The Scientific Observer Issue 31
Magazine
Published: October 31, 2023
|
Last Updated: February 29, 2024
Credit: Technology Networks
In issue 31, we’re exploring the expanding realm of oncology. From the use of AI in cancer studies, to a story of tragic loss that inspired one scientist’s quest to find a cure, we’re uncovering the latest advances in cancer research and more.
Issue 31 highlights:
- HPV Is Not Just a Women’s Health Issue
- The Little Things: An Inspired Scientist’s Pursuit for a Cancer Cure
- Long COVID Research Is a Bit of a Mess
A Green Approach
To Upcycle Vegetable Waste
HPV Is Not Just a Women's
Health Issue
ISSUE 31, OCTOBER 2023
Little
Things
AN INSPIRED SCIENTIST'S PURSUIT FOR A CANCER CURE
The
Sponsored by
2
CONTENT
FROM THE NEWSROOM 05
ARTICLE
HPV Is Not Just a Women’s
Health Issue 07
Molly Campbell
ARTICLE
Four Spooky Sounding
Halloween-Inspired
Scientific Terms 10
Laura Elizabeth Lansdowne
RESEARCH SPOTLIGHT
A Green Approach To Upcycle
Vegetable Waste 12
Daphne Ng
FEATURE ARTICLE
The Little Things: An Inspired
Scientists Pursuit for a
Cancer Cure 16
Anthony King
ARTICLE
Advances in Cancer Biology 21
Sarah Whelan
ARTICLE
Long COVID Research Is
a Bit of a Mess 24
Leo Bear-McGuinness
10 24
16
FEATURE
The Little Things:
An Inspired
Scientist's Pursuit
for a Cancer Cure
Anthony King
iStock
3
EDITORS’ NOTE
CONTRIBUTORS
Have an idea for a story?
If you would like to contribute to
The Scientific Observer, please
feel free to email our friendly
editorial team.
Anthony King
Anthony King is a freelance
science journalist who
reports on a variety of topics
in chemical and biological
sciences, as well as science
policy and health.
Daphne Ng, PhD
Daphne is the Assistant
Director and Science
Communication Lead at
Nanyang Technological
University.
Laura Elizabeth Lansdowne
Laura is the Managing Editor
for Technology Networks.
Leo Bear-McGuiness
Leo is a Science Writer
for Technology Networks.
Molly Campbell
Molly is a Senior Science Writer
for Technology Networks.
Sarah Whelan, PhD
Sarah is a Science Writer
for Technology Networks.
Dear readers,
Welcome to the 31st issue of Technology Networks’ monthly
magazine, The Scientific Observer.
In this issue, we're exploring the realm of oncology and the
latest advances in cancer research.
HPV infection is the most common sexually transmitted
disease, and over one-third of men are infected with one
or more strains considered to be “high risk”. Join Molly
Campbell as she explores why HPV is often discussed in
the context of women’s health, how transmission occurs
and methods to prevent infection.
This month’s feature article by Anthony King delves into
the deeply personal and inspiring story of a scientist whose
life's work has been galvanized by a tragic loss. As a child,
Dr. Darrell Green witnessed the devastating impact of bone
cancer when his dear friend Ben fell victim to the disease.
His relentless quest to discover a cure is an emotional testament to the human spirit and the power of science. Join
us as we follow the journey of this determined scientist
who has turned his grief into a driving force for change.
Also in this issue, Leo Bear-McGuinness provides an
in-depth analysis of the current state of long COVID
research. The COVID-19 global pandemic has left in its
wake a baffling array of symptoms, affecting many survivors for months after the virus has run its course. Through
the voices of those grappling with this enigmatic condition, and the scientists in pursuit of answers, you’ll gain a
profound understanding of the challenges and hopes that
surround long COVID research.
And, of course, it wouldn't be October without a nod to the
spooky and supernatural. Check out Laura Lansdowne’s
fun dive into the “spookiest” sounding Halloween-inspired
scientific terms.
This, and much more, in issue 31 of The Scientific Observer.
The Technology Networks Editorial Team
A full slate of extremely high-quality recombinant proteins, antibodies, and
CUSTOM development and production services
www.sinobiological.com
Sino Biological US Inc. (U.S.A.)
Tel: +1-215-583-7898
Email: order_us@sinobiologicalus.com
Sino Biological, Inc. (Global)
Tel: +86-400-890-9989
Email: order@sinobiological.com
株式会社日本シノバイオロジカル (Japan)
Tel: 044-400-1330
Email: order@sinobiological.co.jp
Sino Biological Europe GmbH (Europe)
Tel: +49(0)6196 9678656
Email: order_eu@sinobiologicaleu.com
Comprehensive Solutions
for Life Sciences
Solutions covering phases from lead discovery to process development and
clinical studies
Multispecific Antibody Development
Supporting the assessment of vaccine safety, immunogenicity, and protective efficacy
Influenza Vaccine Development and Production
Complete solutions covering each step from CAR development to CAR-T cell quality control
CAR-T Therapy Development
One-stop research support covering the entire CAR-NK development process
CAR-NK Therapy Development
Multi-dimensional efficacy evaluation system to accelerate antibody drug discovery
In Vitro Efficacy Evaluation
5 FROM THE NEWSROOM 5
From the Newsroom
FROM THE NEWSROOM
National Museum of Health and Medicine, Otis Historical Archives New Contributed Photo Collection / Wikimedia Commons., iStock, Magda Pawluczuk/Unsplash
A new study challenges the long-standing belief that the
1918 influenza pandemic disproportionately killed healthy
young people.
JOURNAL: The Proceedings of the National Academy of Sciences.
The 1918 Flu Pandemic Did Not
Disproportionately Kill Healthy
Young People
MOLLY CAMPBELL
Gene variants inherited from Neanderthals are associated with a
lower pain threshold in modern-day humans.
JOURNAL: Nature.
Genes From Neanderthals Linked
to Lower Pain Threshold
MOLLY CAMPBELL
A new study has raised a “warning” that the hygiene hypothesis
might not fully explain why allergies are on the rise.
JOURNAL: Science Immunology.
Hygiene Hypothesis Study
Suggests More Microbes Might Not
Be the Answer to Allergies
RUAIRI J MACKENZIE
6 FROM THE NEWSROOM
Johansen et al/Allen Institute for Brain Science, iStock
Want to learn more?
Check out the Technology Networks newsroom.
A research consortium has published a flurry of papers detailing a
“major step forward” in our knowledge of the human brain.
World-First Human Brain Atlas
Reveals New Cell Types
RUAIRI J MACKENZIE
A new study has detailed the potential of a new drug to mimic the
beneficial effects of exercise in mouse models. The drug induced
weight loss and improved endurance in obese mice, enabling
them to run 50% further and lose 12% of their body weight.
JOURNAL:Journal of Pharmacology and Experimental Therapeutics.
Exercise-Mimicking Drug
Helps Mice Lose Weight and
Boost Endurance
SARAH WHELAN
A clinical trial has shown that ketamine nasal spray treatment
led to higher rates of remission than standard intervention
with the antipsychotic drug quetiapine in patients with
treatment-resistant depression.
JOURNAL: The New England Journal of Medicine.
Ketamine Nasal Spray Sees
Success in Trial for TreatmentResistant Depression
SARAH WHELAN
7
iStock
Human papillomavirus (HPV) is
a group of related viruses that
infect the skin and mucosal
membranes. HPV infection is
the most common sexually transmitted
disease (STD) worldwide; nearly all
sexually active men and women will be
infected at some point during their lifetime according to the Centers for Disease
Control and Prevention.
While HPV is often discussed in the
context of women’s health and cervical
cancer risk, a recent study published
in The Lancet Global Health found that
over one-third of men aged 15 years
and over are infected with at least one
type of HPV. One in five men is infected
with one or more types of HPV that
are considered “high-risk” strains.
“This statistic might be surprising to
some, however, HPV affects both men
and women, with a substantial impact
on public health,” explains Christine
Meyer, MD, practicing physician and
founder of CMMD and Associates
medical practice.
Here, we explore how HPV viruses cause
infection and – in some cases – cancer,
and what the findings of the new study
mean for HPV prevention efforts.
HOW DOES HPV INFECT
HUMAN CELLS?
There are over 200 types of HPV that can
be transmitted sexually, and individuals
can be infected by more than one strain
at the same time. “These viruses are categorized into low-risk and high-risk types
based on their association with health
problems,” says Meyer. Low-risk forms of
HPV do not typically cause disease, but
high-risk forms of HPV can lead to the
development of various types of cancer.
HPV is primarily transmitted through
direct skin-to-skin contact. “The virus
enters the body via breaks in the layer of
cells (epithelial cells) which make up our
skin and also the internal linings of our
mouth, anus and vagina to name a few,”
explains Dr. Gareth Nye, senior lecturer
at the University of Chester, program
lead for the BMedSci Medical Science
Program and expert in maternal and fetal
health. “Once the virus has bypassed this
layer, it infects the cells leading to the
virus being protected from our immune
system. From here they can replicate and
spread to neighboring cells, damaging the
body’s cells as it does so.”
THE HISTORY OF HPV
AND CERVICAL CANCER
RESEARCH
Nowadays, the link between HPV and
cervical cancer is well established. Its
discovery dates back to the 1970s, when
German virologist Harald zur Hausen
went against the grain by proposing that
HPV could be a causal agent behind this
type of cancer. In pursuit of answers, he
spent several years studying a variety
of HPV strains and analyzing patient
biopsies for HPV viral DNA. Ultimately
zur Hausen discovered that patients with
HPV16 and HPV18 were more likely
to develop cervical cancer, a groundbreaking feat that earned him a share
of the 2008 Nobel Prize in Physiology
or Medicine.
Over 95% of cervical cancer cases are
due to HVP infection according to the
World Health Organization, and HPV16
HPV Is Not Just a Women’s
Health Issue
MOLLY CAMPBELL
8
and HPV18 are found in ~70% of cancer
biopsies worldwide. zur Hausen’s work
paved the way for the first HPV cervical cancer vaccine, developed at the
University of Queensland in Australia
throughout the 1990s and approved for
human use by the United States Food
and Drug Administration in 2006.
HPV IS A GLOBAL
HEALTH ISSUE AFFECTING
WOMEN AND MEN
Extensive research has explored the epidemiology of HPV in women, perhaps
owing to its association with cervical
cancer. But over recent decades, HPV’s
association with other types of cancer
has been determined, including oropharyngeal cancer, anal cancer, penile
cancer, vaginal cancer and vulvar cancer. An estimated 69,400 male cancer
cases were attributed to HPV infections
in 2018 alone, according to The International Agency for Research on Cancer.
“While there are many studies conducted looking at HPV in women, very few
address HPV in males and even fewer
are conducted globally,” says Meyer.
This is problematic as, without a complete understanding of HPV prevalence
across men and women, data on the
overall global disease burden and transmission risk is skewed. It also becomes
increasingly challenging to create, implement and evaluate HPV and cancer
prevention programs.
The majority of existing studies on HPV
prevalence in men – the last of which was
published in 2011 – have been conducted
in high-income countries, or in populations that are at an increased risk of HPV
infection, such as men that have sex with
men, men with HIV or HPV-symptomatic
men, according to the authors of the new
The Lancet Global Health study. The lead
author of the work, Laia Bruni Coccoz,
MD, is head of the Unit of Infections and
Cancer Information and Interventions
(UNIC-I) in the Cancer Epidemiology
Research Program and coordinator of
the Institute of Oncology/International
Agency for Research on Cancer HPV Information Center. Alongside colleagues
in the field, Coccoz aimed to provide
updated and global data on HPV infection in men.
The researchers conducted a systematic
review and meta-analysis, analyzing
studies on the prevalence of genital
HPV infection in males that had been
published between 1995–2022. Approximately 31% of men are infected with
one strain of HPV, and 21% are infected
with high-risk strains, the data suggests.
Prevalence of HPV was higher in young
adults, particularly those between 25–29
years old. “This statistic emphasizes the
need for comprehensive HPV prevention
strategies that include both genders. It
highlights that HPV is not just a women's
health issue but a broader public health
concern, given its association with
various cancers in men and women,”
says Meyer.
“It remains true that males remain key
in the biology of this disease, and we
should be considering them in all HPV
prevention attempts including education
and awareness. If more males understand
the role they play, many more cases could
be prevented,” adds Nye. “This study is
a strong piece of research. The methods
here involve combining the finding
from other peer-reviewed sources and
undertaking new analysis to gain a larger
overview of the patterns of disease.”
HOW CAN HPV BE
DETECTED AND PREVENTED?
Most often HPV infection does not
cause noticeable symptoms, particularly in its early stages, which means
those affected might not be aware of it.
In some individuals, HPV might cause
visible warts to form on the genitalia,
the anus, mouth or throat, but this is not
always the case.
“The most reliable way to detect an
HPV infection is through medical tests,
such as pap smears for cervical HPV
infections in women and specific HPV
DNA tests,” Meyer explains. “Regular
screening and healthcare check-ups are
essential for identifying and managing
HPV infections and associated health
risks.” Currently, a simple screening
test for HPV is lacking for men, which
in Meyer’s opinion is further reasoning
why The Lancet Global Health study is
“so important.”
As HPV infection is often symptomless,
prevention is key, explains Nye: “Safe
sex practices in particular are so important. Using condoms is a very good
way of reducing the risk of infection.
Avoiding the sharing of sex toys without
through cleaning is also advised,” he
says. “Anyone who is engaging in regular sexual activity either with multiple
partners or a new partner should be
getting regular sexual health screens
to ensure infections of any kind are
recognized as soon as possible. It’s also
crucial if you do have an infection to
tell recent partners, so they too can get
tested and treated.”
Beyond practicing safe sex, HPV vaccines are now available for both males
and females. “These vaccines are most
effective when administered before sexual activity begins, because they protect
against the most common high-risk
HPV types that can lead to cancer. HPV
vaccination is recommended for adolescents and young adults,” says Meyer.
Nye emphasizes that, though Coccoz
and colleagues’ study is a stride forward
for understanding HPV prevalence in
men, further research is still warranted:
“Although this is strong evidence, it is
not current and newly undertaken research and so you can only take so much
from the findings. This will become a
solid basis for future studies targeting
HPV spread around the world but for
now, the findings should be taken very
seriously,” he concludes. ⚫
HPV VACCINES
The HPV vaccine is an
example of a preventative
vaccine, meaning it are
designed to prevent,
not treat, HPV infection.
Current HPV vaccines use
a combination of viruslike particles to trigger an
immune response and the
production of neutralizing
antibodies against HPV.
Disseminate Your
Research With Us
We know how important it is to disseminate your findings
when working in research, but also what a challenge it can be
to find opportunities beyond the conference hall. We want to
address this!
Technology Networks is spearheading
a project to help researchers raise
the profile of their work to a wider
audience and increase coverage of
the fantastic research papers out
there that may not get the media
attention they deserve.
There is a lot of great
research output and a very
engaged audience that wants
to hear about it, so share your
work with us!
Find Out
More
10
iStock
R
esearchers spend their lives in
pursuit of a scientific breakthrough. So, when that "eureka" moment finally arrives,
of course it is tempting to give that
groundbreaking discovery an absurd
and memorable name. In honor of this
year’s “spooky” season, we’re highlighting several Halloween-inspired
scientific terms.
GRIM REAPER
The Grim Reaper, a striking skeletal
figure, covered by a black cloak,
clutching a scythe and set on harvesting human souls *shiver runs
down spine*.
Or perhaps your first thought was:
weren’t grim and reaper those two
genes discovered in 1994 in the
Drosophila melanogaster fly? Indeed,
they were.
Twenty-four years ago, a team
identified a strain of fly that was
resistant to cell death. This strain
possessed a homozygous genomic
deletion (known as H99); grim and
reaper were two of the three genes
mapped to this deletion and were
consequently identified as regulators
of programmed cell death. More
recently, sickle was identified, which
appears to act in parallel with reaper
and grim. Sickle is capable of inducing
cell death when it is overexpressed
in both mammalian and insect cells,
and acts as an inhibitor of apoptotic
protein antagonists. I can’t help but
think “scythe” would have been a
better choice if the plan was to stick
to the Grim Reaper theme?
THE HALLOWEEN GENES
You are probably familiar with the
Addams family, a supernatural black
comedy film featuring a bizarre aristocratic family.
But I’m guessing few of you will have
heard of the “Halloween genes” a
lesser-known family, of cytochrome
P450 genes, which were discovered
in the Drosophila melanogaster fly.
The members include; the spook
gene, the phantom gene, the disembodied gene (perhaps inspired by
“Thing” – a disembodied hand?), the
shadow gene, the spookier gene and
the shade gene. Mutations in members of the Halloween gene family
results in embryonic lethality – scary!
ZOMBIE… GENE, PROTEIN OR
CELL… YOU NAME IT, THEY
HAVE TOO!
Although none are officially termed
“zombie” – cells, proteins and genes
have all been referred to as “zomFour Spooky Sounding HalloweenInspired Scientific Terms
LAURA ELIZABETH LANSDOWNE
11
iStock
bie-like” by scientists, who have
chosen to use the word to describe
their characteristics or behaviors.
Here we take a look at an example of each:
ZOMBIE GENE PROTECTS
ELEPHANTS FROM CANCER
A study published in Cell Reports
described how elephants have developed a way to resist cancer, by
resurrecting a “zombie” gene called
leukemia inhibitory factor 6 (LIF6),
which can respond to damaged DNA
and destroy cells that are destined to
become cancer cells.
LEUKEMIA ZOMBIE PROTEINS
COULD BE THERAPEUTICALLY
TARGETED
The TRIB2 protein is a member of the
Tribbles family of pseudokinase proteins, which are sometimes referred
to as “zombie enzymes” as they are
unable to catalyze chemical reactions.
TRIB2 proteins can promote cell
survival – a key hallmark of cancer,
making them an attractive therapeutic
target for cancer researchers. Using
biochemical drug repurposing methods, a team have now identified compounds capable of degrading TRIB2
leading to cancer cell apoptosis.
ZOMBIE CELLS IMPLICATED
IN NUMEROUS AGE-RELATED
DISEASES
Reporting their findings in Nature,
Mayo Clinic researchers show,
using a mouse model of Alzheimer’s
disease, that senescent “zombie”
cells accumulate in the brain prior to
cognitive loss. The researchers were
able to reduce neuronal death, loss of
memory, and tau protein aggregation
by preventing the accumulation of
the “zombie” cells.
DRACULA
As well as being a gothic horror
novel published in 1897, dracula,
also known as drc, is a gene found
in the zebrafish that encodes ferrochelatase, an enzyme involved in the
heme biosynthetic pathway.
Researchers demonstrated using a
Zebrafish model that draculam248 mutant embryos with a G»T transversion
within the gene generate a premature
stop codon. This resulted in both
light-dependent hemolysis and liver
disease phenotypes. Zebrafish drc
mutant phenotypes are comparable to
those seen in humans suffering from
a specific type of porphyria known as
erythropoietic protoporphyria (EPP).
EPP causes severe photosensitivity,
and is caused by either; mutation
in the human ferrochelatase gene
(FECH), or in some cases, mutation
in the delta-aminolevulinic acid synthase-2 gene (ALAS2).
Surely the name choice “dracula”
must be inspired by the vampire-like
symptoms – light-sensitivity, the
gene’s impact on red blood cells? ⚫
12
iStock
A Green
Approach
To Upcycle
Vegetable Waste
Daphne Ng, PhD
NANYANG TECHNOLOGICAL UNIVERSITY, SINGAPORE
RESEARCH SPOTLIGHT
Scientists at Nanyang Technological University (NTU) Singapore have
devised an environmentally friendly method that turns vegetable waste
into health and personal care products. Their approach could give
vegetable waste a new lease of life and make the extraction of beneficial
plant compounds more sustainable and cost effective.
The study was published in Separation and Purification Technology.
Research
Spotlight iStock
12
13
iStock
GIVING VEGETABLE WASTE
A NEW LEASE OF LIFE
Millions of tons of food waste are discarded annually around the world,
with fruits and vegetables making up
more than one third of it. Vegetable
waste is generated at various stages
of the food supply chain. Farmers
often cut off the outer leaves as
they are harvested for leafy vegetables like kale to sell aesthetically
pleasing vegetables with no signs of
damage or yellowing. When the vegetables reach the supermarket, large
quantities are also rejected due to
their size, shape or color imperfections. These practices result in the
disposal of substantial amounts of
edible vegetables.
Vegetables contain many beneficial
compounds that can also be extracted and added to food or cosmetics.
Cruciferous vegetables such as kale
are considered superfoods as they
contain high levels of phytochemicals that have many health benefits.
Organic solvents and pressurized
carbon dioxide are commonly used
to extract and recover these compounds from plants. However, these
solvents are often toxic, volatile or
not economically viable when used
on an industrial scale.
Solvents made from plant-based
metabolites, called natural deep
eutectic solvents (NADESs), could
be safer alternatives for extracting
phytochemicals. Unlike organic
solvents, NADESs do not evaporate
quickly and are biodegradable. They
are also able to dissolve a wide range
of natural products.
EXTRACTING BENEFICIAL
COMPOUNDS FROM
VEGETABLE WASTE
Researchers led by Prof. Hu Xiao
from NTU’s School of Materials Science and Engineering, and a program
director in the Nanyang Environment
and Water Research Institute (NEWRI), tested the ability of NADESs
with various formulations to extract
phytochemicals from kale.
First, the kale waste was blended
into a paste or dried and ground into
a powder (Figure 1). The researchers
then mixed the kale paste (or powder) with their specially formulated
NADES and stirred it at room temperature before filtering the mixture
to extract the beneficial compounds.
When the NADES mixture is allowed
to stand, it naturally separates
into layers, facilitating the easy
extraction of phytochemicals from
kale (polyphenols, carotenoids and
chlorophylls) without heating, unlike
current energy-intensive industrial
methods (Figure 2).
As heating is not required, the NTU
method prevents the temperature-sensitive phytochemicals from
degrading. The extraction process is
quick and can be completed within
30 minutes.
First author Dr. Lee Sze Ying, a research fellow at the Environmental
Chemistry and Materials Program at
NEWRI at the time of the study, said,
“Our extraction approach is unique
because it allows for the simultaneous recovery and separation of multiple valuable compounds from the
RESEARCH SPOTLIGHT 13
Figure 1: Kale in various forms.
Figure 2: The NADES (orange layer) and ethyl acetate solvents (green layer) can be added
sequentially or simultaneously to extract various bioactive compounds from kale waste.
NTU Singapore
14
iStock
RESEARCH SPOTLIGHT
vegetable waste in a single process
without using heat.”
The key findings of the study are:
• The green solvent system gave
the highest yield of polyphenols, more than two times
higher than conventional methanol methods.
• The polyphenol extract was
stable in the new green solvent
system, retaining 91.7% and
88.6% of the original contents
after 30 days of storage at 4 and
25 ⁰C, respectively.
• Other green solvents such as
ethyl acetate can be added to
the solvent mixture to obtain
a polyphenol-rich extract and
an extract rich in carotenoids
and chlorophylls.
GROWING INDUSTRIAL
APPLICATIONS OF PLANT
COMPOUNDS
The researchers say that manufacturers can add the extract directly
into the formula of their cosmetic
products without further processing, reducing production time.
Prof. Hu, the corresponding author,
said, “The use of non-toxic and
naturally derived solvents in our
method makes it a food-safe technique. At the same time, our method
preserves the potency of the extracted active ingredients, making
it highly attractive for industry
adoption. The extracted nutrients
can be used for applications in
personal care products, cosmetics,
food supplements and even herbal
medicinal ingredients.”
However, one of the major limitations of using NADESs as solvents
is that they are highly viscous,
which hinders the diffusion of the
compounds into the mixture, thus
reducing extraction efficiency. To
make NADESs less viscous and improve extraction efficiency, water is
usually added to dilute the solvents
during the extraction process.
In the study, the researchers found
that almost all bioactive compounds
were more effectively recovered
from the wet kale paste than the
dried powder, as the water in the
paste diluted the NADESs. This
simplifies the extraction process
as no additional water is required,
and also removes the need for an
energy-intensive step to dry the
kale waste.
Co-author Dr. Liang Yen Nan, senior research fellow, Environmental
Chemistry and Materials Program at
NEWRI, explained, “Our method essentially manipulates the chemical
nature of NADES and other green
solvents to maximize the extraction
efficiency of the bioactive compounds found in kale. This approach
induces simultaneous recovery of
multiple phytochemicals from the
kale and can easily be adapted for
use in other types of vegetable and
fruit wastes. Moreover, we have
demonstrated that our approach
remains viable even if we were
to eliminate the energy-intensive
freeze-drying of the kale waste, making our technology greener, cheaper
and scalable for industry use.”
SEEDING A SUSTAINABLE
FUTURE FOR FOOD WASTE
The team has filed a patent in Singapore for the innovation. For their
next steps, the researchers are investigating if their newly developed
method can extract beneficial compounds from other types of fruits and
vegetables, like dragon fruit, spinach,
lettuce and other medicinal plants.
The team is exploring new partnerships to scale up their technology
towards commercialization. ⚫
iStock
14
It’s simple, just choose the groups and
click the bubble.
Our Facebook groups allow you to keep up to
date with the latest news and research and share
content with like-minded professionals. With three
diverse groups there is something for everyone.
Hi. How are you? Have you seen our
Facebook groups?
Thanks! I’ll come join the conversation.
Come join the Neuroscience, News
and Research Group here.
Discover the Analytical Science
Network Group here.
Explore The Science Explorer Group here.
No I haven’t. Could you tell me more?
Sounds great! How do I join?
Anthony King
iStock
Little
Things
AN INSPIRED SCIENTISTS PURSUIT FOR A CANCER CURE
The
A CHILDHOOD TRAGEDY
PUSHED THIS SCIENTIST
TOWARD A REVOLUTIONARY
BONE CANCER TREATMENT
At 12 years of age, Darrell Green’s
best friend began complaining of
knee pain. Both Green and his friend,
Ben, were avid footballers, playing for rival local teams in Thetford,
Norfolk. The boy’s parents figured
their son’s knee was a run-of-the-mill
sports injury. But after a few weeks,
the knee pain was still there, and
Ben’s injured leg began to swell.
“My friend was lucky in that the GP
recognized quickly that something
was not right,” recalls Dr. Green,
now a researcher at the University
of East Anglia. Tests confirmed a
bone tumor and chemotherapy was
quickly started. Ben ended up having
an amputation yet, within months,
the cancer was discovered to have
spread to his lungs and he was
told he was terminally ill. “Just before
his 14th birthday, he passed away,”
recalls Green.
The harrowing experience stayed
with Green, who has been striving
to unearth a new drug to treat bone
cancer. Treatment for the most common types of bone cancer in children, osteosarcoma and Ewing sarcoma, has not changed much since
the late 1970s. Improvements in
surgery mean that half of patients
now survive to five years compared
to the previous prognosis of three
years. Yet there has been little sign
of new therapies on the horizon.
“There have been no successful clinical trials looking at targeted drugs
in bone cancer,” says Green, frustrated by this lack of progress. Tragically, bone cancer is an extremely
aggressive, mostly childhood disease.
DISCOVERY
Advances in Green’s lab this year,
however, sparked hope and headlines that heralded a revolutionary
new treatment. The Bone Cancer
Research Trust in the UK welcomed
it as what could be “the most important drug discovery in the field for
more than 45 years.” Part of the
advance happened when samples
from patients at the Royal Orthopaedic Hospital in Birmingham revealed
that a gene, RUNX2, was “switched
on” in bone cancer and seemed implicated in its spread. “This isn’t the first
time that RUNX2 has been implicated
in bone cancer, but it is the first time
that we could see how it operates and
use that knowledge to develop a new
medicine,” says Green.
The idea that Green now has is that,
in the future, doctors could give
micro-RNAs to treat kids with bone
cancer. These small pieces of RNA
are our body’s way of dialing up or
down the volume of genes, which
are themselves the recipes for making proteins in the body. Proteins
should be considered akin to biological robots and can carry out varied –
and often unknown – molecular tasks.
micro-RNAs could be introduced
as a drug to damp down or turn the
volume up on genes that make proteins suspected of encouraging or
discouraging cancer.
There is no quick fix for bone cancer. Around 600 people in the UK
develop the disease each year. It is
relatively uncommon, the research
field is small and funds for investigating the disease are invariably
in short supply – but Green is not
discouraged. He is driven by witnessing his friend Ben’s traumatic
disease. “I was personally affected
by bone cancer, so I’m not going to
be easily swayed by its difficulty,”
he explains.
As was the case for Ben, many children who develop a bone tumor are
unfortunately faced with the cancer
rapidly spreading to other parts of
the body, especially the lungs. This
is because the cells originate from
mesenchymal stem cells that are
naturally inclined to wander. One in
three patients diagnosed with bone
cancer will already have detectable
metastasis – a cancer that has spread
to another part of the body – by the
time they are diagnosed. “We know
that another one of those three will
have undetectable metastasis that
ends up relapsing later,” says Green,
who has studied cancer progression
and metastasis. Even the one-in-three
diagnosed with localized disease only
have a ~60% chance of still being
alive in five years.
This is yet another motivation for
Green in his push to treat bone
cancer. His scientific training has
been steeped in investigating the
outsized role of micro-RNAs, which
can be just 22 nucleotide letters in
length. “I’ve combined my interest
in micro-RNAs with bone tumors,”
says Green of his recent advance. In
“I want to see a new treatment
that is available to kids with
bone cancer, because the treatments that my friend Ben received 21 years ago are the same
treatments that are still being
used today. This just isn’t good
enough,” says Green.
17
18
order to understand the relevance of
micro-RNAs, one needs to consider
how our cells manufacture proteins.
EMBRYO GENES REAWAKEN
The blueprint for the string of amino acids that make up a protein is
contained within the DNA of our
chromosomes. This DNA must first
be transcribed, letter-for-letter, as a
messenger RNA (mRNA). The mRNA
molecule then exits the nucleus and
goes to a miniature protein factory
(a ribosome) that translates the RNA
code into a string of amino acids to
make the protein. Some of these
proteins may be anti-tumor machines,
such as the p53 tumour suppressor,
while others may promote cancers,
such as HER2 in breast cancer.
micro-RNAs work by matching up
with letter sequences on mRNAs in a
way that stops them from being made
in the protein factories. This means
that a tiny piece of RNA introduced
into cells might shut down or dramatically curtail the production of
a protein that is encouraging cancer.
Indeed, the recent breakthrough
in Green’s lab centers on RUNX2,
a “master regulator” protein that
directs and controls other proteins
that are responsible for building
the skeleton during embryo development, encouraging cells to move
up and down the growing skeleton.
“Cells moving from place to place as
an embryo develops is quite normal,
but is actually very dangerous once
we are born,” Green explains. As a
result, genes such as RUNX2 – which
encodes the protein – are tuned down
dramatically after birth.
“We are thinking now that bone
cancers somehow reactivate this
embryonic gene and that is how the
cancer cells move around the body,”
says Green, explaining that the result
of these peregrinations can be catastrophic. He knows of one patient
in particular who underwent surgery
to remove a large lung tumor, but
surgeons were shocked to discover
over 100 individual miniature tumors
that had spread from the original
tumour in bone. Green suspects
that the RUNX2 master regulator
is facilitating the spread of bone
cancer throughout the body; yet his
scientific sleuthing suggested that
the problem starts even before that.
THE LITTLE THINGS
First, he and his team looked at differences in low-, medium- and highgrade bone cancer to see if there
were clues as to what happens at the
start of a cancer. Unfortunately, bone
The University of East Anglia, Darrell Green
Dr. Darrell Green at the Biomedical Research Centre, Norwich Medical School at the
University of East Anglia.
Darrell (right) pictured with his friend Ben (left) on a school trip in the late 1990s.
19
cancer is usually so aggressive that
kids have advanced-stage tumors
by the time they are diagnosed. The
experiments revealed that levels of
a molecule called micro-RNA 140,
or miR-140, shot up in high-grade
tumors, which in turn stoked up
RUNX2 levels.
The complexity did not stop there.
This is a situation where a cell resembles highly intricate clockwork.
While miR-140 and RUNX2 were
elevated in high-grade tumors, there
was a reduction in an RNA fragment
known as tRF. Green believes that
the heart of his mystery lies with such
small fragments of RNA. As Sherlock
Holmes said: “It has long been an axiom of mine that the little things are
infinitely the most important.”
A study of RUNX2 and tRF revealed
a matching sequence. Green realized
he had seen this sequence before; it is
used as an anchor for another protein,
YBX1, a well-known villain in driving
cancers. “It became clear now that
RUNX2 was just part of the story,”
recalls Green, who revels in such
complex biological riddles.
Further experiments in the study
revealed that YBX1 physically interacts with RUNX2. “We think that
the [RNA fragment] is a ‘decoy’ that
stops that interaction from happening,” says Green. “In a low-grade
tumor, the RNA fragment binds YBX1
via the shared sequence and stops it
from binding cancer-promoting proteins such as RUNX2.” But as is the
case with most cancers, the tumor
cells can find a way around the body’s
defenses. “The RNA fragment is gotten rid of and switched off, and in its
place, YBX1 is now free to bind and
support cancer-causing molecules
such as RUNX2,” Green explains.
One solution to the puzzle is to
introduce again the small fragment
of RNA as a therapy to stop the
master regulator from embryonic
times being switched on. Or another
approach, which attracted headlines
earlier this year, is to block RUNX2
from sticking to the DNA using a
hoped-for drug, named CADD522
When scientists administered this molecule three to five times a week to mice
with bone cancer, the tumor’s size decreased, and metastasis-free survival
increased. A group of scientists led
by Professor Antonino Passaniti at
the University of Maryland pursued
the same strategy for breast cancer.
Now, scientists in the US and the UK
plan to pool their efforts and get the
drug through all the necessary safety
tests required before it can be tested
in patients, says Green, though he is
unable to name his collaborators at
this stage.
“There is a possibility that one day
it could be just taken as a pill with a
glass of water,” says Green – though
he is not counting his chickens just
yet. Getting from this promising
place to crossing the finish line will
be an uphill slog. “If everything goes
smoothly, we could be testing this
compound in patients in three years.
But the reality is things will not run
smoothly, and it is taking time to find
funding,” says Green.
As one might expect, he remains
undaunted by the challenges ahead.
“My drive in all of this isn’t to make
money, become a millionaire and
disappear on my yacht,” says Green.
“I want to see a new treatment that
is available to kids with bone cancer, because the treatments that my
friend Ben received 21 years ago
are the same treatments that are
still being used today. This just isn’t
good enough.” ⚫
Sophie Taylor, aged 5, who was at the heart of the “Take A Sophie” campaign to
“Stick Your Tongue Out At Cancer”. Sophie and her family were invited to Dr.
Green’s lab to see her tumour before it was molecularly profiled.
Alex and Kirsty Taylor, iStock
Six appeal
QX600 Droplet Digital PCR System
with more colors for greater multiplexing capabilities
21
iStock
Cancer is defined as the
uncontrollable division
and proliferation of abnormal cells, leading to their
dissemination and invasion of distant
sites around the body. These cells
form malignant tumors which spread
and metastasize, destroying tissues
and disrupting organ function.
According to the World Health Organization (WHO), cancer is a leading
cause of death worldwide. Almost
one in six deaths were attributable
to cancer in 2020, and the number of
new cancer cases – the incidence rate
– has been rising. Furthermore, recent
estimates predict that as many as one
in two people could develop a form of
cancer in their lifetime.
Nevertheless, scientists and researchers continue to develop sophisticated
and innovative strategies to manage
the growing disease burden caused by
cancer. Research into cancer biology
entails the study of intricate interactions between the genes, proteins
and biological pathways that drive
the growth and development of the
disease. In essence, cancer biology is
the study of what makes cancer cells
different from normal cells in order
to provide clues for how we might be
able to treat it.
With advancements in our knowledge
of cancer, ever more effective treatments and technologies are being developed which is helping to increase
survival rates.
IMMUNOTHERAPY
The immune system attacks cells that
are “non-self ”, such as infected or
cancerous cells. However, the immune
system can struggle to keep pace
with the proliferation of cancer cells
and can have difficulty preventing
tumor growth, as cancer cells employ
several methods to evade detection
and destruction by the immune system.
In these cases, immunotherapies are
designed to stimulate and augment
the immune system’s ability to target
cancer cells.
In 2018, the Nobel prize in physiology
or medicine was presented to Prof.
James Allison and Prof. Tasuku Honjo
for their contributions to immunoAdvances in Cancer Biology
SARAH WHELAN
22
therapy research. Specifically, for their
discoveries of programmed cell death
protein 1 (PD-1) and its ligand PD-L1,
as well as the development of neutralizing antibodies for these proteins that
increase the anti-cancer capabilities of
the immune system.
Examples of immunotherapies include
monoclonal antibodies, cytokines and
immune checkpoint inhibitors. The
first immune checkpoint inhibitor
was the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor
ipilimumab, approved by the FDA in
2011 for use in patients with advanced
melanoma. However, many obstacles
for the use of immunotherapies
remain such as difficulties predicting
which patients will respond to therapy, the development of resistance as
well as high treatment costs. To this
end, researchers continue to advance
our knowledge of immunotherapies to
overcome these complications.
A recent advancement in this field
came from researchers that demonstrated the overwhelming success of a
new “immunoablative” immunotherapy in a small Phase 2 clinical trial. This
treatment was designed to replace the
need for surgery or chemoradiation for
cancer treatment. Fourteen patients
with DNA mismatch repair-deficient
(MMRd), locally advanced rectal cancers were treated with dostarlimab
(an anti-PD-1 antibody) every three
weeks over a six-month period. Dostarlimab is already established as a
treatment for metastatic MMRd colorectal cancer – therefore, the team
hypothesized that dostarlimab for
locally advanced disease may alter the
requirements for additional therapy.
All trial participants demonstrated a
complete clinical response, whereby
multiple imaging techniques revealed
no signs of tumors after 6–25 months
of follow-up. This supports the neoadjuvant use of similar therapies, i.e.,
treatment to first shrink the tumor
prior to other major treatments such
as surgery or radiation.
Other advances include the development of a small synthetic molecule
as an alternative to antibody-based
immunotherapies. The use of monoclonal antibody therapies is limited
due to their high cost in addition to
their large size, which prevents them
from reaching the less accessible
areas within solid tumors. In this case,
researchers used computer-aided
drug design and bioinformatics approaches to develop small synthetic
molecules that would inhibit PD-L1
as an alternative to therapeutic antibodies. Experimental data confirmed
the final candidate molecule was
effective at inhibiting PD-L1 in mice
that expressed humanized T cells. The
molecule requires further evaluation
in cancer models, but if successful,
could potentially be cheaper to
produce than antibody therapies and
could be suitable to take as an oral pill.
AI/MACHINE LEARNING
AI describes technologies designed to
mimic human intelligence, simulated
by machines and computer systems.
Machine learning is an application
of AI, designed to adapt algorithms
and predictions based on experience.
The use of AI tools in research and
medicine can aid the identification of
patterns across enormous datasets,
helping to make decisions or predictions. For cancer, this could potentially assist with screening, diagnosis and
establishing treatment plans. A recent
study identified that, as of 2021, a
total of 71 AI-based medical devices
have been approved by the FDA in
oncology-related fields. Most of these
focus on radiology and pathology disciplines, with breast, lung and prostate
cancers receiving the most benefit.
To tackle the issue of low response
rates to immune checkpoint inhibitors, researchers have used
network-based machine learning
to identify biomarkers that could
indicate favorable immunotherapy
responses. Their machine-learning
algorithm analyzed the clinical outcomes of over 700 melanoma, gastric
and bladder cancer patients alongside
the transcriptomic analysis of their
tumor tissue. The newly discovered
biomarkers were able to successfully
predict which patients would respond
to immune checkpoint inhibitors – a
breakthrough that could help the
identification of patients ahead
of treatment.
Additionally, another research team
have developed an AI they call
“ikarus” which they demonstrated
to be successful in differentiating
between cancerous and healthy cells
from single-cell sequencing data. In
the study, ikarus was initially trained
using data from colorectal and lung
cancer cells, but the researchers later
demonstrated it was also able to distinguish cancerous from healthy cells
in liver and brain cancers.
Advances in AI and cancer biology
have also been made in the field of
radiology. Cedars-Sinai researchers
developed an AI that was able to
identify individuals that would go on
to develop pancreatic cancer from
their CT scans taken years before
they were ever diagnosed. Pancreatic
cancer has some of the worst survival
rates of any cancer type, with just
two to 9 patients surviving five years
after their diagnosis. Diagnosis of
pancreatic cancer is frequently made
With advancements in our knowledge of
cancer, ever more effective treatments
and technologies are being developed
which is helping to increase survival rates.
23
iStock
late due to its vague symptoms, which
allows the cancer to advance into
severe disease. Therefore, improving
rates of early diagnosis may help to
increase survival. With further study
of its prediction capabilities, the AI
could eventually be used to indicate
the possibility of future pancreatic
cancer for patients undergoing CT
scans for other concerns.
CANCER VACCINES
The first vaccines used to prevent bacterial diseases were developed some
200 years ago. In modern research
settings, cancer biologists have been
using this knowledge to develop vaccines against cancer, though efforts to
design and produce effective vaccines
have proved challenging. Tumor antigens targeted by vaccines may not
produce strong immune responses,
or indeed tumor cells may mutate to
evade destruction.
Nevertheless, the COVID-19 pandemic has brought with it a new interest in
mRNA vaccine technology that may
help efforts to develop effective cancer vaccines which aim to stimulate
or enhance anti-tumor immune responses. Most mRNA cancer vaccines
are currently in Phase 2/3 trials and
none to date have been approved by
the FDA. Recently, a preclinical trial
in mice demonstrated the efficacy of
modified lipid nanoparticle “bubbles”.
Other lipid nanoparticles, like those
used in some COVID vaccines, can
favor delivery of the vaccine to the
liver, potentially resulting in inflammation. These newly developed lipid
nanoparticles favored delivery of the
vaccine into the lymphatic system,
where immune cells are “trained”, to
provoke a stronger immune response.
The vaccine, which contained mRNA
molecules encoding tyrosinase-related protein-2 (TRP-2), a tumor-associated protein expressed in melanoma,
was tested in mouse models of the
disease. The findings showed that
increased delivery into the lymph
by the modified lipid nanoparticles
led to a stronger immune response.
This significantly inhibited tumor
growth, leading to a 40% complete
response rate in combination with
anti-PD-1 therapy.
Another research team used a different
method of development to produce
an “off-the-shelf ” vaccine. Cancer
vaccines often require tailoring to an
individual patient’s neoantigens produced by their tumor. This treatment
targeted MICA and MICB, stress proteins expressed in many cancer types
in response to DNA damage, which
flag damaged cells to be eliminated by
the immune system. Cancer cells can
evade this mechanism and cleave MICA/B from their surface to escape detection. The vaccine, which produces
antibodies that bind to MICA/B, prevents the cleavage and loss of these
proteins. Together, this strengthens
the immune response from both T
and NK cells against tumor cells,
delivering a powerful “double-punch”
that reduced the rate of metastasis
in mouse models of melanoma and
triple-negative breast cancer.
TURNING TODAY'S
DISCOVERIES INTO
TOMORROW'S TREATMENTS
Cancer biology is a diverse discipline
which includes many other sub-fields
such as genetics, cell biology, pharmacology and medicinal chemistry.
Stepwise advances in these fields
made over the past several decades
have improved our knowledge of
the biological processes underpinning cancer development. Together,
these advances could enable the
development of new and innovative
technologies and therapies with the
aim of turning today’s discoveries into
tomorrow’s treatments. ⚫
24
iStock
“I couldn’t believe that this could happen
to someone.”
B
ack in March 2020, as the
COVID-19 pandemic descended over the world, Naïma was
a busy tech worker, zipping
around London, speaking to clients
and jogging on the weekends.
“I was very, very busy,” she says. “I did
triathlons and [was] running 10Ks all
the time. I was living a normal life, a
full life.”
Then, like every other person in the
UK, her life came to a standstill as the
country’s first lockdown began. Only,
Naïma was even more sedentary than
most; she was ill with COVID-19.
“I had quite a few symptoms: headache,
fever, full-body soreness, sore throat,
a bit of a cough and I felt very weak,”
she explains. “That lasted a couple
of weeks.”
It would have been easy to panic,
contracting the very virus that had just
shut down the world, but Naïma was
relatively calm. “Because I was so fit,
I wasn’t too worried,” she says. “The
only real story that was happening was
the hospitalizations. The line was: ‘Unless you have underlying conditions or
you’re much older, you’ll be fine’.”
And for a while she was, mostly.
“I had this niggling sensation in my
chest that would pop up every couple
of days, just for a few seconds. And in
those few seconds, I couldn’t breathe
properly. But that didn’t develop into
anything else for several months.”
When it did, Naïma wasn’t just
troubled with a tight chest; she was
debilitated with palpitations and
crippling fatigue. She could barely
walk. “My world was turned upside
down from that point in October,
when those severe symptoms kicked
in. I spoke to general practitioners; I
said, ‘I can’t move at all. It feels like
there are bricks on my chest and
shooting pains that come whenever I
get up’. They said, ‘You know, you’re
so young and fit, but this sounds like
a heart attack’.”
It wasn’t. It was long COVID. Naïma
was part of the first batch of people
in the world to develop ongoing,
disabling complications following an
un-hospitalized COVID-19 infection.
Unfortunately, she’s still ill, more than
three years later.
“It took me a couple of months to
realize that this wasn’t going anytime
soon. I was convinced I’d just wake up
Long COVID Research Is a Bit
of a Mess
LEO BEAR-MCGUINNESS
25
and be fine. And, yeah, that obviously
never materialized.”
RESEARCH REQUIRED
How could a fit and healthy 26-yearold go from running triathlons to
being bed-bound for months, just
from a passing viral infection? Why
were she and people like her left with
life-altering symptoms, while others
could move on from their infections,
seemingly unchanged? Back in 2020,
no one had answers to these questions.
No one really knew how to help those
struggling with the illness. Research
was desperately needed.
And, as 2021 dawned, research arrived. The UK government awarded
£18.5 million to four studies that
set out to define long COVID. The
European Union gave €27.9 million
to a larger research initiative, known
as ORCHESTRA, to study how
COVID-19 was impacting people’s
health. And in February 2021, the US
National Institutes of Health (NIH)
raised the bar and allocated $1.15
billion to research the causes of long
COVID and its possible treatments.
So, two and a half years later, what
has been learned? Perhaps more
importantly, have any treatments
been produced?
The short answers: a lot. And not quite.
WHAT EXACTLY IS
LONG COVID?
To begin with, researchers set about
defining long COVID as a starting
point. Many understood the condition to involve persisting symptoms
after a SARS-CoV-2 infection, but
that was about it. They didn’t know
exactly what these symptoms were or
who they were affecting. To gather insights, they began profiling patients.
“A lot of these patients were actually
young and healthy, in their 20s and
30s,” says Dr. Ziyad Al-Aly, a clinical
epidemiologist at Washington University. “And everybody at the time
[in March 2020] was telling them
that, ‘If you’re young and healthy,
then SARS-CoV-2, it’s not a big deal;
you’ll recover’. But weeks later, these
people were not recovering. So we
decided to research long COVID to
try to understand what it is.”
Al-Aly and his colleagues began by
looking at patient medical records.
They recently published two years’
worth of observations in Nature,
comparing the medical data of 138,818
individuals who had a SARS-CoV-2
infection and 5,985,227 who hadn’t.
There were some stark differences.
Among the non-hospitalized, long
COVID took away 80.4 disabilityadjusted life years (DALYs), a standard measure of disease burden, per
1,000 people. For comparison, others
studies have estimated that chronic
obstructive pulmonary disease costs
between 3.6 and 6.7 DALYs per 1,000
people, for instance.
Long COVID’s high disease burden is
partly explained by its sheer number
of possible symptoms; Al-Aly and
his colleagues observed more than
80 within the medical records. These
included atrial fibrillation, cardiac
arrest, anemia, diabetes, fatigue, acute
gastritis, myalgia, memory problems
and peripheral neuropathy. Just over
30% of these sequalae remained “significant” in non-hospitalized patients
for two years.
“Long COVID is the long-lasting
legacy of this pandemic,” Al-Aly says.
Al-Aly’s study documented, in unprecedented detail, just how wide-ranging
the effects of long COVID-19 can
be. But what exactly is causing these
symptoms? Parallel research has shed
some light.
One study found that long COVID
patients had 100 times the levels of
SARS-CoV-2-specific T cells normally seen in people who recovered from
the virus – a finding that suggests the
virus is still active in the bodies of
people with long COVID, surviving
in reservoirs, plaguing sufferers for
months. Tiny blood clots have been
found in patients – clots that could be
blocking oxygen from reaching cells,
starving patients of their energy. The
brains of people with long COVID
are also more active in certain areas
than the brains of those without the
post-viral illness – an observation that
could explain the memory loss and
confusion experienced by many with
the condition.
There’s a lot going on under the skin of
long COVID patients, multiple etiologies affecting multiple organ systems.
And this is where the field of long
COVID research gets sticky, because
highly variable diseases are difficult
to study further. What kind of clinical
researcher is best suited to the job?
A cardiologist? A neurologist? An infectious disease specialist? Based off
the mounting data, it seems like long
COVID is a job for all three.
This issue is partly why, more than
three years on from when the illness
was identified, long COVID research
is still stuck in its characterization
phase. Have a Google of “long COVID
research” these days and one will still
come across new papers decrying how
blurry the definition of the disease is
and arguing for more thorough studies to detail it better.
But people with this condition can’t
wait any longer for such preliminary
studies. They’re desperate for interventional clinical trials now. “People
“It’s been three
years. This is
a really long
time to go
without any
hope.”
26
are hanging their hopes on these
trials,” says Al-Aly. “They want them
to be done yesterday. And yet we’re
moving forward at a turtle’s pace.”
Ironically, it’s the same kind of characterization research that demonstrates this desperation best. Almost
one in five UK doctors responding to
a recent BMJ survey said that they
had lost their ability to work due
to their post-COVID ill-health. A
US study, published last year, estimated that long COVID potentially
accounted for 15% of the country’s
whole labor shortage.
Even those who have managed to
keep working through their illness
report life-altering levels of fatigue
(the most common symptom of long
COVID), enough to rob them of
their prior quality of life. One survey
of patients at a long COVID clinic,
published in BMJ Open this year,
found that, on average, the patients’
fatigue scores were worse or similar
to those of people with severe kidney
disease. The respondents’ quality of
life scores were also lower than those
of people with stage four lung cancer.
Most concerning of all, due to the
toll of the illness, people with long
COVID seem to be at a higher risk of
suicide. One US patient-led survey
found that 45% of respondents had
experienced recent suicidal thoughts
– more than 11 times the national
average (4%). Sadly, these data are
supported by a growing number of
anecdotal reports within the long
COVID patient community from
grieving loved ones.
So, with no approved treatments
for the illness or standardized care
plan – and a disease duration that can
span over three years in certain cases
– it’s perhaps no wonder people with
long COVID are crying out for trials.
Fortunately, a few have been greenlit.
WHAT’S BEING TRIALED?
In August 2023, there were 386 trials
underway around the world relating
to long COVID, according to the
ClinicalTrials.gov database. A promising figure, one might think. Only
94 of those studies, however, were
classed as interventional and were
recruiting, and only 12 trials were
testing pharmacological interventions; the rest were testing the effects
of food supplements, psychological
support, acupuncture and other
non-drugs.
What are the 12 drug trials testing,
though? Well, one – led by Yale
University – is studying whether
Paxlovid (a COVID-19 antiviral made
by Pfizer) could benefit people with
long COVID, perhaps by eliminating
any rogue remnants of SARS-CoV-2
that may still be lingering in their
bodies. Another – led by a private US
company – is seeing whether a novel
drug designed to remove pro-inflammatory nucleic acids could reduce
the levels of vascular inflammation
observed in long COVID patients,
thereby reducing their fatigue.
But perhaps the most highly anticipated trial within the long COVID
community is that undertaken by the
relatively small biotech company
Berlin Cures. The German start-up
made headlines back in 2021 when
it announced that it had effectively
treated four people with long COVID
with just a single infusion (per person) of its proprietary drug, BC 007.
Encouraged by these initial results,
the company has since launched a
Phase 2 clinical trial of its neutralizing functional auto-antibody formula,
which recently completed a Phase 2
open study for heart failure.
“We know, and others have shown, that
these functional auto-antibodies play
a key role in the pathogenesis of various debilitating diseases,” says Oliver
von Stein, Berlin Cures’ CEO. “Long
COVID, we believe, is one of them,
heart failure is potentially another.”
To be included as a participant in the
company’s trial, potential patients
have to test positive for these pernicious auto-antibodies, so the Berlin
Cures team can later test if a reduction in auto-antibody levels correlates
with a reduction in fatigue (the prime
symptom assessed by the study).
Thanks to this level of rigor built into
the trial, and the early results of BC
007, von Stein and his colleagues
iStock
27
iStock
are expecting promising results by
the second half of next year – results
that they hope will attract a new
wave of investment for a Phase 3
trial and, beyond that, other trials for
other maladies.
“We are optimistic and expect good
data from our ongoing Phase 2 study,”
von Stein says. “And, if this is the case,
this will provide a lot of momentum
to tackle other diseases, similar
conditions – for example, chronic
fatigue syndrome.”
THE “ME” IN THE ROOM
Chronic fatigue syndrome – or myalgic encephalomyelitis (ME) – is the
elephant in the long COVID room. For
the past three years, much of the media
and discussion around long COVID
has treated the post-viral condition as
an entirely new illness, a view that has
been reflected in its research; scientists
from around the world have scrambled
to study the disease from scratch.
But if ME had been studied more thoroughly — or even just believed — years
ago, much of the foundational work
of long COVID research may already
have been achieved. That’s certainly
the belief of many of those suffering
from ME, who often live exceptionally
stationary lives due to their condition.
Some are bed-bound, quite literally,
for decades.
“Half of long COVID symptoms are
basically equivalent to ME symptoms,”
says Chris Ponting, a professor at the
University of Edinburgh’s Medical Research Council Human Genetics Unit
and lead investigator of its Decode
ME project.
If anyone is compensating for these
“lost years of ME research”, it’s
Ponting; he and his colleagues are
currently conducting the largest study
of ME ever undertaken. By analyzing
the DNA samples of 25,000 patients,
they hope to identify genetic markers
that could underpin a person’s susceptibility to the disease. With that
information in hand, they could then
both validate the existence of the
malady and identify targets for future
drugs to treat it.
“We anticipate that we’ll be able to
find a bunch of places in our genomes
that scream at us: immunology, or
mitochondria or some neurological
phenotype in the genome,” says
Ponting. “Then, through joining up the
dots, we can make an evidence-based,
cogent explanation for what is going wrong.”
It all sounds quite promising. But
there’s an obstacle to follow-up
studies, the same one that prevented
ME research for decades: funding.
“Our study was funded prior to the
COVID-19 pandemic,” Ponting says.
“There has not been further funding
since then.”
Contrary to the hopes of many in
the ME community, the relative
surge of interest in long COVID has
not translated into a research boon
for other fatigue-inducing, likely
post-viral conditions, according to
Ponting. “There has been a shift in
the dial in acceptance of ME,” he
notes, “which has not translated to
substantial research funding that this
disease deserves.”
And unfortunately, at the tail end of
2023, it’s not just ME that’s being
starved of vital research. The funding
well for long COVID is drying up, too.
GOODBYE, PANDEMIC,
AND GOODBYE, RESEARCH
GRANTS
“All of these scientists, they’re back in
the usual hurdles that scientists go
through to try and get research up
and running in this country. There
is no sense of urgency at all,” says
Even those who have managed to keep
working through their illness report
life-altering levels of fatigue.
28
iStock
Margaret O’Hara, founder trustee
of Long Covid Support, a UK-based
charity supporting people with
long COVID.
O’Hara liaises with researchers on
behalf of the charity. Two years ago,
many of the scientists she spoke to
were getting their funding from the
UK’s National Institute for Health
and Care Research (NIHR), which
launched rounds of commission calls
that were worth millions in 2021.
Now those funding rounds are a distant memory.
“Then NIHR said, ‘right, no more commission calls’,” says O’Hara. “’Long
COVID’s not special anymore, and
if you want money to research it, you
[must] go through the usual channels – RFPB [Research for Patient
Benefit] – and you compete with all the
other diseases. So, what we find now is
that [research grant applications] are
just getting knocked back.”
The situation seems much the same
across the Atlantic. Remember that
$1.15 billion the US NIH allocated to
long COVID research? Well, it’s pretty
much all been spent, largely on observational, characterization research,
according to an analysis by STAT, and
there’s been no announcement of any
follow-up funding, despite calls from
US researchers. Some long COVID
studies in the country have since relied
on charitable donations to keep going.
Why has the money dried up? Fittingly,
one could blame fatigue. There is a
bitter feeling within the long COVID
community that the rest of the world
has grown tired of all things COVID
and no longer wants to hear from – or
fund studies affecting – those damaged
by the virus.
“We think there’s a bit of a message
coming from the top to say, ‘Yeah, let’s
downplay long COVID because, you
know, COVID’s over,’” says O’Hara.
Whether accurate or not, this sentiment that “the top” has lost interest
in long COVID is a doubly frustrating one for those researching the
disease because, right now, the field
could really do with some leadership.
LONG COORDINATION
“[There is] no coherent approach to
studying long COVID. No coherent
strategy,” says Al-Aly. “I liken it to if
you have a bunch of musicians, and
everybody is singing their own tune,
and there’s no conductor harmonizing all of this.”
Al-Aly’s exasperation is shared by
many of his fellow researchers. At a
time of disappearing grants, many say
the field needs a conductor – some
governing body with a comprehensive, coordinated plan of action.
“We think there should be a coordinated effort by UKRI [UK Research
and Innovation] to say, ‘OK, long
COVID is a disease of great interest
and we need to coordinate responses,’” says O’Hara.
“We need to put these scientists together so that they’re not all repeating the same thing.”
O’Hara and her colleagues at Long
Covid Support have been calling for
this kind of managed response since
2020. The charity recently wrote to
the UK government, recommending
that it declare long COVID a public
health emergency and prioritize research into treatments. These pleas
have so far gone unheeded, which
may be unsurprising given recent
political revelations. In October
2020, when presented with the
health department’s first guidance on
long COVID, the then prime minister
Boris Johnson scrawled “bo***cks,”
in capitals, on the document.
But this offensive dismissiveness
from “the top” doesn’t mean a topdown research strategy, if coordinated by health departments and
research funders, is an impractical
suggestion, researchers insist.
“The funders will say that’s up to
the scientists to coordinate,” says
Ponting. “And they would have a
point; it has to be from the ground-up
mostly rather than from the topdown. But top-down does work.”
“The response to mad cow disease did
come from the top,” he adds. “There
have been international efforts on
many different diseases going back
29
iStock
decades, including polio. So, the answer that it is up to the scientists to
organize ourselves in a competitive
world, where we compete for funding because there’s so little of it, is
missing part of what should happen,
which is that we need coordination.”
STUCK IN COVID LIMBO
While all this disarray between researchers, funders and governments
plays out, long COVID patients
watch on, many despondent. Some
are relatively new to the illness. Some
have been coping with it for over
three years with little improvement.
Others have improved over time,
gaining back enough physical capability to return to work. But this
remission is fragile. According to
a Long Covid Support survey of
people who had recovered from the
illness, 60% got long COVID again
following a reinfection of COVID-19.
This happened to Naïma, twice.
“It’s very much a relapsing and remitting story,” she says. “I’ve had periods
where I can work part-time, nearly
full time. And then I’ve had periods
where, right now, I can’t work at all
because of a reinfection.”
To protect herself from worsening
symptoms, Naïma still practices strict
infection protocols. She restricts her
socializing. She wears a mask on public transport. She routinely tests for
COVID-19 and asks others she sees
to do the same. She’s still behaving
like many people did in 2020. Without long COVID treatments, she
can’t afford to change her habits.
“I’ve been lucky in terms of my life beforehand,” she says. “I no longer feel
that way. I live with fear every day
of reinfection.”
What does she make of the state of
long COVID research, then? Does it
give her hope for a return to a normal,
fear-free future? Not quite. While she
is part of a characterization study
being conducted at Imperial College
London, and is optimistic that such
research will one day bear useful results, she says those who have been
struggling with their long COVID for
years need better outcomes now.
“A lot of studies are moving on to:
‘who is getting this?’ I’m part of a
study now with Imperial taking blood
samples. It’s just [about] understanding: why are we so greatly impacted
by this? Is there a specific gene that
we have? I think that [answer] would
really go a long way to understanding
this. And then, of course, treatments
for people who have been suffering
now for years…”
She pauses.
“It’s been three years. This is a really
long time to go without any hope.”
“I think, because I’ve had improvement,” she adds. “I have more hope
because I know that I do have
better points and worse points. But
some people have not had any good
moments; they’ve been around for
three years and had no improvement.
I think we really need to be able to
offer something to those people, to
all of us.” ⚫
Those interested in following Naïma’s
journey of long COVID recovery can
subscribe to her Substack journal.
For those living with long COVID, links
to support groups and symptom management guides can be found at Long
Covid Support.
Those with ME can find similar support
resources at ME Association.
For those struggling with suicidal ideation in the UK, Papyrus and Samaritans offer 24/7 support. Those living
in the US can call the 988 Suicide &
Crisis Lifeline.
ISSUE 04, JULY 2021
cy in
rain:
of
ology
ISSUE 06, SEPTEMBER 2021
Molecules,
Mountains and
Making the World
a Better Place
Regulating Heavy
Metals in Baby Food
#PostItNotePhD
The Alpha and Omega
of COVID-19: Yes,
the Pandemic Will
End (but Not Soon)
ISSUE 08, NOVEMBER 2021
Sustainable
Science
and the
Road to
Net Zero
Uncovering Key
Interactions
Between CancerDriving Proteins
Addressing
Disparities in
Healthcare and
Clinical Research
Closing the
Vaccine Gap
ISSUE 03, JUNE 2021
s a
HaulerISSUE 01, APRIL 2021
The Physicality
ofConsciousnessISSUE 07, OCTOBER 2021
Return From
Extinction
The Neuroscience
of Creativity
Hidden Secrets of the
Human Microbiome
COVID-19: Vaccine
Stockpiling
ISSUE 10, JANUARY 2022
What the World’s
First Pig to Human
Heart Transplant
Could Mean for the
Future of Transplants
Unpicking the
Complexities of the
Cancer Microbiome
A New Approach to
Treating Superbugs
Influenza and
the Holy Grail
Vaccine
ISSUE 09, DECEMBER 2021
Lost Women
of Science
Why the Meat
Paradox Causes
Cognitive Dissonance
for Millions of People
The Omicron Variant
Highlights the Need
for Smarter, FutureProof Vaccine Design
The Pursuit
ofGlobal,
Sustainable and
Cooperative
Open Science
ISSUE 02, MAY 2021
Biodegradation of
Synthetic Plastic in
the Marine Habitat
A Step Closer to
Orally-Delivered
Insulin for Diabetes
ThreePsychologyHistory, Mystery
and DNA Analysis
ISSUE 05, AUGUST 2021
Mental Health and
Mental Illness in
Higher Education
Tapping the Ancient
Power of Microalgae
Turning On the
Vaccine Tap
All
Cancers,
Great and
Small
Pio cae publicae, ad rem deffre, cre
meripie ntimus se nossoltum inclutum
esulabe mnihil te nos vatudes, unter
Download CTA
Make sure you never miss an issue
of The Scientific Observer.
Subscribe Now
Sponsored by
Download your copy below
Information you provide will be shared with the sponsors for this content. Technology Networks or its sponsors may contact you to offer you content or products based on your interest in this topic. You may opt-out at any time.