Professor Dame Sarah Gilbert delivers 44th Dimbleby Lecture

Featuring notable speakers from across the fields of  business, science or politics  almost every year since 1972, Prof. Gilbert joins Oxford alum including the Right Honourable Baroness Greenfield in delivering the lecture, held this year at Oxford's Blavatnik School of Government.

The lecture is available (in the UK) via the BBC's iPlayer.

The full transcript of the lecture follows.

Vaccine vs the Virus: This race, and the next one

I know that the newly-discovered Omicron variant is on everyone’s minds. And I will say what I can about that later on.

But I would like to start by asking you all to think back to New Year’s Day 2020. A pre-pandemic time. No one had ever heard of Covid-19 – a disease that has since taken millions of lives, emptied schools, savaged economies, kept us from our loved ones, closed down entire societies. Most people neither knew nor cared what a spike protein was. And had never worn a surgical mask in a lecture hall. We each of us had our hopes and expectations for the year ahead.

As a vaccinologist, I was planning to continue my work on developing vaccines against influenza, Lassa fever, Nipah and various other unpleasant diseases. I was also working out which flowers I wanted to grow for my garden, and when to start sowing the seeds.

At some point on New Year’s Day 2020 I found myself at my computer, checking emails and browsing websites, including one on infectious diseases. There was a report of ‘pneumonia of unknown cause’ in Wuhan, China. Four cases. Not responding to antibiotics. The first patient worked at a seafood market. A mention that this might be SARS – Severe Acute Respiratory Syndrome.  This caught my attention. I made a mental note to check back later. 

The next day, a new report on the same website said 27 people had now been hospitalised and the market – which, it now appeared, sold rabbits, snakes and pheasants as well - had been closed.  

By the 3^rd I was checking in regularly for updates, looking for new details – new clues – and running through the possibilities in my mind.

Perhaps whatever it was would simply fizzle out. A crucial - and so far missing - piece of information was whether the disease could be passed from one person to another – we call this human-to-human transmission -- or whether people could only catch it from infected animals. One possible scenario was that there was no human-to-human transmission and everyone affected had come into contact with the same group of infected animals at the market. If that was the case, the outbreak would quickly be contained by closing the market, removing the livestock and deep cleaning the site. There would be no time to develop a vaccine, and no need for one.

Another possibility was that this was SARS, or SARS-like. In which case, we were in trouble. In 2002, a previously unknown virus that came to be known as SARS had caused a disease outbreak starting in China. It killed 10% of those infected. There was no vaccine and no treatment.

And of course there was also the possibility it was not SARS, or SARS-like, but something even worse.

By Monday the 6^th of January, when I went back into the office, I was following developments closely, as were many of my colleagues.

Very late at night on the Wednesday came official confirmation that what we were dealing with was a novel coronavirus. There were other coronaviruses that regularly infected people, but this was a new one.

Experts in the spread of infectious diseases immediately started saying ‘I told you so.’ And they had. They had been warning for some time that we needed to be ready for an outbreak of a novel coronavirus, probably starting in China.

This was the third novel coronavirus that had spread from animals to humans in the last 20 years. The first, SARS, had been relatively easy to eradicate using the centuries-old methods of isolating the infected and their contacts. So there had been no immediate need for a vaccine and none had been developed. The second, causing MERS -- Middle Eastern Respiratory Syndrome -- still causes cases every year, although there have been no large outbreaks recently. Work on vaccine development had begun, but it had not been seen as a high priority and progress had been slow. 

On the Friday, China reported its first fatality. By the end of the day, my long-time colleague and friend, the immunologist Dr Tess Lambe, and I had decided that as soon as we had its genome sequence, we would start work on a vaccine against this virus, and go as fast as we could. 

Tonight I am going to tell you how, during those frightening, dislocating, urgent days, weeks and months of 2020, thousands of heroes – dedicated scientists here in Oxford and across four continents, but also clinicians, regulators, manufacturers, and volunteer citizens – came together to achieve something extraordinary. Within less than a year, together we had designed, made, tested, manufactured at scale and started to distribute a vaccine that was very safe, that was highly effective, and that would be available around the world in huge quantities at low cost. Together we had made a vaccine for the world.

At the same time others were working out how to prevent this disease spreading, how to treat those infected, and how to make other vaccines using alternative materials and technologies. As a result, a year after the virus was first identified, the world had surveillance systems in place to track the evolution of the virus as it mutated; knowledge of which drugs worked, and which ones didn’t; and several very safe and highly effective vaccines. In recent years we have been told that the public is tired of hearing from experts. It is now clear that it is experts who have provided and will continue to provide the route out of the pandemic, as well as the communication of reliable information at every new turn.

I will explain, tonight, why we were confident we could do it. How we were able to go so fast. What went right. What went wrong.

And I will leave you with my thoughts on the future for the struggle I and my colleagues are, quite obviously, still engaged in: humanity against the viruses. Can we beat this one? I am confident we can. Omicron notwithstanding. Can we beat the next one? That depends.

Some of the most important moments in this story had actually happened well before I first read that report from Wuhan, China. A large part of the reason we were able to move so fast in 2020 was the work we and others had already done, both on other vaccines against other diseases, and on planning for Disease X.  Disease X was a placeholder representing a future, hypothetical disease. No one knew what it would be, or when it would emerge, but experts agreed that the emergence of something, sometime soon, was inevitable. 

Viruses are fascinating. Visually fascinating, as Angela Palmer’s powerful and beautiful representation of the SARS-CoV-2 virion demonstrates. And biologically fascinating. They cannot replicate themselves unaided, and when not inside a living cell they are completely inert. But once they do get inside a living cell, they can take it over, turning it into a factory to make more copies of the virus instead of doing whatever it would normally do. This process usually kills the host cell. So viruses have to be able to spread from one cell to another, in order to survive. As a virus spreads to more and more of our cells, and those cells stop doing their normal jobs, we start to get symptoms.    

However at the same time as the virus is infecting us, it is also being detected by our immune system, which has evolved to be able to detect intruders and then destroy them, in the process laying down a memory so it can respond quicker next time.

Our immune systems are generally very good at this. The reason viruses can nevertheless make us ill is that they act so quickly. A viral infection can take hold before the immune system has had time to mobilise. This is where vaccines come in. Vaccines give your immune system the memory of what a virus looks like, but without you having to get sick with that virus in the first place. And vaccines all work on the same basic principle: they all present your immune system with some kind of harmless mimic of the virus.

The famous vaccine against smallpox developed in the late eighteenth century by Edward Jenner, for example, used a related but less harmful virus, cowpox. Traditional vaccines present the body with a weakened or inactivated version of the virus. Modern platform or ‘plug and play’ technologies show the immune system only the part of the virus that it needs to recognise to produce an immune response. Usually this will be a protein on the surface of the virus, completely harmless on its own.

The work that had gone into platform technologies by the end of 2019 was crucial to the world’s ability to move fast in 2020. A platform technology is a multi-use vaccine ‘vehicle’ that can be adapted to make many different vaccines. Its great advantage is that it means we don’t need to repeat every one of the many, many aspects of vaccine development every time we make a new one. We can build up and bank our knowledge of how to manufacture it, how to store it, what dose to give and so on. That saves time and it saves money.

So, even when confronted in 2020 with a virus we had never seen before, we did not need to start from scratch.

Work on our platform and on others -- the vaccines from Pfizer and Moderna are also built on platform technologies – really took off in the wake of the world’s inadequate response to the 2014 outbreak of Ebola, in West Africa.

The world had known about Ebola since 1976, but there had been no sense of urgency. By 2014, there was no specific treatment, no vaccine, and no plan to develop one. Around 28,000 people became infected, of whom more than 11,000 died. Liberia lost 8% of its doctors, nurses and midwives. Around 30,000 children were orphaned.

Vaccines were developed and tested, but too slowly and too late. Afterwards, relief that the outbreak had finally been contained - through public health measures, not vaccines - was tempered by anxiety that there were still plenty of other viruses out there that could wreak similar havoc, or worse. It was a wake-up call and a turning point. International organisations, including the World Health Organisation began to draw up lists of dangerous diseases against which we really should be developing vaccines. 

Platform technologies would be key: using the same technology to produce multiple vaccines would reduce development time and, crucially, development cost.

There was a further development in 2018 when to this list of dangerous diseases was added ‘Disease X’. This was recognition that we needed to prepare not just for the diseases we already knew about, but also for those we didn’t. How do you prepare for a disease you don’t yet know about? By developing platform technologies suitable for rapid response.

Funding was still slow to materialise though. Research crept forward at a frustratingly slow pace. Our particular platform technology was recognised as promising, but our bid for funding to work on speeding up the early part of our process was not successful. The reviewers were not convinced that we could move quickly enough in the event of a Disease X outbreak. Luckily – at the time we could not know just how lucky - the UK government had in the meantime decided to channel some of its overseas aid budget into vaccines. And I had secured some of that funding, to work on a vaccine against MERS.

I wish I had time to talk about all the many other fortuitous moments that led up to January 2020. Whenever you are working at the cutting edge of science you are building on decades of meticulous and laborious work that has come before. I have to mention in particular the debt we owe to Professor Adrian Hill, the Director of the Jenner Institute where I am based, and to PhD student Matt Dicks and post-doctoral researcher Matt Cottingham, without whom our platform, ChAdOx1, would not exist.

What it all meant was that as soon as Tess and I knew, on the 8^th of January, that we were dealing with a coronavirus, we knew we could make a vaccine against it, and we had a template to follow. We knew vaccines made with our platform generated a strong immune response and were safe, including for children, older adults, and people with suppressed immune systems. More specifically, we had made a vaccine against MERS, another coronavirus. It had already been through two early clinical trials and it had raised immune responses as we hoped it would. 

At this point this all felt quite theoretical. It was still very possible that the outbreak would be controlled quickly and a vaccine would never be needed. But if it was going to be needed, it would be needed fast. There was no time to test different vaccine designs. We had one shot. So the decision was straightforward. The design for our new vaccine would be based on the design for our MERS vaccine.

The next day, Saturday the 11th of January, Chinese scientists made the genetic sequence of the novel coronavirus publicly available online. That code – specifically, the 3, 819 letters that coded for the spike protein – was what we needed to finalise our design. Within 48 hours, we had worked out the exact genetic sequence we needed to make our vaccine.

Those years of preparation were also what enabled us to make the first doses of vaccine so quickly.

The very first, very small batch of vaccine was made in my lab. We started to test it on mice and sent some to our long-time collaborators at the National Institutes of Health, Rocky Mountain Labs – who had sprung into action in January 2020 just as we had -- to be tested on monkeys.

But vaccines that are going to go into human bodies – clinical-grade vaccines -- have to be produced in highly specialised, highly regulated facilities, not university research labs. Happily, since 2005 we had had such a facility – the Clinical BioManufacturing Facility or CBF now run by my colleague Dr Cath Green - right on our doorstep. The first vaccine the CBF had made for us, back in 2007, had taken eighteen painful months. Since then, we had worked to reduce the time, and the pain. As we set out this time, Cath’s most optimistic estimate was that she might have 500 doses ready within six months – so by the end of July. Although to hit those dates, she was keen to emphasise, everything would need to go right.

In fact many things did go wrong. As they do when you are working with biological processes. There were tears and there was swearing. But there was also determination, innovation and resilience.

The CBF had 438 doses of vaccine ready for clinical trials by the 22^nd of April, with a further 124 doses soon afterwards. 

562 doses. After three months of intense effort. We needed much more, much faster, to support our phase III clinical trials – the trials that tell you whether the vaccine is effective. 

In February, at a point when there had been just a handful of confirmed cases in the UK, another researcher at the Jenner Institute, Dr Sandy Douglas and his group, were already thinking about how we could scale up our processes to manufacture millions of doses. It was as if, having just made an excellent sourdough in your kitchen, you now had to work out how to supply every supermarket in the world.

Again Sandy benefited from the work that had gone before: not only the processes he and his colleagues had developed, but also their connections with colleagues in the private sector. When Cath put out the call to the UK BioIndustry Association, explaining our confidence in our technology and our need for assistance, the response was pretty incredible. Offers of support, equipment loans and expertise-sharing, at minimal or no charge, came flooding in. 

Professor Andrew Pollard and his team at the Oxford Vaccine Group had the task of designing and running our ever-growing, ever-changing clinical trials. Again, happily, they were able to draw on both the existing national infrastructure through the National Institute for Health Research, and their huge network of trusted colleagues across the UK and around the world. 

If the vaccine was going to be used around the world we were going to need data from around the world. When we wanted to set up trials in Brazil and South Africa, Andy wasn’t just pitching up unannounced at a hospital in Rio or Johannesburg. He knew all the people already. Andy reached out to Professors Sue Ann Costa Clemens in Brazil and Shabir Mahdi in South Africa, knowing that they would be able to conduct high-quality clinical trials without delay. They overcame enormous challenges and made a huge contribution.

So. It all came together. Between us, we had everything we needed to design, manufacture, and test a new vaccine.

Well. Not quite everything. We are academics. We had no money.

For the first few months that I was working on this project, my main preoccupation was funding. This, not the science, was the most likely reason we would fail to make a vaccine. 

The truth is that previous vaccine development – including for diseases of significant global burden like malaria, and against viruses that could do as much damage as Covid, like influenza A – previous vaccine development has been slow, not because it was impossible or unsafe to go fast, but because going fast was not seen as a high enough priority. Developing vaccines is expensive and funding usually comes in tranches. You apply for a tranche of funding. You wait to hear. That can take a year. You do a bit of work. You publish the results and present at conferences to attract the attention of funders for the next stage. That can take another year or two. Maybe, if your results look promising, you apply for the next tranche. You wait to hear. That takes a year. This time you aren’t successful. You apply again, wait another year. And so on.

Meanwhile, we try to make sure we have the funds to keep the research group employed, so that if we do get the funding, we are able to carry out the research. When that is not possible, there will be more delays while new staff are recruited and trained. 

In the early months of 2020 as we went from reassuring words about the UK’s state of preparedness to scrambling for PPE and clapping for carers, this kind of limping along obviously would not do.

In January I found a small pot of funds I could use to make a start.

In February, two funders put in place vastly streamlined and accelerated funding application processes. I duly applied. 

But I knew it would be weeks before we heard back from either of them. So in February, March and the first weeks of April, we decided we just had to get on with it. We went ahead and spent money we did not yet – and might not ever – have. We would ask for forgiveness, not permission. It was not a comfortable place to be.

Things became much easier once the UK Vaccines Taskforce, led by Kate Bingham, began to make investments. Coming from a venture capital background, Kate set up a team that made bold choices to invest in a range of vaccine technologies, understanding that more than one vaccine would be needed, and not all attempts would succeed. However there was no mechanism to fund global trials so we had to open separate conversations about those. The trials in South Africa were funded by the Gates Foundation and those in Brazil by the Lemann Foundation.

In January, February and March, my colleagues and I were out on a financial and reputational limb.

But by April there was widespread recognition that this was an urgent priority. Funding cycles were compressed, cutting years out of the development process. The usual amounts of money were also hugely increased. For once, we could focus on the research rather than the fund-raising.

The third reason we were able to move so quickly in 2020 was that from the start we proceeded ‘at risk’, doing in parallel and back-to-back things that would usually be done in sequence and with long pauses. To be clear, ‘at risk’ did not mean at risk to the safety of the vaccine. The risk was to those of us working on the vaccine, that we would have wasted our time, efforts and money.

So for example, usually we would not start work on the design of a clinical trial until we had completed all the animal trials. That way, if the animal trials showed the vaccine was not safe, or not effective, we would not have wasted time preparing clinical trials that could not go ahead. This time, we did all the clinical trial preparation while the animal trials were still going on. That way, it was within days of receiving the safety data from our animal trials that we were putting the vaccine into the arms of our first volunteers. 

Similarly millions of doses of vaccine were manufactured before we had data showing that the vaccine worked. If the vaccine hadn’t worked they would have all been thrown away. And the MHRA, the UK’s regulatory body for medicines, reviewed our data on a rolling basis, rather than waiting until we had provided every last piece of evidence.

We were able to go fast in 2020 not because we cut corners or took risks with our product. We did every single thing that needed to be done. We did not miss any steps. Nor was any individual task – filling a vial, vaccinating a volunteer, analysing data – done with less than the usual care and attention. We went faster because, when we had to, it turned out we could. 

Journalists always seem to want to know about the ‘Eureka’ moment. Or the occasions when we celebrated. I tend to disappoint them.

Though there was plenty of drama there was not one big breakthrough moment, in a bath or under an apple tree. There were, rather, lots and lots and lots of small moments. Detail after detail that we had to get completely right, item after item to be ticked off the list, problem after problem that had to be solved.

And though there were, looking back, things to celebrate, actually, we didn’t. There was no time, and, since we were locked down, no possibility of coming within two metres of each other, let alone throwing a party. Cath remembers some socially distanced slices of cake. I remember taking a few sips of champagne from a coffee mug, whilst looking at my exhausted colleagues. 

Having said all of that, I can pick out a small sample of momentous days; and some key challenges.

One day in early March, when for most people in the UK day-to-day life was still carrying on as normal, Cath’s team isolated the first vaccine particles from which every single dose of our vaccine ever administered was made. We have a lovely photo of the view down the microscope. It looked like a tiny heart.  

On the 27th of March, just four days after the Prime Minister had announced that we must all stay at home, the CBF’s production manager Dr Cathy Oliveira removed a single transparent plastic tube from a centrifuge. There was a fuzzy cloud right in the centre of it – our first batch of vaccine. Cath Green says this was the moment she believed we might be able to pull this off. 

By the middle of April, we had established, working with our private sector partners who had come forward in answer to Cath and Sandy’s call, that it would be possible, with the help of a big pharma partner, to produce our vaccine at scale – that is, millions and potentially billions of doses. Up until then we had an idea. The clinical trials would show whether the vaccine would work. But even assuming it did, it would remain just an interesting piece of academic research unless we found a way to make it at scale. A vaccine’s ability to save lives is not just about its efficacy. It is also about how much you can make, how easily you can get it to people, and then, ultimately, how many people are willing to receive it.

On the 23^rd of April we vaccinated our first human volunteers. By this point we had been locked down for a month. The Prime Minister had still not returned to work having been in intensive care, PPE shortages were so bad that some doctors and nurses were being asked to work in bin bags, the UN had warned that Covid-19 could cause famines of ‘biblical proportions’ and Chris Whitty, the chief medical officer, had used the previous day’s government coronavirus briefing to say that it was ‘wholly unrealistic’ to expect life to return to normal soon. Because of social distancing I couldn’t be there for this moment of hope as our first two vaccines went into the first two arms, but I watched Fergus Walsh reporting it on the news that night. At the time it felt like an enormous milestone. Looking back it was barely the beginning.

On the 30^th of April the partnership between Oxford University and the global biopharmaceutical company AstraZeneca was announced. We already had a manufacturing process that could produce millions of doses. But the logistics of actually making them, and then distributing them across the world, were daunting. This deal was transformative. AstraZeneca brought manufacturing and distribution capabilities well beyond the scope of a university-led project; they were thinking big from the start; they wanted to work alongside us rather than completely take over which was very unusual; and crucially they agreed to supply the vaccine on a not-for-profit basis for the course of the pandemic , and to low-income countries in perpetuity. The team felt strongly that this was the right approach. 

On the 23rd of November after much impatient waiting, we finally announced the results of the clinical trials that had started seven months earlier. Thanks to Teresa Lambe and her team of immunologists we knew that our vaccine was producing a good immune response. But how protective against infection was that immune response? The only way to establish that – the vaccine’s efficacy - was to give some people a vaccine and some people a placebo, and then wait for enough people to get infected. The numbers infected in each group would tell us whether the vaccine was protecting those who received it. 

Much was made at the time of the complicated results. With perspective, we can see what was important: we had a vaccine that was very safe and highly effective against an unbearably awful disease.

There followed more dizzying weeks, for the team and for the country. The Pfizer vaccine slowly began to be rolled out for healthcare workers and the most vulnerable members of society. Case numbers soared. Tighter and tighter government-mandated restrictions were being announced almost daily. There was a last-minute admission that we would not, after all, be able to go ahead with plans to relax restrictions over Christmas. 

And on the 30^th of December 2020, the MHRA, the UK’s regulator, approved our vaccine for emergency use. Rollout could start in the New Year.

There were some key challenges along the way.

I’ve talked about funding. That was certainly a key challenge.

And I have talked about the work that had come before. The flipside is that, if we had been better prepared, we could have gone faster. We had seen it coming, we had started preparing, but we were not fully prepared. Requests for funding had been turned down. The focus had been on influenza or a more localised outbreak of a novel disease, and in neither case were preparations complete. 

So in 2020 we were using several techniques we had never tried before. Some of them worked first time, but some failed. And even though we usually had an old method as a slower back-up, each failure was devastating. By the time we were designing new versions of our vaccine to deal with the various Greek alphabet variants at the start of 2021, we had a much improved, faster method to follow. But that had taken time, and funding, and practice.

The sheer logistics of doing something at this pace and this scale were a big challenge. We kept making plans – but things kept getting more urgent, or our knowledge expanded, and we would have to make a new plan. There were continual problems getting the vaccine for the trials safely to all the right places. The very first ‘shipment’ of vaccine to trial site involved two people from the CBF carrying a cool-box -- complete with vaccine, temperature tracker and all the paperwork -- across the road to the clinical trial centre. Later we would have vans lining up outside the facility every evening to distribute around the UK. Then so much work went into getting doses to international trial sites with all the labels and approvals in place. Once in desperation we even chartered a private jet. The vaccine was in Italy, the volunteers were in the UK, and all flights had been cancelled.

One thing we were definitely unprepared for was this: how do you fight a pandemic, when you are in a pandemic?

At times we had no PPE. No thermometers. No needles. We quickly adapted to video calls rather than in-person team meetings: I didn’t see many of my colleagues in person for months on end. But it was hard to implement social distancing in the clinical trial centre. We had to borrow facilities at other hospitals and then build our own temporary buildings. We obviously couldn’t afford for team members to become infected so when there was a run on hand sanitiser we used lab materials to make our own; and lab staff who had been in shared accommodation with healthcare workers were moved into college accommodation. When the schools closed, we scrambled to get letters confirming that team members were key workers so that their children could continue to go to school. When the campus catering facilities closed, things got really desperate. No one had time to join the long queues outside supermarkets so we fed ourselves from the vending machines until we ran out of loose change. We were all hugely thankful to the group of philanthropists who decided to pay for healthy meals to be sent in to sustain us.

Another somewhat unexpected challenge was getting the communication right. Given the extent of interest in our work before 2020, we hadn’t really prioritised media training. So while everyone was stepping up to the task of their life, we were also on a steep and sometimes scary learning curve.

Our aim is always to provide clear communication, including explanations for why we sometimes do not have all the answers. We are trying to promote scientific understanding, not ourselves, which is often misunderstood in the age of TikTok celebrities. The Science Media Centre and University Press Office help enormously.

Sometimes journalists help us to manage the tensions and communicate these often complex issues. Like us, most are doing their best in difficult circumstances. At times though we are frustrated at the way information gets distorted or sensationalised in the reporting.

We had a stark awakening to the negative power of social media. Three days after we vaccinated our first two volunteers, a false report that one of them had died went viral. The report itself was not convincing, but part of the lesson was that many people only read the headline, and others then reported it.  Even in reputable publications headlines are sometimes written to catch attention rather than to accurately convey the less sensational content. The problems become amplified when others re-report the headlines rather than studying the facts.

Reality is complex. Knowledge gets built up over time as more data is gathered. Accurate communication takes time, and care.

Take the situation in the spring of 2021 when reports started to appear of very rare but serious adverse events after vaccination: the formation of blood clots at the same time as a very low platelet count. Tens of thousands of people had been vaccinated in clinical trials but this problem was so rare it could only be detected after tens of millions had been vaccinated. Expert clinicians worked to understand the problem, enable those affected to be identified quickly, and determine the best treatment. The risk was still tiny, and much, much lower than the risk from getting a blood clot from Covid, but since there were alternative vaccines available this led to recommendations to use our vaccine only in older age groups. We now have data showing that the risk differs in different parts of the world, and is very low in Southern Europe and non-European populations. The communication of this issue has not been straightforward. Communication about risk is notoriously difficult, and with very rare events it takes time to gather and analyse data.

We have also not done well in communicating about the safety and benefits of vaccinating pregnant women. A year ago, when vaccines were first being rolled out, vaccinating pregnant women was not universally recommended. This is the usual approach with new drugs or vaccines: we wait for special studies in animals, vaccinating before or just after conception, and waiting for the offspring to be born. Then we do a study in pregnant women. And only then is the vaccine recommended for use in pregnant women generally.

A year on, it is clear not only that the Covid-19 vaccine is safe for pregnant women and their babies, but also that unvaccinated pregnant women and their babies are at high risk if they become infected with Covid. This information has been slow to reach pregnant women and even some midwives and vaccination centres. Although by April 2021 it was being recommended that they be included in the vaccination roll-out in the UK, by the end of October only 15% of pregnant women had received two vaccinations. In hindsight, pregnant women should perhaps have been identified as a priority group for vaccination starting from April. If we had highlighted the benefits, rather than only seeking to remove concerns about the risks, we could have avoided some very poor outcomes for pregnant women and their babies.

There were also completely unfounded scare stories that vaccines would affect fertility. To be clear, data from vaccine trials and fertility clinics has demonstrated that there is no basis in fact for this claim. But communicating this to people who do not receive their information from mainstream media is a problem we have not yet solved. 

And I would say the final challenge has been the overwhelming relentlessness of it all. When we first started, we had no idea the work would be so all-consuming, or continue for so long. Many people joined our team and worked long hours, through the weekends and bank holidays, for months on end. There were threats to our personal security and the security of our families. What started off feeling like an exhilarating sprint became a marathon-like slog, but still at sprint pace. We did our best to support each other, but everyone hit a wall at some point. Even now you may be pleased to know that the work continues at unremitting pace, but there has been no chance to take time out and reflect on what happened to us.

What of the future?

As we reach the end of a second year dominated by this no-longer-novel coronavirus … as we make cautious preparations to move towards living with it … after all that we have been through, it is essential that we do not forget what we got right, and that we seek to learn from the challenges.

The pandemic has had such an enormous impact on all of our lives, for such a long time, and it is understandable that many people are keen to move on. The long-term effects of the pandemic will result in financial costs for years to come. People are tired and money is tight.

But.

First, this pandemic is not done with us. Last month we observed surges in cases and discussions of lockdowns and compulsory vaccination in several countries in mainland Europe. Across the world, we will continue to see cases increasing and decreasing, and governments doing what they can to react, for some time.

And now, the unwelcome but widely anticipated news of a new highly transmissible variant, Omicron, and the need to collect more data on what that will mean.

The spike protein of this variant contains mutations already known to increase transmissibility of the virus. But there are additional changes that may mean antibodies induced by the vaccines, or by infection with other variants, may be less effective at preventing infection with Omicron. Until we know more, we should be cautious, and take steps to slow down the spread of this new variant.  But as we have seen before, reduced protection against infection and mild disease does not necessarily mean reduced protection against severe disease and death.

Every time a new variant arises, vaccine developers​ have started work on a new version of the vaccine, and the same is true for Omicron. The work starts straight away, at risk, without waiting to find out if a change will be needed. But this may not be needed.

Getting vaccinated now, and getting boosted, is still the best way to protect ourselves.  Vaccines are still the way out.

And second, there will be a Disease Y. This will not be the last time a virus threatens our lives and our livelihoods. And I’d like to finish on a high note, but the truth is, the next one could be worse. It could be more contagious, or more lethal, or both.

We cannot allow a situation where we have gone through all we have gone through, and then find that the enormous economic losses we have sustained mean that there is still no funding for pandemic preparedness. The advances we have made, and the knowledge we have gained, must not be lost. The experts who responded rapidly and worked relentlessly in 2020 and 2021 – the experts without whom we would still be at the mercy of the virus -- must not now be asked to fade back into patient and under-funded obscurity. Just as we invest in armed forces and intelligence and diplomacy to defend against wars, we must invest in people, research and manufacturing, systems and institutions to defend against pandemics.

One particular area where investment is clearly needed is vaccine manufacture. Both nationally and internationally we must improve, and spread out, our capacity to manufacture vaccines at scale. That means supporting research into manufacturing methods; and investing in facilities -- and, crucially, the scientists and engineers who are going to work in them. We particularly need to ensure Africa has its own modern manufacturing capabilities to ensure its own local supply.

In Oxford, our defence effort will be led by the new Pandemic Sciences Centre. It will bring together those whose experience and work brought the world the Oxford AstraZeneca vaccine, and the scientists and clinicians, led by Professors Peter Horby and Martin Landray, who demonstrated through the RECOVERY trial which drugs provide benefit to Covid patients. It will include social scientists, virologists, immunologists. And it will bring benefits to health both in pandemic-peace time and during the next crises

Because what we learnt over the last two years is not just about responding faster and better next time – which we must. It is also about doing better right now.

During the pandemic, scientists, working together with industry, the government, national health services and volunteer citizens, delivered both drugs and vaccines in record time. Imagine the lives, and the costs, that could be saved if we could always work at such pace. If rapid progress became the norm rather than the exception.

There is no scientific reason why we could not, in the next few years, stockpile vaccines against MERS and Nipah, and start vaccinating children in West Africa against Lassa fever. Why we could not develop a universal influenza vaccine, to wipe out for good the threat from a disease that has historically caused pandemics several times each century. And after decades of research there is now real progress on a vaccine against malaria.

Over the last two painful years, as we struggled to respond, we made discoveries that will be important for decades to come. Scientific discoveries that I hope a new generation, inspired by what science can do, will build on to achieve amazing, previously unimaginable things. Just as we built on what had come before.

But perhaps above all, as we turn our attention back to climate change, poverty, war, and other problems that never went away, what we discovered, was what we can do when we understand our goal, and really put our minds to achieving it.