Is There a Biological Relationship Between Autism and Suicide?  

Autistic people are 7.55 times more likely to die by suicide than the general population. Abbie Storan explores the evidence that this devastating statistic has roots in biology.

By Abbie Storan 

This article may be distressing for some readers due to its themes of suicide. If you are feeling suicidal, please visit here for help.

Around 800,000 people lose their lives to suicide each year. The World Health Organisation propose that for every person lost to suicide, there will be 20 more attempting suicide. Autistic people are 7.55 times more likely to die by suicide than the general population. Approximately 1% of the population is Autistic, but many will remain undiagnosed1

When you consider a relationship between Autistic Spectrum Disorder, Mental Illness, and Suicide you will not fall short for evidence relating to the psychological nature of their connection, such as the JAMA network report published this January, which states that Autistic people have a “more than 3-fold higher rate of suicide attempt and suicide than neurotypical individuals, and that over 90% of people with ASD who attempted or died by suicide had another comorbid mental health condition2. But what if we want to go deeper? Can we establish a biological explanation for why Autistic people are at such an exaggerated risk of mental illness, suicidal ideation, and death from suicide compared to the Neurotypical population? 

What is Autism

Autistic Spectrum Disorder [ASD] is a neurodevelopmental condition which affects how a person experiences the world around them, how they perceive others, and the way in which they communicate. With ASD, everything is different, and everyone is different. Due to the phenotypic heterogeneity as well as the accompanying differences in things like brain connectivity, it has been extremely hard for research to completely describe ASD neurobiology.  However, promising progress is being made with identifying the molecular pathways underpinning ASD3. With the increasing success in neuroimaging data and genetic analysis, it is likely we could see breakthroughs in the diagnosis and treatment of ASD and co-morbidities in the future.  

Before exploring the biology of ASD and Suicide, we should make note of the psychiatric evidence for relationships between ASD and Mental Illness. In 2017 AUTISTICA – the UK’s leading Autism research charity – partnered with the National Suicide Prevention Alliance. They produced a report wherein it was mentioned that depression is present in 30-50% of adults with Autism4. Meanwhile in a meta-analysis of 21,797 Autistic participants, 11.8% of were also diagnosed with Schizophrenia Spectrum Disorders5. Another large-scale meta-analysis of 26,070 people with ASD reported that the prevalence of co-morbid Anxiety Disorders was 42%. This same study also reported the lifetime prevalence of OCD within participants was 22%6.  

In the UK there are approximately 500,000 adults with Autistic Spectrum Disorder (ASD). Eight in ten of these adults will also suffer from mental illness7. From a study of 374 adults with ASD researchers found that 66% had experienced suicidal thoughts, and 35% had attempted suicide1

Genetic links between Mental illness and Autism 

Thanks to a fascinating review of genetic associations with psychiatric disorders, from Andrade et al, we can now outline a direct biological relationship between ASD, Depression and Anxiety. This connection is facilitated by the dysfunction of genes encoding voltage-gated calcium channels (CaVs). CaV1.2 and CaV1.3 encourage neuronal firing and also couple excitation to gene expression; studies show this activity is linked to a number of psychiatric disorders. In particular CaV1.3 is encoded by CACNA1D genes, which have been associated with conditions such as ASD, Major Depressive Disorder, Schizophrenia, ADHD, and Bipolar Disorder. Andrade et al report that, “The non-coding SNP rs893363, located in the 3’ UTR of CACNA1D and the putative promoter region of the choline dehydrogenase gene was found in a genome-wide analysis of these five major psychiatric disorders”8

We can go on to consider the roles of Cortisol and the Hypothalamus-Pituitary-Adrenal axis (HPA) in relation to Autism and Suicide. Cortisol is colloquially referred to as the ‘stress hormone’, stress is a known biological and psychological response to experiencing threatening stimuli. The effect of acute stress is the Fight or Flight response, wherein the Hypothalamus stimulates the adrenal medulla to secrete adrenaline – which decreases activity of the parasympathetic nervous system while increasing activity of the sympathetic nervous system. Meanwhile chronic stress is regulated by the HPA axis9. Secretion of cortisol is controlled by actions of the paraventricular nuclei in the hypothalamus. Those nuclei secrete Corticotrophin-Releasing Factor to the pituitary, leading to the release of Adrenocorticotropic hormone into the bloodstream which stimulates cortisol synthesis and release from the adrenal glands. The HPA axis is under direct circadian regulation by the hypothalamic body clock, leading to diurnal rhythms in all components including cortisol10.  

Many studies on post-mortem brain samples from neurotypical people who died by suicide, and those who died by other means have highlighted higher concentrations  of corticotropin-releasing hormone12; suggesting that people who commit suicide biologically possess higher levels of cortisol, thus higher levels of stress. This has been supported by a particularly interesting study by McGowan et al in 2009, outlining the direct role of the HPA axis in suicide. From observations of the hypothalamus  in people who died from suicide they found evidence of hypermyelination as well as reduced expression of the NR3C1 gene – a glucocorticoid receptor responsible for weakening cortisol signalling – compared to their control group of people who had died by other means. Their work also revealed that early-life adversity can have lifelong detrimental effects on function of the HPA axis13. Autistic children are 63% more likely to suffer from bullying than neurotypical children; wider research confirms that 16.6-18% of Autistic children are physically or sexually abused14, and that autistic children are over 2.5 times more likely to be reported to child protection services for abuse15. So how is this relevant to ASD? The Diurnal Fluctuation of the HPA axis leads to a maximum concentration of salivary cortisol during the first half hour of waking, which decreases throughout the day10. We know that an increase in cortisol synthesis can dysregulate the HPA axis, and research states that children with ASD have elevated plasma and salivary cortisol concentrations, which we know to be associated with suicide. 

The Role of Serotonin 

We can now consider how serotonin plays a part in Autism and suicide. Hyperserotonaemia – elevated levels of whole blood serotonin – was the first biomarker identified from ASD in 1961, and it is present in more than 25% of autistic people. We can also note that elevated whole blood serotonin has been attributed to OCD too. Although we still do not completely understand how the serotonergic system contributes to ASD pathophysiology, neuroimaging and genetic research has concluded that the following clinical findings are related to both ASD and the serotonergic system: 

  • Reduced platelet 5-HT binding, and reduced brain 5-HT binding. Since 5-HT is degraded by aromatic acid decarboxylase into 5-hydroxyindoleacetic acid (5-HIAA), this means reduced 5-HIAA levels are characteristic too.  
  • Intensified by tryptophan depletion 
  • A genetic linkage to chromosome 17q in males 
  • Rare SLC6A4 amino acid variants leading to low expressions of the Serotonin Transport (SERT) receptor – associated with increase in cerebral cortex grey matter volume16 

Post-mortem studies of people who died by suicide have revealed low levels of 5-HIAA in the brainstem, as well as in the prefrontal cortex. These low levels are also observed in suicide victims known to have depression and schizophrenia. Dysregulation of the serotonergic system predisposes individuals to suicidal and other self-injurious acts – The amount of 5-HIAA metabolite in the cerebrospinal fluid (CSF) is strongly correlated to current and future suicidal behaviour. So, we know that not only do low levels of CSF 5-HIAA predict a higher rate of suicidal acts, but also indicate more lethal suicide attempts. Most serotonin receptor studies focus on SERT, with results showing reduced amounts of SERT binding sites in suicide victims17. This information highlights more neurochemical evidence for the biological relationship between Autism and Suicide.  

Hope For The Future 

There is a lot of work to be done to further our understandings of both Autism biology and the biological basis of suicide respectively. Therefore, primary research into the direct biological relationship of suicide and Autism is understandably lacking. From past investigations discussed here, we can be positive this work is underway, and remain hopeful that in the future we may have answers that could keep more autistic people alive. Unfortunately, Autistic people are more prone to experience discrimination throughout their lives from other individuals and even from services expected to keep people safe – undoubtedly having a severe impact on their mental health. There is also still not even enough resources or support specifically for Autistic individuals with mental health issues, which tells us that equally as much progress is desperately needed on a societal basis to reduce Autistic suicides.  



1.  Cassidy S, Bradley P, Robinson J, Allison C, McHugh M, Baron-Cohen S. Suicidal ideation and suicide plans or attempts in adults with Asperger’s syndrome attending a specialist diagnostic clinic: a clinical cohort study. The Lancet Psychiatry. 2014;1(2):142-147. doi:10.1016/S2215-0366(14)70248-2 
2.  Kõlves K, Fitzgerald C, Nordentoft M, Wood SJ, Erlangsen A. Assessment of Suicidal Behaviors Among Individuals With Autism Spectrum Disorder in Denmark. JAMA Netw Open. 2021;4(1):e2033565. doi:10.1001/jamanetworkopen.2020.33565 
3.  Ecker C. The neuroanatomy of autism spectrum disorder: An overview of structural neuroimaging findings and their translatability to the clinical setting. Autism. 2017;21(1):18-28. doi:10.1177/1362361315627136 
4.  Cusack J, Cassidy S, Spiers J. Suicide and autism. Published online 2017. Accessed March 23, 2021. 
5.  Lugo-Marín J, Magán-Maganto M, Rivero-Santana A, et al. Prevalence of psychiatric disorders in adults with autism spectrum disorder: A systematic review and meta-analysis. Res Autism Spectr Disord. 2019;59:22-33. doi:10.1016/j.rasd.2018.12.004 
6.  Hollocks MJ, Lerh JW, Magiati I, Meiser-Stedman R, Brugha TS. Anxiety and depression in adults with autism spectrum disorder: a systematic review and meta-analysis. Psychol Med. 2019;49(4):559-572. doi:10.1017/S0033291718002283 
7.  Baron-Cohen S. Vulnerability – Autism. Autistica. Published 2020. Accessed March 23, 2021. 
8.  Andrade A, Brennecke A, Mallat S, et al. Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders. Int J Mol Sci. 2019;20(14):3537. doi:10.3390/ijms20143537 
9.  McLeod S. What is the Stress Response. Simply Psychology. Published 2010. Accessed March 23, 2021. 
10.  Sharpley CF, Bitsika V, Andronicos NM, Agnew LL. Further evidence of HPA-axis dysregulation and its correlation with depression in Autism Spectrum Disorders: Data from girls. Physiol Behav. 2016;167:110-117. doi:10.1016/j.physbeh.2016.09.003 
11.  Knapp S. HPA Axis – The Definitive Guide. Biology Dictionary. Published 2020. Accessed March 23, 2021. 
12.  Offord C. What Neurobiology Can Tell Us About Suicide. Sci Mag. Published online 2020. Accessed March 23, 2021. 
13.  McGowan PO, Sasaki A, D’Alessio AC, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009;12(3):342-348. doi:10.1038/nn.2270 
14.  Mandell DS, Walrath CM, Manteuffel B, Sgro G, Pinto-Martin JA. The prevalence and correlates of abuse among children with autism served in comprehensive community-based mental health settings. Child Abuse Negl. 2005;29(12):1359-1372. doi:10.1016/j.chiabu.2005.06.006 
15.  ScienceDaily. Children with autism more likely to face maltreatment, study finds. Published 2019. Accessed March 23, 2021. 
16.  Muller CL, Anacker AMJ, Veenstra-VanderWeele J. The serotonin system in autism spectrum disorder: From biomarker to animal models. Neuroscience. 2016;321:24-41. doi:10.1016/j.neuroscience.2015.11.010 
17.  Wassink TH, Hazlett HC, Epping EA, et al. Cerebral Cortical Gray Matter Overgrowth and Functional Variation of the Serotonin Transporter Gene in Autism. Arch Gen Psychiatry. 2007;64(6):709. doi:10.1001/archpsyc.64.6.709 

Biomedicine Teaching Careers

Dr Gemma Lace gives an overview of careers in teaching after a biomedicine degree and the Biomedicine Teaching Support Group for Salford Students.

By Dr Gemma Lace

Teaching careers are rewarding and varied. They require additional qualifications such as a PGCE but will allow you to work in primary schools, secondary schools and colleges in the UK or even abroad. They allow you to share your passion for and knowledge in a subject with children and young people, and thus be a part of inspiring the next generation of scientists, healthcare workers,  health professionals and teachers.

At our best, we are all teachers.

Maya Angelou

Where it starts after graduating: You will commence postgraduate teacher training, for instance by doing a taught PGCE or enrolling onto teach first.

Where you can end up: You could work as a teacher in primary, high school or even a college. You may end up becoming a subject head, head teacher or principal. You may even join the local council and shape OFSTED or local educational policies.

Benefits of a career in the field: Working closely with students and families is very rewarding. This career offers geographical stability and there is a clear route for career advancement (e.g. to Head of Department, Headteacher). Many teachers also spend time teaching abroad!

The Biomedicine Teaching Support Group has been established to support all those interested in teaching careers. Whether you want to be a primary or secondary school teacher and need application support, or whether you have realised teaching and mentoring skills are key to most areas of graduate employment, this support network can help you develop your CV and enhance your professional skillset.  The network officially launched on the 17th of March with the ‘Teaching Careers Symposium’ which featured external speakers, CV enhancement talks and an engaging panel discussion to help network members get ahead of the game, learn about Salford public engagement and outreach opportunities and receive top advice from experienced teachers.  Join the Biomedicine Teaching Support Group for more information.

Research Careers

Dr David Greensmith explains research careers and details the Salford Biomedicine Research Careers Working Group and why student should join.

By Dr David Greensmith

Research careers are extremely varied, typically covering academic, industrial or clinical research but usually require the continuation of the academic pathway and  strong interest in a specific area of biomedicine.  These careers are competitive but are the literal advancement of science.

Where it starts after graduating: Most research-based careers start by securing a PhD position. You may need to undertake a Masters (preferably by research) first, but this is not an absolute prerequisite; it will depend on the level of research experience developed during your degree. For details see the recording mentioned later.

Where you can end up: There are many research-based careers in a huge range of disciplines. Broadly speaking, they fall into three areas: (1) Academic (undertaking research in a university setting), (2) clinical (for example working on clinical trials) and (3) industrial (product and process development).

Benefits of a career in this field: No two careers are the same and for most you will have a high degree of autonomy; you will heavily shape the exact course of the research you undertake and therefore your job. Successes mean a lot in research and can be incredibly rewarding. For example, you will publish your research and may become an internationally recognised expert in your field. You will likely travel the world to present at scientific conferences and in some cases pass on your knowledge to the next generation of undergraduate scientist.

Salford’s Research Careers Working Group (RCWG) seeks to facilitate undergraduate progression to research-based careers including Masters by research and PhD positions. I established the RCWG four years ago as a platform for students to engage with research and to mentor students through PhD applications. Since then, the scheme has developed, and we now have a dedicated Teams Site, student leads and a growing membership that forms a vibrant community of like-minded students.

The RCWG is suitable for all students at any level. As you progress through your degree, we’ll help you build a research-aligned CV through activities such as a regular journal club, dedicated seminars, discussion groups, learned society engagement, facilitated conference attendance, vacation scholarship and travel grant applications, research career events and scientific writing competitions. Then, when you are ready to apply for research-positions we will mentor you through the process.

On the 24th February, the RCWG hosted the inaugural “An introduction to research-based careers” symposium. Attended by around 40 students, I gave a brief overview of the PhD position then Dr Caroline Topham explained where a PhD can lead and considered the pros and cons of a research-based career. We were also joined by an international panel of scientists at various career stage who shared their experiences, advice and insight. The subsequent Q&A session was incredibly engaging. Don’t worry if you missed the symposium as it was recorded and can be accessed via the RCWG Teams site.

It’s also the first of many exciting events. Membership is free, and virtually all our activities are highly transferable; they will look good on any CV. As such, it’s well worth joining even if a research-based career is only one of many options on your radar.

Prophage-host interactions: lifting the curtain on Pseudomonas’ puppet masters

Dr Chloe James shares her phage research in an interview with Prathyusha Vishwanthan

Dr Chloe James in conversation with Prathyusha Vishwanthan

Humans have been aware of bacteriophages as major players in the microbial world for over 100 years. Their most widely recognized feature is their ability to infect and kill specific bacteria, but they are also known to provide some beneficial characteristics to their bacterial host. Apart from a few famous examples, this aspect of phage biology has been largely neglected and the temperate phage-bacteria relationships are not fully understood. Dr Chloe James, a senior lecturer in Medical Microbiology at the University of Salford, has been very curious about this dynamic and has been working on this for a while.

Recently, Dr  James  started a new project funded by the BBSRC, which aims to observe how bacteriophages affect the behaviour of their bacterial host. It  will focus on a notorious opportunistic bacterium, Pseudomonas aeruginosa, a common cause of respiratory infection in cystic fibrosis patients.

Prathyusha Viswanathan interviews Dr Chloe James about her unique and interesting project:

It is quite a different yet interesting topic. How did it all start?

A few years back, I worked on a project examining cases of cystic fibrosis patients who were chronically infected with the Liverpool Epidemic Strain of Pseudomonas aeruginosa. The team had previously found this stain to cause much more severe disease than other strains and to spread from patient to patient, which seemed very unusual.

After sequencing the genome, they found several never-seen-before co-existing prophages. This is where I came in. I regularly monitored phage and bacteria in the patient’s sputum samples for over 2 years. The most notable finding was that these phages were always active and present in abundance. But we could not find any association between the phages and patient condition or antibiotic treatment.

So, this got me extremely curious, like wow, even though the phages are actively killing their bacterial host, the bacteria are still keeping hold of them which means that they must be helping the bacteria in some manner and this point made me determined to find out what they are actually doing. So, I worked with colleagues [Dr. Ian Goodhead and Dr. Heather Allison] to design a project that would better understand how the phages and bacteria affect eachother’s biology, the hypothesis being that temperate bacteriophages do so much more than what we know and at the moment. I think that they pull all kinds of strings and regulate bacterial behavior in different ways.

The BBSRC awarded us funding for 2 postdoctoral researchers to work full time on the project, but we also have some linked projects that are being explored by research students at Salford and Liverpool University.

What achievements have you made so far?

Some key findings of our work are that for one, each of the LES phages seems to be affecting the fitness of the P. aeruginosa host differently and depending on environmental conditions; secondly, together, these temperate phages seem to facilitate rapid evolution of their bacterial host contributing to their adaptation to the CF lung environment; lastly, we think that phages may have an important role in the competitiveness of the LES in CF lungs by acting as anti-competitor weapons (killing other P. aeruginosa strains). But this new project will delve much deeper into the mechanisms of interaction between these intriguing microbial partners. We have published a lot of this work.

These are two complex creatures; you may have noticed many  interactions – have any been particularly unexpected or peculiar?

Yes, that’s true. We are uncovering all kinds of interesting nuggets to follow up on. So far, the most striking discovery is the evidence that the phages are interacting with each-other. This means that the bacteria behave differently depending on which phage they are infected with, and in cases when multiple prophages co-exist together, we observe a completely different behavior. Of course, we also suspect that the bacteria is affecting the biology of the phages. Seeing how the phage infection progresses differently in other P. aeruginosa host strains has helped me direct my thinking in more broader dimensions.

What have been the most recent outputs from the project?

Grace Plahe, a Salford MRes student, presented her work on how LES phages affect bacterial growth and virulence at three different conferences last year. One of her abstracts has been published, and some of her preliminary data helped us to secure the bigger project funding we have now. Since then, two postdoc researchers have been employed on the project, and they will present their preliminary findings on phage-phage interactions and phage genome annotation at the next Microbiology Society annual conference.

What are the upcoming stages of research?

So, our latest funding is to run for 3 years and there are plenty of upcoming tasks on our list. Firstly, our aim is to thoroughly profile the infection cycles of each phage under a range of environmental conditions, and monitor changes in the expression of genes that reports the key stages of the process. We will then conduct a huge transcriptomics experiment which will map global gene expression of bacteria with and without their phage partners. This will show which phages  are regulating which bacterial genes and vice-versa.

We will also perform experiments by exposing the bacteria to both favourable as well as challenging conditions, so that this will help us to identify why the bacteria is keeping hold of so many elements that could so easily kill it and most importantly, we will also construct a series of mutants and perform functional assays to confirm our theories about how these phage puppet masters are pulling the strings.

it seems that your findings have a wide scope in research and  could help thought processes in other fields, leading to new  technologies; yet temperate phage research is rare and has not yet been given much importance. What do you have to say about this?

Very true, I agree. This aspect of phage research has not been given much attention. Most of the research is concentrated on the destructive nature of bacteriophages towards specific bacteria for developing antibacterial treatments. There is a lot of renewed excitement in that area at the moment, with real potential to improve treatment of infections caused by antibiotic resistant bacteria. Whilst the beneficial effects of prophages on bacteria have not been ignored, the scale of this has been grossly underestimated. There is so much more left undiscovered. There are relatively few published findings on the regulatory properties of temperate phages and yet there is a huge amount of genome evidence to show us that ~60% of the sequenced bacterial strains carry prophages in their genomes, and even more  tantalisingly, over 70% of most prophage genes are of unknown function. We know they are present everywhere, and that bacteria are keeping hold of them even though they can present a considerable cost, but we don’t know what they are doing!

I am sure there are many exciting crossroads for this type of research, and you were absolutely correct, this type of research would also help other research fields to understand the pathology of disease better and could inform completely novel approaches to patient treatment and management. In fact, CRISPR systems were actually invented by bacteria, in order to protect them against bacteriophage attack! So, studying phage-bacteria interactions can indeed trigger revolutionary new fields of research and I hope that some of our findings will lead to new thinking in all kinds of areas that I haven’t even considered.

For the Love of Global Health: Ongoing University of Salford Microbiology Research in Uganda

Professor Richard Birtles shares with us about ongoing University of Salford Research taking place in Uganda.

By Prof. Richard Birtles 

In late 2015 I got an email from Louise Ackers, a Professor in the Health School, asking if there were any microbiologists at Salford University. I told her, yes, there were a few, including me and my colleague Dr Chloe James. Looking back, this was yet another moment of serendipity that changed my life – another “bit of luck out of the blue” that serves to remind me that just when you think life is getting predictable, there’s always a surprise just around the corner. Louise was looking for some help with a project she was planning in Uganda focused on educating hospital staff to improve antimicrobial stewardship.  

Six months later, Chloe and I were in Fort Portal, the biggest town in western Uganda, washing our hands like fury in front of groups of doctors and nurses to illustrate a good way of controlling transmission of Staphylococcus aureus infections. By this point we had learnt a lot about the appalling impact of infection (particularly sepsis) on maternal mortality in Uganda and we wanted to try and do something to help.  

We arranged for the regional hospital to collect Saureus clinical isolates for us and, with the help of a new PhD student, we set about characterising these to see how they were related to one another and the extent of their resistance to antibiotics – hoping to get a better understanding of where mothers pick up infection from and how best to treat  infections. This work involved sequencing bacterial genomes and, with the help of my colleague Dr Ian Goodhead, we were able to do this in collaboration with microbiologists at Makerere University in Kampala as a way of transferring expertise in genomic techniques that are well-established in the UK to Uganda.  

Staff at Fort Portal Regional Referral Hospital use VR developed by Chloe and others at Salford University to learn about antimicrobial stewardship. 

We used our free time in Fort Portal to explore some other avenues – I’m interested in tick-borne infections of livestock, so we had a day-trip to nearby farms to pull ticks off cows (later tested by an MSc student) and Chloe had us collecting chicken poo as part of a project on the epidemiology of the food-borne zoonotic pathogen Campylobacter jejuni.  

Chloe’s PhD student, Paz, collecting faecal samples from Ugandan chickens to screen for Campylobacter jejuni and other zoonotic pathogens. 

Fort Portal is also the “home” of a UK/Uganda charity called Knowledge for Change (K4C). K4C has been offering placements for Salford University nursing and midwifery students for several years and we were very keen that they expand their offering to include Biomed and HBID students. It took a while to get things sorted, but the first group of BMS and HBID students went out to Fort Portal with Chloe in June 2018 and had a wonderful, life-changing month-long experience embedded in local microbiology, parasitology and haematology services. Here’s what BMS student Adrian Beck said: “This placement had a very positive impact on my personality. The most important thing I noticed is Ugandans have so little [materially] but are still so happy; I am grateful now that I have roof over my head and my good health!”. 

Our work on S. aureus as a cause of maternal sepsis and other hospital-acquired infections started to yield results (, and Chloe returned to Fort Portal in January 2020 to share these results with hospital and public health staff. She used virtual reality kits to help her deliver messages about antibiotic resistance and how it develops. Through continuing collaboration with Louise Ackers this work also contributed to improved antimicrobial stewardship both locally and nationally. 

An infectious control ( hand hygiene) class at Kibiito Health Centre.  

In late 2017 we were chosen to showcase the work we’d been doing in Fort Portal to a delegation of academics from the University of Gulu who were visiting Salford University. Gulu is in northern Uganda, a region devastated by civil war in the 1990s and 2000s and now accommodating hundreds of thousands of refugees from South Sudan and the Democratic Republic of Congo. The University in Gulu is new and very keen to establish collaborations with Institutions that have strong global health research, thus in January 2018 Chloe, Ian and I made a reciprocal visit to Gulu aiming to develop these collaborations. 

We had an amazing, exhausting trip, which included me addressing prisoners in a remote jail about body lice and the infections they transmit, and encounter with children suffering from the terrible “nodding disease”, the cause of which remains a mystery. Ian and one of his PhD students were able to carry out field work collecting tsetse flies, which transmit sleeping sickness. We established links with scientists working on black flies that transmit river blindness and are now working together exploring the microbiomes of black fly guts and their possible impact on Onchocerca volvulus transmission.  

The one person we didn’t meet in Gulu was Dr Richard Echodu, the Director of Gulu University’s new multifunctional research laboratories, who was away in Kampala. However, in early 2020 yet another moment of serendipity led to our working together on the biggest Salford-Uganda collaboration to date. Richard and I were talking about a grant application to support the black fly microbiome work mentioned above, when I mentioned COVID-19.  Richard spoke passionately about how unprepared Uganda was for the pandemic and we both agreed to look out for funding that might give us the opportunity to contribute the country’s response to the virus. A week or two later, Ian found a call for the UK Government through its Global Challenges Research Fund that seemed to fit the bill. What followed was pandemonium as Ian, Richard and I raced to submit our application (at the same time as converting all our teaching to online and teaching students as befuddled by all the changes as we were), but submit we did, and a month later we got the surprising news that we’d been funded.  

The project started last August and under the management of the magnificent Dr Judy Mwangi (who just completed her PhD at Salford University) with fantastic support from Louise Ackers and many other people, we are now six months in and still standing. Working in two countries during the pandemic has thrown up many barriers but this week our diagnostic laboratory opened for business with the approval of the Ugandan Ministry of Health. We now aim to test at least 25,000 people for SARS-Cov2 infection in the next few months and to compliment this with genome sequencing by the summer.  

Me playing a rather passive role in collecting ticks off local cattle. Doing most of the work is my ex-Phd student Jess and Philip (right), a Regional Veterinary Health Officer. 

We’re particularly interested in the impact the virus is having on refugee communities and how the epidemiology of infections might be shaped by risk factors quite different to those recognised in the UK, such as age and obesity. Most Ugandans are young and not fat, but they are far more likely to be carrying parasites or be malnourished than Salford residents. Hopefully, this time next year, we’ll have some answers and we’ll also have helped Gulu University establish itself on the national stage as a centre of molecular microbiology research excellence because the need for such expertise will not go away with COVID19.                   

So, as far as this story goes, we’re nowhere near the end, but maybe we’re at the end of the beginning. There will undoubtedly be many opportunities for oldies like me, Ian, Chloe and Louise, who have loved global health for many years, but there are also opportunities for those just starting out; those who recognise that the relevance of biomedicine and bioscience extends way beyond the boundaries of Salford, or Manchester, or the north-west, or the UK. There’s a big world out there waiting!  

K4C placements are available (again) from September 2021 and are open to all, regardless of whether you are still a student or not. For more information, check out their website,

Does our gut microbiome affect the way we think?

Bruce Veloso explores the gut-microbiota-brain-axis.

By Bruce Veloso

Trillions of microorganisms inhabit the human body at any one time, collectively known as the microbiome. The largest proportion of the microbiome (more than 100 million microorganisms) is in the human gut – up to 100 times the number of eukaryotic cells in the body¹.

Dietary content directly affects the composition of the gut microbiome. For example, it was shown that the composition of gut bacteria present in Europeans is significantly different from that of Africans, a phenomenon which may be attributed to the differences in their regular eating habits². It was observed that the gut bacteria present in Europeans was mainly composed of the Bacteroides enterotype. In contrast to this, the African gut microbiome was mainly composed of Prevotella enterotype.

Furthermore, Wu et al. observed from examination of stool samples from 98 people that Bacteroides spp. are mainly associated with a diet high in animal fat, whereas Prevotella spp. are closely associated with a diet high in carbohydrates².

Zhu et al. explain that after many years of co-existence, some gut bacteria – including six predominant phyla of Firmicutes, Bacteroidetes, Proteobacteria, Actinomycetes, Verrucomicrobia, and Fusobacteria – have developed a ‘symbiotic relationship’  with humans by forming a large portion of the gut microbiome and helping us with a multitude of tasks such as digesting food and preventing growth of pathogenic bacteria¹.

However, the influence of the gut microbiome extends far further than previously believed. The gut and the brain form the ‘gut-brain axis’, where changes in either organ directly impact the other. Experimental evidence suggests that the multiform interactions between the gut and brain likely contribute to several neurological and mental illnesses, such as depression, Alzheimer’s disease and schizophrenia¹.

Here are a few examples:

Microorganisms in the gut can affect the brain of the host organism by regulating the brain-derived neurotrophic factor (BDNF, a nerve growth agent which supports and differentiates neurons) and N-methyl-D-aspartate (NMDA, an amino acid that acts as an agonist, copying the action of glutamate, a neurotransmitter) receptors¹. Changes in BDNF expression are associated with cognitive dysfunction of patients suffering from schizophrenia¹. Interestingly, when the expression of NMDA receptors in a host is enhanced, symptoms are relieved and cognitive ability improves¹.

Additionally, studies have shown that the microbiota can influence the central nervous system by altering hippocampal neurogenesis (process in which new nerve growth takes place in the hippocampus)¹. According to Zhu et al, the hippocampus and lateral ventricle areas of the brain have an important function in learning and memory and therefore can influence the pathogenesis of neurological disorders and symptoms in conditions such as epilepsy, depression, Alzheimer’s disease and Parkinson’s disease¹.

Intriguingly, 95% of serotonin, a neurotransmitter mainly associated with mood and emotion, is produced in the gut, and microorganisms present in the gut may be essential for its production: in sterile mice, serotonin production was reduced to 60%¹. Certain compositions of the gut microbiota may promote the development of depressive disorders. It is fascinating to speculate that we may be able to treat depression and related health conditions using specific food types or even by faecal replacement therapy.


1.  Zhu X, Han Y, Du J, Liu R, Jin K, Yi W. Microbiota-gut-brain axis and the central nervous system. Oncotarget. 2017;8(32):53829-53838. doi:10.18632/oncotarget.17754
2.  Wu GD, Chen J, Hoffmann C, et al. Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes. Science. 2011;334(6052):105-108. doi:10.1126/science.1208344

Parasites: Friend or Foe?

Muhammed Amla explains that our relationship with parasites is more complicated than you may think – it’s not all bad!

By Muhammed Amla

Accounting for nearly 40% of all species on Earth1, parasites are organisms which survive and reproduce by forming symbiotic relationships with other organisms (known as hosts in this relationship) which benefit the parasite and generally harm the host. Many parasites cause death and disease, but they also have helpful roles in health, industry, crime, and agriculture.

While they are not holidaying in your guts or using their host as live cocoons2, parasites can actually be greatly beneficial, from improving agriculture to triggering major evolutionary changes.


With an estimated 20-40% of global agriculture lost to insects, parasites may offer a far more effective solution than damaging farmlands with costly pesticides. Parasitoids are insects behaving like parasites that kill their hosts in the process³, with many naturally preying on crop pests. One example is the Aphidius ervi, a parasitic wasp that lays its eggs in aphids, turning the aphids into a parasitised mummy⁴. Within 2 weeks, the offspring eat their way out of the aphid, searching for more aphids and perpetuating the cycle.

UK rapeseed oil production is hindered by midges. Several wasp parotoids, such as the Platygaster subuliformis attack these midges, killing up to 75% of their larvae⁵. This non-chemical control of pests not only reduces damage to farmland, but also to health of the farmers. Indeed, it is widely accepted that long-term pesticide exposure is linked to Parkinson’s disease, asthma, depression, ADHD, anxiety, and cancers⁶.

Boosting the Immune System

Being infected is not always a terrible thing. In some cases, it can supply more benefits, such as increased protection in hosts from infection by pathogens. Enterococcus faecali, a mildly pathogenic bacteria living in worms, can evolve rapidly to protect their hosts from more lethal infections⁷. This blurs the line between parasitic relationships, where the parasite feeds from the host while causing harm, and mutualistic relationships, where the parasite and host both provide benefits to each other.

There are two forms of protection a parasite can provide to its hosts: resistance, and tolerance⁸. Parasites that provide resistance reduce the likelihood of other species infecting. For example, bacteria in the gut resist the invasion of non-native species. This specific example is also known as colonisation resistance⁹. Meanwhile, parasites providing tolerance reduce the harm of another invading species. For example, when Monarch Butterfly Larvae are inoculated with Ophryocystis elektroscirrha, a virulent protozoan parasite, they have a higher chance of survival when attacked by the lethal parasitoid fly, Lespesia archippivora, than if exposed to the parasitoid alone (fig. 1)¹⁰.

Figure 1: Monarch survival to adulthood when exposed to the protozoan parasite, fly alone, and the protozoan and fly combined¹⁰

Research has shown that when infected with an intestinal worm, the number of lymphoid follicles (microscopic compartments storing B cells, which produce antibodies against pathogens) in mice increased.

The body naturally produces more B cells to increase antibody production in response to an infection, but it does not typically increase the number of lymphoid follicles. However, upon infection with intestinal worms, a cytokine molecule (IL-4) is produced which stimulates B cells to produce lymphotoxin. This then interacts with stromal cells, which produce another cytokine (CXCL13) stimulating follicle production in the lymph nodes¹¹.

B cell follicle formation was previously thought to only occur during the post-natal period (immediately after birth), but this research showed that this process can also occur in adult mammals in the event of a worm infection¹². While it is not recommended to use intestinal worms directly to boost the immune system, it is important to note that they do strengthen the immune system uniquely and this may shape novel research and ultimately treatment strategies in the future.

Another study involving amphibian hosts and trematode parasites displayed how parasite richness not only dampens pathogen transmission, but also inhibits the spread of Ribeiroia ondatrae, a deadly parasite which causes limb malformations in amphibians¹³.

Driving Evolutionary Change

While there are a wide variety of other factors that influence evolutionary change and diversity, it can be said that parasitic organisms could also have played a key role. It is important to note that the following are mainly theories, with many other factors contributing towards evolutionary change, as opposed to exclusively or mainly parasites.

It is hypothesised that parasites drive organisms to become more diverse and complex. The constant evolutionary arms race between the two promote increased defences by the host against the parasite, meanwhile the parasite increases its effectiveness to infect its host. Using computer programs and parasitic programs in a simulation, it demonstrated how diverse lineages arise from the coevolution of hosts and parasites, encouraging then to form complex traits¹⁴. Similar demonstrations with bacteria¹⁵ also indicate the importance of parasites, showing a noticeable effect on population dynamics and evolution.

Parasites and Sex

Another hypothesis is parasites could have influenced the existence of sexual reproduction. One advantage gained, from shuffling genes and producing genetically diverse offspring, is surviving parasites more effectively. The presence of parasites can encourage the constant genetic turnover and force hosts to keep evolving¹⁶.

An experiment conducted with worms and parasites displayed how selfing populations were wiped out within 20 generations, as opposed to outcrossing populations which persisted throughout the experiment¹⁷. Male snails also start to disappear from the population in areas where parasites are rare, favouring asexual reproduction over sexual, due to the substantial costs of sexual reproduction¹⁸.

Parasites and the Brain

Certain parasites have been known to manipulate host behaviour, for example Toxoplasma gondii, which diminishes a rodent’s predator evasion around cats, turning it into an easy meal. Other examples include rabies, and some sexually transmitted pathogens have been known to influence sexual behaviour. It can be suggested that the human central nervous system has evolved to be incredibly complex as a protective countermeasure against parasites that influence behaviour.

The blood brain barrier is a first line defence from pathogens and toxins present within the bloodstream¹⁹. In the constant arms race, there are other parasites that have evolved to pass the barrier using white blood cells and monocytes as a mode of transport²⁰. Some parasites can cleverly manipulate behaviour externally, for example Toxoplasma gondii increases dopamine, a behaviour altering substance²¹. Others can secrete different hormones and activate specific immune responses to manipulate their host to complete their life cycle or leach resources.

Another countermeasure to protect the brain against behavioural changes by parasites is an increase in the amount of neurochemicals required to induce responses. Some parasites release neurochemicals to alter behaviour, the more required to create a response, the greater metabolic cost on the parasite. Due to the generally large size difference between host and parasite, it renders the attack ineffective. The relentless pressure from the increasing brain size through the course of human evolution could have led to parasites adopting alternative strategies²².

Rather than the parasites directly attaching and physically affecting the brain, some parasites like Ophiocordyceps unilateralis almost never touch the brain, yet precisely control insect behaviour²³.

Another advantage of increasing brain size is developing higher levels of protective complexity, meaning they can take more damage while maintaining normal functionality and behaviour. For this reason, mind controlling parasites are more commonly seen in insects. Increasing neuro-signalling complexity, with the use of a range of receptors, neurochemicals, and timed pulses, closes off a parasite’s attacking options. While more complex signals have an increased metabolic cost, it is disproportionately more expensive for parasites, forcing other means of manipulation²².


1.  Dobson A, Lafferty KD, Kuris AM, Hechinger RF, Jetz W. Homage to linnaeus: How many parasites? How many hosts? In: In the Light of Evolution. Vol 2. National Academies Press (US); 2008:63-82. doi:10.17226/12501
2.  Gabbatiss J. Prehistoric parasitic wasps found frozen inside fossilised victims named “Xenomorphia” after terrifying creature in Alien films. The Independent. Published 2018. Accessed February 25, 2021.
3.  Natural History Museum. Positive parasites. Published 2016. Accessed February 25, 2021.
4.  Dragonfli. Aphid Parasite Wasp – Aphidius colemani. Published 2018. Accessed February 25, 2021.
5.  AHDB. Encyclopaedia of pests and natural enemies in field crops. Published online 2016. Accessed February 25, 2021.
6.  PAN. Impacts of pesticides on our health. Published 2021. Accessed February 25, 2021.
7.  King KC, Brockhurst MA, Vasieva O, et al. Rapid evolution of microbe-mediated protection against pathogens in a worm host. ISME J. 2016;10(8):1915-1924. doi:10.1038/ismej.2015.259
8.  Ashby B. Parasites inside your body could be protecting you from disease. The Conversation. Published 2017. Accessed February 25, 2021.
9.  Pickard JM, Zeng MY, Caruso R, Núñez G. Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease. Immunol Rev. 2017;279(1):70-89. doi:10.1111/imr.12567
10.  Sternberg ED, Lefèvre T, Rawstern AH, de Roode JC. A virulent parasite can provide protection against a lethal parasitoid. Infect Genet Evol. 2011;11(2):399-406. doi:10.1016/j.meegid.2010.11.017
11.  Dubey LK, Lebon L, Mosconi I, et al. Lymphotoxin-Dependent B Cell-FRC Crosstalk Promotes De Novo Follicle Formation and Antibody Production following Intestinal Helminth Infection. Cell Rep. 2016;15(7):1527-1541. doi:10.1016/j.celrep.2016.04.023
12.  ScienceDaily. Intestinal worms boost immune system in a surprising way. Published 2016. Accessed January 1, 2021.
13.  Johnson PTJ, Preston DL, Hoverman JT, LaFonte BE. Host and parasite diversity jointly control disease risk in complex communities. Proc Natl Acad Sci. 2013;110(42):16916-16921. doi:10.1073/pnas.1310557110
14.  Zaman L, Meyer JR, Devangam S, Bryson DM, Lenski RE, Ofria C. Coevolution Drives the Emergence of Complex Traits and Promotes Evolvability. Keller L, ed. PLoS Biol. 2014;12(12):e1002023. doi:10.1371/journal.pbio.1002023
15.  Betts A, Gifford DR, MacLean RC, King KC. Parasite diversity drives rapid host dynamics and evolution of resistance in a bacteria-phage system. Evolution. 2016;70(5):969-978. doi:10.1111/evo.12909
16.  Jones L. What would happen if all the parasites disappeared? BBC. Published 2015. Accessed January 1, 2021.
17.  Morran LT, Schmidt OG, Gelarden IA, Parrish RC, Lively CM. Running with the Red Queen: Host-Parasite Coevolution Selects for Biparental Sex. Science. 2011;333(6039):216-218. doi:10.1126/science.1206360
18.  Lively CM. Trematode infection and the distribution and dynamics of parthenogenetic snail populations. Parasitology. 2001;123(SUPPL.):S19-26. doi:10.1017/s0031182001008113
19.  Götz J. Explainer: what is the blood-brain barrier and how can we overcome it? The Conversation. Published 2017. Accessed January 1, 2021.
20.  Masocha W, Kristensson K. Passage of parasites across the blood-brain barrier. Virulence. 2012;3(2):202-212. doi:10.4161/viru.19178
21.  Prandovszky E, Gaskell E, Martin H, Dubey JP, Webster JP, McConkey GA. The Neurotropic Parasite Toxoplasma Gondii Increases Dopamine Metabolism. PLoS One. 2011;6(9):e23866. doi:10.1371/journal.pone.0023866
22.  Packham C. Did parasite manipulation influence human neurological evolution? Published 2019. Accessed January 1, 2021.
23.  Yong E. How the Zombie Fungus Takes Over Ants’ Bodies to Control Their Minds. The Atlantic. Published 2017. Accessed January 1, 2021.

Giving new life: Stem cells can be used to regenerate beating heart cells

Muhammed Din discusses how induced pluripotent stem cells are changing the future of heart disease.

By Muhammed Din

Heart disease, linked with a sedentary lifestyle, consuming junk food and smoking, is a leading cause of death accounting for 31% of global mortality. With so many people suffering with heart disease and current therapeutics being inadequate in replacing damaged myocardium, advances in regenerative medicine may offer a means to improve clinical practice. What if we could regenerate heart cells to replace those damaged in heart disease patients?

The human heart is 70-80% cardiomyocytes (heart muscle cells). These contain myofibrils, which house the fundamental contractile units responsible for muscle contraction, called sarcomeres. Loss of cardiomyocytes contributes to disease progression in heart failure¹.

Cardiomyocyte damage correlates with socioeconomic factors which inevitably cause morbidity and mortality¹-². The role of social factors contributing to congenital heart disease (CHD) in developed countries in not well documented, but a large population-based study conducted in Sweden has shown that the incidence of CHD increases in deprived neighbourhoods³.

There may also be genetic factors. An example of an inherited cardiac disease is long QT syndrome (LQTS), an autosomal dominant disorder affecting 1:1000 live births, associated with 500 different mutations in 15 different genes. Patients show prolonged repolarisation phases (the period of time where heart muscle is regaining electrical potential after contraction) which may predispose them to potentially life-threatening Torsade’s de pointe, otherwise known as ventricular arrhythmias. Mutations commonly arise in KCNQ1 and KCNH2 gene causing LQTS1 and LQTS2, respectively⁴.

Induced pluripotent stem cells (iPSC) are generated from somatic cells  harvested from a patient and converted to stem cells, allowing for autologous transplantation, thereby reducing the need for immunosuppressants.

From their induced stem cell state, iPSCs can  be converted into any type of cell present in the adult human body (pluripotency).  When appropriately stimulated in vitro, iPSCs undergo differentiation, becoming cardiomyocytes appropriate for tissue engineering or 3D bioprinting for transplantation purposes¹. This scientific discovery has generated a new practice of converting iPSCs to  heart cells which can be placed into a damaged heart.

In recent times, widespread use of 3D culture models in scientific research has enabled the experimental modelling of beating heart cells. These cultures give a physiological environment for cells to thrive in, thus allowing the generation of cardiomyocytes from iPSCs. These generated cells are morphologically and functionally like the real thing!

A hydrogel-based cardiac patch was developed with self-morphing properties. This gave a stretchable patch with fibre-like arrangements and mechanical features of a human heart. From here, regenerative medicine and stem cell therapy could expand even further¹.

Many methods  have been adopted in regenerative medicine to generate functional sheets appropriate for use in transplantation, an advancement which may eventually remove the need for organ donors. Organ transplantation carries a risk of organ rejection as the immune system discerns the new organ as not being of self-origin, triggering autoimmunity.

Studies have demonstrated the role of innate cells in transplant rejection: they have  been shown to contribute to both graft rejection and acceptance. Transplant rejection takes place in a number of steps involving the rejection response: allograft rejection leading to recruitment of innate cells and cytokines stimulating immune cells. Thereafter graft destruction is initiated by T cells and non-T cells⁵.

3D bioprinting has brought forth new potential for the use of bioengineering in providing new and enhanced technologies for the regeneration of cardiomyocytes, thus allowing the addition of cells and biomaterials to a well organised structure. Using this cutting-edge approach, iPSC derived cardiomyocytes have been bio-printed into vascularized cardiac tissue and transplanted into a defective heart. As well as this, 3D bioprinting was used to embed supporting cells into a defective heart, for instance, fibroblasts and vascular cells leading to improved therapeutic outcomes in mice.

As a result of this, a fully functional patch was created with expected action potential and electrical conduction as observed in a fully functional heart¹.

The ending of the decade came-forth with a breakthrough in stem cell therapy where we witnessed two Chinese men becoming the first to receive iPSCs therapy for heart disease⁶. This laid down the foundation for innovation and breakthrough in regenerative medicine for decades to come shaping medicine for future generations.


1.  Wang K-L, Xue Q, Xu X-H, Hu F, Shao H. Recent progress in induced pluripotent stem cell-derived 3D cultures for cardiac regeneration. Cell Tissue Res. Published online February 5, 2021. doi:10.1007/s00441-021-03414-x
2.  Psaltopoulou T, Hatzis G, Papageorgiou N, Androulakis E, Briasoulis A, Tousoulis D. Socioeconomic status and risk factors for cardiovascular disease: Impact of dietary mediators. Hell J Cardiol. 2017;58(1):32-42. doi:10.1016/j.hjc.2017.01.022
3.  Peyvandi S, Baer RJ, Chambers CD, et al. Environmental and Socioeconomic Factors Influence the Live‐Born Incidence of Congenital Heart Disease: A Population‐Based Study in California. J Am Heart Assoc. 2020;9(8). doi:10.1161/JAHA.119.015255
4.  van Mil A, Balk GM, Neef K, et al. Modelling inherited cardiac disease using human induced pluripotent stem cell-derived cardiomyocytes: progress, pitfalls, and potential. Cardiovasc Res. 2018;114(14):1828-1842. doi:10.1093/cvr/cvy208
5.  Liu W, Li XC. An overview on non-T cell pathways in transplant rejection and tolerance. Curr Opin Organ Transplant. 2010;15(4):422-426. doi:10.1097/MOT.0b013e32833b7903
6.  Mallapaty S. Revealed: two men in China were first to receive pioneering stem-cell treatment for heart disease. Nature. 2020;581(7808):249-250. doi:10.1038/d41586-020-01285-w

Can Fight or Flight Turn hair White? 

By Bruce Veloso

An old tale going back to the 1789-1799 French revolution says that Marie Antoinette, the last queen of France, was sentenced to the guillotine after being accused of treason, it is said that her hair turned white overnight. It is believed that the stress caused by being sentenced to death resulted in the change of Marie’s hair color.  Although the story may seem farfetched, research suggests that high levels of stress can indeed change the hair to a white color.

Recently, a team of researchers led by Bing Zhang from the Harvard University Stem cell institute, identified a mechanism that links hyperactivation of the sympathetic nervous system and a rise in norepinephrine to a reduction of stem cells that specifically regenerate pigment in the hair follicles of mice. It was clearly noted this linkage turns hair white¹.

For the longest time it’s been said that stress makes the hair turn white, but until now there was no scientific basis for this belief. Our study proved that the phenomenon does indeed occur, and we identified the mechanisms involved. In addition, we discovered a way of interrupting the process of hair color loss due to stress” 

Co-author, Thiago Mattar Cunha. 

When the researchers involved in this study first tried to figure out why acute stress can cause gray hair, the stress hormone cortisol was expected to be the main causative factor for the loss of hair colour, because stress elevates levels of the hormone cortisol in the body. But it came as a surprise to the researchers that once the adrenal gland from the mice was removed so that they could not produce cortisol, the hair still turned grey under stress. This suggested that cortisol was not a main causative factor in the hair turning gray.

Figure 1. Stress turns hair white: Comparison of representative control mouse with black fur (left) to a representative mouse subject to sustained stress for several months (right)1

How does stress change hair color? 

When the researchers involved in this study first tried to figure out why acute stress can cause gray hair, the stress hormone cortisol was expected to be the main causative factor for the loss of hair color, because stress elevates levels of the hormone cortisol in the body. But it came as a surprise to the researchers that once the adrenal gland from the mice was removed, so that they could not produce cortisol, the hair still turned grey under stress. This suggested that cortisol was not a main causative factor in the hair turning gray. This then led to the researchers to expand the focus of the experiment to the entire sympathetic nervous system (SNS), which directly impacts the fight or flight response in both humans and mice. The experiments involved the use of a dark furred mouse and it was noted that the SNS can touch every mouse hair follicle. When pain-induced stress was applied, it triggered a fight-or-flight response from the mice in the autonomic nervous system that caused a rise in norepinephrine levels. This rise in norepinephrine then disabled the pigment-regeneration ability of the stem cells present in the hair follicle. 

Acute stress, particularly the fight-or-flight response, has been traditionally viewed to be beneficial for an animal’s survival. But in this case, acute stress causes permanent depletion of stem cells.” 

Lead author, Bing Zhang. 

This research paper was widely praised within the scientific community in 2020. The significance of this findings can be expanded past hair follicles and allow scientists globally to better understand how acute stress can impact other tissues and organs within the human body. This, perhaps, allowing for different treatments of known conditions, treatments that can reduce the impact of stress on our bodies. 


1.  Zhang B, Ma S, Rachmin I, et al. Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells. Nature. 2020;577(7792):676-681. doi:10.1038/s41586-020-1935-3 

COVID19 vaccines: (almost) everything you need to know

There’s a whole lot of vaccine misinformation out there. Salford microbiology students tell you (almost) everything you need to know, from what is currently available to what new variants mean for vaccination.

By Ashleigh Howard, Maria Roman Masdeu, Reece Robinson, Leon Holmes, Josh Wareing, Tom Churchill and John O’Hara

If there is one thing that everyone has been talking about in 2021, it is vaccines. It has been quite a year – with the science advancing so quickly, there have been many new accomplishments. The year has seen the first ever mRNA vaccine get approval for public use after being developed and evaluated in less than 10 months, making it the quickest vaccine to ever be created. There have been huge clinical trials completed in record time for all approved vaccines, and the UK has become the first country in the world to approve and start delivering COVID-19 vaccines. As of today, there are three vaccines approved for use in the UK, manufactured by Pfizer-BioNTech, Oxford-AstraZeneca and Moderna. This article explores some important topics regarding COVID-19 vaccines and debunk conspiracy theories that may be preventing people from getting vaccinated.

Why is a vaccine against SARS-CoV-2 so important?

Controlling the spread of COVID-19 in an ethical manner is ultimately dependent on mass vaccination – this is the only way the world can return to some degree of normalcy without resulting in excessive fatalities. Vaccines are highly effective in preventing infection with SARS-CoV-2 (the virus that causes COVID-19) and getting vaccinated also provides protection to the people around you. Also, even if the vaccine does not prevent infection, it can effectively prevent serious illness in the incidence of infection: this explains why the first group to be offered vaccinations in the UK have been the elderly, as they are most at risk of severe disease and death. Reducing the amount of severe COVID-19 cases is important because it reduces the strain on the NHS by keeping the number of patients at a manageable number.

Are all the COVID-19 vaccines the same?

No! The technologies used in the three currently approved vaccines are quite different. The Pfizer-BionNTech vaccine and the Moderna vaccine are mRNA vaccines – for an explanation of how these work, see the article ‘Pfizer-BioNTech COVID-19 vaccine explained’ by Nadia Patel in Issue 1.

The Oxford-AstraZeneca vaccine is a “viral vector” vaccine in which a harmless adenovirus is genetically modified so that it expresses the SARS-CoV-2 spike protein on its surface. When this is injected into the muscle of the upper arm, it fools the body into thinking that it is being attacked by SARS-CoV-2 which triggers a strong immune response. Adenovirus vectors are quite new but have previously been used successfully in a vaccine against Ebola virus, and vaccines against Zika virus and HIV using this technology are in development.

Are the current vaccines any good?

At present, only the Pfizer-BioNTech and Oxford-AstraZeneca vaccines are in widespread use in the UK; the Moderna vaccine should be rolled out until next month. All these vaccines have been rigorously tested before being approved, firstly to make sure they do not do any harm and secondly, to quantify how good they are at preventing infection and disease.

The outcomes of these clinical trials were encouraging, if a bit confusing. Clinical trials for the Pfizer-BioNTech vaccine involved 43,000 people (which is much bigger than usual) and indicated that it had an efficacy rate of 95%, which means the proportion of vaccinated people in the trial who got SARS-CoV2 infections was 95% lower than the proportion of unvaccinated people who got infected. These results were very promising. However, protection against symptomatic COVID19 was even better – only one person among the 1000s who were vaccinated got severe COVID19.

The performance of this vaccine in the “real-world” has also been proven; a huge study (1.2 million people!) conducted in Israel showed that two doses of the Pfizer-BioNTech vaccine cut symptomatic cases by 94% across all age groups, and severe illness by nearly as much. The study also showed that a single shot of the vaccine (a strategy currently used in the UK) was 57% effective in protecting against symptomatic infections. Clinical trials of the Oxford/AstraZeneca vaccine, which involved about 12,000 people, indicated an efficiency rate of 70% in term of protecting against infection and, importantly, none of those vaccinated developed severe COVID that required hospitalisation.

So, overall, these vaccines are good at stopping you from becoming ill and, because they also reduce the risk of people being infected and therefore infectious, they are having a positive impact on the epidemiology of the COVID19, curbing the pandemic.

What are clinical trials?

There has been some uneasiness about the speed with which the COVID-19 vaccine trials were completed – so does this mean that they cut corners? To evaluate this, the mechanisms of these trials need to be considered: There are three phases to a clinical (i.e. human) trial, but before these can start, new vaccines are tested  in the laboratory.

In Phase I, the vaccine is given to a small group of adult volunteers (around hundred) to see if it generates an immune response and to make sure there are not any unexpected side-effects. In Phase 2, the vaccine is administered to a larger number of volunteers (several hundreds) and monitored for possible potential side effects and to ensure an immune response is generated consistently in all people, regardless of age and sex. In Phase III, thousands of volunteers are recruited (see above), with about half of participants receiving the vaccine and half a placebo, allowing thorough assessment of the vaccine’s efficiency.

The outputs of phases 2 and 3 must provide evidence of successful prevention of the disease if the vaccine is going to be approved for use. This approval is not given by politicians, but by an independent group of scientists called the Medicines and Healthcare Products Regulatory Agency. They carefully review all the data from clinical trials before deciding if the vaccine is both effective and safe.

The time taken to trial and approve COVID-19 vaccines seemed like a short period, but this was made possible because unprecedented resources were provided for the process. It is truly incredible to witness the achievements of readily available funding combined with willpower and collaboration.

What are the barriers to vaccine roll out?

By the end of February about 30% of the population of the UK will have received at least one dose of a COVID-19 vaccine – that is about 20 million people! Despite this success, there are many reports of people refusing the vaccine, so why is this?

Firstly, many people fear injections – a fear which is termed “trypanophobia” and affects about 10% of people. However, most vaccine refusers appear to worry about the safety of the vaccine, particularly that it may have long-term side effects that are not yet recognised. These fears are heightened by the fact that both vaccines use relatively new technology (mRNA and adenovirus vectors). However, history can testify that vaccines in general are safe – billions and billions of people around the planet have been vaccinated against a range of diseases! In the UK, millions of adults get flu vaccines every year, so maybe 20 or 30 in their lifetime, with no side effects. And this vaccine has been used for about 70 years now, without long-term side effects emerging. The health authorities constantly monitor COVID-19 vaccinations to check for side effects through the “yellow card system”. The most recent analysis of these data, based on 5.4 million people who received their first dose of Pfizer-BioNTech vaccine, showed that about 17,000 “yellow cards” had been reported, but only for side effects such as a sore arm, headache, fatigue etc. These symptoms, and the rate at which they have been reported, are no different to those for other well-accepted vaccines.

Conspiracy theories are also hindering vaccine roll-out. The theory that is currently gaining most attention is that vaccination could cause infertility. This theory is based on apparent similarity between the SARS-CoV2 spike protein and syncytin-1, a protein found in the placenta, and theorises that antibodies produced against the spike protein in vaccines will cross-react with syncytin-1 and provoke immune-mediated damage to the placenta. However, a closer look at the apparent similarity between the two proteins reveals that it is nowhere near sufficient to provoke immunological cross-reaction. Indeed, there are numerous other proteins in the body such as collagen and haemoglobin that are just as similar to the spike protein as syncytin-1 (i.e. not very). Conspiracy theories about vaccines are not new – the most infamous is the Andrew Wakefield study in the 1990s that linked the MMR vaccine to autism. Although this study has been repeatedly disproven, and Wakefield “struck off” after being shown to have misrepresented his data, media coverage of his claims provoked widespread vaccine refusal that resulted in the re-emergence of measles, mumps and rubella in the UK, with some fatalities – highlighting the harm conspiracy theories can have if they are amplified by popular newspapers or social media.

What are SARS-CoV-2 variants and do they threaten the success of vaccination?

SARS-CoV-2 is an RNA virus, which means its genetic information is stored on RNA, not DNA like in most organisms. The enzyme that copies RNA during reproduction is far less accurate than the enzyme that copies DNA, so RNA viruses have very high mutation rates that lead to lots of genetic variation occurring very quickly.

Knowledge on the diversity of SARS-CoV-2 is readily available because many countries have been sequencing viral genomes. It is also known that 1000s of mutations have occurred over the last 12 months. However, most of these mutations do not affect the behaviour of the virus – but there are some important exceptions that are referred to as “variants.”

Mutations have occurred in the genes of these variants which encode the spike proteins. These result is the production of spike proteins with an altered shape, making the variant more transmissible and/or more efficient at invading cells in the lungs.

The two most infamous variants are the Kent variant (B.1.1.7) and the South African variant (B.1.351).

The SARS-CoV-2 spike protein is the target of human antibodies that mediate the immune system killing the virus, and it may be that some antibodies produced in response to the vaccine will not recognise the variant spike protein, resulting in a potential decrease in the effectiveness of the vaccines against these variants. Results of early studies addressing this possibility for the Kent and South African variants suggest the efficiency current vaccines may indeed be compromised, particularly against the South African variant.

So, does this mean that vaccination will soon be worthless? Not really, but it does mean that a vaccine-based strategy for controlling COVID-19 requires seasonal/annual boosters. These boosters can be re-engineered to match whatever SARS-CoV-2 variants are dominant each year, just as happens now with the flu vaccine. The technology to do this re-engineering is already available, so this strategy should not be a problem. The challenge is simply accepting the notion that that life will have to continue alongside SARS-CoV-2, rather than eradicate it completely.