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Tuesday
Oct192021

Children’s book brings our immune system to life

  • ‘Maya’s Marvellous Medicine’, the third children’s book by immunologist Prof. Adrian Liston and illustrated by artist Dr Sonia Agüera-Gonzalez launches today.
  • The book sees Maya learn about the cells that make up our immune system and how vaccinations prepare these cells for battle.
  • The book is available to read for free online, or purchase as a physical copy.

Professor Adrian Liston, Senior Group Leader at the Babraham Institute, and artist Dr Sonia Agüera-Gonzalez have published a captivating story book to teach children about the immune system and why vaccinations are important. As some children begin to receive the flu vaccine ahead of this winter and with pharmaceutical companies applying for approval of their COVID-19 vaccines for children under 12, ‘Maya’s Marvellous Medicine’ can be used by adults to discuss key scientific concepts with them. The book is available on Issuu and Amazon today.

The book is set in a doctor’s office just before Maya receives a vaccination. Maya learns that vaccines are made up of bits of microbes that your body practices fighting, just like Maya practiced for her race at school. The doctor explains to Maya that dendritic cells present B and T cells with the clues that allow them to defeat the real microbes, even if that is years later. 

The message in Prof. Liston’s book is two-fold, he explains: “After reading ‘Maya’s Marvellous Medicine’ I hope that kids will understand what a vaccine is, and how the immune system practices. More important, though, is the underlying message of empathy. Vaccines protect you, but they also protect your loved ones and your community.” Protecting others is the focus of Prof. Liston’s first book ‘Battle Robots of the Blood’, about a boy with a compromised immune system.  

As an immunologist, Prof. Liston hopes his book sparks an appreciation for vaccines and work like his: “I'd love kids to learn just how cool the immune system is, and parents to be reminded that vaccines make us all safe. Vaccines have likely saved more lives than all other medical interventions combined, and yet they've come under targeted attack over the past decade, with deliberate misinformation campaigns. That means we need to be creating positive proactive stories, like Maya's Marvellous Medicine or Battle Robots of the Blood.”

Talking about her experience working on this series of books Dr Sonia Agüera-Gonzalez commented: “I have thoroughly enjoyed bringing Maya to life and telling such an important story. Books like the ones we have made can be a powerful tool for teachers, educators, parents and carers who would like to have conversations with young children about vaccines without glossing over the science behind the jab.”

Prof. Liston added: “I always look forward to seeing the new styles of illustration Sonia brings to a project. I also love seeing my own son’s reaction to the final products. This book is dedicated to him for all the time we spent together in the lockdown.”

Monday
Oct182021

Maya's Marvellous Medicine

Our latest book for children, "Maya's Marvellous Medicine", is now out!

Follow Maya as she learns all about vaccines - the most marvellous medicines. Maya learns how the immune system works, and how vaccines help the immune system to be strong. Whether it is the immune system or a running race, the lesson is clear - practise makes perfect!

Take a look, either to learn all about vaccines and the immune system, or simply to enjoy the gorgeous illustrations by Tenmei.

The book is available freely in a digital format at Issuu, or you can order a paperback copy at Amazon.

Spreek je Nederlands? Met dank aan Erika Van Nieuwenhove, lees "Maya's magnifiek medicijn" op Issuu of Amazon.

Saturday
Oct092021

Congratulations to Ntombizodwa Makuyana

Congratulations to Ntombizodwa Makuyana, for winning the Babraham Institute prize for best poster by a first year PhD student!

A great start to a high potential PhD!

Saturday
Oct092021

Monday
Aug162021

Understanding immune variation

Saturday
Jul242021

New understanding of cell stability with potential to improve immune cell therapies

Researchers identify the origin of potentially dangerous unstable cells

Key points:

  • Researchers have identified the origin of unstable cells, with potential to improve the safety of immune cell therapies.
  • When using immune cells to treat disease, there is a risk that the cells switch from protective to destructive behaviour.
  • Studies in mice have allowed researchers to identify the cells most at risk of becoming harmful.

By purifying cells using markers of instability, or following a two-step purification process, the researchers are able to produce a robust set of protective cells. Research in mice, published today by researchers at the Babraham Institute, UK and VIB-KU Leuven, Belgium, provides two solutions with potential to overcome a key clinical limitation of immune cell therapies. Cell therapy is based on purifying cells from a patient, growing them up in cell culture to improve their properties, and then reinfusing them into the patient. Professor Adrian Liston, Immunology group leader at the Babraham Institute, explained: “The leading use of cell therapy is to improve T cells so that they can attack and kill a patient’s cancer, however the incredible versatility of the immune system means that, in principle, we could treat almost any immune disorder with the right cell type. Regulatory T cells are particularly promising, with their ability to shut down autoimmune disease, inflammatory disease and transplantation rejection. A key limitation in their clinical use, however, comes from the instability of regulatory T cells – we just can’t use them in cell therapy until we make ensure that they stay protective”. By identifying the unstable regulatory T cells, and understanding how they can be purged from a cell population, the authors highlight a path forward for regulatory T cell transfer therapy. The study is published today in Science Immunology.

T cells come in a large variety of types, each with unique functions in our immune system. “While most T cells are inflammatory, ready to attack pathogens or infected cells, regulatory T cells are potent anti-inflammatory mediators”, Professor Susan Schlenner, University of Leuven, explains. “Unfortunately this cell type is not entirely stable, and sometimes regulatory T cells convert into inflammatory cells, called effector T cells. Crucially, the converted cells inherit both inflammatory behaviour and the ability to identify our own cells, and so pose a significant risk of damage to the system they are meant to protect.”

The first key finding of this research shows that once regulatory T cells switch to becoming inflammatory, they are resistant to returning to their useful former state. Therefore, scientists need to find a way to remove the risky cells from any therapeutic cell populations, leaving behind the stable regulatory T cells. By comparing stable and unstable cells the researchers identified molecular markers that indicate which cells are at risk of switching from regulatory to inflammatory. These markers can be used to purify cell populations before they are used as a treatment.

In addition to this method of cell purification, the researchers found that exposing regulatory T cells to a destabilising environment purges the unstable cells from the mixture. Under these conditions, the unstable cells are triggered to convert into inflammatory cells, allowing the researchers to purify the stable cells that are left. “The work needs to be translated into human cell therapies, but it suggests that we might be best off treating the cells mean”, says Professor Adrian Liston. “Currently, cell culture conditions for cell therapy aim to keep all the cells in optimal conditions, which may actually be masking the unstable cells. By treating the cultures rougher, we may be able to identify and eliminate the unstable cells and create a safer mix of cells for therapeutic transfer”. Dr Steffie Junius, lead author on the paper, commented: “The next stage in the research is to take the lessons learned in mice and translate them into optimal protocols for patients. I hope that our research contributes to the improved design and allows the development of effective regulatory T cell therapy."

Establishing a thorough process to improve cell population stability in mice helps to lay the groundwork for improved immune cell therapies in humans, although the methods described in this work would require validation in humans before they were used in cell therapy trials. Tim Newton, CEO of Reflection Therapeutics, a Babraham Research Campus-based company designing cell therapies against neuro-inflammation and independent from the research, commented on the translational potential of the study: "This research makes a significant impact on regulatory T cell therapeutic development by characterising unstable subsets of regulatory T cells that are likely to lose their desirable therapeutic qualities and become pro-inflammatory. The successful identification of these cells is of great importance when designing manufacturing strategies required to turn potential T cell therapeutics into practical treatments for patients of a wide range of inflammatory disorders."

Read the full paper here.

Saturday
Jul032021

Wednesday
Jun302021

In praise of metrics during tenure review

Metrics, especially impact factor, have fallen badly out of favour as a mechanism for tenure review. There are good reasons for this - metrics have flaws, and journal impact factors clearly have flaws. It is important, however, to weigh up the pros and cons of the alternative systems that are being put in place, as they also have serious flaws. 

To put my personal experience on the table, I've always been in institutes with 5 yearly rolling tenure. I've experienced two tenure reviews based on metrics, and two based on soft measures. I've also been a part of committees designing these systems, for several institutes. I've seen colleagues hurt by metric-orientated systems, and colleagues hurt by soft measurement systems. There is no perfect system, but I think that people seriously underestimate the potential harm of soft measurement systems. 

Example of a metric-based system

When I first joined the VIB, they had a simple metric-based system. Over the course of 5 years, I was expected to publish 5 articles in journals with an impact factor over 10. I went into the system thinking that these objectives were close to unachievable, although the goals came along with serious support that made it all highly achievable.

For me, the single biggest advantage of the metric-based system was its transparency. It was not the system I would have designed, but I knew the goals, and more importantly I could tell when I had reached those goals. 3 years into my 5 year term I knew that I had met the objectives and that the 5 yearly-review would be fine. That gave me and my team a lot of peace of mind. We didn't need to stress about an unknowable outcome.

Example of a soft measurement system

The VIB later shifted to a system that is becoming more common, where output is assessed for scientific quality by the review panel, rather than by metrics. The Babraham Institute, where I am now, uses a similar system. Different institutes have different expectations and assessment processes, but in effect these soft measurement systems all come down to a small review panel making a verdict on the quality of your science, with the instruction not to use metrics.

This style of assessment creates an unknown. You really don't know for sure how the panel will judge your science until the day their verdict comes out. Certainly, they have the potential to save group leaders that would be hurt by metric-based systems, but equally they can fail group leaders who were productive but judged more harshly by biases introduced through the panel then by the peer-review they experienced by manuscript reviewers.

This in fact brings me to my central thesis: with either metrics or soft measurement systems, you end up having a small number of people read your papers and make their own judgement on the quality of the science. So let's compare how the two work in practice:

Metrics vs soft measurements

Under the metric-based system, essentially my tenure reviewers were the journal editors and external reviewers. For my metrics, I had to hit journals with impact factors about 10, which gives me around 10 journals to aim at in my field. I had 62 articles during my first 5 years, and let's say that the average article went to two journals, each with an editor and 3 reviewers. That gives me a pool of around 500 experts reviewing my work, and judging whether it is of the quality and importance worthy of hitting a major journal. There is almost certainly going to be overlap in that pool, and I published a lot more than many starting PIs, but it is not unreasonable to think that 100 different experts weighed in. Were all of those reviews quality? No, of course not. But I can say that I had the option to exclude particular reviewers, the reviewers could not have open conflicts of interest, the journal editor acted as an assessor of the review quality, and I had the opportunity to rebut claims with data. Each individual manuscript review is a reviewer roulette, a flawed process, but in aggregate it does create a body of work reviewed by experts in the field.

Consider now the soft measurement system. In my experience institutes reviewed all PIs at the same time. Some institutes do this with an external jury, with perhaps 10 individuals but maybe only 1-3 are actually experts on your topic. Other institutes do this with an internal jury, perhaps 3-5 individuals in the most senior posts. In each case, you have an extremely narrow range of experts, reviewing very large numbers of papers in a very short amount of time. In my latest review I had 79 articles over the prior 5 years. I doubt anyone actually read them all (I wouldn't expect them to). More realistically, I expect they read most of the titles, some of the abstracts, and perhaps 1-2 articles briefly. Instead, what would have heavily influenced the result is the general opinion of my scientific quality, which is going to be very dependent on the individuals involved. While both systems have treated me well, I have seen very productive scientists fall afoul of this system, simply because of major personality clashes with their head of department (who typically either selects the external board, or chairs the injury jury). Indeed, I have seen PIs leave the institute rather than be reviewed under this system, and (in my experience) the system has been a heavier burden on women and immigrants.

Better metrics

As part of the University of Leuven Department of Microbiology and Immunology board, I helped to fashion a new system which was built as a composite of metrics. The idea was to keep the transparency and objectivity of metrics, but to use them in a responsible manner and to ameliorate flaws. The system essentially used a weighted points score, building on different metrics. For publications in the prior 5 years, journal impact factor was used. For publications >5 years old, this was replaced by actual citations of your article. Points were given for teaching, Masters and PhD graduations, and various services to the institute. Again, each individual metric includes inherent flaws, and the basket of metrics used could have been improved, but the ethos behind the system was that by using a portfolio of weighted metrics you even out some of the flaws and create a transparent system.

The path forward

I hope it is clear that I recognise the flaws present in metrics, but also that I consider metrics to confer transparency and to be a valuable safeguard against the inevitable political clashes that can drive decisions by small juries. In particular, metrics can safe-guard junior investigators against the conflicts of interest that can dominate when a small internal jury has the power to judge the value of output. Just because metrics are flawed doesn't mean the alternatives are necessarily better.

In my ideal world (in the unlikely scenario that I ever become an institute director!), I would implement a two-stage review system, using 7 years cycles. The first stage would be metric-based, using a portfolio of different metrics. These metrics would be in line with institute values, to drive the type of behaviour and outputs that are desired. The metric would include provisions for parental or sick leave, built into the system. They would be discussed with PIs at the very start of review period, and fixed. Everything would be above board, transparent, and realistic for PIs to achieve. Administration would track the metrics, eliminating the excess burden of constant reviewing on scientists.

For PIs who didn't meet the metric-based criteria a second system would kick in. This second system would be entirely metric-free, and would instead focus on the re-evaluation of their contributions. By limiting this second evaluation to the edge cases, substantial resources could be invested to ensure that the re-evaluation was performed in as unbiased a manner as possible, with suitable safeguards. I would have a panel of 6 experts (paid for their time), 3 selected from a list proposed by the PI and 3 selected from a list proposed by the department head. Two internal senior staff would also sit on the panel, one selected by the PI and one selected by the department head. The panel would be given example portfolios of PIs that met the criteria of tenure-review, to bench-mark against. The PI would present their work and defend it. The panel would write a draft report and send it to the PI. The PI would then have the opportunity to rebut any points on the report, either in writing or as an oral defence, by the choice of the PI. The jury would then make a decision on whether the quality of the work met the institute objectives.

I would argue that this compound system brings in the best of both worlds. For most PIs, the metric-based system will bring transparency and will reduce both stress and paperwork. For those PIs that metrics don't adequately demonstrate their value, they get the detailed attention that is only possible when you commit serious resources to a review. Yes, it takes a lot of extra effort from the PI, the jury and the institute, which is why I don't propose it to run for everyone.

TLDR: it is all very well and good to celebrate when an institute says it is going to drop impact factors in their tenure assessment, but the reality is that the new systems put in place are often more political and subjective than the old system. Thoughtful use of a balanced portfolio of metrics can actually improve the quality of tenure review while reducing the stress and administrative burden on PIs.

Monday
Jun212021

Career trajectory

Today I gave a talk on my career trajectory for the University of Turku, in Finland. Looking back on the things I did right and wrong at different stages of my career, and a little advice for the next generation of early career researchers:

Monday
Jun212021

My Life in Science

An old talk I gave on my scientific career, with an emphasis on being a parent scientist and on my experience in seeing sexism in action in the academic career pathway:

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