated by writer and historian William Dalrymple, whose book The Anarchy traces the rise of the East India Company, this exhibition brings together works by Indian master painters, commissioned in the 18th and 19th centuries by officials of the trading company that became an engine of British colonialism. “Forgotten Masters showcases the work of a series of extraordinary Indian artists, each with their own style and tastes and agency, whose brilliance has been frequently overlooked until now,” promises Dalrymple.

Forgotten Masters: Indian Painting for the East India Company

Places for a bowl of soup in Marylebone

It’s been 50 years since Paul Rothe took over from his father, Robert—and 119 years since his grandfather Paul opened this Germanish deli. To step inside and survey the 1950s-style tables and gleaming jars of handmade jam and chutney is to feel all is right with the world—at least for the time you’re there. Paul is still serving, alongside his son Stephen, and their soups are as reassuring as they are retro. There’s a vegetable and a meat option, which change daily—pea and mint, celery and stilton, lamb broth, chunky vegetable—and while plain bread is available, the traditional Rothe practice of ordering a sandwich to dip in your soup is advised.

LE PAIN QUOTIDIEN 72-75 Marylebone High Street London W1U 5JW lepainquotidien.com Growing up in Belgium, Alain Coumont spent every Wednesday afternoon at his grandmother’s house, where she treated him to a small bowl of hot chocolate. The memory of cupping his cold hands around it, soaking up its warmth, followed him to the tables of the bakery he founded almost 30 years ago in Brussels—and thence to his opening in Marylebone, where hot drinks and soups continue to be served in wide, round bowls. The soup is organic, seasonal—think icy gazpacho in summer, butternut squash topped with rosemary in winter—and served alongside Le Pain Quotidien’s eponymous daily bread.

GAIL’S 4-6 Seymour Place London W1H 7NA gailsbread.co.uk There are not one, not two, but five richly flavoursome

soups to choose from at Gail’s, each created with the help of a nutritionist to provide maximum nutritional boost for your buck. Choose from hot paprika beef goulash; soothing, protein-rich Moroccan lamb harira; fragrantly spiced sweet potato and coconut; lentil broth bright with lemon and sweet with pumpkin; or chicken and vegetable. And get dunking with the fresh, local, handcrafted sourdough Gail’s serves alongside.

FISCHER’S 50 Marylebone High Street London W1U 5HN fischers.co.uk Those looking for the ultimate soup for sore bodies (chicken) can rest easy.

Fischer’s chicken soup with spätzle is the platonic ideal of Jewish penicillin: silky, buttery, laced with noodles and studded with just the right amount of chicken broth-infused veg. Enjoyed in the decadent comfort of this wood-panelled, marblefloored homage to the grand cafés of 19th century Vienna, this—and maybe a small, restorative glass of Austrian riesling—is the culinary equivalent of a Lemsip all-inone capsule.

LA BRASSERIA 42 Marylebone High Street London W1U 5HD labrasseria.com Tomatoes, pasta, parmesan, beans. When it comes to comfort food in a bowl, it’s hard to beat minestrone— especially when that minestrone is made to a Milanese family recipe and served in the soothing surrounds of teal blue walls and velvet chairs. Order Nonna Rosa’s focaccia alongside—another family favourite—and soak up the bustling, buoyant atmosphere and Italian hospitality. The experience of a holiday, but in your lunch break.

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pink Scottish granite, the imposing Hamilton memorial in Portman Square was one its installations—and among the finest, the grandeur of its design rendering it as much a work of public art as a functional piece of infrastructure. Donated by Lady Hamilton in memory of her late husband, this Grade II listed memorial was recently restored to full working capacity by The Portman Estate.

Hamilton memorial drinking fountain

THE GUIDE

A tour of Marylebone’s most notable memorial sculptures

JOHN F KENNEDY MEMORIAL After the assassination of John F Kennedy in 1963, an appeal in the Sunday Telegraph led to more than 50,000 readers making individual donations of up to £1 to create a memorial.

The bust, commissioned from Cubist sculptor Jacques Lipchitz, was unveiled on 15th May 1965 by the late president’s brothers, Robert and Edward Kennedy, outside the new International Students House on Marylebone Road.

In 2017, the sculpture was attacked by vandals, who caused significant damage to the plinth. It was returned to public display on a new plinth and in a new location—inside the lobby of International Students House, but viewable through the windows.

THE TRITON FOUNTAIN This ornamental fountain, a bronze sculpture of the Greek god Triton, which stands in

An appeal in the Sunday Telegraph led to more than 50,000 readers making individual donations of up to £1 to create a memorial to JFK

the middle of a pool in Queen Mary’s Gardens, Regent’s Park, was erected in memory of Sigismund Goetze. Goetze, now largely forgotten, was once a renowned artist—his 1904 painting Despised and Rejected of Men, was an “artistic sensation” at the Royal Academy, and the vast patriotic murals he created for the Foreign Office are a sight to behold—but it was as a donor of public art, including the park’s ornate Jubilee Gates, that he is best remembered.

In 1936, he commissioned the sculptor William McMillan to design the Triton Fountain, but the outbreak of war meant it was not finished until 1950, when it was installed by Goetze’s wife Constance.

HAMILTON MEMORIAL DRINKING FOUNTAIN The Metropolitan Drinking Fountain and Cattle Trough Association was set up to improve access to free, clean drinking water in public places. Rendered in

THE RAOUL WALLENBERG MONUMENT Raoul Wallenberg was a Swedish diplomat who helped save the lives of more than 100,000 Jews in Nazioccupied Hungary toward the end of World War II. The Great Cumberland Place monument, which depicts Wallenberg against a 10-foot bronze wall, made up of 100,000 Schultz Passes—a pseudo-legal document that made Hungarian Jews honorary Swedish citizens, thus exempting them from wearing the yellow star and, in many instances, being sent to concentration camps—and draped in the Swedish flag, is the work of Scottish sculptor Philip Jackson. It was unveiled by the Queen in 1997 in a moving ceremony attended

by Holocaust survivors.

WILLIAM PITT BYRNE MEMORIAL FOUNTAIN This elaborate drinking fountain in Bryanston Square was erected in 1862 in memory of the journalist and newspaper proprietor William Pitt Byrne, who inherited responsibility for The Morning Post newspaper from his father. Designed by his wife, the novelist Julia Clara Pitt Byrne, it includes a plaque with a wordy and rather breathless testament to Pitt Byrne’s qualities as a man (“noble disinterestedness … forgiving temper … unobtrusive piety”) that sits somewhere between touching and embarrassingly over-egged.

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Rent a property in Marylebone directly from The Howard de Walden Estate

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The Howard de Walden Estate owns, manages and leases one of the largest property portfolios within Marylebone

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