an autodidact meets a dilettante…

‘Rise above yourself and grasp the world’ Archimedes – attribution

Posts Tagged ‘research

the science of Covid-19: vaccines and trials in the pipeline

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Experts are still claiming 18 months at best for an effective vaccine, and with reports of re-infection, or resurgent virus activity in supposedly recovered subjects, it has become clear (or seems to have?) that we don’t know quite what we’re dealing with. Which of course poses problems for immunologists.

Still, the race is on. The WHO recently reported ‘more than 5 dozen vaccine candidates being pursued around the world’. The essential reason for the ‘delay’, however, is the three-phase human testing program that has become de rigueur for vaccine development. This video from YourekaScience, made five years ago, goes through the process, and note that it talks about a 6 to 10 year process, sometimes longer. The first phase focuses on safety (e.g. are there notable side-effects?), tolerability (does the vaccine cause pain, if so, what type, how long etc) and immune reaction (does the immune response look like being effective?). Phase 2 will involve larger numbers of volunteers to further test safety, and to determine proper dosage and timing of vaccines for strongest immune response. If all goes well, testing will move to phase 3, the largest trials, in which the drug will be compared with placebo and its ability to prevent infection can be more accurately measured – for example, whether it’s more effective in some sub-groups than others. Efficacy will determine approval, with possible recommendations, positive or negative, for different sub-groups. (I should add, after further reading, that stage 2 trials are often further divided into a and b phases).

So first-step safety tests on individuals have begun, in China, the USA and no doubt elsewhere. China’s vaccine is a version of a genetically engineered product developed against Ebola, while the USA’s different candidates are made from copies of a part of the SARS-CoV-2 genetic code.

Meanwhile, in Western Australia, volunteers are being recruited from the staff of a group of hospitals for an interesting experiment. They will be given the Bacillus Calmette–Guerin (BCG) injection, developed against tuberculosis. The jab is also known to boost immunity to other respiratory infections, and has a long history of safe clinical use. The trial has already been endorsed by the WHO. A similar trial, using healthcare workers, is planned for South Australia.

Australia also has a potential Covid-19 vaccine ready to go into first-phase testing in mid-May. It’s called NVX-CoV2373 (remember that name – or maybe not). Its developer, the biopharma company Novovax Inc, has partnered with Australia’s Nuclear Network, a clinical trials specialist, for the trials. The online mag Biowold reports:

The candidate, NVX-CoV2373, is going to have “a very similar safety profile” to Novavax’s phase III Nanoflu nanoparticle vaccine and, given preclinical findings, appears to be stable and productive, [Gregory Glenn, Novovax president of R&D said]. “The conformation is exactly what you need. And now we’re seeing that manifest after immunizing animals [in which we’re seeing] very, very high neutralizing antibody, which I think everyone would agree is highly likely to be protective,” he added.

Although we may be able, with the sort of effective collaboration this pandemic requires, to reduce the time-frame for a vaccine, reducing the current fatality rate is also a priority, hence the importance of the Australian (and other) trials. We are benefitting from the experience of a host of immunologists and biochemists whose experience has helped us to to look at solutions in this area. An article in The Lancet from a week ago is a good example. The authors suggest that anti-tumour necrosis factor (TNF) therapy is a therapy well worth trying:

Anti-tumour necrosis factor (TNF) antibodies have been used for more than 20 years in severe cases of autoimmune inflammatory disease such as rheumatoid arthritis, inflammatory bowel disease, or ankylosing spondylitis. There are ten (as reported on Sept 29, 2019) US Food and Drug Administration approved and four off-label indications for anti-TNF therapy,4 indicating that TNF is a valid target in many inflammatory diseases. TNF is present in blood and disease tissues of patients with COVID-195 and TNF is important in nearly all acute inflammatory reactions, acting as an amplifier of inflammation. We propose that anti-TNF therapy should be evaluated in patients with COVID-19 on hospital admission to prevent progression to needing intensive care support.

Whether the WHO or national government bodies or private companies take up this proposal is a question, but this is a time when investments of this sort should be made, and the results shared worldwide. This and other pandemics should provide the best opportunity for the kind of collaboration that transcends boundaries and individual reputations. We’ve done inspiring work on so many diseases that once thrived in our own ancestral communities – smallpox, leprosy, cholera, typhoid, scurvy, polio, tuberculosis, measles, whooping cough and many more. Our detailed knowledge of our immune system and how it can be primed and harnessed is distributed in researchers and their writings worldwide. All we need is the collective will and the appropriate collaborative approach to take advantage, for humanity’s sake, of all we’ve learned.


Vaccine Clinical Trials 101: How do we develop and test new vaccines? (video)

Written by stewart henderson

April 15, 2020 at 8:55 pm

more about ozone, and the earth’s greatest extinction event

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the Siberian Traps are layers of flood basalt covering an area of 2 million square kilometres

Ozone, or trioxygen (O3), an unstable molecule which is regularly produced and destroyed by the action of sunlight on O2, is a vital feature in our atmosphere. It protects life on earth from the harmful effects of too much UV radiation, which can contribute to skin cancers in humans, and genetic abnormalities in plant life. In a previous post I wrote about the discovery of the ozone shield, and the hole above Antarctica, which we seem to be reducing – a credit to human global co-operation. In this post I’m going to try and get my head around whether or not ozone depletion played a role in the so-called end-Permian extinction of some 250 mya. 

I first read of this theory in David Beerling’s 2009 book The emerald planet, but recent research appears to have backed up Beerling’s scientific speculations – though speculation is too weak a word. Beerling is a world-renowned geobiologist and expert on historical global climate change. He’s also a historian of science, and in ‘An ancient ozone catastrophe?’, chapter 4 of The emerald planet, he describes the discovery and understanding of ozone through the research of Robert Strutt, Christian Schönbein, Marie Alfred Cornu, Walter Hartley, George Dobson, Sidney Chapman and Paul Crutzen, among others. He goes on to describe the ozone hole discovery in the 70s and 80s, before focusing on research into the possible effects of previous events – the Tunguska asteroid strike of 1908, the Mount Pinatubo eruption of 1991 and others – on atmospheric ozone levels, and then homes in on the greatest extinction event in the history of our planet – the end-Permian mass extinction, ‘the Great Dying’, which wiped out some 95% of all species then existing.

According to Beerling, it was an international team of palaeontologists led by Henk Visscher at the University of Utrecht who first made the claim that stratospheric ozone had substantially reduced in the end-Permian. They hypothesised that, due to the greatest volcanic eruptions in Earth history, which created the Siberian Traps (layers of solidified basalt covering a huge area of northern Russia), huge deposits of coal and salt, the largest on Earth, were disrupted:

The widespread heating of these sediments and the action of hot groundwater dissolving the ancient salts, was a subterranean pressure cooker synthesising a class of halogenated compounds called organohalogens, reactive chemicals that can participate in ozone destruction. And in less than half a million years, this chemical reactor is envisaged to have synthesised and churned out sufficiently large amounts of organohalogens to damage the ozone layer worldwide to create an intense increased flux of UV radiation.

However, Beerling questions this hypothesis and considers that it may have been the eruptions themselves, which lasted 2 million years and occurred at the Permian-Triassic boundary 250-252 mya, rather than their impact on salt deposits, that did the damage. There’s evidence that many of the eruptions originated from as deep as 10 kilometres below the surface, injected explosively enough to reach the stratosphere, and that these plumes contained substantial amounts of chlorine. 

More recent research, published this year, has further substantiated Visscher’s team’s finding regarding genetic mutations in ancient conifers and lycopsids, and their probable connection with UV radiation enabled by ozone destruction. The mutations were global and dated to the same period. Laboratory experiments exposing related modern plants to bursts of UV radiation have produced more or less identical spore mutations.

The exact chain of events linking the eruptions to the ozone destruction have yet to be worked out, and naturally there’s a lot of scientific argy-bargy going on, but the whole story, even considering that it occurred so far in the past is a reminder of the fragility of that part of our planet that most concerns us – the biosphere. The eruptions clearly altered atmospheric chemistry and temperature. Isotopic measurements of oxygen in sea water suggest that equatorial waters reached more than 40°C. As can be imagined, this had killer effects on multiple species. 

So, we’re continuing to gain knowledge on the ozone shield and its importance, and fragility. I don’t know that there are too many ozone hole skeptics around (I don’t want to look too hard), but if we could only get the same kind of apparent near-unanimity with regard to anthropogenic global warming, that would be great progress. 

Written by stewart henderson

October 10, 2018 at 3:15 pm

women in science, solutions, and why nobody reads my blog, among other things

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Okay I’ve written facetiously about getting rid of men, or seriously (but facetiously) reducing their proportion of the populace, but in future I want to look at real solutions to a problem that I think is already being addressed but far too patchily and slowly – the problem of male power and dominance. The general solution, of course, is the ascent of woman, to paraphrase Jacob Bronowski via Darwin, and how to promote and quicken it. (Incidentally I’ve just discovered that ‘The Ascent of Woman’ is a four part documentary on women’s history, recently produced for the BBC by Dr Amanda Foreman – look forward to watching it).

However, before continuing I want to issue a plea for help. My blog, which I’ve been writing for many years now, has never had much of a readership, due probably to my inability to network, or even communicate much with others (I’d rather not think it’s anything to do with my writing skills). However, last month even that minuscule readership virtually collapsed, as I recorded my lowest number of hits since my first month of blogging. I’ve soldiered on, but now at the end of September I find this month’s numbers even worse. I feel I need to make a decision about the blog’s future – How do I increase the numbers? Does the blog need a makeover? Can I blame the attention-span of others? I find if I write short pieces, they don’t really cover anything in depth, but I know also that the in-depth pieces, the ones I work on hardest, often get the least attention. Should I just give up and go back to journal writing? At least that way I won’t be faced with the world’s indifference…

Anyway, enough about me – it’s interesting that when you start focusing on an issue, you hear about it everywhere, everybody seems to be talking about it. Today, listening to a podcast of the ABC Science Show, I heard that teenagers are our biggest killers, worldwide, predominantly through motor vehicle accidents. And of course we’re talking largely of male teenagers. The researcher announcing this was female, and, typical female, she was complaining about us tackling this old problem (this has been the global situation for some sixty years) in the same old piecemeal way, rather than though global collaboration in researching and trying to figure out workable solutions to what is clearly a global problem. It was clear from this passionate speaker (and mother of teenage children) that with more females leading research in this and other fields, we’ll get more collaboration and quicker and more effective solutions. And when Robyn Williams, our honourable Science Show anchor, asked the researcher a double-barrelled question – is this teenage problem a male one, and should teenage boys be banned from driving? – her honourable response was ‘yes, and yes’.

The question is – would a law specifically targeting boys/young men as drivers ever be implemented? Of course, many males would describe it as discriminatory. And of course it does discriminate, because the statistics are clear. But why, a young male might ask, should I be treated as a statistic? I’m not like other young men.

It’s a valid point, and I can’t see an obvious way of screening out the potentially safe young men from the potentially dangerous ones. So all we could acceptably do is raise the driving age for all, preferably globally, which would effectively discriminate against the statistically safer drivers, the females. Still, I like the idea of a push, led in the main by women, for a discriminatory driving age policy backed by science. It would raise the profile of the issue, bring women together in an excellent cause, potentially save lives, and feature as another small episode in the ascent of women.

Of course it wouldn’t solve the terrible wee problem of young kids stealing cars and killing and maiming others and themselves for pumped-up kicks…

Written by stewart henderson

October 1, 2016 at 8:39 am

can your shoes help you run faster?

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time to ditch your adidas microbounce plus trainers for neutral to underpronating runners, with lightweight heel-to-toe bounce technology, etc etc - it's all just a load of expensive shite unless you're deeply into the status doo-doo

time to ditch your adidas microbounce plus trainers for neutral to underpronating runners, with lightweight heel-to-toe bounce technology, etc etc – it’s all just a load of expensive shite unless you’re deeply into the status doo-doo

Some years ago, when I was a bit more financially solvent than I am these days, I went to a gym for a while, and even employed a personal trainer. I learned from that experience, thanks to some simple exercises the trainer put me through, and my own quick development through these exercises, that, once I’d gotten this kick start, I didn’t need the expense of a gym, or a personal trainer for that matter, which is just as well, as I soon went broke and abandoned both.

Since then I’ve been using a combo of my trainer’s tips and some CSIRO-recommended exercises to stay moderately in shape at home, happily far from the sight of buffed-up men hefting obscene weights, not to mention bubble-butted women with sweat sparkling from their flawless sun-tinted flesh..

Anyway, one of the things that sometimes worried me when I turned up for gym was my footwear. I noticed that most of the inhabitants wore all the ‘right’ gear including what looked like the latest state-of-the-art top-brand ‘gym shoes’ or running shoes or whatever. I wore a pair of $10 canvas slip-ons, and I always expected the trainer to query them, though I’d also heard or read somewhere that all these expensive ‘scientifically tested’ exercise shoes were a load of malarkey, and you’re possibly better off with good old-fashioned plimsolls, or even nothing at all…

So it was with some interest that I listened to a little segment on a recent science show podcast, dealing precisely with this subject. An English researcher, Mick Wilkinson, who’s also a keen amateur runner, has been looking at running barefoot v running shod, and he ran a half-marathon barefoot in 2011 just to test things out. He came out of it more or less unscathed in spite of some less than barefoot-friendly surfaces.

As to the evidence, much of it was a summary of what a Professor Lieberman of Harvard has found, findings published in Nature and a recent issue of New Scientist. Basically, Lieberman has found that we are born – that’s to say, evolutionarily adapted – to run, considering our skeleton and muscles, and issues of endurance and heat loss (the latter being an obvious consideration in going barefoot). An analysis of ‘peak impact forces and the rate at which those forces are absorbed by the body’ indicates that barefoot running, because it favours a ‘forefoot landing’, a type of foot strike pattern that’s associated with ‘a lower loading rate’ (presumably meaning less overall pressure), is less jarring than its alternative.

Looking at joint movements and rotational forces around the ankles and the knees, the evidence is that, with barefoot running, forces around the ankles are increased, forces around the knees are decreased. This is very interesting to me, as I stopped jogging years ago because one of my knees would stiffen up every time I did it. I was running in fairly basic running shoes, but more importantly to my mind I was running on a hard gravel track. Years later when I did a bit of jogging on grass I didn’t have a problem. Generally though I hate jogging and much prefer cycling, with a nice café at the end.

But what about the effect on the ankles? According to Lieberman the evolution of structures on the rear of the leg, the Achilles, the calf and the soleus (a powerful muscle in the lower calf) have generally evolved to cope with these stresses on the ankle region. More research needs to be done, but there are some pretty serious difficulties, as Wilkinson points out:

So we’ve got biomechanical aspects linking forces, we know that forces are theoretically linked to some kinds of injuries, but that’s where it stops. What is missing is the next piece of the puzzle which would be the randomised control prospective studies examining injury rates in people who are learning to run barefoot, people who are learning to run in shoes. But the design of the study would be so complex, it would be prohibitive. I mean, you’d have to get people who were matched for training history, matched for age, matched for injury status. In fact it would probably be better to start off with people who had never run at all and just say, right, randomly allocate you into a group who are going to learn to run in shoes, you’re going to learn to run barefoot, and then track them over a very long period of time to find out what injury rates are per so many thousand miles. But again, it’s so difficult to operationalise a study like that, probably why one hasn’t been done.

In any case these studies wouldn’t so much answer the question of whether you run faster in shoes, as whether you run better – that’s to say, with less general impact on the body. It, not quite the same thing, though they are connected. And obviously there are hazards in running barefoot in modern urban environments. But there doesn’t seem to be much evidence to support all the advertising claptrap trying to get you to buy ultra-expensive running shoes. In fact, there’s been little noticeable difference in times for running marathons – the real test for shoes v bare feet – in spite of, not only high-tech footwear but all the other-high tech analysis in terms of diet, running technique and so forth. Wilkinson tells us that the American distance runner Steve Prefontaine still holds the American marathon record from the early seventies (Prefontaine was killed in a car crash in 1975, aged 24), and he always wore a standard pair of plimsolls.

So it looks like another case of advertising, and dare I say pseudo-science, winning out over the evidence..

Written by stewart henderson

October 1, 2013 at 12:01 pm