mr-psci

[mr-psci]

Upcoming: Pfizer BioNTech Cancer Vaccine Research review.

Co-founders of Pfizer-BioNTech have stated that they’re developing a new vaccine for cancer by repurposing their revolutionary mRNA vaccine which helped to ease the worst of COVID-19 pandemic. They say that the vaccine will be ready for use by 2030. However is this seemingly miraculous vaccine all it’s cracked up to be? Brace yourselves for a full review of everything we know about this upcoming Cancer Vaccine so far!

[mr-psci]

Yours, Mine and Our Exosome - a cellular game of pass the parcel.

Cells. Little blobs with a surface of lipid and protein. Like the frozen moons of Jupiter, under the surface lays a whole world of more lipids and proteins, messenger RNAs, folded membranes and the mother of all life, the DNA.

This tiny little blob spends its usually short life, blind, deaf and mindless, smelling chemicals from the surrounding goo and bodily humour, telling it when to move, when to stay, when to grow and when to die. The loneliest organism in the world…

Well, that is until we found out that they talk all the time! In 1983, two papers published within a week of each other in JCB, both reported that the precursor cells to red blood cells displayed receptors, known as transferrin receptors, which were associated with tiny vesicles ~50nM in diameter. For those unfamiliar, vesicles are tiny envelopes of lipids containing other biological materials such as RNA, proteins, essential ions etc. What was peculiar about these vesicles is that they were found outside the cells they originated from - whereas the vesicles we had previously been familiar with only served as an internal comms system for the different departments within their home cell.

So what? The cells were spitting out some of their contents to be picked up by others. What does this game of gooey blowback have to do with anything? Well, it was later reported, that exosomes make for pretty efficient indicators of disease.

Exosomes form when biological products, namely messenger– and microRNAs, are sent from the endoplasmic reticulum to the cell membrane. Here, the cell membrane “blebs”, enclosing these RNAs inside little lipid bubbles which pinch off the main body of the cell, very much like when a tiny soap bubble forms on the side of a larger one and splits off in the breeze. Now, these RNAs are often used by the cell to instruct itself to produce proteins which can alter the state of the cell from an inactive to an active state in response to a larger stimulus - for example, a cancer cell or a pathogen.

Sharing these essential RNA messages with surrounding cells can act like a fast track to stimulating neighbouring cells into action. In the case of an immune response to a cancerous/pathogenic element, by producing exosomes, the first fell to detect them will then jumpstart its neighbouring cells into the same active state. Once active, these cells can begin producing the SOS protein signals, namely cytokines and chemokines such as histamine, which alert the innate immune system to the problem and initiates an immune response.

Figure 1: Synthesis of Exosomes. Exosomes are generated in one cell and released into the intercellular space to bind to and release their contents into a neighbouring cell. 

So good! We now understand another aspect of cell communication that helps the immune system fight off infections. So where does their use as biomarkers come into play?

Well as with most biological superpowers, exosomes can be used for good and evil. Cancer cells are the body’s own cells with have suffered DNA mutations which turn them from an altruistic blob to parasitic monsters. But they are, ultimately still cells. Cells which can produce exosomes. For those of you who are unfamiliar, angiogenesis is the process by which new blood capillaries are formed. Cancer cells are known to recruit the surrounding tissue capillaries into remodelling themselves to benefit tumour growth at the expense of starving the host tissue cells. Exosomes have been reported to be a major contributor to this process as they are known to carry biomolecules known to promote angiogenesis. This is the sinister process by which malignant cancer cells recruit the growth of new blood capillaries which would otherwise be supplying healthy tissue with oxygen and other nutrients. Exosomes that promote angiogenesis are known as Tumour-derived Exosomes (TEXs). 

Pretty awkward to have your TEX and your Exosome at the same party, right?

Well, depends on your perspective. Scientists are interested in Exosomes because, like many newly discovered biological mechanisms, they have the potential to be reverse engineered for human use. In this case, Exosomes could be synthesised to contain biomolecules that are toxic to cancer cells. The best part of Exosomes is that, unlike radiation and chemotherapy which broadly target any rapidly dividing cancer cells (including essential Precursor Stem Cells which are important for producing immune cells), Exosomes can be given a unique membrane composition (almost like their own ID badge) allowing them bind exclusively to cancer cells, leaving the healthy cells unaffected.

Sounds exciting! However, we still have much to learn. Exosomes were only discovered in 2019 and, as of 2022, there’s still much we are learning about them. As research continues, we will no doubt learn more about these bubbly little blobs and hopefully, one day can use them to benefit human health.

[mr-psci]

AstraZeneca Vaccine: Blood Clot  Danger? Think again...

So for those of you who’ve been living under a rock this last year, since November 2019, the threat from COVID-19 has been very real, putting the world into lockdown, wrecking the economy, turned politics into a war-ground and, much closer to home, has led to severe mental health implications for countless people since we’ve all been trapped indoors for over a year. 

 In Europe, the UK has been spearheading the biggest vaccination program its ever undertaken, with three  different vaccines from three big Pharma companies: the Pfizer Vaccine, the Moderna Vaccine and the Oxford-AstraZeneca vaccine. 

It’s that final one that is probably the most well-recognised one, given the notoriety it’s gained in the media these last few weeks. Now why is that? 

Well, to understand why many are opposed to this COVID-19 vaccine, we need to understand why this vaccine has been surrounded by so much controversy. 

At the start of the pandemic, the University of Oxford, in conjunction with AstraZeneca, worked day and night to develop a vaccine quickly because in the early days of the pandemic COVID-19 had not yet begun to mutate into genetically distinct strains. This window of opportunity was critical because SARs-CoV2 is a virus whose genetic material is encoded by RNA rather DNA (like humans) and because of this, the COVID-19 genome is more liable to mutate quickly, as RNA does not come equipped with the ‘proof-reading’ mechanisms that DNA comes with. So, when AstraZeneca had completed the clinical trials, in line with government requirements, the BBC reported that the UK government approved the vaccine on December 30th 2020, after carefully reviewing all the evidence from the trials.

Now at this point, the Pfizer Vaccine had already been approved and, in the South East of England, a new, much faster-spreading variant of COVID-19 had arisen in Kent, because (as we feared) the virus’s genome had mutated in a position in a way that caused the time between when a person was infected and when they became infectious to decrease significantly. This new variant then warranted another lockdown, because it was faster than the original virus and, eventually, it took its place as the new ‘apex predator’. 

The AstraZeneca vaccine was rolled out from Monday 4th January 2021 and soon people began to speculate, leading to cruel (and untrue) rumours that the vaccine had been rushed and that the government had waived some of the assessment criteria out of desperation. In fairness, 2020 had been a crazy year, and given the desperate situation, the rumours weren’t totally insane...

But they were still untrue. The BBC released a statement from the University of Oxford which revealed that they had, in fact, been developing a new type of vaccine that was more effective than traditional vaccines since the Ebola crisis ended in 2016. Using this technique, they began studying coronaviruses such as SARs and MERs and had even successfully created one of these new vaccines to target MERs because they had realised that all coronaviruses have a vital weak spot: the spike protein that gives coronaviruses their name. The fact that they were able to develop a vaccine for SARs-Cov2 in 10 months (a process that does take 10 years usually) is because they already had a molecule to target (which usually is why vaccine development takes so long because scientists need to study the virus for longer to learn which physical features it has that would make a good vaccine target) and because of the amount of help they had: Oxford gained a tremendous amount of funding and support across the UK to help in their research centres and take part in their clinical trials. 

So to reiterate: the AstraZeneca vaccine’s fast development was not due to cut corners. It was because everyone chipped in. Everyone pulled their weight together giving more time, money, effort and attention than has ever been given to any vaccine before. And instead of recognising the unprecedented amount of co-operation and effort that went into developing this vaccine, all the public could say about it was: “we don’t believe it”. 

It didn’t help that the AstraZeneca Vaccine can occasionally cause side-effects in 1 in more than 10 people - which if you think about the number of people in the UK, that is a lot of people who were complaining about side-effects, so unsurprisingly the public learnt about this quickly and immediately rushed to criticise the vaccine further. 

However, the side-effects are not severe, as the UK government’s Public assessment of the vaccine summary states, those who’ve had the vaccine’s first dose may feel “tenderness, pain, warmth, itching or bruising where the injection is given, generally feeling unwell, feeling tired (fatigue), chills or feeling feverish, headache, feeling sick (nausea), joint pain or muscle ache”. Or to put it simply, you feel a bit poorly for 1-3 days (maximum) and then you feel fine. You may feel like this because either you are allergic to some of the vaccine serum ingredients - which the nurses will ask before the injection and will take precautions as appropriate - or, the most likely explanation is that it’s just your immune system doing what it’s supposed to be doing.

One thing that is commonly overlooked when it comes to viral infections is that, unlike bacteria - which release toxins to cause cell damage which causes the symptoms of illness - the symptoms experienced when infected with a virus is purely down to your body’s immune response. If you have a temperature, it’s because the hotter your body is, the faster the essential chemical reactions and protein interactions that go into ridding the body of an infection can occur. Symptoms of illness that arise from the AstraZeneca vaccine are no different - your body is just practicing what it would do if it met the actual virus for the first time - once its done that, you will very unlikely suffer any symptoms in the future should you be exposed to the virus again because your body remembers how to deal with an infection and will do it so quickly, you will be virus-free before you can say “achoo”.

So, now that the first myth about the AstraZeneca vaccine has been busted (don’t believe us? Read the listed sources!), let’s talk about the current problem: the blood clot rumour. 

So, not to inflame rumours, but yes it has been found that very rarely a blood clot in the brain (Specifically a Cerebral Venous Sinus Thrombosis or CVST) which can be fatal if it goes undetected - the UK’s Medical Regulation body (the MHRA) have reported that in a survey of 79 people (two-thirds women) who had the first dose and suffered a blood clot, 19 people died. However there was not enough evidence to say that the vaccine was the cause of a CVST. Just because something coincided with something, doesn’t mean that it was the cause. The likelihood that the vaccine was the direct cause for a blood clot in these people is further diminished by the fact that CVSTs only affect 5 in 1,000,000 (1 million) people! So those of you who roll your eyes when you hear that “birth control is more likely to give you a blood clot”, it’s true! And on top of that the vaccine has not even been proven to cause blood clots.

So in conclusion, does the vaccine have side-effects? Yes. Are you going to die from them? No. Does the vaccine cause blood clots? There’s not enough evidence to say yes or no, but the type of blood clot that the vaccine has coincided with is so rare, that it shouldn’t be an issue. The bottom line, is that the AstraZeneca vaccine shouldn’t be refused or suspended just because there might be a problem. The MHRA will review the safety and they’ll let us know if they find anything of concern. In the meantime, if people want this pandemic to finally end after nearly 18 months of death and misery then we need to start listening to health professionals and scientists who’ve worked long and tirelessly to return things to normal and trust that they know what they’re doing.

[mr-psci]

Are we in the Middle of a 6th Mass Extinction?

Short Answer: It’s complicated

Long Answer: 

We don’t really know because if this is an extinction event it doesn’t compare easily to the previous confirmed five mass extinctions. The previous five mass extinction events were global disasters set in motion by natural disasters that could not be avoided or predicted - it was a game of chance and Earth got dealt a few very bad hands in the last 443 million years: one of the Big Five Events, dubbed the Great Dying, happened 248 million years ago and it wiped out 96% of all species! By the time of the Next Mass Extinction (Triassic-Jurrasic), Life was still recovering from such a devastating blow. 

That said, The decline in global biodiversity (the number of species of animals and plants on earth) seen in the Big Five Extinctions occurred over thousands to millions of years - This is where the ambiguity starts: How do we define a Mass Extinction Event?

According to a 2017 study by David P.G. Bond at the School of Environmental Sciences, University of Hull and Stephen E. Grasby, Department of Geoscience, University of Calgary, all Mass Extinction events follow the same route: oxygen levels (atmospheric and/or oceanic) fall, whilst carbon dioxide and other greenhouse gas levels rise in the atmosphere, then global warming occurs because of the change in the atmospheric CO2, which leads climate change as a result of global warming and, finally, a period of global cooling occurs as the photosynthesizing organisms regain their foothold and begin leeching the CO2 from the atmosphere. As seen with the Ordovician-Silurian extinction, this process can happen in reverse where the atmospheric composition changes in favour of oxygen rather than CO2 leading to a period of global cooling before a period of global warming.

Suffice to say, as a consequence of human influence, the levels of oxygen in the atmosphere  and- most noticeably - in the oceans, is decreasing and carbon dioxide levels are rising due to humanity’s use of fossil fuels. This in turn has led to a period of rapid global warming. So following the Bond-Stephen Definition of an Extinction Event, the current global situation appears to fit the criteria of a Mass Extinction.

There is a lot of evidence to suggest that we are in a period of global biodiversity decline - what this means is that we are seeing a very rapid loss of animal and plant species (almost 2 species every year in fact). 200 species of vertebrates and 15 marine species have gone extinct in the last 100 years and 42% of 3,623 land invertebrate species, and 25% of 1,306 species of marine invertebrates on the ICUN Red List are facing extinction.  According to the UN’s 2019 mass extinction report many species have disappeared within decades, with the rate of extinction tens-to-hundreds of times higher than it has been in the last 10 million years. 680 animals have gone extinct since the 16th century and 1 million of the Earth’s 8 million known species (12.5% of all species) are due to go extinct in the next few decades. Extinction also encompasses plant life: 571 species are confirmed to have gone extinct in the last three centuries.

Sounds grim doesn’t it?

But... All the loss we are currently seeing, may not be as bad as we think. For one thing, we actually don’t know a lot about the Earth’s biodiversity: a 2011 study predicts that  86% of land species and 91% of marine species have yet to be discovered. Back in 2011 the current estimate for the number of species on earth was 8.7 million and this figure has not changed significantly in the last decade. On top of this, our system for declaring plants extinct has a high error margin for different groups of species: for seed plants alone in the last three decades, species are rediscovered at a rate of 16 species per year. So if we don’t know enough about the Earth’s biodiversity, we cannot be 100% sure that our predictions for the next few decades will have the impact we fear it may have.

So, it would appear we are seeing the beginnings of a Mass Extinction, but at the same time, our predictions are based on information that isn’t as representative as we’d like it to be. That is not to say we should be brushing off the obvious decline in biodiversity because if we as a species are not proactive enough, we will suffer for the damage we have caused. Ultimately the evidence seems to suggest that we have caused so much change in the environment that we are making the Earth less diverse every year and if the current trend continues it could lead to the catastrophic levels of extinction seen in the past.