stardom on tv: p.16 group system: p.22 p.28 biomedical ...€¦ · duffy blood group an...
TRANSCRIPT
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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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BIO.08.18.002.indd 2 18/07/2018 10:13
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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
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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: [email protected]: 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 [email protected]
CHARTERED [email protected]
P05 IBMS Aug18_Ed Leader_v2gh.indd 5 20/07/2018 11:04
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BIO.08.18.006.indd 6 18/07/2018 10:15
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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
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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
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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
WH
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P8-11 IBMS Aug18_News_v2gh.indd 9 20/07/2018 11:05
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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
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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
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Multimers
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BIO.08.18.012.indd 12 18/07/2018 10:17
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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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Serum Copper, Selenium & ZincCopper, Zinc and Selenium are essentialtrace elements. Deficiency and toxicity canmanifest as severe clinical symptoms. Regular monitoring in patients on parenteral nutrition and patients requiring long-term nutritional support is crucial for improving clinical outcomes.
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P13 IBMS Aug18_Tech News_v2gh.indd 13 20/07/2018 11:07
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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
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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
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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
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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
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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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PHOT
OGRA
PHY:
RIC
HARD
GLE
ED19THE BIOMEDICALSCIENTIST
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
PHOT
OGRA
OGRA
PHY:
PHY:
RIC
RICH
ARD
HARD
GLE
GLEE
DED19THE BIOMEDICALSCIENTIST
SCIENCEPathology networks
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P18-21 IBMS Aug18_Pathology Networks_v3gh.indd 19 20/07/2018 11:10
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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
P18-21 IBMS Aug18_Pathology Networks_v3gh.indd 20 20/07/2018 11:10
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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.
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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)
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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
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SCIENCEThe big story 25THE BIOMEDICALSCIENTIST
P24-27 IBMS Aug18_Tumour Markers_v1gh.indd 25 20/07/2018 11:12
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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
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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
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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