some more stuff we’ve learned about vaccines
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
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