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Archive for the ‘vaccines’ Category

Covid-19: the USA and a bit of ranting

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failed state anyone?

Jacinta: So I note that, unsurprisingly, there are some Americans protesting about physical distancing and lockdowns, while their nation has proved to us all that their overall handling of this pandemic has been the worst on Earth by a long way. I mean, apologies to all those who are working their arses off on the frontline, and to the innocent victims, and to the governors and other leaders trying their level best, but the sheer size of the US failure compared to just about any other country is a fantastic advert for American exceptionalism.

Canto: Well yes, the USA has failed massively in its handling of Covid-19, though of course the virus has been very patchy in its incidence around the nation, for reasons nobody can quite understand. But here’s an interesting metric in comparing the USA to Australia, and anyone can check this on the Worldometer figures. The USA’s population is approximately 13 times that of Australia, but as of today, April 21, the death toll from Covid-19 in the USA is approximately 600 times that in Australia. Compare also Taiwan, one of the world’s best performed country so far, which has a similar population to Australia. This very close neighbour of China has a death toll so far of 6, compared to the USA’s 42,518.

Jacinta: Yes, yes, so what does this say about the USA when you get so many otherwise intelligent people there still clinging to the bullshit claim that their country is the greatest on the planet? Adam Schiff said it in his otherwise excellent speech at the end of the impeachment process – and today, listening to a Sam Harris interview with Caitlin Flanagan (someone I’ve never heard of but who seemed otherwise perfectly rational), I heard her say exactly the same thing – or not exactly. She said that she really believed (almost as if she wished it were so) that America is the world’s greatest country. As if intensity of belief counted for anything. But I doubt that the USA is ahead of the rest of the world in any field worthy of measuring, apart from military might, and that’s surely a questionable value.

Canto: Hmmm, so why don’t you tell me what you really think? But isn’t this just a bit of harmless patriotism after all? We’re expected to love our country, as a value.

Jacinta: Well, I just don’t. I’ve just never had that feeling. Call me aberrant. Or contrary. I’ve often been described as a contrarian, but on this I agree with Venki Ramakrishnan, the Nobel Prize-winner, whose excellent book Gene Machine we’ve just read. He was inundated with congratulatory calls and honorary awards from India after winning the prize, even though he’d had nowt to do with the country since he was a teenager. It started to annoy him, because as he wrote, we don’t get to choose where we’re born. An obvious truth that seems to escape most people. But I’m also a contrarian in that I often find myself undermining my own responses. For example, I want to respond to patriots by calling myself a humanist, but then I think ‘I didn’t get to choose to be a human, why should I be jingoistic about humanity? Birds are pretty cool too.’ Isn’t that contrarian?

Canto: Hmmm. Ramakrishnan was tragically led astray by the transnational values of science haha. And birds can’t do science. I wonder about the blow to US credibility of this event though. They’ve completely failed in the readiness and collaboration Bill Gates wrote about in that New England Journal of Medicine article back in late February. I mean, they’re advancing with possible treatments no doubt, but testing is a shambles from what I’ve heard, and the federal government is non-existent under the boy-king. What little there is of it just gets in the way.

Jacinta: The irony of it is that the more their government fails, the more the libertarians and the knee-jerk anti-government loons will feel vindicated. And now I hear that our own Dear Leader thinks that we should have a more co-ordinated international response but maybe without the WHO. I mean, wtf? Seems to be trying to crawl up the boy-king’s capacious arse. Wrong side of history, mate.

Canto: So I’ve been avidly watching this series of Medcram videos on the pandemic. They’re informative on the science, on immunology and new types of vaccines and treatments, but they’re also a fascinating look back on the innocent-seeming days of six or seven weeks ago, when there were hardly any deaths outside of China. Watching them only adds to my sense of the unreality of it all, somehow. Anyway, microbiology’s a fun topic to learn about don’t you think?

Jacinta: Along with all the others. It’s certainly a lot more calming and inspiring than politics.

References

https://www.nejm.org/doi/full/10.1056/NEJMp2003762

Gene machine, by Venki Ramakrishnan

Written by stewart henderson

April 22, 2020 at 11:37 pm

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.

References

https://abcnews.go.com/Health/wireStory/search-covid-19-vaccine-heats-china-us-70147204

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

https://7news.com.au/lifestyle/health-wellbeing/coronavirus-vaccine-west-australian-hospital-workers-to-take-part-in-covid-19-experiment-c-974237

https://www.9news.com.au/national/coronavirus-cure-covid-19-vaccine-testing-in-australia-novavax-nucleus-network/73bb2d7b-f7bf-4f83-8a30-74cd1d6c3bff

https://www.bioworld.com/articles/434286-novavax-coronavirus-vaccine-bellerophon-covid-19-therapy-near-phase-i8

Written by stewart henderson

April 15, 2020 at 8:55 pm

the science of Covid19: testing

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filched from the excellent JAMA website

So here in South Australia we have fairly drastic social distancing rules with pubs and restaurants and many businesses closed and so on, though in terms of case numbers we’re doing better than other states, and Australia in general is doing a lot better than other countries with comparable populations. Our crude case fatality rates (deaths per million) are smaller than any country ahead of us in number of cases in general – we’re currently ranked twentieth in case numbers. All of this is based on worldometer figures, which we can only hope are as reliable as they can be.

Our relative success has been attributed by some to our testing system. Worldometer has recently added a couple of new lines to their country-by-country statistics, ‘total tests’ and ‘tests per million’, which gives some idea of the testing rate, though little idea of the testing criteria, or the spread of testing throughout the country. According to these figures, the testing rate here is impressive compared to any other country of similar or larger population. Of course, there are just too many variables to make a direct connection between testing and fatality rates, but all experts agree that high rates of testing are beneficial. Worldometer also allows us to make some telling comparisons. For example, neighbours Sweden and Norway are recording a similar number of Covid-19 cases, 6400 and 5500 respectively, though Sweden has almost twice the population. That looks bad for Norway. But Sweden has had 373 fatalities compared to only 62 for Norway. That looks very bad for Sweden. And when we compare the testing, we find that, for half the population, Norway has carried out almost three times the number of tests that Sweden has. That’s almost 6 times the rate of testing. In fact Norway has the highest testing rate in Europe (apart from those with much smaller populations such as Iceland and Luxembourg). Other countries that appear to have greatly reduced fatality rates through comprehensive testing include Germany and South Korea. Clearly, large scale testing is working to keep fatalities down. It’s not unreasonable to attribute the escalating rate of infections in the US to the lack of a co-ordinated and comprehensive testing system, though the fatality rate there is relatively low. It’s clear that, with testing as well as with other responses, the states have failed to unite, largely due to a complete absence of federal governance.

The essential test for Covid-19 is polymerase chain reaction (PCR), and the detection process is well explained in the illustration above, and a little more fully on the JAMA (Journal of the American Medical Association) website. Or, at least, I assume so, as a non-scientific person. But in order to fully understand the process I need to capture it in my own words.

So SARS CoV-2 infects humans by binding to their ACE2 receptors by means of their spike proteins, one of four types of structural proteins pertaining to the virus. Studies have found that SARS CoV-2 has ‘a higher affinity to human ACE2 than the original SARS virus strain’, which presumably goes some way to explain its greater infectiousness. A PCR test is able to detect specific genetic material within the virus. A swab sample is taken from the throat or the nose or the lower respiratory tract or the stool, depending on test type. The JAMA website puts it this way:

After a sample is collected, RNA, which is part of the virus particle, is extracted and converted to complementary DNA for testing. The PCR test involves binding sequences on the DNA that only are found in the virus and repeatedly copying everything in between. This process is repeated many times, with doubling of the target region with each cycle. A fluorescent signal is created when amplification occurs, and once the signal reaches a threshold, the test result is considered positive. If no viral sequence is present, amplification will not occur, resulting in a negative result.

Australia’s Department of Health describes two types of test for the presence of SARS-CoV-2, nucleic acid/PCR tests (as above) and serology antibody tests, but the department sounds a warning:

The reliability of COVID-19 tests is uncertain due to the limited evidence base. Available evidence mainly comes from symptomatic patients, and their clinical role in detecting asymptomatic carriers is unclear.

This statement is dated March 27, and with the fast-moving situation, may no longer be relevant. And speaking of fast-moving situations, here in South Australia we’ve had our first recorded death from the virus, while I’ve been writing this. There’s also news overnight that a tiger from the Bronx zoo has tested positive. This has been confirmed by further testing. Other cats there are showing milder versions of the same symptoms but haven’t been tested. The tiger is described as being in a stable condition, and authorities are claiming that there’s no evidence of transmission from zoo or domestic animals to humans, but this kind of news may well lead to a public panic. And after all, absence of evidence doesn’t necessarily mean evidence of absence. There’s no doubt that the tiger’s infection raises a host of worrisome questions. Was the tiger infected by humans, as seems likely? If not, where did it get the virus from? And if the other cats are positive (they haven’t been tested due to problems with anaesthetics), then where will it end?

Antibody tests look not at infection but immunity. An effective test will show whether a person’s immune system has detected and neutralised the virus. Demand for these types of tests is extremely high, as immunity would mean that these people would be able to return to normal activity., with all the attendant economic benefits. Antibody detection would be of particular importance for current health workers. Such tests would show that the workers have already been infected by SARS-CoV-2 (perhaps without symptoms), and have developed immunity. Widespread use of the tests would also reveal the number of asymptomatic cases. Currently the number of people infected can only be an estimate based on current testing (the worldometer figures tell of confirmed cases, which can only be confirmed by testing). Children, for example, may be infected (and infectious) but asymptomatic, but the extent of this is pure guesswork. Getting real data would be useful in determining schools’ operations.

However, there are difficulties with antibody tests. According to The Lancet,

the technology behind antibody tests is fundamentally distinct and generally harder to get right. “If you have a sequence today, you have a PCR tomorrow”, says Linfa Wang, director of Duke-NUS Medical School’s programme in emerging infectious diseases, in Singapore. “Whether the sensitivity [of PCR] will be enough is another thing, but usually in the first round, it will give you data that you can use. Serology is different.”

One of the issues is knowing which protein, or antigen, on the virus to target. The spike protein is seen as the obvious target, as it’s the means of entering the host cell. Virologists in China have been using the spike protein (due to its specificity) and the nucleocapsid protein (due to its abundance). At least ten antibody test types have already been used throughout China. Specificity is important because, according to The Lancet, ‘the more unique [the protein] is, the lower the odds of cross-reactivity with other coronaviruses—false positives resulting from immunity to other coronaviruses’. These include those that cause the common cold, as well as SARS-CoV.

So that’s enough for now, I’ll continue to try and inform myself, having nothing better to do, and post some more results from that process next time. Keep well!

References

https://jamanetwork.com/journals/jama/fullarticle/2764238

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30788-1/fulltext

https://www.livescience.com/how-coronavirus-tests-work.html

Written by stewart henderson

April 7, 2020 at 12:34 pm

the science of Covid-19: the virus, symptoms, spread, vaccine, incubation period, crude case fatalities

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So I’m now embarking on a series devoted entirely to the virus that’s shutting so many of us in our homes, feeling slightly (or considerably) fearful, for our lives as well as our livelihoods, feeling both frustrated and fascinated, both mystified and enlightened about human behaviour, governmental responses and the like.

First, some people call this virus Covid-19, some call it SARS-CoV-2, and most just call it coronavirus. But most well-informed people know by now that coronaviruses are quite commonplace RNA viruses (numbering in the hundreds). They’re relatively large and get their name from the corona or crown of proteins that spike out from the virus membrane. The official name of this new coronavirus is SARS-CoV-2 (that’s severe acute respiratory syndrome), and Covid-19 is the name of the disease or condition that the virus causes.

This is the third coronavirus in the last 20 years to infect large numbers of humans. Coronaviruses are zoonotic – they spread from animals to humans, becoming more potentially lethal in the process. The others were SARS in 2002 and MERS (Middle East respiratory syndrome) in 2012. The immediate species origin of this new strain is still unclear. According to leading epidemiologist Dr Edison Liu, sequencing has shown that it arose from a bat coronavirus, but it probably passed through a series of vectors before passing to humans. It appears to be less lethal than SARS or MERS, but its spread has been far more rapid. In an interview on the Jackson Laboratory website (JAX), Liu explains that the Covid-19 epidemic occurred at the same time as an influenza epidemic, and while the symptoms are very similar, Covid-19 has about ten times the mortality rate. The essential symptoms are fever, shortness of breath and coughing. Acute symptoms appear to result from a mix of direct viral damage and intense immunologic response in some cases.

The virus is spread primarily by coughing and sneezing, and from the time of contact with it until the time of symptoms is approximately four to seven days. The virus passes from the body in about 14 days on average – hence the recommended minimum quarantine period.

Liu had this to say about a vaccine. Vaccine development generally takes 12 to 18 months, not only to prove its efficacy but to scale up production to the required level. Animal models are needed to test the efficacy of any antiviral treatment. Covid-19 enters our cells through the ACE-2 receptor (angiotensin-converting enzyme 2). Mice, which are often used as test animals, don’t take up Covid-19 through their ACE-2 receptor, but scientists at Iowa University have developed an animal model for infection, in which the human ACE-2 receptor has been engineered into the animal (a mouse). So the effectiveness of antiviral drugs can be tested on these animals, which can apparently be provided en masse, with the Jackson Lab as a premier provider.

The invaluable worldometer website has regularly updated stats on total cases (about 1.1 million as of today, April 4), total deaths, total recovered, death rates and much else, as well as a country-by-country breakdown. It also has well-sourced and referenced info on symptoms, incubation period and other useful stuff. The incubation period is defined as the time from exposure to the development of symptoms. Worldometer sets this period as 2 to 14 days, according to data from WHO, China’s National Health Commission and the USA’s Center for Disease Control. Note that this period is longer than that stated earlier, in information from Jackson Laboratory CEO Edison Liu. Similarly a Chinese online community for physicians and healthcare workers has reported an incubation period of ‘3 to 7 days, up to 14 days’. However, rare outliers have been reported, with incubation periods up to 27 days. The WHO has considered these might be due to second exposures – incidentally raising the issue of re-infection. However, most experts feel that re-infection is unlikely, and this appears to have been borne out as the global spread advances.

Over the past day I’ve listened to two Sam Harris podcasts on Covid-19, interviews with experts conducted in early March – already long ago, it seems. The second, which I listened to first, was with Dr Amesh Adalja, of the Johns Hopkins Center for Health Security. He made an educated guess of the death rate for Covid-19 at 0.6%, based on his analysis of South Korean figures. This is approximately six times the rate for seasonal flu (though it should be mentioned that the most recent seasonal flu has been the most fatal for children in many years), but somewhat lower than many of the predictions of other experts. He also seemed, at that point, less concerned about the need for social distancing and other mitigating measures than others, but it seems that the rapid spread of the virus and growing public concern has rendered obsolete his nonchalance in this area. Also, stop press, a New Scientist article posted yesterday (April 3) has this to say on the South Korean data:

Crude case fatality rates are so-called because they don’t take into account the fact that some of the people counted in the infected numbers have not recovered yet and may still go on to die. Early in March, for instance, South Korea had a crude case fatality rate of just 0.6 per cent. That has risen to 1.7 per cent.

As to the fatality rate of Covid-19 at present, this is difficult to assess, largely due to ‘severity bias’, which means that many milder infections may be going untested, with only the more severe cases capturing the attention of the health care system, or even the infected. New Scientist reports ‘a wide range of estimates, from as low as 1 in 1000 to as high as 1 in 30’. It seems clear from current figures that death rates vary wildly from region to region, and country to country, but the reasons for this are still very unclear. To give some examples of the variation, the current crude case fatality rate for the UK is around 9%, for Italy it’s nearly 12%, but for Germany it’s only 1%. Here in Australia, it’s considerably less even than that, and no doubt governments around the country will be keen to take the credit. But there seems to be more to this variation than government action/inaction. This question along with many others will be explored in future posts.

References

https://www.jax.org/coronavirus

https://www.worldometers.info/coronavirus/#countries

https://www.worldometers.info/coronavirus/coronavirus-incubation-period/

https://samharris.org/podcasts/191-early-thoughts-pandemic/

https://samharris.org/podcasts/190-respond-coronavirus/

https://www.newscientist.com/article/2239497-why-we-still-dont-know-what-the-death-rate-is-for-covid-19/#ixzz6IcFSF3pZ

Written by stewart henderson

April 4, 2020 at 4:01 pm

some more stuff we’ve learned about vaccines

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Vaccinology, I would say that it’s not rocket science. It’s a lot harder than rocket science.

Alan Schmaljohn, virologist, 2014

 

Canto: So, reading The Vaccine Race, by Meredith Wadman – maybe we should just do book reviews? – I find myself getting excited, or confused, by a passage, and wanting to do more research, and then forgetting about it…

Jacinta: It’s probably pretty normal to forget 95% of what you read within a week or so of having read it. You just hope the things you retain are the principal things.

Canto: Yeah well, I was probably hoping the book would help me get my head around how vaccines work, as well as providing juicy and inspiring tales of heroism and malpractice in the history of vaccine development, and it has helped, but I think I’d need to read half a dozen such books and watch a dozen videos before it penetrated my thick skull…

Jacinta: Yes, for example, when I found myself reading, well into the book, about Leonard Hayflick’s human diploid cells, taken from the lungs of an aborted foetus, which were used to provide a sort of base for creating vaccines against all sorts of diseases, most notably rubella, I thought ‘obviously the author has explained human diploid cells, probably in great detail, before, but I can’t recall a whit’…

Canto: That’s what comes of reading too many books at once, and spreading your focus. You know it’s a myth that women can multi-task better than men, but the major finding of research is that multi-tasking is bad for everyone. Let’s resolve to read books one at a time, from start to finish.

Jacinta: Resolved. Anyway, diploid cells are just standard human cells, with 23 pairs of chromosomes. The only other human cells are haploid sperm and eggs, with 23 unpaired chromosomes. Hayflick’s cell line, gathered in the fifties, was ‘cleaner’ than the cells previously used from other animals, such as monkey kidney cells, which contained many viruses. I used the index.

Canto: So these cells were taken from the lungs of a foetus, and Hayflick was able to produce a cell line from them, that’s to say a line of almost endlessly reproducing cells, I’m not sure how that worked, but these cells, which had to be free of every virus or pathogen, would then be somehow injected with, say, the rubella virus, in some sort of reduced form, so as to produce antibodies in those who are vaccinated. The trick with vaccinology, it seems, is to produce a safe vaccine with no side effects, or minimal side effects, but with enough potency to produce a reaction, thus producing antibodies to the antigens in the vaccine. The vaccine must contain antigens, must have some potency, otherwise it’s useless. And every immune system is subtly different, so producing a one-size-fits-all vaccine is in many respects a monumental undertaking. I may have this completely wrong by the way.

Jacinta: Probably only partially wrong, let’s not be absolutists. What about this difference between killed vaccines and live vaccines. Can we talk about that?

Canto: Well first I want to understand how a ‘cell line’ is produced. How were Hayflick’s famous WI-38 (human diploid) cells produced in a constant stream from the lungs of a single legally aborted foetus in 1962?

Jacinta: Let me try to summarise Wadman’s description of the process from this online article. The tiny lungs were minced up and then placed in a container with a mix of enzymes that separated them into individual cells. These cells were separated again into small glass bottles, and a ‘nutrient broth’ was added, causing the cells to divide. thus began the most thoroughly described, studied and utilised human cell line to date, from which was created vaccines for rubella, rabies, adenovirus, measles, polio, chicken pox and shingles.

Canto: A nutrient both? You mean ‘at this point a miracle happens’?

Jacinta: Well, this was a well-established miracle, only previously it was done with non-human cells, and still is. Monkey and canine kidney cells, chicken embryo fibroblasts, hamster ovary cells… Of course using human cells was bound to be controversial.

Canto: So – obviously the cells in these tiny lungs would’ve gone on dividing had the foetus survived, so microbiologists had worked out a way, of making this happen – mitosis, isn’t it? – outside the host. How long have they been able to do this?

Jacinta: Well the first vaccine was created by Edward Jenner in the late eighteenth century, but they weren’t actually culturing cells then. Cell culture is a broad term meaning a process of growing cells – obviously by cell division – outside of their natural environment, usually in a lab. A cell line (e.g. Hayflick’s WI-38 cells) is ‘a population of cells descended from a single cell and containing the same genetic makeup’, to quote Wikipedia. Cell culture started with the maintenance of cell tissue independent of the host animal in the late nineteenth century, but techniques advanced rapidly in the 1940s and 50s to support virology and the manufacture of vaccines. A key event was the growing of poliovirus in monkey kidney cells in 1949, for which John Enders, Tom Weller and Fred Robbins won the Nobel Prize. Their methods were used by Jonas Salk and others to produce the first polio vaccine.

Canto: But the problem with using monkey kidney cells was that they potentially carried their own viruses, right? Which may or may not be harmful to humans, and how would they know? Without using human guinea pigs?

Jacinta: Human subjects, yes. And there’s also the question of the potency of the virus being used, presumably to stimulate the production of antibodies. Is it just a question of stimulating enough antibodies? And isn’t there an obvious danger of infecting subjects with the virus itself? Presumably a killed virus solves that problem, but is it really effective?

Canto: Yes, Wadman’s book has been fascinating on the politics of the vaccine race, but I’m still left much confused – probably due to stupidity or inattentiveness – as to how some vaccines work better than others, and how a cell line – I know it’s essentially about exponential growth – can produce enough material for millions of vaccine doses.

Jacinta: Yes it’s about exponential growth, and it was once thought that, given the right conditions, these cells could go on multiplying ad infinitum, to immortality so to speak, but it was Hayflick who showed this not to be true in a much-cited paper. Even so, the number of replications of individual cells assured a sufficient supply of cells for generations. And since then, much more has been discovered about cell ageing and its causes, what with telomeres and telomerase, but that’s another story. As to why vaccines developed from the WI-38 cells have been so much less problematic than others, it clearly has much to do with their being ‘clean’ human foetal cells, with no other lurgies lurking.

Canto: So let me get this clear. The WI-38 cells are provided to different labs that are wanting to create a vaccine for, say, measles. Or that have already created a vaccine, or at least have isolated the virus – but then of course viruses can’t be isolated, they need cells to survive in. So they get the WI-38 cells, and then they inject them with the virus – killed or attenuated – and then they start trialling it on rats or mice or something, trying out different strengths of the virus, without really having much idea whether the dose will translate to humans, so they must find some willing volunteers (or, in the early days, orphaned or intellectually disabled kids) to experiment on, making sure they err on the conservative side initially, then upping the dosage? I’m no doubt simplifying and speculating wildly here.

Jacinta: yes and I’m no wiser  than you, but it’s a good thing we have people taking these risks, and working so hard in this field –  with clearer ethical guidelines than before – because millions of lives have been saved by vaccines, and so much has been learned about our immune system in the process of developing them.

 

Wadman, Meredith. The Vaccine Race. Doubleday 2017.

https://www.historyofvaccines.org/content/articles/human-cell-strains-vaccine-development

http://www.nature.com/news/medical-research-cell-division-1.13273

https://www.ncbi.nlm.nih.gov/pubmed/25903999

https://en.wikipedia.org/wiki/Cell_culture

Written by stewart henderson

June 11, 2017 at 7:39 pm