There are no guarantees in science | Keith Chappell | TEDxBrisbane

i knew from when i was in high school that i wanted to make a difference in this world for me a career in science seemed like the best way to address some of the problems that the world is facing this year i had a shot at that life goal i am one of the co-lead investigators in uq's program to create a covert vaccine i'm also one of the inventors of the underlying technology that looked like it would make this a reality we were close but it didn't quite play out the way we had hoped right now there are tens of millions of doses of our vaccine we've shown that it's safe and then it can generate an immune response that's likely to be just as protective as any of the other candidates being progressed and are sitting in freezes likely to never be used it's just a tad soul destroying but a vaccine needs to be perfect in every way the vaccine we produce is what is called a subunit vaccine for this we just produce a part of the virus and not the whole thing for covert we just make the spike protein that sticks out from the surface of the virus but it's held in the right shape so that it exactly matches the shape that is present on the virus the spike is held together by what we call the molecular clamp you can think of the molecular clamp like a bulldog clip holding the protein together so it's in the exact same shape as was present on the virus surface we give this as a vaccine to teach the body's immune system what to be on the lookout for so it's important that the shapes exactly match the issue with our vaccine is that the molecular clamp technology is based on a small fragment of one of the hiv proteins we chose this fragment because it is well understood and a highly stable structure it is so stable in fact you would have to heat this bulldog clip up to about 90 degrees before it would open and drop its papers we knew that people who received this vaccine would likely generate a response to the sequence within the molecular clamp we also knew that it was a possibility that this response could be cross-reactive to some of the hiv diagnostics all participants were advised that there was a possibility of falsely testing positive for hiv however we didn't think that was likely however science is hard and that's exactly what happened it in no way diminished the immune response that would be protective against covert but if the vaccine was used in a population wide scale it would create problems for hiv diagnosis it's disappointing and frustrating yes but in science this isn't unusual this type of thing happens every day just not usually in the middle of a global pandemic and vaccine race when the eyes of the whole world are upon you the fact that this vaccine will not progress does not diminish all of the work that went in by many of people to its development and so to honor the work that everyone has contributed i'd like to highlight exactly what goes into a vaccine to do that we need to go back in time all the way to 2011. at the time i was thinking about the need for something like a clamp to stop the proteins i was working on from falling apart that was when the idea came to me to use the highly stable structure within gp41 from hiv as a clamp to hold these proteins into the correct shape and then use them as a vaccine as is the first step with any a great idea i discuss this with my best mate over a few beers at the pub dan watterson is not only my best mate but is a work colleague and the most passionate and intelligent scientists that i know dan and i usually enjoy discussing some crazy and out there ideas however we both knew that this was legitimately a good idea and we could both see the potential we then pitched it to our boss paul young who has always been a supportive and great mentor and paul gave us the go-ahead to work on this as a side project it was around a year before we got the first results showing that this technology could work this is with the virus called respiratory sensitive virus it is a common cause of bronchiolitis in young children within another five years of working on this as a side hustle before we receive the first funding for this what to support this work over that time we had shown that the technology worked for eight different viruses including ebola influenza and middle east respiratory coronavirus over that time i wrote and applied for 12 separate research grants all of which were unsuccessful and then finally 13th time lucky i received my first grant in 2018. it was a year later that we received 15 million dollars from seppi the coalition for epidemic preparedness innovations this was to use the clamp technology to establish a rapid response vaccine pipeline the idea being that we would have three years to put in place everything that was required so if hypothetically the world was confronted by a global pandemic we would be ready we were just one year into that project when the world was confronted with the perfect storm of the virus one that could spread silently before people even knew they were sick one that was just mild enough in the majority of people that some within the community would deny it was even a problem and one that would go on to cause the hospitalizations and deaths of millions of people within 2020 this was covert 19. we had only just hired and trained our new team and set up our new lab we had never even produced a vaccine for a clinical trial in any other year and by any other definition we were not ready but we had a bunch of scientists and a plan in place and we were willing to give it everything that we could when reports of the new virus first emerged none of us thought that it would explode the way that it did at first we thought of it just as a good means to test out new technologies that we were working on on january 12th when the sequence of this new virus was released by chinese authorities we could get to work you see to start our process for producing a vaccine all we need is that sequence of asgs and c's and t's that encode the virus dna on the very day that the sequence was released we submitted an online order for dna and six days later a bunch of tiny tubes arrived in the mail and we were away for the next four weeks we worked in shifts with stacks of lab consumables piling to the roof notes and lists and codes were scribbled on paper so we could keep track of what we were doing whatsapp messages were flying amongst the team so we could coordinate tag team activities so we people could sleep without the work pausing for a minute in those four weeks our view of the unfolding outbreak quickly changed from this is a good test case to oh this is a real thing in those four weeks we had no idea whether what we were working on would actually work or whether we would fail when it came to the crunch a phrase that constantly circulated in the lab was there are no guarantees in science we've produced and screened over 200 versions of the vaccine over those four weeks to select the version that was easiest to produce at high levels and that was likely to be the best match for this new virus we knew little about we had to weed out any versions that wouldn't work i was we knew there was a little time later on to come back and start again we also knew that any improvements we could make in production would likely translate to additional doses available down the line on valentine's day february 14th just 35 days after the sequence was released we had selected a lead and produced just enough vaccine to immunise mice from then on it was one thing after another every day was a roller coaster ride of ups and downs there was a thousand different problems to solve and a thousand different ways in which the project could fail our team grew constantly over this time with us needing to bring in experts and collaborators across all the different areas we have collaborations with anu university of melbourne csiro and many private companies who are with us every step of the way by this stage our team was not just limited to scientists there were many other people working around the clock to make this dream a reality the university's legal team were working in overdrive to put in place all of the legal agreements that underpin this work 117 separate legal agreements were drafted negotiated and executed over this time our finance team needed to keep track of all of the donations coming in from many different sources and being spent by us just as quickly over 20 million dollars was being spent on this work the comms team as well will run off their feet with hundreds of articles being published on the uq covered vaccine throughout it all we watch the case numbers and death toll climb already by april 7 000 people were dying every day that weight weighed heavy on all of us how could we move this along more quickly was weighed up against the knowledge that healthy volunteers would be needed for testing if we got anything wrong they would be the ones who could be harmed the stakes were as high as they come as any potential mistake could jeopardize the already shaking public confidence in vaccines any negative outcome could not only affect our vaccine but could extend to the other vaccine developers working on the same thing with the eyes of the world upon us a negative outcome could also impact the well-proven vaccines that are currently in use by july we had this this is a dose of the vaccine that was used in the clinical trial this was a mammoth achievement that is completely invisible you can't see the vaccine because it is smaller than the wavelength of light to see this vaccine you need to use an electron microscope that will fire a beam of electrons through the sample but by using this technique we were able to generate this this is a 3d model of the vaccine almost down to the atomic scale by using this technique we were able to see that the vaccine is in the exact same shape as the spike on the surface of the coronavirus this part here on the bottom is the clamp holding the three molecules of the spike together in each dose of this vaccine there are 15 micrograms of the protein we designed that's 15 one thousandth of a one thousandth of a gram that's as much as if you took one single grain of salt and cut it in four and said oh no i don't like a lot of salt and threw three pieces away 15 micrograms is not a lot but in actual raw numbers it equates to 15 trillion spiked molecules that's 15 with 12 zeros after it 15 trillion spiked molecules sitting in a syringe waiting to be injected into somebody's arm because it is such a minuscule amount one quarter of a grain of salt of a highly purified protein we need to include an adjuvant otherwise the body wouldn't even recognize that it was there the adjuvant is what triggers a dangerous signal so that your immune system will mount a response against the vaccine the adjuvant we use in our clinical trial was mf59 this is a organic compound produced from shark liver oil mf59 has been used in flu vaccines for over 20 years and over a hundred million doses has been given so it has a well and truly proven safety track record in the clinical trial when we tested this vaccine we were able to show that it was completely safe and it seemed to work well 75 of the participants who received this vaccine generated a neutralizing immune response that was more effective than the average covert 19 patient and in just under 40 percent of participants there was an immune response that was twice that level however there was a problem the client component at the base of the molecule was creating an immune response that was being picked up on some hiv diagnostics participants in the trial were testing positive for hiv even though they didn't have hiv throughout this year the team had worked their way through thousands of different problems but this was one we hadn't foreseen it could be fixed but it would take time and means starting over up until then we hit every timeline we set for ourselves through sheer determination and by telling ourselves that even a single week's delay would mean lives we couldn't save we now have tens of millions of doses of a covert vaccine in freezers ready and waiting but to use these would mean disruption of the systems put in place to detect people still being infected by another pandemic the hiv pandemic has been raging for 40 years and 33 million individuals have lost their lives in addition many people may think that a false positive for hiv is not a big deal in exchange for protection against the much bigger threat that is covered however there is still stigma associated with those three letters hiv and there's no real way to know how those negative effects could flow on to this vaccine program and as well as others we have therefore stepped back from our efforts to develop a covert vaccine however we will be even more prepared if or when the next pandemic occurs there are many other viruses without a treatment or vaccine for which our next version of this technology could and i hope will be effective this year has been a roller coaster ride it's been intellectually stimulating challenging and at times frustrating it has been emotionally and physically draining beyond anything i could have imagined but watching my colleagues within australia and around the world rise to the challenge has been inspiring and has affirmed in me that science is the place where i want to be to make a positive impact in the world the recent developments that a place to hold on our vaccine do not change that or diminish it in any way science can save lives and change the world but science is hard you won't get it right every time it won't go the way you expect or the way the world hopes but the important thing is that when it doesn't go your way you pick yourself up dust off your lab coat and give it another shot you

Channel: TEDx Talks

Views: 1,455

Rating: 4.625 out of 5

Keywords: English, Failure, Global issues, Pandemic, Science, Science (hard), TEDxTalks, Vaccines, Virus

Id: OOrEA52Cz0A

Length: 15min 22sec (922 seconds)

Published: Tue Jun 01 2021