Leadership through adversity by Prof Keith Chappell

I believe most scientists are driven by the goal of making a positive difference in the world. That is certainly true of my team. Last year we had a shot at achieving that goal. Our team at the University of Queensland was one of the first groups tasked with creating a vaccine for the novel coronavirus outbreak in Wuhan, China.

In 2019 we began working with the Coalition of Epidemic Preparedness Innovations (CEPI), the idea being to conduct proof of principle studies with our vaccine platform so that if hypothetically there was ever a novel pandemic we would be ready. Just 12 months into that three-year project the call came through that we were to immediately redirect all activities towards the unfolding COVID-19 pandemic.

Cutting to the end of the story, our vaccine is not one of those currently being rolled out around the world. We were close. Our vaccine was shown to demonstrate a promising initial safety profile and to generate a strong neutralizing immune response in clinical trials. We’d also partnered with ‘big pharma’, CSL/Seqirus and they were already doing commercial-scale cGMP manufacturing of doses every fortnight. However, then there was an issue. Our vaccine produced an immune response that could be picked up on some HIV screening tests. Practically overnight this led to the decision that our vaccine would not progress.

Our teams’ journey through 2020 was a wild ride with many ups and downs, stress, jubilation and devastation. What has this journey taught me about leadership? I’ll divide the experience into three sections: the climb, the summit and the fall.

First the climb

It’s not easy to make a vaccine. No one would think it is, but trying to do it quickly during a global pandemic increases the difficult setting to maximum. On top of that, our team had never even made a vaccine that had been tested in humans. We’d put our hands up to say that we could do it and now we had the world watching on. However, the pressure from outside did not even compare to the pressure each of us put onto ourselves. Like the rest of the world, we were watching case numbers climb and the virus take hold in new regions. We were seeing images people struggling to breath as they waited for a hospital bed and of mass graves being dug as authorities struggled to keep up with the skyrocketing cases. With those images playing in our minds none of us felt we could take a break. We couldn’t leave something undone at the end of the day, when every single day over 5,000 people were losing their lives.

Working under that pressure is not easy but human beings have an amazing ability to rise to the occasion. The truth is that I didn’t need to do as much leadership as you would have thought. Everyone was ready and willing to give everything that had. I think we all felt fortunate to be able to come to work and feel like we were doing something rather than being stuck in lockdown feeling helpless.

I was conscious of the potential for the team to overwork themselves or for the stress to become too much to handle. I tried to emphasize that it wasn’t all on our shoulders. There were hundreds of teams around the world using every possible vaccine technology to produce a COVID vaccine. It didn’t matter if our vaccine failed. Most of the vaccines in development will stumble at some point but as long as a few make the finish line and the world will have the best possible vaccine to counter this pandemic.

Teamwork and communication were crucial. There were so many little parts that needed to fit together perfectly.

We needed to arrange backups, and backups for backups. As everyone whose been involved in research knows, experiments don’t always work. They fail either because a tiny mistake is made or one of the parameters is just a bit off. The key to progressing science quickly is to think about everything that can go wrong and have measures in place so that when something doesn’t go right it costs you the minimum amount of time before you get it working.

But when something does work, no matter how small the piece of the work, that rush of endorphins is what keeps us scientists going. A major skill in leadership for a large team is to ensure those positive outcomes get shared around so that every member of the team can receive that little boost in motivation.

To me this is the essence of teamwork. Those thousands of little pieces together add up to something as big as producing a vaccine against the deadliest pandemic of our lifetimes. Individually the pieces may not seem so important but without every single one the program won’t succeed.

The summit

The summit is a myth. In climbing a mountain, every ridge looks like the top from below, but when you reach that point you see that there is still a long way to go. There were certain points in our journey through vaccine development when we felt on top of the world.

The moment when we first produced enough vaccine to immunise mice and when we that the immune response in mice could neutralise the virus. The moment when we saw the first data coming back from the phase I trial confirming the vaccine was both safe and able to stimulate a strong neutralising immune response. And the moment when CSL completed their first full scale manufacturing batch and reported that they had successfully obtained enough material for millions of potential doses.

Success comes with its own challenges in leadership. A successful project evolves and matures away from many of the individuals who played a central role in the beginning. The scientists who produce the very first test material and administer it to mice are not the same ones who produce the material that is given to healthy volunteers who enrol in a clinical trial. It is therefore inevitable that people who poured their heart into a piece of work become dispensable once their job is done.

The challenge then for leadership is to ensure that no one is forgotten. As new results continue to role as a team leader it is your duty to relay these back down the line. Those individuals who made the work possible have a right to hear about progress and continue to feel involved as the work progresses to the next stage.

The fall

It came as a shock when we received the call that the vaccine would not progress. Vaccine doses had been shipped around the globe and everything was in place for the phase 3 efficacy trial, which planned to enrol more than 30,000 participants in over 100 sites. We were of course aware of the issue with HIV diagnostics, but we were convinced the benefit of a safe and effective vaccine would out weight the downside of having to change the HIV testing procedures.  Especially since, just months before we come from a position of not even knowing if an effective vaccine could be made for COVID-19.

The leadership team at UQ found out less than 48 hrs before the decision would be made public. It was our job to break the news to the team.

We had begun the year by telling ourselves that it was not a race but 11months later in December 2020 we wanted to win. Hundreds of team members had poured absolutely everything they had into the work and we now had to take that away from them.

Although we spoke the truth our words felt hollow.

“We did absolutely everything we could.”

“We can hold our heads high and be proud of all we achieved.”

“We can be thankful that the other vaccines are showing great efficacy so ours is not needed.”

I cannot explain the feeling of devastation that gripped us all. There were feelings of anger, there was denial that manifested in the form weeks of ‘what if we….’, and above all there was a great sadness.

As a leader I experienced all of these emotions. It was important to not shut these out but to also not allow myself to be consumed when helping the team get through this period. Although I was bitterly disappointed about the decision, I explained that there were valid reasons behind this decision. While I obsessively searched for a way through the dead end, I reiterated to the team that it was important that we now threw our support behind the other vaccine developers. And while I experienced that loss and dealt with my own depression, I told everyone that we will get through this and there are better days ahead.

Getting back up.

So, there is another section to the story – I lied when I said there were three. It’s been nine months now since our COVID-19 vaccine hit the end of its journey. It has taken most of that time to get back to our feet.

There have now been over 4.3 billion doses of COVID vaccine administered around the world, including into my own arm. These are saving millions of lives even as this virus evolves and seeks out a way around our best efforts. I am truly proud of the work of my fellow scientists around the world and every single individual who has contributed a small piece that has added up to this impossibly mammoth effort to get us to this point.

Our team are also back with renewed effort and pouring everything we have into a second generation vaccine. While we have a long way to go, small pieces of progress are being made. Once again we are feeling that rush of endorphins that comes with every little milestone and that will keep us going until we reach the summit which is just above.

Prof Keith Chappell

Prof Keith Chappell is a Molecular Virologist and group leader within the School of Chemistry and Molecular Biosciences, Australian Institute for Biotechnology and Nanotechnology, at the University of Queensland (UQ). His research is focused on vaccine development and the understanding of medically and environmentally significant viruses. Keith is one of the inventors of a UQ’s molecular clamp platform technology for generation of subunit vaccines against a wide range of novel viruses. Keith was the co-leader on a project funded from the Coalition for Epidemic Preparedness Innovations (CEPI) in Jan 2019 to establish a rapid response vaccine pipeline based on this technology and with the outbreak of novel coronavirus in January 2020, Keit co-lead research activities to produce a vaccine for COVID-19. This vaccine progressed from sequence information to clinical trial dosing within 6 months. UQ’s molecular clamp COVID-19 vaccine was shown to be safe and to produce a strong neutralising immune response in Phase I clinical trials, however the vaccine did not proceed into further clinical trials due to the interference with some existing HIV diagnostic tests.

Declaration of interests

I have read and understood the BMJ Group policy on declaration of interests and declare the following interests: none.

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