BIO-CHEM ENGINEERING MATHS PHYSICS - Wilson's School

Page created by Zachary Hernandez
 
CONTINUE READING
BIO-CHEM ENGINEERING MATHS PHYSICS - Wilson's School
BIO-CHEM

    ENGINEERING

         MATHS

        PHYSICS

1
BIO-CHEM ENGINEERING MATHS PHYSICS - Wilson's School
Introduction
With a new editorial team taking over, we have brought some fresh
ideas with us. We really hope you enjoy the new font, the new
Maths section, the book reviews and the “Intrigued?” page in
addition to the articles, which span from superhero science to
quantum tunnelling.
The team of writers and editors is very proud to welcome you to
the fifth issue of the Wilson’s Intrigue STEM, written for students
by students.

Our Mission
•     Expand your knowledge
•     Contribute to the Wilson’s community
•     Make complicated parts of science more accessible
•     Popularise science and make it more interesting
•     Inspire creativity through wider research

Acknowledgements
The magazine simply could not be produced with such finesse
without the inquiring journalism of the writers and the multiple
zoom calls the new editors have attended to learn and master
formatting in Publisher. A massive thank you to all students
involved for their contributions!
A special thanks must go to Mr Benn, Mr Carew-Robinson, Dr
Cooper, Mr Jackson, Mr Lissimore, Miss Roberts and Dr Whiting for
proofreading and verifying the accuracy of our articles and the
magazine as a whole.
If you would like to write in the sixth issue of the STEM magazine to
research and discover a new aspect to the subjects, please email
me (Divy) at DAYALD@wilsonsschool.sutton.sch.uk for more
information.

Founded by Devanandh Murugesan and his team of
editors in September 2019

Front Cover: This majestic deep sea creature is known as a siphonophore. It is
estimated that there are 175 different species of this class, and although it appears
to be one large organism, it is in fact a colonial organism composed of two
specialised zooids.

                            2
BIO-CHEM ENGINEERING MATHS PHYSICS - Wilson's School
The Wilson’s Intrigue Team
                             Editors
                    Divy Dayal (Chief Editor) Y12
                    Nabeel Abdul Rasheed Y12
                        Aditya Chougule Y12
                          Aditya Jain Y12
                       Atharva Narkhede Y12
                          Mann Patira Y12
                              Writers
   Adam Ali Y12          Kinshuk Jain Y12          Sanuka
  Arya Narang Y11   Karun Kirubananthan        Gunawardena Y12
 Dulain Gamage Y12          Y12              Shinujan
 Folaju George Y11   Matteo Cascini Y11 Saravanamuthu Y12
                                          Syed Shah Y12
Jonathan Peter-Rajan Mohamed Ahmed
         Y11                Y12             Tathushan
                    Moksh Sachdeva Y12   Subenthiran Y12
   Junaid Ali Y12
Junayd Soobratty Y12 Prabhas Vedagiri Y12

                                  3
BIO-CHEM ENGINEERING MATHS PHYSICS - Wilson's School
Contents
 If you are viewing this digitally, you can click on the titles of the articles or sections.
 BIO-CHEMISTRY                                      MATHS
RNA Vaccines: The Copycats                  6       Accuracy of Modelling                39
Inside the Cytokine Storm                   8       Wonders of Euler’s Number            41
Curing Acute Lymphoblastic Leukaemia       10       Doomsday Argument                    43
A Vaccine and a Virus                      12       Prime Tuples                         45
The Heart that Never Beats                 14       Infinite Series and the Real World   47
Growing New Teeth                          16
New: Intrigued? - Organ Donation           17
Can Chloroquine Treat Malaria?             19
How to Use Antibodies to Treat Asthma      21

 COMPUTING                                          PHYSICS
Neuromorphic Computing                    25        Quantum Tunnelling                    50
Quantum Computing: The Future?            27        Startling Subatomic Particles         52

                                                    Volumetric Displays                   54

 ENGINEERING
 The Flying V                             30

 It’s Nanotech, You Like It?              32

 Autonomous Vehicles                      34

 Hydrogen or Electric Cars?               35

 How Accurate is the Flash?               36        REFERENCES                            56

                                                4
BIO-CHEM ENGINEERING MATHS PHYSICS - Wilson's School
DID YOU KNOW?
Dragonflies were one of the first flying
winged insects (almost 320 million years
ago). Today the biggest dragonflies have a
wingspan of 14 cm, however, fossil records
suggest ancient dragonflies had wingspans
of up to two feet!
                                       5
BIO-CHEM ENGINEERING MATHS PHYSICS - Wilson's School
Bio-Chemistry Section
   Inside the Cytokine               Lymphoblastic                       Heart that Never              Growing New Teeth
   Storm                             Leukaemia                           Beats
                                                                                                       What has
   The immune system                 Cancer in the blood                 Artificial Hearts in          translational dentistry
   in action p8                      p10                                 action p14                    discovered? p16

                                                                                         One vial (0.45ml) contains 5 doses
                                                                                         of 30 micrograms of BNT162b2 RNA

                                                                                        entire complex in place while a peptide
                                                                                        bond forms between the two amino
                                                                                        acids through a condensation reaction.
                                                                                        The ribosome then moves along the
                                                                                        mRNA molecule, repeating this
                                                                                        process until a stop codon (UAA, UAG
                                                                                        or UGA) is reached. At this point, the
                                                                                        polypeptide chain stops growing and
                                                                                        detaches from the ribosome [5].
                                                                                        The polypeptide later folds into its
                                                                                        precise three-dimensional shape,
                                                                                        specifically an antigen of the infectious
                                                                                        agent that the vaccine is tailored
                                                                                        towards. In the case of Covid-19, this
                                                                                        antigen comes in the form of the
                                                                                        crown-like spike protein which gives
                                                                                        the coronavirus its name. As is typical

RNA Vaccines: The Copycats
                                                                                        during a primary immune response,
                                                                                        the antigen is displayed on the
                                                                                        surfaces of specific cells known as
                                                                                        antigen-presenting cells or APCs
How RNA vaccines are the key to future pandemics
                                                                                        (which include macrophages, dendritic
By Nabeel Abdul Rasheed (Y12)                                                           cells and B cells). Here, it acts as a

M
                                                                                        signal to trigger an immune response
            any a GCSE biologist is well-   enclosed within a special coating to        which eventually leads to
            acquainted with the             protect the mRNA from extracellular         immunological memory (through the
            traditional vaccine –           RNA-degrading enzymes in the body           production of B memory cells and T
            memorised religiously and       (which detect and eliminate aberrant –      memory cells). In effect, the immune
reproduced on exam paper as ‘a dead         meaning atypical or deviant – mRNAs         system can now respond much more
or weakened form of a disease-              as part of cellular homeostasis) [2,3].     quickly and on a larger scale if the
causing pathogen’. But more recently,       Once the mRNA reaches the target            actual pathogen were to enter the
indeed in the last few weeks, scientific    cells, it is thought to settle into small   body [1,6].
discussion has shifted away from            cup-like depressions in the plasma
                                                                                        Benefits and Drawbacks
these classical live-attenuated or          membrane known as caveolae (Latin
inactivated versions and instead            for ‘little caves’), before entering the    As you might imagine, a novel
towards a newer, altogether more            cell through caveolar endocytosis in        technology like the RNA vaccine comes
exciting prospect: the RNA vaccine.         membrane-bound sacs called vesicles         with more than its fair share of risks
                                            [4]
                                               .                                        and rewards. Chief among the
Details & Mechanism
                                                                                        advantages are:
                                            Having entered the cell, the mRNA can
As is the case in all other types, the
                                            then bind to a ribosome floating in the     Safety: Despite the government’s best
purpose of the RNA vaccine is to train
                                            cytoplasm or one attached to the            efforts, the issue of vaccine safety is
your immune system to respond
                                            rough endoplasmic reticulum, ready          one of continued public concern, as
rapidly to a specific infection by
                                            for the familiar process of protein         illustrated by the ever-growing anti-
mimicking the infectious agent. What
                                            translation. Two transfer RNA (tRNA)        vaccine campaign. In the case of the
distinguishes it from more established
                                            molecules, each carrying a specific         RNA vaccine, there is no chance of
counterparts is the mechanism by
                                            amino acid, align themselves next to        infection because it is entirely free of
which this agent is introduced into the
                                            mRNA codons which are                       pathogen particles. Once the antigen is
body: rather than injecting the
                                            complementary to their own                  ‘memorised’ by B and T memory cells,
pathogen itself, the RNA vaccine
                                            anticodons – the start codon being          the mRNA is degraded by intracellular
comprises a messenger RNA (mRNA)
                                            AUG, which codes for the amino acid         ribosome-degrading enzymes – a
strand that codes for a disease-
                                            methionine. The ribosome holds the          process likened quite aptly by
specific antigen [1]. This sequence is

                                                               6
BIO-CHEM ENGINEERING MATHS PHYSICS - Wilson's School
THE WILSON’S INTRIGUE | BIO-CHEMISTRY                                                                Issue 5 | April 2021

ScienceNews to “a Mission Impossible message that self-            Delivery: As mentioned previously, the RNA-degrading
destructs once it has been played” [2,7].                          enzymes in the body make delivery of the vaccine to body
                                                                   cells quite challenging. The most common drug delivery
Efficacy: The most striking example of an effective RNA
                                                                   system used to combat this are lipid nanoparticles, tiny
vaccine is undoubtedly the most recent one of them all.
                                                                   spherical molecules which can carry lipid-soluble drugs in
BNT162b2, as it is fondly named, was developed by
                                                                   their cell membrane bilayer. They contain protruding
biotechnology giants Pfizer and BioNTech and consists of
                                                                   surface proteins known as homing peptides which allow
a modified mRNA encoding a mutated form of the SARS-
                                                                   for specific, targeted drug delivery. What’s more, lipid
CoV-2 spike protein. Large-scale clinical trials involving
                                                                   nanoparticles ensure high encapsulation efficiency of
more than 43,000 participants demonstrated a vaccine
                                                                   mRNA, ease of transport and reduced risk to body cells
efficacy rate of 95%, measured from seven days after the
                                                                   and immune system compared to alternative methods
second of two doses [8]. This was consistent across most           [12]
                                                                       .
demographics, so much so that in early December 2020,
the UK became the first country in the world to approve            Storage: Many RNA vaccines need to be frozen or
the coronavirus vaccine – ordering over 800,000 within             refrigerated, owing to the instability of the RNA molecule
the first few days [9]. Up to now, the largely successful          itself and the temperature-sensitive nature of the lipid
results of this project serves as testament to the                 nanoparticles. The Pfizer-BioNTech vaccine must be
potential of the RNA vaccine. Even so, in the context of           stored at -70°C, almost four times colder than the
vaccine trials, a sample size of 43,000 may not represent          average household freezer [7]! Such demanding
all demographics to the degree of validity associated with         requirements may be difficult to reach for countries with
other, non-emergency use vaccines – thus paving the way            limited or no refrigeration facilities; even for those
for more extensive research in the near future.                    privileged with this infrastructure, the cost of
                                                                   procurement and transportation acts as yet another
Production: RNA vaccines have the added advantage of
                                                                   barrier to large-scale vaccine distribution [2].
being produced much more rapidly and easily in
standardised laboratory procedures than traditional                The Future
vaccines. In fact, the German biopharmaceutical company
                                                                   Unsurprisingly, a strong focus of current RNA vaccine
CureVac (which specialises in mRNA technology) believes
                                                                   research is aimed at developing and improving the
that it would only take two months to produce an RNA
                                                                   current mRNA sequences used in the COVID-19 vaccines –
vaccine for influenza. Perhaps more importantly, the
                                                                   particularly minimising side-effects and making the
drastically lowered production period would enable swift
                                                                   molecule more suitable to everyday conditions. However,
rollout of vaccines during pandemics, once again
                                                                   this looks likely to be overshadowed by the even more
illustrated by the invaluable efforts of Pfizer and
                                                                   daunting prospect of new, emerging variants of the virus
BioNTech [1,2].
                                                                   – growing areas of concern for governments and
Equally, however, the problems associated with any                 biotechnological companies alike.
medical treatment cannot simply be ignored. Just as
                                                                   Looking further ahead, RNA vaccines may well hold the
there have been major reasons to celebrate, we are also
                                                                   key to further advances in multi-purpose treatment,
faced with numerous challenges when it comes to RNA
                                                                   providing protection for more than one disease at a time
vaccines:
                                                                   (as has already been achieved in conventional vaccines
Side-effects: While the RNA vaccine may be free of                 for a select few diseases – most notably the MMR vaccine
pathogenic material, it can on rare occasion induce                which protects against measles, mumps and rubella) [3].
adverse effects on users, the most recent of which                 Research and clinical trials are also being carried out on
involved two NHS workers suffering allergic reactions to           RNA vaccines that could be used to encode cancer
the Pfizer-BioNTech vaccine just one week after it was             antigens and stimulate immune responses against
approved for use in the UK. Both suffered an                       malignant tumours [3]. This may even become a form of
anaphylactoid reaction (not to be confused with immune-            personalised treatment by tailoring the mRNA to the
mediated and life-threatening anaphylaxis), but were               unique properties of the tumour cells of that particular
later treated and soon restored to full health. Some               individual [1].
allergists and immunologists believe this type of reaction
                                                                   Whatever the future holds, it seems increasingly likely
to BNT162b2 could be linked to the compound
                                                                   that RNA technology will play a major part in it, making it
polyethylene glycol (PEG) contained in lipid nanoparticles
                                                                   of greater interest to us than ever before. Our role both
used to package the mRNA [10]. They believe that a small
                                                                   as students and members of the public is to continue
number of people previously exposed to PEG may have
                                                                   educating ourselves of the advances and the shortfalls
high levels of antibodies against it, putting them at risk –
                                                                   encountered along the meanders of its development.
however small – of an anaphylactic reaction to the
                                                                   Only then can we hope to leave behind a society rife with
vaccine [11]. Nevertheless, this theory is supported by
                                                                   uncertainty and scepticism into one which offers hope
limited evidence as of yet, and the general consensus is
                                                                   and remedy for all.
that initial side-effects are “common with new
vaccines” (the words of Professor Stephen Powis, medical           Edited by Aditya Chougule
director for the NHS in England) [10].

                                                               7
BIO-CHEM ENGINEERING MATHS PHYSICS - Wilson's School
THE WILSON’S INTRIGUE | BIO-CHEMISTRY                                                           Issue 5 | April 2021

                             Inside the Cytokine Storm
                                            By Aditya Chougule (Y12)

O
         ur immune system is both a blessing and a curse. Its intricacies allow for a phenomenal structured
         defence against invaders but these intricacies also mean a great deal more places for mistakes to be
         made. As such many diseases arise from malfunctioning of the immune system, the very organ that
         swore to protect us. One poignant example of this is the cytokine storm. Particularly relevant at the
moment, the cytokine storm is a terrifying condition whereby an overabundance of cytokines can cause
hyperinflammation and can lead to multi-system organ failure and eventually death.

                                                            cellular apoptosis- programmed cell death- and
                                                            inhibit carcinogenesis and viral replication [3].
                                                            Essentially, all these cytokines play a wide variety of
                                                            roles and communicate with a multitude of organ
                                                            systems, making their betrayal even more
                                                            frightening.
                                                         Those reading this will likely have heard of cytokine
                                                         storm from the news in relation to COVID-19 but in
                                                         fact there are quite a few triggers for cytokine storm
                                                         besides a viral pathogen. Indeed, there are three
  Cytokine distribution [1]                              types of cytokine storm: iatrogenic, pathogen-
                                                         induced and monogenic. Pathogen-induced cytokine
  Key to the disease process of cytokine storms is (you
                                                         storm probably sounds more familiar than the other
  guessed it) the role of cytokines; these tiny proteins
                                                         two since it is the most common cause for the
  are tremendously important in coordinating the
                                                         condition; it results from naturally occurring
  immune response since they act as regulatory
                                                         microbial infections and viral invaders. In sepsis-
  signals that activate effector cells and also help to
                                                         associated cytokine storm (sepsis being a life-
  resolve the immune response. There are a few
                                                         threatening reaction to an infection), very often the
  cytokines that have a higher significance over others
                                                         collateral damage caused by the immune response
  in the context of a cytokine storm- specifically
  interferon-γ, interleukin-1, interleukin-6, and TNF-
  and as such they are usually found in elevated
  levels in the midst of a cytokine storm. Interferon-γ
  is primarily secreted by activated T cells (Th1 and
  cytotoxic T lymphocytes) and natural killer cells
  and is a potent activator of macrophages, which
  engulf pathogens and cells by phagocytosis [1]. The
  interleukin-1 cytokines are a family of 11 cytokines
  that have a wide range of biological functions,
  including acting as a leukocytic pyrogen (mediator
  of fever) and activating macrophages and Th17
  cells, the latter acting as helper cells that
  coordinate the immune response [2]. Interleukin-6                       Cytokine storm pathway [1]
  is one of the more complex cytokines since it is
  produced by and acts on immune and nonimmune
  cells across multiple organ systems- it is an
  important mediator of the acute inflammatory
  response and in increasing antibody production.
  And last but not least, TNF (tumour necrosis factor)
  is a proinflammatory cytokine with a vast array of
  functions; although its primary role is to induce
  fever, augment inflammation, and activate
  antimicrobial responses through interleukin-1 and
  interleukin-6 producing cells, TNF can also induce

                                                        8
BIO-CHEM ENGINEERING MATHS PHYSICS - Wilson's School
THE WILSON’S INTRIGUE | BIO-CHEMISTRY                                                            Issue 5 | April 2021

  as it attempts to clear the pathogen can be more         (sensitivity measuring the proportion of positives
  deadly than the pathogen itself, which is why            that are correctly identified) and specificity of 0.73
  sepsis has such a high mortality rate [4]. Iatrogenic    (specificity measuring the proportion of negatives
  and monogenic cytokine storms are quite different        that are correctly identified) in patient trials- very
  but equally as terrible. An iatrogenic trigger is that   encouraging figures [6].
  caused by medical treatment, for example,
                                                           As for treatment, very often it simply involves
  infusion of CAR T cells (T cells which have been
                                                           supportive care to maintain critical organ function
  genetically engineered to target cancer cells) has
                                                           as well as control of the underlying disease- in the
  been shown to induce cytokine storm with excess
                                                           case of a bacterial trigger this would include
  levels of interferon-γ and interleukin-6 [1].            antibiotics, for example- and immunosuppression,
  Additional iatrogenic causes of cytokine storm           such as with the use of corticosteroids like
  include gene therapies, immune checkpoint                dexamethasone, to limit collateral damage
  inhibitors, cardiac-bypass surgery and allogeneic        induced alongside the cytokine storm. Eliminating
  stem-cell transplantation. Furthermore,                  a particular cytokine that is elevated in the blood
  monogenic disorders- genetic disorders caused by         using treatments such as anti-interleukin-6, anti-
  a single gene mutation- can also trigger cytokine        TNF, anti-interferon-γ, or anti-interleukin-1β
  storm, although this is rare, along with
                                                           antibody therapies may be effective in some
  autoimmune and neoplastic diseases. For
                                                           instances. However, it may also propagate the
  example, in patients with primary HLH autosomal
                                                           underlying disease if given too soon, especially if
  recessive monogenic abnormalities this leads to
                                                           the cytokine storm has been caused by a
  defects in effector and regulatory mechanisms in
                                                           pathogenic invader. Hundreds of
  the immune system, which results in overactive
                                                           immunomodulatory drugs are currently under
  histiocytes and lymphocytes without a pathogenic
                                                           investigation for treatment of COVID-related
  trigger [5]. In patients with secondary HLH, viral,
                                                           cytokine storm; successful examples include the
  autoimmune or neoplastic disorders lead to a
                                                           interleukin-6 receptor antagonists tocilizumab and
  cytokine storm. For example, patients lacking
                                                           sarilumab- drugs used to treat rheumatoid
  functional perforin, which is critical for resolving
                                                           arthritis which have showed to reduce mortality
  infections and inflammation, have prolonged T-cell
                                                           from 35.8% to 27.3% when compared with
  production of interferon-γ and TNF, so when they         standard care and found to significantly improve
  are infected with a viral pathogen, secondary HLH-       survival as well as cutting time spent in hospital by
  associated cytokine storm develops and it                a week to ten days in patients with severe COVID-
  becomes very difficult to shut off the immune            19 (REMAP-CAP trial) [7].
  response; a self-reinforcing inflammatory spiral
  ensues, leading to multi-organ failure and likely   I’d like to finish by lauding the work of healthcare
  death [1].                                          professionals and scientists in helping the world
                                                      get a grip on this pandemic. While there are many
  In the COVID-19 sphere, a distinct positive         lessons to be learned from the past year, we must
  correlation between the nasopharyngeal viral load stop to appreciate the selfless work that these
  and cytokine levels in ICU patients suggests that   people carry out and what they are willing to risk
  those with high viral loads are more susceptible to to help others. So, THANK YOU!
  cytokine storm [1]. Also, comorbidities such as
  hypertension, diabetes and obesity are associated Edited by Mann Patira
  with more severe cases of COVID-19, possibly
  because of the pre-existing chronic inflammatory
  state or a lower threshold for the development of
  organ dysfunction, thereby increasing
  susceptibility to cytokine storm in these patients.
  Surprisingly, it has been found that classic
  cytokine storm identification methods, such as the
  2004 HLH criteria and the 2016 macrophage
  activation syndrome criteria, each missed at least
  75% of COVID-associated cytokine storm patients,
  while classifying many others as false positives.
  Lacking an acceptable scale, scientists at Temple
  University in Philadelphia created their own
  Temple Criteria using patient data to determine
  whether a patient had cytokine storm from COVID-
  19; the method had a sensitivity of 0.84
                                                           9
BIO-CHEM ENGINEERING MATHS PHYSICS - Wilson's School
THE WILSON’S INTRIGUE | BIO-CHEMISTRY                                                    Issue 5 | April 2021

Can Stem Cells Help Cure Acute Lymphoblastic Leukaemia?
                                         By Aditya Jain (Y12)
What is leukaemia?                                          into a different type of cell, for example, a skin

L
                                                            cell cannot create a neuron. Our body does,
        eukaemia is a cancer caused by the
                                                            however, have some multipotent stem cells left.
        uncontrolled division of white blood
                                                            They are stored in the bone marrow, brain and
        cells. There are two categories of
                                                            some other organs. There are three types of
        leukaemia: fast spreading acute
                                                            stem cells: totipotent stem cells – the best
leukaemia and slow spreading chronic
                                                            example of which is the zygote and can
leukaemia [1]. Acute leukaemia further splits into
                                                            differentiate into any cell and create a whole
two categories: acute myeloid leukaemia and
                                                            organism; pluripotent stem cells – the ones in
acute lymphoblastic leukaemia. In this article I
                                                            the embryo four days after fertilisation which
will focus on acute lymphoblastic leukaemia
                                                            can also differentiate into any cell in the body
which, unfortunately, is one of the most
                                                            but not a whole organism; multipotent stem
common cancers in children.
                                                            cells – found in the foetus and in specific tissues
How does acute lymphoblastic leukaemia                      in the body and can only differentiate into those
occur?                                                      tissues [4].
Acute lymphoblastic leukaemia is a condition
that affects the bone marrow. The cells of the
bone marrow have a mutation in which portions
of two non-homologous chromosomes are
switched. As a result, the cells are stuck in the
early stages of development and are immature.
This means that they do not function effectively,
so lose their ability to properly produce mature
blood cells and uncontrollably divide,
overcrowding the bone marrow and causing
cytopenia. These faulty chromosomes also
cause the intracellular proteins of the cell to fold
incorrectly and so the cells cannot function and
divide as they normally would be able to. Acute
lymphoblastic leukaemia leads to the release of
large volumes of premature white blood cells.               Stem cell potency hierarchy
As a result, this means that the number of red
blood cells and platelets are reduced (cytopenia)           Why are stem cells vital?
which can cause tiredness and breathlessness.
Being premature, the white blood cells are                  The stem cells in our body help promote normal
ineffective in fighting off viruses and other               function and allow the body to produce new
infections, allowing the viruses to proliferate to          cells to repair minor damage, for example. The
other places like the brain and liver [2].                  adult blood stem cell in our bone marrow can
                                                            differentiate into different types of cells that are
What are stem cells?                                        vital to normal body function as displayed in the
Stem cells are undifferentiated human cells that            diagram. Without the adult bone marrow stem
are able to develop into many different cell                cell, we would not have any white blood cells
types. This can range from muscle cells to brain            that protect us from pathogens or the red blood
cells. In some cases, they can also fix damaged             cells that are essential to allow aerobic
tissues [3]. Most of the cells in our body are not          respiration and not even the platelets that help
stem cells, they can only replicate through                 stop bleeding. Therefore, stem cells are
mitosis, creating copies of themselves. These               extremely necessary & vital to the body. When
therefore are very specialised and adapted to               stem cells stop functioning properly, the
their function; they cannot just suddenly turn              patient’s immune system is likely to be

                                                       10
THE WILSON’S INTRIGUE | BIO-CHEMISTRY                                                   Issue 5 | April 2021

compromised; the likelihood of catching                    with either healthy stem cells from a donor
infections, therefore, increases.                          (allogenic) or the patient’s own stem cells
                                                           (autologous), which are purged and frozen for
Blood stem cell differentiation                            preservation, removing any leukaemia cells from
                                                           the sample, and then infused back into the
                                                           blood, after chemotherapy [6].
                                                           This treatment can significantly improve the
                                                           survival chances of cancer patients. In a study of
                                                           508 patients the eight-year survival average was
                                                           65% in patients less than 30 and 38% in patients
                                                           less than 60 [7]. This treatment provides many
How does stem cell therapy help cure acute                 benefits and forms of the treatment are already
lymphoblastic leukaemia?                                   in use. For example, in Europe, more than
                                                           26,000 patients are treated with blood stem
Stem cells are extraordinary in our body
                                                           cells and this is only going to grow with time [8].
considering their ability to develop into different
cell types. They can, therefore, help to prevent           Drawbacks of therapy
or cure diseases such as heart disease, spinal             There are many potential concerns with stem
cord injuries and diabetes, as well as cancer. As          cell therapy:
part of multipotent stem cell therapy, the cells
used here form a specific germ layer after the             •     Risk of cancer: the stem cells could divide
differentiation of pluripotent stem cells, and can               uncontrollably and cause cancer once
give rise to one or two specialised cells. This                  again; this means that it could actually
type of therapy is proven to be effective and has                harm the person even further, affecting
been used for decades in haematopoietic stem                     their normal function and not actually
cell transplantation. Haematopoietic stem cell                   helping them.
transplantation uses either allogeneic stem cells          •     Rejection: the immune system attacks and
(stem cells from another individual) to replace                  destroys these stem cells since they are
the defective ones found in the bone marrow or                   foreign; to reduce risk of this the patient
autologous cells from the patient’s own body                     could take immunosuppressants and also
that have the leukaemia cells removed. These                     take cells from a blood relative to help
cells will now produce the correct lymphocytes                   reduce the chance of rejection.
that function properly and do not uncontrollably
divide.                                                    •     Graft vs Host disease: transplanted stem
                                                                 cells or bone marrow contains cells from
This type of stem cell therapy involves the use of               the donor’s immune system; these cells
bone marrow as a treatment to haematologic                       can sometimes recognise your own tissues
and lymphoid cancers – mainly acute                              as being foreign and attack them.
lymphoblastic leukaemia. The underlying cause
of the cancer may be that the patient has faulty           Although stem cell therapy is still in its infancy,
genes producing defective cells which can cause            its benefits and widespread uses mean that it is
problems like the uncontrollable division of T-            likely going to flourish in the future. With further
cells. The way this treatment works is that bone           research and development, I believe stem cell
marrow from a healthy individual with matching             therapy will be at the forefront of our fight
antigens (to help avoid rejection) is transplanted         against cancer, and will be the next major
into the bone marrow of the patient. Replacing             revolution in patient healthcare, just like
the bone marrow means that healthy                         antibiotics and vaccines were before it.
intracellular proteins are produced which yield            Edited by Aditya Chougule and Atharva
healthy precursors, thereby, reducing the                  Narkhede
production of unhealthy and defective
lymphocytes [5]. The old cancerous cells are
either already killed due to previous
chemotherapy or surgery. These are replaced

                                                      11
THE WILSON’S INTRIGUE | BIO-CHEMISTRY                                  Issue 5 | April 2021

A Vaccine and a
Virus
By Moksh Sachdeva (Y12)

W
              hat is a virus?
              A virus is an
              obligate
              parasite made
of proteins and
sometimes a membrane
made of lipids containing
single stranded or
double stranded DNA or
RNA. Viruses cannot
replicate on their own
however they can
replicate in living cells. A    spherical with                themselves into a
virus can also affect the       icosahedral symmetry.         modified form of a cell
behaviour of the host           Prolate – this is a           membrane where either
cell. It is estimated that      common arrangement            an internal membrane
over one million different      for bacteriophage (a          (such as the nuclear
viruses infect                  virus that infects            membrane) or the outer
invertebrates on earth.         bacteria) heads and           membrane (that
Viruses can be argued to        consists of an                surrounds the infected
be alive since they can         icosahedron elongated         host cell) allows them to
persist independently,          along one axis.               gain a viral envelope.
however some may                Helical – this shape may      Complex – this shape
argue viruses are not           consist of a central cavity   possesses a capsid that
alive since they are            or hollow tube and tend       is unlike the other
unable to replicate             to form a helical             shapes and may also
independently [1].              structure since they tend     possess other structures
                                to be stacked a central       such as a complex outer
What is the structure of        axis.                         wall or a tail of protein.
a virus?                        Envelope – these types
Viruses don’t have a            of viruses envelop
specific shape since they
display a variety of sizes
and shapes otherwise
known as morphologies.
In general, they can be
summarised into five
main morphological
virus types [1]:

Icosahedral - these are
most animal viruses
however some animal
viruses may be near

                                             12
THE WILSON’S INTRIGUE | BIO-CHEMISTRY                                 Issue 5 | April 2021

A virion, which is more         the surface antigens due      weakened or inactive
commonly known as a             to point mutations. A         pathogen into the body
complete virus particle,        point mutation is a           where white blood cells
has a protective coat of        genetic mutation where a      then produce antibodies
protein called a capsid         single nucleotide base is     that would be able to
which surrounds the             changed, inserted or          combat the virus if it were
nucleic acid. The virus         deleted from the DNA or       encountered by
may also have gained a          RNA sequence of an            traditional infection.
lipid envelope from the         organism. This results in     Vaccines harness the
membrane of the host            the wrong amino acid          natural activity of the
cell. Proteins encoded          being produced, thus          immune system to better
from the viral genome           altering the shape of the     prepare it for the
make up the capsid and          protein. Often, when a        exposure of a particular
the shape of the capsid         virus drifts a vaccine may    virus [3].
allows for morphological        still be effective. This is
distinction.                    due to the change in the      The different types of
                                protein structure being       vaccines [4]
How does a virus work?          minimal and so the virus      The Oxford vaccine is
Viruses work by attaching       is still recognised by the    composed of a weakened
onto specific molecules         antibodies. However,          version of the common
on the cell surface. A          when a virus shifts the       cold virus which has
penetration virus will be       vaccine is no longer          indeed been genetically
endocytosed into the cell.      effective. When a virus       engineered to produce
The capsid will remove          shifts, a major change in     proteins from the
the exposing nucleic acid       the antigens surface          coronavirus.
and then the replication        occurs accompanied by         Nuclei acid (mRNA) host
of nucleic acid and             virus fusion. Virus fusion    makes spike protein.
synthesis of protein coats      can be described as the       These are safe and quick
will occur allowing the         process by which              to develop but difficult to
virus to replicate.             enveloped viruses enter       store and this is similar to
                                the host cells. The shift     the vaccine developed by
Why is it so hard to            leads to a major change in    Pfizer for Covid.
control viruses?                the antigens and so they
Whilst a vaccine may help       are much less likely to be    Edited by Aditya
the body to produce             recognised by the             Chougule
antibodies to combat the        antibodies which were
virus, the vaccine cannot       produced in response to
eradicate the virus from        the vaccine. Thus, the
the general population          vaccination is not very
since it is not feasible to     effective [2].
have everyone
vaccinated. Furthermore,        What is a vaccine?
over time a vaccine may         A vaccine is a device that
no longer be effective for      helps prepare the body to
preparing the body to           produce antibodies for a
produce the required            virus so that it can fight
antibodies since the virus      the virus when it
would have mutated. A           encounters it. Vaccines
virus mutates through           are designed to prevent
either drifting or shifting.    the replication of a virus
When a virus drifts, a          in a cell rather than treat
minor change occurs in          them. A vaccine injects a

                                            13
THE WILSON’S INTRIGUE | BIO-CHEMISTRY                                     Issue 5 | April 2021

                        The Hearts that Never Beat
                               By Shinujan Saravanamuthu (Y12)

T
         he heart is the          blood? Not quite.             Jarvik began his work on
         driver of the body,      However, mechanical           artificial organs in 1971
         with a simple            hearts may be humanity’s      and the Jarvik-7 was
         function yet with        next evolution in our         conceived around 1982 [3].
such complex intricacies,         quest to become cyborgs;
giving it the strength to         a hunk of titanium            The Jarvik-7 was designed
channel up to 9000 litres         strapped to the chest with    to completely replace the
of blood a day. When the          a motor spinning at           heart so the diseased
heart fails many face the         10,000 RPM seems to be        heart had to be removed
only option of a heart            the vital next step-          for its installation. It is
transplant- receiving a           impractical maybe- but        composed of two bell-
donor heart is life               lifesaving indeed, and in     shaped plastic, shown to
changing, a second chance         the medical world that will   the right and titanium
at life but granted at the        do.                           pumps that take the place
expense of another.                                             of the two ventricles (the
Unfortunately, however,                                         main chambers that
this is not accessible to                                       deliver the final flow of
everyone; as of July 2020                                       blood to the lungs and
there are 343 patients in                                       body). It works by sewing
the UK who have been                                            on the cuff end of the
placed onto a waiting list                                      pump to portions of the
for a donor heart [1]. Even                                     atria that remained when
though donor numbers                                            the heart was originally
are increasing, with                                            removed. After attaching
people now having to opt                                        the pump the chest is
out of being a donor, it is                                     closed, leaving two
still not meeting demand                                        flexible plastic tubes
with patients having to           Robert Koffler Jarvik         extruding from the torso,
wait on average 1085                                            which are attached to an
days for a transplant- one                                      external air compressor
in six patients do not            With all great inventions,    which draws and pumps
receive the heart they            there is a mastermind,        blood to the heart.
require in time [2]. Instead      pioneer and successor; for
of a donor heart what else        artificial organs it was
can be done…                      Robert Koffler Jarvik, with
permanently have                  the Jarvik-7. Born in
someone strapped to a             Michigan, in 1946, he was
cardiopulmonary bypass            a curious man: always
machine? As well as being         either elbow deep into his
impractical, this machine         research or a patient
does not maintain blood           (quite literally) and
flow, can only sustain the        inventing the surgical
body for 45 minutes and is        stapler just as a teenager.
only used as a stopgap            Working under the wing of
measure during surgery.           Williem Johan Kloff- the      Jarvik-7
Maybe implant vibranium           inventor of the dialysis
to magnetically control           machine during WW2-

                                                  14
THE WILSON’S INTRIGUE | BIO-CHEMISTRY                                   Issue 5 | April 2021

 The first patient to receive    2000, and the birth of the      implantations [6]. Finally,
 the Jarvik-7 was retired        Jarvik 2000: a motor            the ‘bridges to transplant’
 dentist Barney Clark on         designed to fit onto the        could evolve to become
 December 2nd 1982. After        heart with a maximum            the ‘bridges to
 the operation Clark awoke       output of up to seven           destination’, where the
 and was able to live            litres per minute [5]. It was   pumps could take over
 another 112 days; the           first implanted into a 61-      the heart either giving
 Jarvik-7 had extended           year old man with               enough time for a donor
 Clark’s life, but it could be   cardiomyopathy- an              to be found or for the
 argued that he was not          inspiring procedure…            heart to recover again.
 truly living as he was                                          With the leading causes of
 mostly bed bound during         A skull pedestal, is            death in the UK since 2001
 this period, trapped within     attached to the head as         being ischaemic heart
 the confines of the             the connecting point            disease and
 hospital. The media             between the motor on the        cerebrovascular disease,
 documented Clark’s              heart and the external          complete artificial hearts
 condition on the road to        battery. This is done           demonstrate increasing
 recovery, however, it was       because the scalp tissue is     potential in treating
 soon clear that Clark was       fixed closely to the skull      today’s biggest diseases,
 not to get any better with      so can reduces risk of          and with upcoming
 the major problem being         trauma and damage to            inventions such as Total
 that the site where the         soft tissue- maceration.        Artificial there is much
 tubes were attached to                                          more to look forward to
                                                                 [7]
 the chest were prone to         Then a posterolateral               .
 infection; this resulted in     thoracotomy incision- just
 the lungs being                 below the shoulder blade-       Edited by Aditya
 compromised and                 is made and a cruciate          Chougule
 significantly weaker so         (cross-shaped) incision is
 unable to support the           made at the apex of the
 artificial heart. This was in   heart, which is then cored,
 addition to the high            removing a section of
 velocity blood that, due to     myocardium. When this
 constant compression            occurs, the pump is then
 from the pump, was being        inserted to minimise
 damaged resulting in the        bleeding. The right motor
 blood clotting and leading      is connected at the now
 to a stroke which left          open ventricular apex and
 Clark paralysed [3].            the blood is then run
                                 through a Gore-Tex sleeve
 This sequence of events         which is connected to the
 led to the fall of the Jarvik   descending aorta. During
 -7 with the media seeing        implantation, the power
 it as doctors playing God       cable is carried from the
 and extending life in           apex up to the scapula
 return for one at a lower       where it is then connected
 quality; which was also         to the pedestal described
 presented in the second         above.
 patient, William
 Schroeder. Ultimately, the      This miracle procedure
 FDA discontinued the            was performed by Dr
 Jarvik pumps due to             Stephen Westaby as well
 quality control resulting in    as Bud Fraizer, who
 the end for the ‘bridges to     impressively improvised
 transplant’ [4].                much of the operation,
 Fast forward 18 years, to       paving the way for future
                                             15
THE WILSON’S INTRIGUE | BIO-CHEMISTRY                                               Issue 5 | April 2021

Can We Grow New
Teeth?
By Mohamed Ahmed (Y12)

T
         ranslational dentistry (a
         collective term for
         regenerative dental
         medicine and dental
tissue engineering) has been an
active frontier of research over
the past 100 years and it seems
that it may soon be fit for use
today [1].
To understand why dentists
have been looking for ways to
                                     effectively digest or obtain their   the adult gum can respond to
grow new teeth back, we have to
                                     food, which demonstrates that        ‘tooth-inducing’ signals from
ask why we cannot replace our
                                     evolution has favoured well          embryonic tooth mesenchyme in
teeth- like many reptiles and
                                     aligned teeth that are produced      a way that is appropriate for in
fish who regrow a new set of
                                     once.                                vitro (in a living organism)
teeth every few months [2]! In
                                                                          growth, which would contribute
fact, leopard geckos have been       While the process of tooth
                                                                          to tooth formation.
the ideal model organisms to         creation is complicated, it is
use when researching                 luckily well understood:             The issue we face today is in the
mechanisms of teeth growth.          essentially, soft and connective     ethics of obtaining embryonic
                                     tissue, nerves and blood vessels     cells for tooth replacements,
                                     (all found in the pulp at the        which may be considered a
                                     centre of the tooth) are bonded      frivolous use of the resource
                                     to 3 types of hard tissue:           when extractions and other
                                     dentine, enamel and cementum.        treatments are available and
                                     Using RNA sequencing,                these cells could be used for
                                     researches have deduced              more critical procedures (or
                                     differentiation pathways of          certainly those who are ethically
                                     stem cells to odontoblasts and       opposed to the use of the
                                     ameloblasts which are cell           embryo in its entirety), and a
                                     populations that give rise to        lack of understanding in the cell
                                     dentine (the softer- but still       dynamics- how the cell interacts
In humans and other mammals,         harder than bone- tissue closest     with its environment- involved
the relevant stem cells needed       to the pulp) and enamel (a           over the differentiation process.
to build up the adult teeth when     harder protective coating of the     Research is currently being
we were children die later on in     tooth) [4].                          conducted to induce the same
our lives whereas these geckos                                            differentiation pathways
                                     The fruits of this research have
form new generations of teeth                                             possible in embryonic stem cells
                                     expedited efforts to replace
(from retained stem cells) which                                          from adult stem cells and to
                                     missing teeth in places such as
grow in size under the tissue,                                            understand how these cell
                                     King’s College London who have
until they surface and displace                                           populations respond to a variety
                                     published their research in the
the more mature tooth above                                               of environmental factors.
                                     Journal of Dental research
the tissue [3]. This is much rarer
                                     where they are able to produce       Edited by Aditya Chougule
in mammals due to the
                                     dentine, enamel and roots by
specialization of our teeth in
                                     cultivating adult human gingival
response to more specific and
                                     tissue (from the gums)
evolved dietary needs. For
                                     combined with embryonic tooth
example, carnivores and
                                     mesenchyme (loose multipotent
omnivores have developed
                                     cells in a protein and fluid
canine teeth and molar teeth
                                     mesh). The epithelial cells from
respectively to allow them to

                                                     16
Intrigued? Organ Donation
Here at the Wilson’s STEM Intrigue, we are very curious and this often leads to big discussions and
debates of scientific news within the magazine writers.
Our new “Intrigued?” section hopes to shed some light on one of our most heated debates, while
hoping to inform and update news you may have missed, and tackle the big questions with STEM.
We surveyed our editors and writers and below are some of the responses.

                                                        Poll One :
The New Law:
20th May 2020 marked a defining moment in the
history of organ donation as the new opt-out
system first came into effect in England. Also
known as Max and Keira’s law, this system means
that all adults in England will be “considered
potential donors unless they choose to opt out or
are excluded” (gov.uk). Those excluded from the
plans include: children under 18; people who lack
the mental capacity to understand the changes for
a significant period before their death; people who
have not lived in England for at least 12 months
before their death.

      Great! From what I had heard, hospitals were
      always short on organ donors, despite the
      fact that so many people would happily                         Slightly queasy but it would help lots of
      donate their organs to save other people's                     people
      lives. Having sensible defaults is important                   William Y12
      for anything, but especially where people's                    @Wilson’sIntrigueOrganDonation
      lives are involved.
      Michael Y13
      @Wilson’sIntrigueOrganDonation                                 The idea is there and it is a good one,
                                                                     however, I feel that there has been a lack of
                                                                     effort by the NHS that the law has changed;
     I believe that it was a valid decision to make,                 yes I have seen and heard adverts to opt out
     seeing as the majority will be willing to donate                but I still don't believe that it it sufficient. Thus
     their organs. This would ultimately make life                   it can lead to controversies and future
     easier for many, whilst preserving the freedom                  problems for organ donation, however , it may
     to choose.                                                      have seen daunting for people to think about
                                                                     organ donation especially during the current
     Ishan Y11                                                       climate.
     @Wilson’sIntrigueOrganDonation
                                                                     Shinujan Y12
                                                                     @Wilson’sIntrigueOrganDonation

Poll Two:

                                                                     As a devout Muslim, my stance on most issues
                                                                     of morality is motivated by my faith. In the
                                                                     case of organ donation, many modern Islamic
                                                                     scholars differ in opinion. Although the most
                                                                     recent fatwā (Islamic scholarly opinion) is that
                                                                     organ donation is permissible in Islam
                                                                     following circulatory arrest, I would rather in
                                                                     this case err on the side of caution.
                                                                     Nabeel Y12
                                                                     @Wilson’sIntrigueOrganDonation
                                                        17
THE WILSON’S INTRIGUE | BIO-CHEMISTRY                                                  Issue 5 | April 2021

    Arguments supporting this system include: 80% of people in England support organ donation but only
    38% have opted in. This means that families are often left with a difficult decision when a loved one dies.
    Moreover, in 2019, 408 patients died in the UK on the transplant waiting list and as part of the law, the
    prospective donor’s family will continue to be involved prior to organ donation.

    Nevertheless, there are concerns that inaction in an opt-out system may lead to false positives, where
    individuals who do not wish to donate eventually become a donor. An opt-out system may also increase
    proportions of deceased donations, which are less likely to be suitable on account of possible brain inju-
    ry, trauma, hypoxia or cancer prior to death. In the UK, it is estimated that only around 1% of patients
    who die do so in circumstances that allow organ donation to proceed. On top of this, some religious be-
    lief systems discourage or prohibit organ donation, attaching greater ethical implications to any poten-
    tial false positives.

    More information can be found at:
    https://www.organdonation.nhs.uk/helping-you-to-decide/about-organ-donation/faq/what-is-the-opt
    -out-system/
    https://www.gov.uk/government/news/opt-out-organ-donation-max-and-keira-s-bill-passed-into-law

                                                                Although I am in favour of the opt-out scheme
                                                                law, I believe that an opt-in donation scheme
                                                                would be better, because it ensures that everyone
                                                                who actually wishes to donate their organs are
                                                                doing so. It eliminates the cases of uncertainty
                                                                where it is unclear whether the donor actually
We need more organs. Opt-in may                                 wishes to donate their organ(s).
prevent those pesky false positives,
                                                                Shanjeev
but there is always discussion with the
donor’s family beforehand whether or
not to proceed with the donation. In
most cases, the family should be            It saves essential time, and
                                                                                         OPT-IN
aware of the donor’s decision.              therefore lives, for those who
Koushikk                                    are in need of organs, which
                                            require extensive waiting lists    Control over our own bodies, dead or
                                            which can go on for years.         alive, should not be superseded by a
                       OPT-OUT              Opting out increases the           need for organs in a hospital.
                                            availability for organs in the     Haris
                                            future. However, in the
                                            coming years use of stem cells
  It is not worth giving people an opt in   and dying hearts are becoming
  system when thousands of people are       increasingly promising and
  dying - action needs to be taken to       maybe the need for organs
  help these people. Also, when people      will decrease.
  die, they wouldn’t care whether they
  have their organs in their body or not    Shinujan
  so it shouldn’t be a problem for them
  either. It’s a win-win situation.
  Arya
                                               What do you think: OPT-IN or
                                               OPT-OUT?
                                                         18
THE WILSON’S INTRIGUE | BIO-CHEMISTRY                                                      Issue 5 | April 2021

Is Chloroquine an
Effective Medication
for the Prevention
and Treatment of
Malaria?
                                                                    Where Malaria Occurs Across the World
By Junaid Ali (Y12)

M
         alaria is a parasitic     causes the most deaths                     parasite must reproduce. To
         disease spread by         worldwide [5].                             do this, it requires energy for
         female Anopheles          It is also capable of avoiding             metabolic processes and
         mosquitoes. It is         detection from the immune                  amino acids to create new
widely spread in many tropical     system.                                    proteins. The parasite
regions, mainly areas in Africa,                                              achieves this by breaking
Central/South America, Asia        Whenever a red blood cell is               down haemoglobin. As well as
and parts of the Middle East,      infected by P. falciparum, it              proteins, haemoglobin is also
because mosquitoes are able        expresses a molecule on its                made of a heme unit. The
reproduce and complete their       surface: P. falciparum                     heme molecule is toxic to the
growth cycle in areas with         Erythrocyte Membrane Protein               parasite and soluble. To
high humidity and high             -1 (PfEMP1). PfEMP1 is coded               protect itself, the malarial
temperatures [1]. Symptoms         by var genes in P.falciparum               parasite crystallises heme into
may begin any time from 7 to       and it is this protein that acts           hemozoin – a non-toxic
18 days after being bitten by a    as the antigen which should be             molecule that forms insoluble
mosquito that carries the          detected in an immune                      crystals.
pathogen. Symptoms can vary        response. However, in a P.
and include a high                 falciparum genome, there are               When chloroquine is taken
temperature (>38°c),               50-60 var genes and only one               into the body, it enters red
headaches, vomiting, muscle        gene is expressed at a time [6].           blood cells by diffusion and it
pains and diarrhoea [2].           This means that the surface                occupies the parasite’s
                                   antigen is able to repeatedly              vacuole where the
Malaria is caused by single-       change so that it is not                   haemoglobin is digested. The
celled eukaryotes known as         detected by the host’s                     vacuole is acidic, so the
Plasmodium parasites [3].          immune system. In 2018, P.                 chloroquine gains H+ ions
Plasmodium species develop         falciparum made up 99.7% of                (protons) and it can no longer
in blood-feeding insect hosts.     estimated malaria cases in the             leave the vacuole by diffusion.
When the mosquito bites the        World Health Organisation                  Chloroquine is able to limit the
host’s skin, the parasite enters   (WHO) African Region, 71% of               amount of hemozoin
their bloodstream through the      cases in the Eastern                       molecules that the malarial
mosquito’s saliva. The             Mediterranean and 65% in the               parasite can crystallise.
parasite can then reproduce in     Western Pacific [7].                       Therefore, after a certain
the liver asexually. The new                                                  point, the parasite can no
parasites then infect red blood    Chloroquine is a medicine that             longer continue to crystallise
cells and begin to multiply        is commonly used in the                    heme into hemozoin, so heme
asexually. This causes the cell    treatment and prevention of                begins to build up. Heme binds
to burst, allowing the             malaria. It is composed of a               to chloroquine to create an FP
parasites to infect more cells     combination of various                     -chloroquine complex. FP-
and the cycle repeats.             antimalarials and is typically             chloroquine is very toxic to the
                                   taken with another medication              parasite and disturbs its usual
There are 5 different species      called proguanil [8]. It is able to        membrane function. In the
of Plasmodium: P. falciparum,      prevent the spread of the                  end, the parasitic cells break
P. malariae, P. vivax, P. ovale    malarial parasite by                       down and undergo lysis.
and P. knowlesi [4]. P.            interfering with the processes
falciparum is the most             carried out while it is in the             Chloroquine was first
dangerous as it is the most        host’s red blood cells. During             discovered in 1934 by Hans
common malarial parasite and       this phase of the lifecycle, the           Andersag. Only in 1947 was

                                                    19
THE WILSON’S INTRIGUE | BIO-CHEMISTRY                                          Issue 5 | April 2021

 enough learnt about its            concern. For example, the          malaria may arise if
 properties for it to be            interaction between                chloroquine-resistant P.
 incorporated into clinical         chloroquine and another drug       falciparum develop in a certain
 practice [8]. Chloroquine is now   named cimetidine may lead to       area, which could lead to a
 a part of the WHO’s Model List     increased levels of chloroquine    wider spread if it is not
 of Essential Medicines and it is   in the body due to the             controlled. Chloroquine should
 available as a general             inhibition of chloroquine          still be used, but I believe only
 medication [9]. The first          metabolism [8]. Additionally,      under controlled
 recorded resistance of the         chloroquine in overdose has a      circumstances for cases where
 parasite towards chloroquine       20% chance of death and can        there is shown to be no
 was in the 1950s and ever          cause problems with vision,        resistance to it.
 since, chloroquine has             breathing, the heart or
 gradually become less and less     sleeping. Build-up of              Edited by Aditya Jain
 effective against P. falciparum    chloroquine deposits in the
 [10]
      . This is because the         body can result in blurred
 parasites have evolved due to      vision and blindness.
 natural selection and are able
 to channel chloroquine away        Overall, it is clear that
 from its vacuole. This means       chloroquine is an invaluable
 the drug is incapable of           medicine as it is extremely
 interfering with the parasitic     useful in the prevention and
 cell’s processes. Parasite cells   treatment of malaria,
 that have developed                particularly malaria caused by
 resistance can drain               P. falciparum, which is a highly
 chloroquine at 40x the rate of     deadly infection. However, it is
 a cell without chloroquine         also clear that resistance to
 resistance.                        chloroquine is becoming more
                                    widespread across the world
 In places where chloroquine        with many countries opting to
 resistance has not yet been        use other treatments such as
 discovered amongst P.              artemisinin combination
 falciparum, chloroquine is still   therapy (ACT) as the first-line
 shown to be highly effective as    drug for the treatment against
 a form of treatment. From          P. falciparum. I believe that it
 2008-9, a study was carried        is necessary for countries (at
 out in the municipality of         high risk especially) to be
 Puerto Lempira, Gracias a Dios,    ready to use ACT if they are
 Honduras, in order to evaluate     not already using it, as the
 the use of chloroquine. A total    WHO advises ACT to be used in
 of 68 patients from ages 6         areas where chloroquine-
 months to 60 years of age          resistant P. falciparum are
 completed the entire trial and     present [12]. Small outbreaks of
 each patient was positive for
 malaria due to P. falciparum
 according to light microscopy.
 Each patient was given a dose
 of chloroquine of varying sizes
 over the first 3 days,
 depending on their body
 weight. Patients received
 supervised treatment until day
 28. The data showed that the
 parasite density in most
 patients had dramatically
 decreased by day 3 and by day
 7 all patients were parasite
 negative (shown by no
 detected asexual stages in the
 blood) [11].
 Chloroquine can have several
 side effects on the body,
 including nausea, vomiting,
 headaches and diarrhea. It also
 has several interactions with
 other drugs, which may be of
                                                 20
THE WILSON’S INTRIGUE | BIO-CHEMISTRY                                                Issue 5 | April 2021

 What is the Effectiveness of the Use Of Antibodies when Treating
  Paediatrics Patients with Mild/Severe, Acute/Chronic Asthma
                          Exacerbation?
                                       By Junayd Soobratty (Y12)

A
         n asthma exacerbation is distinguished          part of the immune system produced in the bone
         by the swelling or inflammation of the          marrow. However, high levels of eosinophils can
         airway [1]. Respiratory difficulties are        cause inflammation in the airways, affecting the
         caused due to the narrowed bronchial            sinuses and nasal passages as well as the lower
tubes. The word exacerbation (more commonly              airways [5]. The majority of asthmatic conditions
referred to as an attack) denotes the event              can be controlled with conventional treatment
caused by a trigger such as an allergen leading          such as inhaled corticosteroids (ICS) appropriate
to the airways constricting. Triggers may                for their severity. However, some types of
include, animal fur, pollen, dust or exercise            asthma, known as ‘refractory asthma’ which is
where the trachealis muscles contract,                   when the patient experiences persistent
producing more than standard levels of mucus.            symptoms, frequent asthma attacks or low lung
Asthma is the most common obstructive                    function despite taking asthma medications as
pulmonary disease in children affecting one in           they do not respond to high doses of this
eleven in the UK [2].                                    conventional treatment. Some refractory
An asthma exacerbation can be categorised in             asthma patients have to take oral steroids such
two main ways which can further be subdivided            as prednisone to manage their asthma.
into six classifications [3]:                            In general:
A) Intermittent asthma                                   Short-term treatments [6]:
1)     Mild intermittent asthma: where the               •     Short-acting beta-agonists; first choice for
       paediatric patient will only experience                 quick relief of asthma symptoms as they
       slight tightness of the airways on rare                 are used as muscle relaxants so decrease
       occasions                                               the contraction on the trachea by the
2)     Moderate Intermittent asthma: where the                 Musculus trachealis
       asthmatic will feel some respiratory              •     Anticholinergic agents; acts swiftly to
       distress in exceptional cases                           instantly relax airways
3)     Severe intermittent asthma: where the             •     Oral and intravenous corticosteroids;
       person would feel significant tightness of              relieve airway inflammation but can cause
       the chest and pain sporadically                         serious side effects when used long term
B) Persistent asthma                                     Treatment used in long-term:
1.     Mild persistent asthma: where the person          •     Inhaled corticosteroids; the most effective
       would be wheezing or whistling when                     long-term control medicine usually
       breathing, with slight swollen airways;           •     Inhaled long-acting beta-agonists; open
       symptoms occur more than twice a week                   the airways by relaxing the smooth
       but less than once a day                                muscles around them
2.     Moderate persistent asthma: wheezing to           •     Combination inhaled medicines; an inhaled
       an extent of murmured speech, coughing,                 corticosteroid along with a long-acting
       swollen airways, development of mucus in                beta-agonist
       the airways, some chest tightness or pain;        •     Biologics; target a cell or protein in the
       experience asthma symptoms every day                    body to prevent airway inflammation
3.     Severe persistent asthma: where the               •     Long-acting bronchodilators; possibly
       paediatric patient will feel significant                tiotropium (Spiriva) along with
       respiratory distress. There may be a                    corticosteroids even though daily inhaled
       display of nasal flaring and paradoxical                steroid is taken. Long-acting
       thoraco-abdominal movement; experience                  bronchodilators alone as a long-term
       asthma symptoms every day and at least                  asthma treatment is ineffective as it does
       one night per week [4].                                 not prevent and has short term effect for a
Key characteristics of an asthmatic paediatric                 long-term use
patient is the reversible airway obstruction,
airway hyper-responsiveness and chronic airway
inflammation typically with eosinophil
infiltration. Eosinophilic asthma involves
abnormally high levels of a particular type of
white blood cell called eosinophils which are

                                                    21
You can also read