ONE TO ONE

DAVE SPIKEYFrom haematology in Bolton to comedy stardom on TV: p.16

TRANSFUSION SCIENCE

DUFFY BLOOD GROUPAn introduction to the Duff y blood group system: p.22

LAB EQUIPMENT

THE TEST TUBEThe history and the symbolic power of this iconic piece of kit: p.28

PATHOLOGY NETWORKSWhat progress has been made on the consolidation to 29 networks

and what happens next?

THE BIOMEDICAL SCIEN

TIST AUGUST 2018 BIOMEDICAL SCIENTIST

THE

THEBIOMEDICALSCIENTIST.NET AUGUST 2018

ONE TO ONE

DAVE SPIKEYFrom haematology in Bolton to comedy stardom on TV: p.16

TRANSFUSION SCIENCE

DUFFY BLOOD GROUPAn introduction to the Duff y bloodgroup system: p.22

LAB EQUIPMENT

THE TEST TUBEThe history and thesymbolic power of this iconic piece of kit: p.28

What progress has been made on the consolidation to 29 networks

and what happens next?

THEBIOMEDICALSCIENTIST.NET AUGUST 2018

P01 IBMS Aug18_Cover_v9gh.indd 7 19/07/2018 16:41

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EDITORIAL5 Biomedical scientists have a lot

to off er outside the laboratory

NEWS7 News in numbers

8 Research, funding, developments and clinical updates

13 Product advances and launches

OPINION14 The big question: Does

biomedical science still represent a career for life?

16 One-to-one: Dave Spikey may be a famous comic and actor now, but in the late sixties he was starting a biomedical science career

SCIENCE18 Consolidation of

pathology networks: Progress made on the 29 networks and a look at the next steps and future plans

22 Duff y Blood Group System: Laboratory Manager Martin Maley gives an introduction

24 The big story: A brief review of the development, analysis and clinical application of important tumour markers

28 The test tube: Review of the history and symbolic power of this iconic piece of lab kit

CONTENTS34 British Journal of Biomedical

Science: Synopsis of all the papers featured in the third issue of 2018

ADVICE36 How to… prepare to meet

potential employers

38 Biomedical Science Day: A round up of the events

MY IBMS40 Institute news: The latest

from the IBMS

43 Journal-based learning: CPD exercises based on journal articles

44 CPD update: Training courses, events and activities

45 Here to help: Advice for those undertaking IBMS examinations

MY LAB50 Norbert Sene gives a

guided tour of Gibraltar’s Department of Pathology

24

22

16

AUGUST 2018IBMS.ORG

COVERFEATURE

RECRUITMENT ADVERTISINGKaty Eggleton

ISSN 1352-7673© 2018 Institute of Biomedical Science

PRINTED BYWarners Midlands plcThe Maltings, Manor LaneBourne, Lincolnshire PE10 9PH

Neither the publisher nor the IBMS is able to take responsibility for any views or opinions expressed in this publication. Readers are advised that while the contents are believed to be accurate, correct and complete, no reliance should be placed upon its contents being applicable to any particular circumstances. Any advice or information published is done so without the Institute, its servants or agents and any contributors having liability in respect of its content.

PUBLISHED BYRedactive Publishing LtdLevel 5, 78 Chamber Street, London, E1 8BL+44 (0)20 7880 6200 redactive.co.uk

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3THE BIOMEDICALSCIENTISTAUGUST 2018

Contents

P03 IBMS Aug18_Contents_v1gh.indd 3 20/07/2018 11:03

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BIO.08.18.004.indd 4 18/07/2018 10:14

Afew months ago I

accompanied my mother to

an outpatient appointment

and, as usual, I asked various

pertinent questions of the

consultant to ensure I was

clear about her follow-up

and actions required.

Unfortunately, my attitude to clarity,

accuracy and planning wasn’t shared, and

I have just spent the past week discovering

a trail of misinformation that has resulted

in my mother having to be referred back

to the consultant. My frustration is

without limit.

I am sharing this with you because, as

a profession, we understand the need for

clear, well-communicated messages; a

good unambiguous instruction or

statement means we all know where we

stand and can act or plan accordingly.

I was, therefore, very pleased with the

rewrite of the Institute’s guidance on

communicating results; it covers every

eventuality and provides good, clear

advice. It is a pity that our attention

to detail wasn’t mirrored in the

aforementioned outpatient encounter.

This leads me on to the results of an

exercise undertaken by the executive

team at the Institute that consisted of

a personality test and team role feedback.

As with any team, we are a mixture of

personalities and our strength is in our

complementary diff erences. What was so

striking is that I share my “type” with my

closest colleagues and we apparently

operate with a biomedical scientist “group

mindset”. The attributes we possess

SCIENTISTS DELIVER

The NHS is missing out on what biomedical scientists have to off er beyond the door of the laboratory.

that have been associated with the

revised train timetables could have been

anticipated and avoidance actions built

into the plans.

Now there is something else I would

like to share with you: apparently I have

a tendency to catastrophise. Yes, I can

spot a potential disaster a mile off and

extrapolate that potential to any one of a

number of ghastly outcomes unless I take

appropriate preventative action. Perhaps

I’d better give Govia Thameslink a call...

include “considerable analytical and

problem solving skills”, “an affi nity for

accuracy and maintaining high

standards” and “favouring practical

action”. Sound familiar?

I think the various management boards

in our hospitals and trusts are missing out

on what biomedical scientists have to

off er beyond the door of the laboratory. I

believe that we share certain professional

characteristics and, while we may not all

be the best “baby-kissers”, and were not

showcased as health service heroes in

the NHS 70th birthday celebrations,

we possess skills that are essential to

planning and delivering sound strategies.

In fact, if Govia Thameslink employed

biomedical scientists among its planning

staff , it’s possible the service problems Sarah MayDeputy Chief Executive

5THE BIOMEDICALSCIENTISTAUGUST 2018

Sarah May

Institute of Biomedical Science is the professional body for the biomedical science profession.

INSTITUTE OF BIOMEDICAL SCIENCE12 Coldbath SquareLondon, EC1R 5HLUnited Kingdom+44 (0)20 7713 0214+44 (0)20 7837 9658Email: mail@ibms.orgWeb: www.ibms.org

FOLLOW THE INSTITUTE

Join us on facebook.com/biomedicalscience

Follow us on Twitter@BiomedScience Find us on LinkedIn

PRESIDENTAlison Geddis CSci FIBMS

CHIEF EXECUTIVEJill Rodney

DEPUTY CHIEF EXECUTIVESarah May CSci FIBMS

EXECUTIVE HEAD OF EDUCATIONAlan Wainwright CSci FIBMS

EXECUTIVE HEAD OF MARKETING AND MEMBERSHIPLynda Rigby

EDUCATION AND TRAININGeducation@ibms.org

EXAMINATIONSexaminations@ibms.org

MEMBERSHIPmc@ibms.org

CHARTERED SCIENTISTchartered@ibms.org

P05 IBMS Aug18_Ed Leader_v2gh.indd 5 20/07/2018 11:04

BIO.08.18.006.indd 6 18/07/2018 10:15

RIP: 456

80%

TheNHS: Then

vsnow

“Cancer in elderly to surge” The number of elderly people in the UK diagnosed with cancer each year is set to rise by 80% in less than 20 years, a report predicts.Cancer Research UK estimates that by 2035 about 234,000 over-75s will get cancer each year – up from 130,000 at present.

Hay feverThe percentages of those from the UK who believe that they suffer from hay fever:

At least 456 patients died after being given powerful painkillers inappropriately at Gosport War Memorial Hospital, a report has found. An independent panel said that, taking into account missing records, a further 200 patients may have suffered a similar fate.

● Breast cancer

● Colorectal cancer

● Lung cancer

● Pancreatic cancer

● Lung disease

● Respiratory infections (such as pneumonia)

● Stroke

● Heart attacks.

A think tank report comparing the NHS with 18 similar nations finds it is performing below average on 8 of the 12 most common causes of death. These are:

The amount spent on health is now 12 times more than it was when the NHS started. This is the case after

inflation is taken into account.In real terms, the increase is from

£12.9bn in 1949-50 to £149.2bn in 2016-17.

£149.2bn

SCIENCE NEWS

IN NUMBERSbn£ nn

33%Women

31%Adults overall

28%Men

Excellent

Good

Average

Below average

7THE BIOMEDICALSCIENTISTNEWS

In numbers

p07 IBMS Aug18_News In Numbers_v2gh.indd 7 20/07/2018 11:05

SCIENCE

NEWS

A gene signature in the bloodstream could reveal whether someone is going to develop active tuberculosis (TB ) m onths before any symptoms begin.

Such a signature has now been developed by a team led by the Francis Crick Institute and University of Leicester.

The research looked at 53 TB patients in Leicester and followed 108 of their close

contacts over two years to see who developed active TB.

They found that those who remained healthy showed no sustained gene signature, while six of the nine who went on to develop active TB showed a strong, sustained signature.

This is the fi rst study to link the presence of signature and the onset of early TB before the patient has symptoms.

This small proof-of-principle

study shows a potential new direction for TB detection.

Anne O ’ Garra, senior author of the paper, said: “ This study was a promising proof-of-principle, offering new insights into how to develop gene signatures for active TB.

“The next step will be to develop and test different gene

signatures in larger groups of people, with

the aim of being able to offer validated tests to patients within the next decade.”

The research was carried out in

collaboration with BIOA STER and bioMér ieux and the University of Cape Town.

go.nature.com/2MJYYVI

A genetically modifi ed poliovirus therapy shows

signifi cantly improved long-term survival for patients

with recurrent glioblastoma.

The therapy, developed at Duke Cancer Institute in the

US, has a three-year survival rate of 21% in a phase 1

clinical trial. In comparison, just 4% of patients at Duke

with the same type of recurring brain tumors were alive

at three years when undergoing the standard treatment.

Darell D Bigner, senior study author, said:

“Glioblastoma remains a lethal and

devastating disease, despite advances in

surgical and radiation therapies. There is

a tremendous need for fundamentally

diff erent approaches. With the survival

rates in this early phase of the poliovirus

therapy, we are encouraged and eager

to continue with the additional studies.”

bit.ly/BS_AugNews02

PROOF-OF-PRINCIPLE

BLOOD SIGNATURE COULD IMPROVE EARLY TB DIAGNOSIS

BRAIN TUMOURS

Poliovirus therapy for recurrent glioblastomaExercise can reduce infl ammation in obese people by changing the characteristics of their blood, according to new research.

The blood cells responsible for causing infl ammation are

formed from stem cells within the body.

This new research is the fi rst to show that exercise alters the

characteristics of these blood-forming stem cells and reduces the

number of blood cells likely to cause infl ammation.

These fi ndings provide a new explanation of how exercise may

improve health in adults with obesity.

Young, lean adults and young, obese adults were recruited for

this study. Comprehensive physiological characterisation of all

participants occurred before and after completion of a six-week

exercise programme.

This consisted of three bicycling or treadmill running sessions

per week, with each session lasting approximately one hour.

Blood was collected before and after the exercise training

intervention to quantify blood-forming stem cells.

The results demonstrate that exercise reduced the number of

blood-forming stem cells associated with the production of the

type of blood cells responsible for infl ammation.

bit.ly/BS_AugNews01

HAEMATOLOGY

“EXERCISE MAKES THE BLOOD OF OBESE PEOPLE HEALTHIER”

8 THE BIOMEDICAL SCIENTISTNEWSScience

P8-11 IBMS Aug18_News_v2gh.indd 8 20/07/2018 11:05

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HOT

MOSQUITOESResearchers at O hio State University say that mosq uitoes are the inspiration for their work to create a painless medical microneedle.

NOT

MEDITERRANEAN DIET

The New England Journal of Medicine has pulled a 20 13 paper showing that

eating a Mediterranean diet reduced cardiovascular disease. It issued a rare

retraction, amended and republished the article.

HOT

FOSSILSThe cranium of a

four-million-year-old fossil from South Africa

shows similarities to our own when scanned

through high-resolution imaging systems.

NOT

MOUTH ULCERS Scientists have developed a plaster that sticks to the inside of the mouth and administers steroids directly to oral ulcers.

HOT

PIANO LESSONSNew research indicates piano lessons have a specifi c effect on young children’ s ability to distinguish different pitches, which translates into an improvement in discriminating between spoken words.

NOT

TEENAGERSA new study from the

University of Waterloo highlights a low level of

awareness among young people around the

hygiene precautions req uired when handling food.

BIOENGINEERING

BLOOD TEST FOR AUTISMIt may soon be possible to determine whether a child has autism

from a blood test.

At present, it is determined by clinical examination, meaning

detection does not usually happen until the child is four years old.

However, scientists have been trialling a new test that uses an

algorithm to predict if a child has autism spectrum disorder,

based on metabolites in a blood sample.

The tests were carried out on 303 children in groups and

reported 88% accuracy.

Juergen Hahn, lead author, said: “This is an approach that we

would like to see move forward into clinical trials and ultimately

into a commercially available test.

“The most meaningful result is the high degree of accuracy we

are able to obtain using this approach on data collected years

apart from the original dataset.”

The study has been published in the journal Bioengineering and

Translational Medicine.

bit.ly/BS_AugNews03

Keystone virus has made the jump from mosquitoes to humans, with a case now confi rmed in Florida.

A 16-year -old boy is the fi rst confi rmed case and researchers believe the virus could be widespread in North Florida.

It is spread by a mosquito cousin to the Aedes aegypti, which was responsible for spreading Zika. R esearchers from the University of Florida

identifi ed the Keystone virus in the teenager after he visited an urgent care clinic in North Central Florida.

Medical professionals suspected he had Zika vir us, as his case was seen during a Zika outbreak. But he tested positive for the Keystone virus.

A report of his case has now been published in the journal Clinical Infectious Diseases.

bit.ly/BS_AugNews04

VIROLOGY

FIRST KEYSTONE HUMAN INFECTION

9THE BIOMEDICALSCIENTISTNEWSScience

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AT’

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P8-11 IBMS Aug18_News_v2gh.indd 9 20/07/2018 11:05

A new technique has been developed

that may be the solution for the live

monitoring of biomarkers.

This sensing technology enables the

super-sensitive measurement of

biomarker concentrations over time.

It is based on the fact that tiny particles

in liquid are continuously in Brownian

motion because water molecules collide

with them.

The researchers, from Eindhoven

University of Technology, bound the

particles through a nanostrand to a

glass plate, causing the particles to

wiggle back and forth.

The biomarker to be measured

binds temporarily to specifi c adhesive

molecules that are fi xed to both the

particles and the plate.

When a biomarker molecule attaches

itself to both a wiggling particle and to the

plate, the particle suddenly becomes

attached, which greatly reduces its mobility

– until the biomarker is released again.

The mobility of the particles, which are

coupled to the transparent glass, could be

easily observed by the researchers with light.

go.nature.com/2zgnewW

Some bacteria can release toxins that

provoke their neighbours into attacking

each other, says a new study.

The authors state that this is a tactic

that could be exploited to fi ght infections.

Bacteria often engage in “warfare” by

releasing toxins or other molecules that

damage or kill competing strains.

This war for resources occurs in most

bacterial communities, such as those

living naturally in our gut, or those that

cause infection.

As well as producing toxins that directly

kill their competitors, bacteria can release

toxin “provoking agents” that make other

strains increase their aggression levels by

boosting their toxic response.

In a new study, led by Imperial College

London and the University of Oxford,

researchers used a combination of

experiments and mathematical models to

see what happens when bacteria provoke

their competitors.

When used against a single competitor,

they found that provocation backfi res: the

provoked strain mounts a strong toxic

counter-attack and harms the provoking

strain. When three or more strains are

present, provocation causes competing

strains to increase their aggression and

attack each other. This can lead to the

competitors wiping each other out,

especially when the provoking strain is

shielded from, or resistant to, their toxins.

Lead author Diego Gonzalez said:

“By provoking other strains to attack

each other, the toxin of the provoker

is more eff ective than what would be

expected based on its real toxicity.”

bit.ly/BS_AugNews05

NHS patients in England will not

be eligible for a range of procedures

deemed “ineff ective or risky” under

new cost-cutting measures.

The 17 routine procedures include

tonsil removal, breast reduction and

varicose vein surgery, among others.

The treatment will be off ered only

if it is judged to be of “compelling”

benefi t and there are no alternatives.

NHS England said the move would

aff ect about 100,000 people every

year and would free up an

estimated £200m.

Patients at risk of

serious harm from

their condition will

continue to be

off ered treatment,

it was confi rmed.

HUMAN BIO MOLECULES

Monitoring biomarkers liveNHS FINANCES

“INEFFECTIVE OR RISKY” PROCEDURES CUT

MICROBIOLOGY

BACTERIA PROVOKE “WARFARE”

10 NEWSScienceTHE BIOMEDICAL SCIENTIST

P8-11 IBMS Aug18_News_v2gh.indd 10 20/07/2018 11:06

UNDER THE MICROSCOPEThis month: Cyan

As in the colour cyan?That’s the one – the blue-green that is one of the primary colours in the subtractive colour model.

What’s the latest?University of Manchester researchers believe that the colour is a hidden factor in encouraging or preventing sleep. They say higher levels of cyan

keep people awake, while reducing cyan is associated with helping them sleep. The impact was felt even if changes were not visible.

Wasn’t this the case recently with blue light? Yes. Researchers have already established the link between colours and sleep – and blue light was previously identifi ed as more likely to delay sleep. "Night mode" settings have since been created for phones and laptops,

which have reduced blue light in an attempt to lessen the damage to sleep.

What’s next for cyan?Researchers are now calling for devices for computer screens and

phones that could increase or decrease cyan levels.

Why would you want to increase levels? While lowering levels can help

people sleep, increasing cyan could be helpful for the

screens of people who are working at night and need to stay awake.

How easy is it to reduce cyan?It’s not too tricky, apparently. The researchers say that they can create the same colours without using cyan.

What about just not looking at your device late at night? That's a good idea. A recent study of 91,000 people said screen use after 10pm could increase the likelihood of developing depression, bipolar disorder and neuroticism.

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Stopping cholera spreading between

members of the same household

could be key to reducing cases.

The claim comes from a new large-scale

genomic study looking at how samples of

cholera are related to each other.

The authors found that nearly 80%

of infections were related to the fi rst

case of the disease entering the

household, rather than to other strains

of the disease that were circulating in

the same area.

There are up to fi ve million cases per

year globally and around 120,000 deaths

every year, according to Unicef.

Researchers at the Wellcome Sanger

Institute in Cambridge looked at

samples taken from cholera patients at

the International Centre for Diarrhoeal

Disease Research in Bangladesh.

They sequenced the genomes of all 303

samples to see how the strains were

related to each other and compared them

with strains from other parts of the globe.

They found that nearly 80% of the

secondary infections were linked to the

fi rst case in that household within the

fi rst fi ve days.

Daryl Domman, lead author

of the study, said: “Preventing this

spread within the household could

enormously reduce cholera outbreaks,

and highlights the need for

prioritising local control strategies.

“This could have a huge impact,

not only on the individual households,

but also on the entire region.”

go.nature.com/2NoFIhG

GENOMIC RESEARCH

HOW TO STOP CHOLERA

A prostate cancer drug has been

provisionally rejected as a fi rst-line

treatment on the NHS in England.

The draft recommendation from the

NICE means abiraterone (Zytiga) won’t be

made routinely available for men with

newly diagnosed prostate cancer that

has spread to other parts of the body.

As it stands, the NHS in England can

only prescribe abiraterone for these men

once standard hormone treatment or

chemotherapy has failed.

Results from recent clinical trials have

shown that giving abiraterone alongside

steroids and hormone therapy as a

fi rst-line treatment can reduce the

chance of the cancer coming back

and improve survival, when compared

with hormone therapy alone.

Harpal Kumar, Cancer Research

UK’s Chief Executive, called the

decision “disappointing”.

The committee that made the decision

concluded that it could not accurately

estimate the drug’s cost eff ectiveness

based on the data that was submitted.

bit.ly/BS_AugNews06

FIRST-LINE TREATMENT

PROSTATE CANCER DRUG GIVEN INITIAL “NO” FOR NHS

11THE BIOMEDICALSCIENTISTNEWSScience

P8-11 IBMS Aug18_News_v2gh.indd 11 20/07/2018 11:06

Hydragel von Willebrand

Multimers

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BIO.08.18.012.indd 12 18/07/2018 10:17

Synbiosis’ eAST software for automatic

zone measurement of antimicrobial

susceptibility testing (AST) plates has

been upgraded to improve antibiotic SIR

(Susceptible, Intermediate, Resistant)

category determination.

It rapidly generates and analyses AST

data, making it ideal for regulated clinical

and antibiotic development laboratories.

The new eAST software now has all

the 2018 breakpoint values for European

Committee on Antimicrobial Susceptibility

Testing (EUCAST) and Clinical Laboratory

Standards Institute (CLSI) guidelines

included in its expert rules database.

The plate images can be stored in a

secure SQL database for cross-referencing.

synbiosis.com

SYNBIOSIS

MEASUREMENT SOFTWARE UPGRADE

Nightingale Health will analyse the

biomarker profi les of 500,000 blood

samples from UK Biobank.

Nightingale’s biomarker profi ling

technology will be used to analyse UK

Biobank blood samples by measuring

metabolic biomarkers that recent studies

have found are predictive of future risk for

heart disease, type 2 diabetes and many

other common chronic diseases.

Until recently, technological constraints

and prohibitive costs have prevented the

analysis of comprehensive metabolic data

from large-scale biobank collections.

nightingalehealth.com

NIGHTINGALE HEALTH

BLOOD SAMPLE ANALYSIS

With expanded imaging capabilities,

Olympus has launched version 2.1

of its imaging platform cellSens.

Enabling researchers to create

clean and detailed images in

less time, it delivers faster

deconvolution and improved

feature sets across all levels.

cellSens Dimension and Standard

now feature fully integrated multi-

channel acquisition and support for

the latest high-end devices. The

capabilities of cellSens Entry

have also been expanded, so

users can now manage encoded

devices, perform measurements

and export the results to Excel.

olympus-lifescience.com

OLYMPUS

DRIVING RESEARCH FORWARD

TECH

NEWS

13THE BIOMEDICALSCIENTISTNEWS

Technology

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Trace Elements LaboratoryCity Hospital, Dudley Road

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P13 IBMS Aug18_Tech News_v2gh.indd 13 20/07/2018 11:07

THE BIG QUESTIONTHIS MONTH WE ASK

“Does biomedical science still represent a career for life?”

14 THE BIOMEDICAL SCIENTISTOPINIONBig question

P14-15 IBMS Aug18_Big Question_v1gh.indd 14 20/07/2018 11:09

Maria HaynesConsultant Biomedical Scientist

Maidstone and Tunbridge Wells NHS Trust

Y es. Now more than ever there are increasing options for career opportunities that are more diverse. A “career” is no longer about choosing your discipline, working

through the grades to one day become a

manager. Management is not where

everyone wants to ultimately end up. We

have seen an increase in specialties and

additional qualifi cations at FRCPath level

for those who want a career with hands-

on practical applications, off ering better

job satisfaction.

Ian DaviesHealthcare Science Course Leader

Staffordshire University

I n short, yes. But it is an interesting question that opens up discussions about roles of biomedical scientists across healthcare and beyond.Firstly, I suppose it depends what your

vision of a biomedical scientist is.

Traditionally, we undertake laboratory-

based diagnostics, and that role will

certainly continue to be a pivotal and

exciting area of practice, as test

repertoires increase and the possibilities

of the genomic era expand.

Importantly though, we need not

confi ne ourselves to that role and must

consider the skills and knowledge that

biomedical scientist education brings

and how we can apply these across the

wider healthcare and life sciences sector

– for example product development,

management and public health.

Using myself as an example, my

background is as a biomedical scientist

within an NHS clinical chemistry

department. A few years ago, I decided

that I wanted to change focus and began

a journey into academia – although I am

no longer on the “laboratory bench”, I use

the knowledge, behaviours and skills of a

biomedical scientist every day, whether it

be in delivering education, identifying

research opportunities or counselling

students. I identify primarily as a

biomedical scientist and the same would

be true if my career path had led me into

healthcare management or research and

development, for example.

So yes, it can provide a lifelong career,

especially when entered into with an

open mind and the ability to diversify.

It is no longer just about progressing to management, there has been an increase in specialisms

IMAG

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Chris ChasePathology Training Manager

Hull and East Yorkshire Hospitals NHS Trust

A bsolutely, yes. With more and more clinical decisions being made from the information gathered from laboratory testing, there will always be a need for biomedical scientists.

That is not to say that the job will not

change – with the introduction of

automation, robotics and artifi cial

intelligence, biomedical science is at the

forefront of advances in technology, and

with a greater diagnostic use of molecular

biology and genomics, job roles will

undoubtedly change, with a greater

emphasis on the science.

With the traditional boundaries that

are being broken down within healthcare

science, such as in advanced practitioner

roles within cellular pathology and

equivalence routes, there is now a greater

opportunity for career development for

biomedical scientists.

There are many routes now open

for biomedical scientists to follow

– education and training, quality, higher

management, or advanced scientifi c roles.

These routes to progression are very clear

and prescriptive and with a wide range of

postgraduate qualifi cations now available,

career progression should be not too

arduous for ambitious scientists, provided

the appropriate resources and supportive

mechanisms are available.

The work biomedical scientists do now

and will do in the future is vital within

the healthcare environment and

opportunities within the profession will

only increase and yes, biomedical science

can be a career for life. It has been for me.

15THE BIOMEDICALSCIENTISTOPINION

Big question

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16 THE BIOMEDICAL SCIENTISTOPINIONOne-to-one

“I did an event for a room full

of clinical biochemists; it

was an interesting gig.

What I hadn’t realised and

I should have done is that

you can’t tell a clinical

biochemist just one joke.

You’ve got to tell them a

joke that’s not very funny, a joke that’s

funny and a joke that’s hilariously funny

so they’ve got a low and high control –

that’s the only way it’s going to work.”

Dave Spikey knows what he’s talking

about. Unusually for a stand-up comic he

started his career as a biomedical scientist

– joining Bolton Royal Infi rmary in 1968

as a Junior Medical Laboratory Technician

and rising up the ranks over a 30-year

career to become Chief Biomedical

Scientist in haematology at the Royal

Bolton Hospital.

The year 2000 came and he found

himself one Monday morning in a rainy,

windswept Bolton carpark, dressed as a

giant berry and singing the Katrina and

the Waves classic Walking on Sunshine. He

was fi lming an episode of Channel 4

sitcom Phoenix Nights, which marked his

move into full-time comedy. But this

didn’t come overnight: he’d been doing

stand-up and writing comedy in his spare

time since 1987.

Early yearsComedy has always been a huge part of

Dave’s life. “I remember an essay I wrote

about what I did on my holidays during

primary school, and the teacher wrote,

‘Another good essay from David, but why

does everything have to have a comedy

element?’ I wasn’t even aware I was doing

that – it was just the way I was seeing

life,” he says.

Dave was academic – he passed his

11-plus, went to grammar school and was

sitting his A-levels with plans to become a

doctor when his father (then a painter

and decorator) had an accident and

couldn’t work; as the eldest child Dave

needed to become breadwinner.

While in hospital, he saw a job advert

for medical laboratory technicians and

encouraged Dave to apply – suggesting it

would stand him in good stead once he

could resume his studies. “I went to the

interview on the Friday from the comfort

of my new home, the sixth-form common

room, and found myself on the Monday

morning in a white coat in a microbiology

lab helping sample phlegm.”

Starting outDave was one of seven basic-grade juniors

who did the rounds in the hospital in

microbiology, histopathology,

biochemistry and haematology,

while working towards their

Ordinary National Certifi cate

on day release. “I found my

home in haematology – I

thought it was the SAS of

pathology. I aspired to be on call

at night and come in and help save lives,”

he says. “I loved haematology.”

Dave progressed on to the Higher

National Certifi cate and went on to do the

two-year Special Examination leading to

Fellowship. He got the senior post at the

hospital following his viva for the Special

exam. “I instigated a thalassaemia and

haemoglobinopathy screening programme

for our population in Bolton and

introduced all the techniques for that.”

Career successHe also improved other areas of the

laboratory. “We were a very basic lab.

Haematology was really expanding back

in the mid-1970s and we were getting left

behind. There was an old-fashioned

attitude of sending everything to

be tested at Manchester Royal

Infi rmary. We thought: ‘No, we

can do it here.’ I introduced

cytochemistry techniques

– PAS, Sudan Black, etc – I got

all that started. Those areas I

am immensely proud of, mainly

Dave Spikey may be a famous comic and actor now, but in the late sixties he was starting a biomedical science career.

FROM HAEMATOLOGY TO STAND-UP COMEDY

P16-17 IBMS Aug18_OnetoOne_v1gh.indd 16 20/07/2018 11:09

17THE BIOMEDICALSCIENTISTOPINION

One-to-one

because I instigated them,” he adds.

The career didn’t come without its

challenges, and the biggest in his early

days in microbiology was having to kill

mice and guinea pigs that had been

tested on, then dissect them. “I was so

inept at it that it’s a whole comedy sketch

right there – I feel guilty even joking

about it,” he says. “I’ve always been a

massive animal lover and I refused to do

it in the end. I was threatened with the

sack, but I didn’t lose my job.”

Move to comedy“Hospitals provide a brilliant little arena

for comedy. In certain situations things

can get quite dark and they just need

somebody to diff use them. Sometimes

you get it right and sometimes you get it

wrong,” he adds.

This kind of environment provided

fertile ground for Dave and his colleagues

to put on pantomimes. He originally

wrote and directed them, but when one

performer took exception to his directing

and walked off stage, Dave had to go on

and act himself. “I was terrifi ed but once I

saw them laughing, it was like a drug.”

After a colleague told him he should

be a comedian, he started doing talent

shows, later playing one gig a month

as a hobby: “It took me three years or

so to get a bit of motion.”

Originally performing in the ubiquitous

working men’s clubs, Dave “died horribly

in half of them” because his observational

comedy wasn’t popular, but a comedy

seminar evening in Bolton started

featuring comics doing similar

conversational humour to Dave.

“I got more and more work that way,

then I started to go to gigs in London.

That’s where it became hard. I would

work my days until quarter past fi ve, then

drive down to London, do a spot in a grotty

pub and then drive all the way back up, all

for nothing.”

Comedy successThe fi rst turning point was an open spot

at the Comedy Score in London, which

went so well that the management took

him on as one of their acts. “The other

massive turning point was meeting Peter

Kay when he won the North West

Comedian of the Year [Dave had won the

award the previous year and as a result

was compering the event].

“We got on straight away and wrote

That Peter Kay Thing together, then we

wrote Phoenix Nights.”

Dave’s fi rst career has infl uenced his

second. “Over the years I’ve garnered so

many stories. I never just tell one gag

after another.” And despite his huge

success, he misses it: “As soon as I walked

in the lab I loved being part of that team.

You met everybody, you knew everybody;

it was a fantastic family, it was a fantastic

place to work.”

ALL ABOUT DAVE Won Mastermind with the highest-ever score with the specialist subject, human blood: “I told the producers I’d love to do the red blood cell as my specialist subject. They said: ‘The red blood cell – it’s a bit narrow though, isn’t it?’ I thought: ‘A bit narrow?! It’s bloody microscopic!’”

Introduced column chromatography in the lab, which led to screening programmes in Bolton for hypochromic microcytic anaemia.

Had an animal sanctuary at home – rescuing dogs, goats, ducks, battery hens – and works with a range of charities, including Animals Asia, Pet Rehome and Paws for Kids.

Has won two British Comedy Awards and been nominated for a BAFTA, appeared on Parkinson and the Royal Variety Performance, and is most proud of the Performance of the Year award for his first-ever tour show.

* Dave Spikey’s 30th Anniversary Tour, Juggling On A Motorbike, is at theatres around the UK from 27 September 2018. For details, visit davespikey.co.uk

P16-17 IBMS Aug18_OnetoOne_v1gh.indd 17 20/07/2018 11:09

18 THE BIOMEDICAL SCIENTISTSCIENCEPathology networks

CONSOLIDATION OF PATHOLOGY NETWORKS

18 THE BIOMEDICALSCIENTISTSCIENCEPathology networks

P18-21 IBMS Aug18_Pathology Networks_v3gh.indd 18 20/07/2018 11:09

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SCIENCEPathology networks

As the NHS enters its 70th

year, one constant has been

the provision of universal

healthcare, the other

constant has been change.

Change in approach, change

in patients, change in

technology, change in

treatment and change in staff . Change for

organisations as large and complex as the

NHS is challenging. In pathology it has

been long known that the current

confi guration of services is ineffi cient and

demonstrates variation in terms of cost

and quality. When compared to

international services we do not operate

at the size and scale of other services

meaning that we require more people and

more expensive equipment to provide our

services. Innovation and adoption of new

methods and techniques takes longer and

is adopted inconsistently across the

country. This is all at a time when we

have a demonstrable workforce shortage,

when funding for capital equipment is

becoming harder to secure and when

adoption of new techniques to support

personalised medicine is becoming an

im perative to diagnose disease earlier and

improve our patient outcomes. This lack

of size and scale also means we operate

with several single points of failure that

impacts upon hospital and community

care. The most recent report authored by

Lord Carter of Coles for the Department of

Health, entitled Operational Productivity and

Performance in English NHS Acute Hospitals:

Unwarranted Variations, demonstrated that

this is true across healthcare not just in

pathology. One of the biggest obstacles

in driving change has been a clear

national plan and comparative data.

NHS Improvement was given the task

to change that.

In September 2017, following the

largest ever data collection undertaken in

pathology services in England, NHS

Improvement wrote to all acute hospital

trusts, setting out a plan. The plan was to

establish 29 pathology networks. These

networks were modelled on the “Hub and

Essential Services” laboratory approach.

All hospital trusts, and later, all specialist

hospital trusts were mapped into these

networks and asked to form plans to

deliver these changes. The data collected

from providers (now available on Model

Hospital, the online productivity and

effi ciency tool) show unwarranted

variation in terms of pay and non-pay

cost. This variation is not linked to size or

type of hospital, however, can be linked to

the service adopting best practice and

innovative ways of working.

The benefi tsOne of the challenges to this change is for

trusts to understand the clinical as well as

economic benefi t. We know that in some

areas of diagnostics patients do not

currently receive the turn-around time

needed to adequately support their care.

Networking can deliver these faster and

more appropriate turn-around times.

Working in larger networks, patients

– irrespective of where they live – should

be able to access specialty expertise,

which is not always available. Working at

scale across networks can enable service

resilience; consistent protocols,

workforce, and equipment across multiple

centres will ensure, in the event of a

single laboratory being unavailable for

whatever reason, there will be other

laboratories capable of maintaining

services. This scale can also ensure

optimum equipment can be purchased,

allowing laboratories to provide a wider

repertoire of tests utilising the best

methodologies. The latest sequencing

technology or point-of-care testing

(POCT) equipment purchased to serve a

larger population is utilised more

effi ciently, meaning that business cases

are more robust and more likely to be

successful and, vitally, patients get access

to the latest and best diagnostic tests and

treatments. Interoperable IT systems with

high levels of redundancy and immediate

back-up and disaster recovery become

aff ordable when serving multiple

hospitals. We have seen a number of

high-profi le issues across the country,

where IT systems have failed or back-up

systems do not have the immediacy to

Head of Pathology Services Consolidation at NHS Improvement, David Wells, sets out the progress made on the 29 networks and looks at the next steps and future plans.

PHOT

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SCIENCEPathology networks

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P18-21 IBMS Aug18_Pathology Networks_v3gh.indd 19 20/07/2018 11:10

It is an opportunity to put into place

the advanced roles envisioned

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20 THE BIOMEDICAL SCIENTISTSCIENCEPathology networks

provide seamless continuity, these

failures have led to issues for service

provision, and ultimately suboptimal

patient care.

The greatest benefi t is to the workforce.

Training opportunities and advanced

roles are more consistently available

when services cover larger populations.

The medical workforce in certain

disciplines within pathology is in short

supply and biomedical and clinical

scientists are well placed to adopt new

and innovative roles to not only enable

networks to progress, but also to deliver a

high-quality timely diagnostic service to

patients. This is an opportunity to put

into place the advanced roles envisioned

by the modernisation of scientifi c careers

programme and ensure all staff work to

their top capability and competence.

ProgressSince the publication of NHS

Improvement’s operational productivity

report into the consolidation of

29 pathology networks, we have been

progressing a number of workstreams

to support providers in delivering the

changes essential for sustainable, high-

quality, clinically-focused pathology

services in England. NHS Improvement

has issued a number of toolkits to share

learning, provide best practice advice and

guidance. The Pathology team at NHS

Improvement have been engaging with

providers, arm’s length bodies, professional

bodies and industry experts to ensure all

parts of the system work together to

support this change. This includes work

that is on-going in genomics,

antimicrobial resistance, screening,

workforce, digital/AI innovations and other

innovative disruptive technologies. This is

to ensure the system makes one change to

a truly interoperable system that will

deliver on the national grand challenge to

diagnose disease earlier and improve

patient outcomes.

To date, over 80% of trusts are making

progress towards networking their

pathology services, others are going

through the processes to enable them.

To date, only two hospital trusts have

found themselves unable to agree with

the proposed model.

We continue to work with trusts,

collecting and validating data, making

some changes to the original networks or

confi rming the proposed confi guration.

We have completed our series of CEO

workshops for most regions, these

sessions have been very useful to all

involved and have helped us move with

pace in carrying out the work of

modelling and forming networks.

During the year we also mapped

specialist trusts into the 29 pathology

networks with an ambition for them to

work collegiately with other trusts locally,

but also to work on a national level to

ensure patients have access to expert

clinical diagnostic services whilst

supporting the sustainability of these

services, recognising the challenges they

face in training, recruitment, retention

and adoption of new technologies.

The announcement in the spring by the

Secretary of State for Health and Social Care

awarding a total of £68m to organisations

progressing projects networking their

pathology service demonstrates the

commitment to delivering this change to

the sector. In addition to that, we have been

working closely with the Offi ce of Life

Science to support the adoption, at pace, of

the Life Science Industrial strategy for the

benefi t of our patients and the NHS.

Next stepsThere is still much to do. Some networks

move at pace, as named networks making

ambitious plans for the future of

pathology in their region, and existing

networks embrace the “at scale” drive and

have begun active discussions with other

networks to see how they can deliver on

a larger scale. Disappointingly, some

networks are yet to get off the ground

and some are not seeking to work at the

Left. Ratio MLA to total lab staff for acute teaching trusts (high to low)Right. Ratio BMS to total lab staff for acute teaching trusts (high to low)

VARIATION IN USE OF MLA AND BMS STAFF IN ACUTE TEACHING TRUSTS

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21THE BIOMEDICALSCIENTISTSCIENCE

Pathology networks

required level of consolidation. These

services are in the minority. The sector,

both inside the NHS and industry, reports

that, unlike previous pushes, the

commitment to change is palpable. NHS

Improvement will continue to support

and monitor development of these

networks, feeding into the Care Quality

Commission’s Use of Resources

inspections, where trusts are not making

progress in removing unwarranted

variation in cost and quality. We are also

exploring working with commissioners

who ultimately buy pathology services to

identify best price and quality supporting

those that do network.

Committing to qualityNHS Improvement is charged with rolling

out the national Pathology Quality

Assurance Dashboard (PQAD) proposed by

the Barnes review in 2012. This

dashboard, which will be issued in the

summer, will hold trust boards to account

for the pathology service they provide to

their patients. Measuring not only

clinically appropriate turn-around times

but also: adoption of NICE guidelines;

number of training posts in the service;

number of tests provided under ISO 15189;

and how many community point of care

audits performed, amongst other metrics.

We have worked closely with the

professional bodies to ensure these

metrics are appropriate and relevant.

Historically, creation of networks has not

led to a deterioration in quality, we expect

networks once transition is complete to

be ISO 15189 accredited for all tests that

are provided. This may mean

consolidation of certain tests into

specialists testing centres with the

relevant clinical and scientifi c expertise.

Pathology Optimisation Delivery BoardAs well as working with the aspirant

networks, NHS Improvement hosts the

Pathology Optimisation Delivery Board,

chaired by the National Clinical Advisor

for Pathology, Professor Adrian Newland

and vice-chaired by the President of the

Royal College of Pathologists, Professor

Jo Martin. The board is attended by a

representative from the IBMS and

representatives of the other professional

organisations of the Pathology Alliance,

NHS England, Health Education

England, and senior leaders from

existing networks. The Board’s role is to

hold us to account and provide expert

advice to ensure creation of clinically

safe and sustainable pathology services

for the future. It is important that we,

as well as individual trusts, maintain a

high level of transparency through staff

and system engagement to ensure

successful change. We also work closely

with the national unions, industry and

UKAS to ensure the whole sector is

informed of the changes.

LeadershipWe are under no illusion of the challenge

that the creation of 29 networks brings to

trusts and staff . The networks will need to

cover the needs of several hospitals,

providing the services essential for

patient care, reaching out into the

community providing direct access

diagnostic testing as well as introduce

new and innovative approaches to

pathology, such as digital pathology and

personalised medicine. It is vital that the

profession gets behind the change,

providing the expertise to the local

networks, identifying the needs and

opportunities to ensure a high-quality

good value pathology service. This

presents the profession with a unique

opportunity to develop not only new

advanced clinical roles, but also new

senior operational leadership roles for

those prepared to take on the challenge.

FuturePathology has a huge part to play in

supporting the future of healthcare in

England. Pathology cuts across the

traditional boundaries of primary and

secondary care, it has the data that can

drive clinical pathways and testing

strategies. We will need to challenge

traditional delivery models, such as

employing POCT to support not only a

personalised approach to medicine but

also a public health imperative. It is

encouraging that other devolved nations

are following the progress of the 29

pathology networks carefully and have

commenced similar programmes.

ℹ For extra diagrams and fi gures, visit thebiomedicalscientist.net

THE PRINCIPLESAll networks were modelled on the following principles:

Patient referral routes, population size (1.5m minimum to 2.5m maximum), existing partnerships, such as STPs (Sustainability and Transformation Partnerships) or existing networks and geography was also considered for certain networks.

The way the networks would operate would be for the local network to decide. Networks currently operating in England are either an alliance of partners working together, a public joint venture where one trust takes on the running of services for the other hospitals, or a private joint venture where a new provider runs the services for the networked hospitals.

All activity that is not required to support direct acute patient care would be done in one place for the whole network (either as a single hub or a disturbed hub).

Essential service laboratories will be just that, only services that are essential to support the acute delivery of healthcare will be available.

P18-21 IBMS Aug18_Pathology Networks_v3gh.indd 21 20/07/2018 11:10

SCIENCEBlood group systems

When it comes to

learning more about

an interesting blood

group system (BGS),

Duff y is probably

perfect. Not too many

antigens; well-

documented, clinically

signifi cant antibodies, disease association

(malaria being the prime example) and, in

the current climate of the proliferation of

DNA testing, interesting genetic

mutations (GATA-1) are always a bonus.

Duffy BGS antigensThe Duff y BGS has fi ve main antigens

recognised by the International Society

THE DUFFY BLOOD GROUP SYSTEMHead of RCI Laboratory Martin Maley gives an introduction to the Duff y blood group system.

Caucasian populations Black populations Chinese populations

Fy(a+b+) 49% 1% 9%

Fy(a-b+) 34% 22% 1%

Fy(a+b-) 17% 9% 91%

Fy(a-b-)

23THE BIOMEDICALSCIENTISTSCIENCE

Blood group systems

counterpart, anti-Fyb can also cause

occasional severe HTR, but is usually only

associated with mild HDFN.

Anti-Fy3 was described in 1971 in a

previously transfused pregnant Australian

woman. Because the antigen is resistant

to enzyme treatment the urge to name it

anti-Fyab was also resisted. This was

fortunate, as it is now known that the Fy3

antigen is geographically remote from the

position of the Fya/Fyb polymorphism.

Anti-Fy3It has been known for years that people

within the Black populations, with the

Fy(a-b-) phenotype have been transfused

with Fy(a+b-), Fy(a+b+) and/or Fy(a-b+)

blood, and yet most do not produce anti-Fy3.

Many people within the Black

populations are homozygous for a mutation

within an erythroid-specifi c, GATA-1,

transcription-factor binding site, upstream

of the coding region of the Duff y gene.

This mutation prevents expression of

the Duff y glycoprotein on red cells, but

not on other cells.

Duff y glycoprotein was found to be

expressed in endothelial cells lining

post-capillary venules of soft tissues and

splenic sinusoids.

Duff y mRNA was not detected in the

bone marrow of such individuals, but was

present in their lung, spleen and colon.

This coding sequence is usually

identical to that of FYB, although amongst

people from Papua New Guinea, the

coding sequence is often identical to FYA

The immune system of such individuals

does not recognise the Fya and/or Fyb

antigen as “foreign”, and they will not,

therefore, produce anti-Fy3.

Disease associationThere are numerous examples of Duff y

system antigens being linked to disease

states – the classical example being its

involvement in susceptibility to certain

strains of malaria.

There is a selective advantage in being

Fy(a-b-) in areas where malaria is

endemic. Miller et al found Fya and Fyb

antigens act as receptors for malarial

infestation of red blood cells and that

Fy(a-b-) red cells are resistant to invasion

by Plasmodium knowlesi and P. vivax.

Duff y antigen receptor for chemokines

(DARC) has been found to be associated

with a survival advantage in leukopenic

HIV patients. The recessive African-

specifi c DARC null allele increases the

risk of HIV-1 infection approximately

three-fold.

DARC has also been implicated in the

regulation of the growth of prostate

cancer tumours, and its interaction with

CD82 due to its presence on vascular

endothelial cells acts to inhibit the spread

of cancer cells.

two letters of his surname were taken to

be used to denote the name of the

antigen. Anti-Fya can cause mild to severe

haemolytic transfusion reactions (HTR),

and mild to severe (but only rarely)

haemolytic disease of the fetus and

newborn (HDFN). Anti-Fya, in particular,

is classically found in combination with

other antibodies, and these mixtures can

make positive conclusive antibody

identifi cation diffi cult. This, in turn, can

lead to issues in fi nding compatible blood,

should transfusion be required.

Identifi cation of the Fyb antigen

followed in 1951, when it was shown to be

antithetical to the Fya antigen. Although

found much less commonly than its

Martin Maley is Head of RCI Laboratory

at NHS Blood and Transplant and a

member of the IBMS Transfusion

Advisory Panel. He would like to credit

Geoff Daniels’ book Human Blood

Groups, published by Blackwell Science,

which infl uences this article.

To see the article with full references,

visit thebiomedicalscientist.net

Position 42.

Proposed position of Fy3

COOH

Glycine FyaAspartic Acid FybCHO

CHO

336 Major (α)

NH2

338 Minor (ß)

CHO Position of Fy6

IMAG

ES: I

STOC

K/ M

ALCO

LM N

EEDS

(Diagram courtesy of Malcolm Needs)

P22-23 IBMS Aug18_Duffy_v2gh.indd 23 20/07/2018 14:24

24 THE BIOMEDICAL SCIENTISTSCIENCEThe big story

In a previous article in this series,

tumour markers were defi ned as

substances released by a tumour

into blood or urine, or from the

host in response to the tumour.

Their measurement in serum or

urine may be used in screening

asymptomatic patients for

diagnosis, prognosis, monitoring

treatment and recurrence detection.

CA125 – an ovarian cancer marker and analysis The existence of ovarian tumour-associated

antigens was established by a US team led

by Michael Levi in 1969 using Ouchterlony

double diff usion and gel fi ltration.

In 1974, Suzanne Knauf and her

colleagues used immunodiff usion and

immunoelectrophoresis to demonstrate

antigens in three subtypes of ovarian

cancer. Four years later, Bhattacharya

and Barlow detected an ovarian

cystadenocarcinoma-associated antigen

specifi c to serous or mucinous types of

ovarian cancer, which was measured by

radioimmunoassay inhibition and found

to be raised in the sera of ovarian cancer

patients. In a landmark paper in 1981,

with Robert Bast Jr leading a US combined

research team at Brigham Hospital

and Harvard, Boston reported the

development of a highly specifi c

murine monoclonal antibody against

This series continues with a brief review of pioneering work in the development, analysis and clinical application of important tumour markers, with two examples from the CA serum series – CA125 and CA15-3.

human ovarian cancer. The 125th most

promising clone was termed OC125 and

the reacting antigen CA125. A serum

radioimmunoassay using OC125 was

developed by Bast and colleagues in 1983

to monitor epithelial ovarian cancer.

From 1991, immunometric assays

became available, often using two

epitopes, one recognised by OC125 and the

other by M11, an antibody developed by

Tim O’Brien and colleagues at Arkansas.

This assay, designated CA125II, showed

improved assay precision. Commercial

assays from seven major suppliers were

compared in 1998 and found to be

clinically reliable for quantitation of

CA125. Modern automated two site

CLINICAL CHEMISTRY CLASSICS: TUMOUR MARKERS

P24-27 IBMS Aug18_Tumour Markers_v1gh.indd 24 20/07/2018 11:12

SCIENCEThe big story 25THE BIOMEDICALSCIENTIST

P24-27 IBMS Aug18_Tumour Markers_v1gh.indd 25 20/07/2018 11:12

26 THE BIOMEDICAL SCIENTISTSCIENCEThe big story

immunoassays use-high sensitivity

fl uorimetric and chemiluminescent

tracer detection assays. It has been

proposed that the major forms of CA125 in

serum have molecular weights 200-

400kDa and the most often quoted serum

reference range for females is 0-35kU/L

(0-35 IU/ml). However, it is signifi cant

that this value is exceeded in many other

malignancies, such as pancreas, liver and

lung and several “benign” conditions, e.g.

uterine fi broids and endometriosis.

CA125 structure and functionCA125 is a high molecular weight

glycoprotein epitope on a large

transmembrane mucin glycoprotein

MUC16, but due to its complexity and

mucinous nature, there are confl icting

views on its true molecular structure. The

MUC16 gene is expressed under normal

conditions in epithelial tissues, such as

breast and lung, but overexpressed in

epithelial cancers. It has been proposed

that it may have a lubricating function

and protect against foreign particles and

infectious agents. It may also act in a

more sinister manner to promote cancer

cell proliferation and metastases, and

inhibit anti-cancer immune responses.

CA125 and ovarian cancerOvarian cancer is the sixth most common

UK female cancer, with a low prevalence,

particularly in premenopausal women.

Often, vague symptoms lead to a late

diagnosis and a relatively poor prognosis,

with a 46% fi ve-year survival rate. Risk

factors include age, a close family history

of ovarian cancer and inherited mutations

in the BRCA1 and BRCA2 genes.

CA125 is only raised in 50% of stage 1

patients which, with low

specifi city, severely limits its

role in screening. Nevertheless,

there have been a number

of clinical trials in

postmenopausal women

involving serum CA125 alone,

or combined with transvaginal

ultrasound or a variety of risk algorithms.

The largest randomised controlled trial of

over 200,000 postmenopausal women in

UK took place in 2001, led by Ian Jacobs

and Usha Menon at University College

London with three study groups – CA125

and risk algorithm, annual transvaginal

ultrasound, or no screening. It was

claimed that the results suggested that

there may be a reduction in mortality

with CA125 and risk algorithm.

However, the main clinical roles of

serum CA125 are twofold: to diff erentiate

benign and malignant pelvic masses in

postmenopausal women combined with

ultrasound and, secondly and most

notably, serial measurements to monitor

the response to chemotherapy treatment

following surgical resection and the

subsequent detection of recurrence. Other

proposed biomarkers for ovarian cancer

include HE4 – human epididymis protein

4, which may be combined with CA125 to

improve both sensitivity and specifi city,

and mesothelin – a small protein which is

over expressed in ovarian cancer.

Breast cancerBreast cancer has been known from

ancient times but most progress was

made during the 19th and 20th centuries,

notably following the US National Cancer

Act in 1971 with its generous funding for

cancer research (see table for the most

signifi cant achievements).

Despite all this valuable research, it

remains the most common cancer in

women worldwide and the second most

common cause of cancer death in females

in the UK. However, it is more

encouraging that with early and

personalised treatment, 87% of breast

cancer patients have a fi ve-year

survival rate. Tumours may

occur in the breast ducts or

less often aff ect lobular cells,

and around 80% of invasive

breast cancers are ductal and

metastases may result in the

lungs, bones or brain.

CA15-3 a serum tumour marker for breast cancerStudies, notably in the US and Italy

by ME Edynak (1971) and G Fossati (1972)

respectively, helped to establish the

existence of tumour-associated antigens

in breast cancer. It was further shown

that the antigen could be characterised

by sequential solubilisation, protein

fractionation and polyacrylamide agar gel

electrophoresis. Much was gained for our

understanding of the structure of the

glycoprotein MUC-1 associated with

breast cancer by the studies of the British

biologist and geneticist Joyce Taylor-

Papadimetriou. MUC-1 is a large

transmembrane mucin glycoprotein

encoded by the MUC-1 gene and is present

in normal secretory epithelia acting as a

preventive barrier to pathogenic invasion

but may also play an active role in

oncogenesis and is overexpressed in

breast cancer and shed into the

circulation. One antigen on MUC-1,

known as CA15-3, can be measured using

a variety of immunological methods

using the murine monoclonal antibodies,

115D8 & DF3, developed by J Hilkens and

colleagues (1983) and a group led by D

Kufe (1984), respectively. With further

P24-27 IBMS Aug18_Tumour Markers_v1gh.indd 26 20/07/2018 11:12

27THE BIOMEDICALSCIENTISTSCIENCE

The big story

90s were optimistic of the clinical value of

CA15-3; however, it was quickly

recognised that it was another non-

specifi c marker with low sensitivity in

preoperative breast cancer and unsuitable

for screening asymptomatic patients.

Elevated serum levels were found in a

number of non-mammary cancers, such

as lung, colon and ovary, and in benign

breast and ovarian conditions. Sensitivity

was found to be 10-15%, 20-25% and 30-35%

for stages 1, 2 and 3, respectively. It had

been previously shown that increasing

levels may be useful in detecting

advanced disease, and combination with

serum carcino-embryonic antigen (CEA)

allows early diagnosis of metastases in

60-80% of patients with advanced disease.

Expert group the American Society of

Clinical Oncology released a 2007 update

that reports present data is insuffi cient to

recommend serum CA15-3 for screening,

diagnosis and staging and for monitoring

recurrence after primary breast cancer

therapy, but permits monitoring of

metastatic disease during active therapy

when combined with diagnostic imaging,

history and physical examination. Later

reports and recommendations tend to

limit CA15-3 to this clinical application

and propose the use of oestrogen

receptor tissue assays to predict the

response to hormone treatment and

the measurement of human epidermal

growth factor receptor 2 (HER2) to

identify patients to respond to combined

monoclonal antibody therapy, such as

that with Herceptin.

Concluding commentsWhile much has been achieved in the

diagnosis and treatment of ovarian and

breast cancer, the role of both tumour

markers reviewed appears limited to

monitoring treatment. The focus of

attention in breast cancer patients at

present is on the results of the (TAILORx)

trial, using a combination of HER2 results

and a 21-tumour gene expression

microarray to determine the benefi ts or

otherwise of adjuvant chemotherapy.

The research performed by Robert Bast,

Joyce Taylor Papadimitriou, Mary-Claire

King, Donald Kufe and John Hilkens was

fundamental in achieving signifi cant

progress during the last four decades.

Stephen Clarke is a retired IBMS Fellow.

To see the references, view the article

online at thebiomedicalscientist.net

developments during the next decade,

automated two site immunoassays

became available using a variety of

capture and detection systems for serum

CA15-3. With assays, more robust and

sensitive numerous clinical trials were set

up to assess clinical values. A number of

tumour markers for breast cancer,

including CA15-3, were reviewed in 1993

and found that CA15-3 refl ected tumour

burden and was clinically useful in

monitoring therapy. On a technical note,

the standard reference range for females

is

“The test tube has this metaphorical meaning that has

gone far beyond its physical form”

SCIENCELab equipment28 THE BIOMEDICAL SCIENTIST

P28-32 IBMS Aug18_Test Tubes_v1gh.indd 28 20/07/2018 11:14

THE TEST TUBE: A SYMBOLIC STORY

The test tube is possibly the

most unobtrusive piece of

equipment in the lab: its

workaday function and sheer

ubiquity render it more or less

invisible. Scratch beneath the

surface, though, and you’ll

fi nd… well, not a whole lot.

It has little in the way of an arresting

origin story – indeed, the inception of the

test tube is as opaque and colourless as

many of the solutions it holds. The

materials that go into manufacturing test

tubes are generally unexceptional (mostly

plastic or glass, though Pyrex is mildly

diverting), and otherwise there is little to

diff erentiate one test tube from another,

apart from the size, which, roughly

speaking, varies from 10 to 20mm wide, 50

to 200mm in diameter, and 100 to 150mm

long. We could talk about test tube racks

and brushes, but they’re not about to set

the imagination on fi re, are they?

Yet despite this lack of any real defi ning

character or compelling backstory, if one

piece of lab equipment has come to

symbolise chemistry, and in some ways

the whole of modern science, it is the test

tube. How on earth did that happened?

Historic origin Of all the many basic shapes and

sizes of equipment that populate the

average chemistry lab, the test tube

appears to be a relatively new addition:

no mention of it, or anything like it,

While the test tube is hardly the most imposing item of glassware on a scientist’s workbench, its symbolic power is second to none.

29THE BIOMEDICALSCIENTISTSCIENCE

Lab equipment

P28-32 IBMS Aug18_Test Tubes_v1gh.indd 29 20/07/2018 11:14

appears before the 19th century.

One version has it that the test tube

sprang from the imagination of the

Swede Jöns Jacob Berzelius (1779-1848).

Considered one of the fathers of modern

chemistry, Berzelius has more than

enough achievements to his name, not

least discovering silicon, selenium and

thorium, devising the chemical notation

system, and establishing the

diff erences between organic and

inorganic compounds. In light

of that, conceiving the

test tube could have

been something

he tossed off in an

idle moment one

rainy afternoon.

According to the

evidence he

described

something very

similar to what we

know as the test

tube in an article he

normally reach for when they needed to

store or mix small amounts of liquids. In an

article for Chemistry World, the science writer

Philip Ball also points out that Faraday’s

letters were littered with descriptions and

drawings of test tubes: “He sketches one,

for example, in a letter to the German-

Swiss chemist Christian Friedrich

Schönbein in 1854.”

Perhaps Faraday picked up on Berzelius’

idea, scaled it down so that it would fulfi ll

a specifi c practical purpose, and in that

way made it his own? We’ll likely never

know, but whatever the truth it’s fairly

certain that Faraday, Berzelius or anybody

else who might have “invented” the test

tube could not possibly have imagined