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hello and welcome to technically speaking where scientists and Engineers come together to chat about a common interest to share knowledge and satisfy some curiosity I'm Laura and I'm joined by Emma and Antonia to talk about vaccines and how they're developed so Emma you're doing research in biophysics which I guess relates to some of the biological processes that involve vaccine development but does vaccine work feature in your research at all it doesn't feature directly in my research
but my research is about drug design and kind of has a strong Healthcare motivation and so I do find it very compelling to read about it and also my masters was on antimicrobial resistance so I feel like my research interest is very Healthcare oriented so I like keeping up to date with things and I think the recent discoveries in new vaccines and you know the Nobel Prize um kind of is keeping it really relevant so it's nice to stay on top of it I think yeah I agree wider research wider
reading when you're doing research is always helpful especially if you're at a conference and it just happens to come up yeah cool and Antonia I know we I've said this many times before your background is a bit different you work in sustainability but I can see that you would have an interest in vaccines what's your take on this so my interest comes from a couple of places one was when I was at Uni and looking at International Development the talk of vaccines and Healthcare and access to
healthare was something quite important and kind of I don't know taken taken for granted in in developed countries um so when when you know covid came around and the covid vaccine was being developed I heard mumblings from you know people who I wouldn't say come from a science background saying they don't trust it because it was developed too fast and from my experience and seeing how there was standards to things there was processes I did kind of have faith or I
trusted in the process having been followed and that kind of was at odds with what some people kind of think you know science is supposed to be about process feelings and I guess I kind of felt like people would have followed the right process for for vaccine development that's interesting because I would have said the same thing I paid not a lot of attention to the development process way back when before I had the injections and I just figured obviously there are so many people
around the world working on this they must know what they're doing they wouldn't Mass produce this thing that would be incredibly unsafe right but I mean that kind of leads to the question what is the covid vaccine and how was it so rapidly developed is there something you might know something about Emma yes hopefully hopefully I can explain it well enough to um for those that don't know this um 2023 Nobel Prize in physiology or medicine was awarded for the MRNA
vaccine so in terms of popular kind of science it's kind of right here at the moment and it was happening a lot maybe if they won the Nobel Prize in 2020 people wouldn't have suspected so much I think people hadn't heard enough about it but people hear around about Nobel prizes and so why they got the Nobel Prize was for the development of the MRNA vaccine against covid-19 but if you look into the history of mRNA vaccines you know I'm reading that in the 1990s a
flu vaccine was tested on mice that was mRNA and then in humans in 2013 and so it has has been tested for different viruses you know for years like decades even and uh it was actually found that they were used it for another kind of pandemic epidemic uh for bowla virus um as well the Mr vaccines were developed and so it's been used and it's been around but I think people were afraid because also covid-19 is very similar to flu or a cold and there isn't a vaccine for that so I think people
also are kind of scared about that but um I don't think many people that were afraid did much research into what an M vaccine is and how it works and how it's safe mRNA that's messenger RNA so it's kind of related to DNA but it's not the same yeah they're not the same so yeah messenger RNA or M RNA is one of the types of RNA and RNA is different to DNA even though they sound similar because DNA is this double stranded Helix structure that we know and it's very
stable it's very strong it's it's long and it you know is passed through generations uh whereas RNA is kind of a temporary section of DNA but it's single stranded and so it's made to replicate the DNA um Gene structure onto this smaller segment that can be used and passed into different processes around the cells um so you're not using that DNA to do all these processes you're using it as kind of like a template copy uh and that's how mRNA is used around the cells where you have
different types of RNA which have similar kind of temporary functions but a lot of people also took this RNA to be DNA and that you were injecting yourself with some form of DNA that would also change your DNA which is not possible but also RNA is very kind of safe it's actually not a stable structure in itself and so once it's achieved its job it does kind of degrade anyways right is when I first heard about how this was developed I have no idea how this didn't come up my radar at all
until well after the fact but I thought hang on that involves Gene editing technology in some way how did I not know this so I I'm not just had different priorities at that time I guess yeah it just seems odd that it didn't even pop up on my news feed at all because stuff I'm interested in does and this is something that I'm interested but uh the the gene editing side of it I initially thought oh that does actually sound a little bit scary and I've already had the injections so it clearly
isn't but do you know how like what the basis for it is and how that works how it featured in the research yeah I think well I know the MRNA itself is like when it's in the vaccine it's encased in kind of some lipid so like fat droplet and that's encased in but how do they get the MRNA um I'm not 100% sure but I think it's using some form of plasmids and some circular DNA cutting and editing like they do for isolating genes from and different DNA sequences um you know
for insulin development they use bacteria and like Gene edit put the coding Gene for insulin in and that allows you to reproduce many many insulin proteins and so I think it's using plasmids and like restriction enzymes I'm saying actually a lot of biology stuff now so I need to maybe calm down um but I think it is to do with I don't want to just use an umbrella umbrella term of Gene editing but it's a very kind of well oiled machine I think in biology to swap out a
gene and to produce a certain Gene and to get a bit of DNA that codes for a particular Gene I think is very well understood and well practice because it makes up basically all of the drug research that is going on okay so I have a vague memory of it sort of it made your cells produce the protein that your immune system could then develop a response to so rather than you having the whole virus or a weakened form of the virus is what I know of um traditional vaccines as it's
just a different way of having the same effect to develop an immune response yeah exactly yeah the MRNA vaccine um the piece of R RNA that's temporary code in covid-19 coded for the spike protein on the outside of covid-19 and so when you had the vaccine uh you would then produce that protein you're not producing the virus you're not producing the DNA of the virus you're not producing any of the kind of viral particles you're just producing this protein on the
outside and then that serves as the kind of red flag for your immune response to develop the antibodies to then destroy that Spike protein so when you were infected with covid-19 then you would have this kind of response already in your system and it is very similar to to typical vaccines which um I was reading more about uh and everyone knows well I thought everyone knew the famous story of uh Edward Jenner and his cowpox small pox Revelation that I guess I have not heard of this
no no me neither so it's it's like a a story time um and so I was read I was reading into it and uh small pox was a very deadly disease um in I think the 18th century but also throughout history actually apparently so maybe it was always a problem um but then they found uh they being the doctors of the time I guess found a method to make it less dangerous and less deadly when you were infected with it and that's um during this process called variolation and if
you look into what that is it's kind of gross because it's where people who had small parts would kind of rub their boils onto non non infect people which is pretty Grim lovely but then they would have they would be infected a little bit but not fully and so then they could have um an immune response to it but they didn't know that at the time they just knew that this worked and people still got it but less people died from it but then uh there was um milkmaids who were working with
cows who would get cowpox and then that's a less deadly disease than small pox and so the milkmaids would recover from this and Ed Jenna noticed that they weren't getting small pox or they weren't dying from small poox and so he related this kind of relationship to this variation method and was like well if we had a weakened form of the virus which is what cowpox is to small poox and expose people to that then they wouldn't I don't know if you knew the ins and outs of why that works but then
they would have an immune response and then wouldn't have these deadly effects of cowp small pox I keep on remembering milkmaid cows small pox not cows um which formed the basis for vaccines as we know and like you said LA with these traditional vaccines being weak or dead was the word that I was taught or like weakened attenuated I think is the correct term form of the virus which I think is more scary than having a little piece of RNA considering we already have RNA and DNA
in our system but maybe that's just me I don't know but if it's dead in verted commas isn't that kind of it's ineffective it can't it can't actually do what it's supposed to do although what is a dead virus anyway what does that even mean does that mean it it's like taken away some of its effectiveness at doing what it does to kill your your cells and multiply well a virus lives to reproduce itself doesn't it it sort of inserts itself into yourself and uses that to create more
virus particles that's like that's why we talk about computers getting infected with viruses because they replicate but I don't think they're actually alive I think that's a bit of a misn Nora computer viruses and viruses that infect people and animals alike they're not alive yeah they just reproduce what I thought attenuated was was that you've weakened the virus so much that it can replicate slower like it can't have this effect where it takes over your body and cuz they've made some
part of the replication process not work somehow for attenuated viruses dead viruses I don't know if that's just what they tell you when you're younger so you don't get scared a virus or a vaccine I feel like that's a bit like saying you're being injected with dead bodies though sounds worse I don't know why like a virus but with little X over it where its eyes would be just laid into your body and just kind of like look that's what the rest of them look like remember this you're now a virus
graveyard I heard read that one way of uh weakening or attenuating them is to get them to reproduce in um a different life form like chick embryos I think is quite a common one because the virus gets so used to replicating in that environment that it then struggles to replicate in a different host but your body can still pick up on like the proteins or whatever is on the outside and form an immune response so very much alive just not able to do what it wants
to do yeah alive it's not dead I should stop using that phrase really yeah yeah it sounds like there are a bunch of different ways of doing it and I guess they're not super relevant there's no need to go into all the details of it I think it's just worth knowing that essentially they're not able to do what a virus wants to do which is to replicate itself while also affecting what your body does this is what I don't quite get what is the benefit to it in effectively damaging the host gets into
your cell starts replicating itself and then you get really ill is that just some unfortunate side effect like wouldn't it be better for the virus to if you didn't know it was there yeah maybe it's a side effect I think it is accidental I think it's like taking over your cells to use that energy and then it replicates but may actually you know what I don't know about biology so I'm not going say I think you're right I think I think that's what I would say it
was as well like you I think also when viruses reproduce they produce like toxins to you that you know some kind of intermediate process that they have and so you startop you feel the effects of that um and so I think it is a side effect they are not being affected by their own replication process they didn't mean to kill us they just happened to or maybe they did no I think they did mean to viruses feel quite malicious because they require other people to you know replicate yeah but
you could say that about the humans on Earth you know we take the resources so we can live as a byproduct the Earth is depleted of its resources but we're not actively trying to do that are we or are we maybe I guess the main difference is like the virus isn't sentient right it's not deliberately intentionally saying yes we will kill all humans true it's just doing its thing it's just following thermodynamics and biochemistry yeah wow yeah it's just for following
its programming I guess so that makes it seem like it's been programmed to do a specific thing though which just kind of I assume it just kind of evolved in some way isn't that what DNA and RNA kind of are though that it's kind of its programming yeah it's in its nature I guess when you say that it always suggest that there is some like Mastermind behind it all you know like computer programs are written by people yeah but maybe that's just me who wrote the genetic code yeah I also I thought
it was interesting as well because I remember it was a very long time ago and also I think everyone blocked out from their memory but when Co was happening after people had their first you know wave of vaccines there was Omicron that was coming about that was spreading faster and not being 100% effective on the vaccines and so I just did I did a bit of research into what Omicron actually was and it was several mutations in the spike protein so that's why the Mr vaccine was less effective
against Omicron because it was slightly different like it still worked to an extent but maybe wasn't as quick or wasn't as effective and so but I don't know if regular covid vaccines cuz there was a few that were developed in the regular way I don't know if they were more effective against these small mutations or just equally as affected like in in a question of efficiency and durability to mutation I would guess that mRNA vaccines don't feel as versatile as regular vaccines
because they're only able to replicate that one particular protein they're less likely to be able to adapt yeah makes sense but these proteins which the RNA is made of that was what I was confused about that I wanted to ask actually earlier yeah I don't think the RNA is made of proteins it it helps code for proteins it's made of nucleic acids oh okay um so the RNA only gives a specific instruction for a specific protein so if we just so happened to not have that
exact protein in that virus it wouldn't be recognizable to the body yeah proteins and this is this is my research so hopefully I can answer this well but proteins are very complex 3D structures and so if you even if you do have an amino acid substitution and so a mutation uh whether that actually changes the um whether you have a base substitution sorry so three bases code for one amino acid that's just the DNA to amino acid protein coding relation if you have a mutation in one of those
bases it could still code for the same amino acid um some of the mutations don't have uh an effect on the final amino acid sequence some of them do um and then it could change the amino acid you have but whether it changes it from a Charged amino acid to an uncharged one um depends on the mutation and so if you change it to an amino acid of the same amino acid subtype it's likely that the protein will still fold in a similar way and still still have a similar structure
and so it can still be complimentary won't be exact but it should still have some form of similar structure but that's getting into a debate of structure versus function in proteins which is very kind of complex but essentially not all mutations have will have a noticeable effect on the Protein that's produced but sometimes it will have a massive effect it just depends on the specific mutation you've got me thinking about how the immune system recognizes the proteins
now because the little I know about it I sort of came across it during my own PhD because it was um atomistic simulations and trying to get an accurate representation of all the atoms and how they fit together in a protein is a huge field in itself so just figuring out the structure of it is quite difficult but surely the immune system only L on like one part of the protein cuz there are lots of different parts that can do different things is that right or are
they looking for like multiple different things and that's how it could be effective against Omicron but just not as effective I think for the regular vaccine it's looking for just the virus but the Telltale of but I think the the spike protein is not the only protein on the surface of Co there's different ones that are present that can be recognized by the immune system if it was in a form whereas the spike protein I think is very specific and very Central to the
the identity of covid-19 but that's why the mutations in had more effect on the Mr I mean I I don't know I don't think there was much popularity in the Nonna vaccines with covid because by the time the other vaccines had gone into kind of past all their checks everyone had most likely been vaccinated already with the MRNA and so could you you you had to continue that vaccine regime rather than mixing the two different types yes yeah yeah you did yeah that's actually interesting now
I think about it because I didn't I don't think I thought about it when it was happening why you couldn't mix I just thought of it as yeah like kind of like the whole booster vac vaccine aspect although that's something else I don't understand about vaccines when you first get inoculated you have a booster in a short time and and then the immunity period lasts way longer if you have that second reminder is that cuz after you know 12 months your body's just like chucked out
that information but if it gets it twice it goes right I'll I'll store this in a long-term memory for like decades H that's interesting I guess I'm not sure on the reason why but I think when you have another when you have your booster you're then re- reminded to produce more and so maybe there is a kind of cellular memory well there is a cellular memory because that's how vaccines work but maybe there's more kind of it's a bit more special than we think well more than I know I'm sure
somebody somebody does know about it I have a very weird meta question kind of in relation to that the original Gene editing concept didn't it come from something to do with either viruses it was bacteria protecting themselves viruses wasn't it and they had some DNA that could kind of like snip a bit of the virus DNA and incorporate that into itself so it could then recognize it in the future so we've sort of taken a bacterial defense mechanism against viruses and used it in a more
sophisticated way to protect people against viruses am I remembering that correctly H I think so this the method is right the method is yeah good what they do I learned something yes yeah but yeah and I I can start to see now why the development rate of um the covid vaccine was so much quicker than the more traditional methods that use a weakened or an attenuated form because if you have to get a 100 or 200 replications in a chick emry or whatever you're using to get that weakened virus
that takes time yeah but if you're just using this genetic based technology I can see how that's sort of like a one almost like a one shot there's a lot of development into it obviously L but it's a simpler method if you've got some experience with the gene editing side of it to figure out what the MRNA should look like yeah and when I was reading into it it was a lot of the like trials for developing a regular vaccine it was several stages of this attenuation of
the vaccine and so you would do it once and then that would take a while and then you do it again and then again and then your vaccine is properly attenuated and ready for insertion insertion into the vaccine also I think these the weaker viruses as well um can have a smaller success rate of actually making it I don't know how to say making it into the the vaccine properly but you know it's it's a virus that can degrade in the environment that it's in whereas
I feel like Mr everyone knows everyone's people have been storing mRNA and DNA for years and so it's kind of less complex of a structure that's kind of just I feel like that's a little bit of my own speculation but I feel like in terms of from you know when people say from like from Farm to Table in like restaurants I feel like it's like from Lab to arm it's it's a shorter period but I also I was looking into though as well and I it's it's it is more expensive to develop an MR vaccine is
that because it requires I guess a different type of expertise or a different approach or the ability to understand the gene editing it's called crisper isn't it side of it whereas um weakening of virus is pretty well established there actually is a breakdown of the cost and the largest difference in the price is the material cost so it must be much cheaper to get viruses than it is to obviously make an mRNA sequence and also I guess find the specific sequence of the protein as well
would also be quite expensive and the other percentages for everything else is similar except Capital charge is a lot less for mRNA vaccines so I guess I don't really know what they mean by that actually I feel like I don't know much about bu like what is capital charge that's a business question I don't know what that is that's normally your initial upfront costs to sort of like set up a lab I guess yeah maybe because more labs are set up for traditional vaccines and mRNA wasn't that common
vaccine development pathway was it maybe in the future if fits more established standardized we'll all be doing it like I work in a lab that handles DNA and viruses Royal we the collective Wei of society there also is a significantly 20% to around 2% for mRNA vaccines of others cost I don't know what others is but it's so much cheaper for vaccines but yeah the material cost is the main difference and I guess if we're talking about more Labs getting into this that might mean that vaccines have be
developed for um other infections that we don't yet have vaccines for do you know much about that I thought it was I thought it was interesting when I was thinking about it because if I think of a virus that has taken over kind of in healthcare I always think of HIV it's a very dangerous virus because it just change it changes its protein on the outside often and so regular viruses by the time you have developed it it's changed um whereas mRNA vaccines although they do also code for the
protein on the outside they can be developed quicker and so would it be possible to develop a vaccine for using mRNA for a protein at an instance in time develop it quick enough so the HIV hasn't had time to kind of mutate significantly by that point and then you could essentially have some form of a temporary vaccine for HIV and so I was looking into it and it was from February the 20th of 2023 there was an article about an mRNA vaccine um for HIV where there's kind of things in test and
things in process so I feel like we're kind of just maybe even just at the start of it all maybe there's tests going on right now for it and even different vaccines as well but I feel like that would be pretty nice to finally cure HIV in this because it can be developed quicker and if there's especially more kind of efforts from labs and more money into it maybe it could be even more quicker as well yeah that brings us back to the whole financial side of is it lucrative for
labs to invest in this I mean the Corona virus pandemic there was obviously a huge incentive for all these labs around the world to pretty much drop what they were doing and work together effectively to develop something whereas now we're sort of we're out of that panicked stage and it's uh it's become sort of more normalized a bit like HIV is to an extent I hate to say that because HIV has been around for a long time and it does have huge effect on the people that
have it yeah but it just makes it seem like they may just kind of continue almost plodding along without that incentive I think I'm just really pessimistic here though I suppose the MRNA vaccine development has probably been enough of a change in the whole scene that it could reinvigorate people to to find a solution because it could be that everyone kind of went okay using this method just the difficulty of trying to achieve it and they needed some Innovation I think I get what you mean
so if Ione is saying that the capital cost the cost of setting up a lab to do this is quite High well some Labs have I guess already done that so if they've already got that capability they may as well carry on using it is that a fair summary or have I misunderstood uh kind of kind of more like they hit a wall in development against HIV but now there's a new method that people can try out it's like when you get a new toy you go ah let's figure out all the different
ways that I can do this or or a new tool and then you're like how does it work in this way does it change how I do this and then you move on so it could be a new tool in the different ways of developing vaccine toolbox yeah and I guess like I've heard that um when you get your your flu shot the winter jobs every year to figure out what to put in that jaob they they kind of effectively guess at what mutation might be most prevalent for the influenza virus oh interesting yeah I I didn't know that
yeah and I wonder if that kind of relates you're saying the HIV virus mutates quite rapidly I wonder if there's some sort of parallel there in figuring out what the mutation may be yeah here's another basic question about vaccines is how similar do they have to be to still be considered the same virus because if the HIV virus evolves how is it still HIV that's interesting I feel like my mind this doesn't apply to viruses but it's the classical definition of what is a species and it's
two individuals that can't reproduce to have fertile offspring but you can't reproduce viruses and they can't have fertile offspring so I feel like I'm not sure what the definition is for a virus especially specific virus to whether it's just a different strain unless that's what h i mean maybe HIV is kind of the group term for no it's a specific virus name to be fair I guess it goes back to the ship of Theus philosophy question if if if you keep replacing the
bits is it still the same ship I thought it was a broom is that like another ref I feel like it's another reference if you changed you've had this broom somebody s I've had this broom for 20 years I've changed the head 17 times and the yeah the stem five times that is from uh is that the same room yeah it's from only Falls and horses I think from like is that the 80s or '90s oh wow it's from when I was a kid I'm surprised I'm surprised that's a reference point of
mine but yeah maybe it's the same virus then if you replace the protein but if the other protein and the old mutation is no longer in circulation it doesn't make sense to include that as a part of the conversation if you were you know viral viral scientist doesn't sound right scientists studying virologists viruses I would imagine part of the definition might be based on the effect that it has cuz you have you keep hearing like you know stomach bug could be caused by a virus and that would only
infect your stomach and make you like hideously ill and vomiting whereas SARS C was initially thought to be a respiratory virus so it only affected how you breathe so maybe that's part of how they figure out and what it infects as well because some viruses only affect certain organisms don't they yeah like cowpox yeah like the original I guess precursor sasov because it jumped from was it bats and that's where the term novel comes from that it because it had
jumped it was now novel oh yes yes I see what you mean yeah I'm explaining that poorly I think it's all right I know what you mean as in the virus went from one organism and one species to another yeah it must have developed some mutation that meant it could then get into a host of a different type and replicate itself I guess yeah I didn't know it was called novel novel is just the term for H never mind I was thinking of denovo I'm getting all these terms
there's so many words though by all just sound exactly the same I feel like this might be a point that maybe we should stop talking because we're confusing ourselves but I've got to say I've learned quite a lot about how vaccines were originally developed in the 1800s and I could see how that would have been very different to what we do now because we've learned so much in the intervening years yeah I would be afraid if we had if we went for our covid vaccine and in
there was somebody there with Co who was just breathing on us and they were like there you go there's your vaccine agreed this definitely giving me some food for thought and I'm I think I'm probably going to start looking up some um what some biologists have to say about this now and I think we'll probably share some links in the uh show notes it's been a slightly mad episode but quite an interesting one because it's a bit mad next week next time I think we'll have something slightly more
um down to earth or goer to say so stay tuned and thanks for listening the views expressed in this podcast belong entirely to the person that said them they do not represent any industry or organization if you enjoyed listening to these views it would really help us out if you could rate US leave a review and tell a friend this podcast was sponsored by no one but if you're interested in funding us to continue to have Frank discussions about science and engineering please get in touch