March for Science

London, Saturday April 22nd 2017

The weather is changeable as I leave the flat in the late morning. Sunny spells – dazzling my eyes clad in contact lenses – are abruptly overtaken by the English drizzle that leaves me damp and puzzled because the sun has already regained its prominence. I’m on the Westbound Piccadilly line wearing a Cancer Research UK t-shirt that reads, “I’m a researcher fighting cancer”, and I can’t tell whether I’m getting more looks than is usual on the Tube. I alight at South Kensington to meet a friend of mine, the bubbleologist Li Shen. (And yes, that is now a technical term. Li, who has a degree in mathematics, is a PhD student studying the physics of bubbles, which has far-reaching implications: from the amount of bubbles generated by different types of beer to the undesired foaming of lubricants used in oil extraction.) But we’re not just here to catch up, although it is conveniently close to his lab/office at Imperial College. No, we’re here to join the March for Science. [All of the following images were taken either by Li or by me.]

science march banner.jpg

According to the BBC, “thousands of people” joined the march, the first of its kind taking place on the annual Earth Day and organised around the world. I think the event probably got part of its boost from the Women’s Marches that took place on January 21st, the day after Donald Trump’s inauguration. Certainly, the protesters on both occasions had much in common.

destroy the patriarchy, not the planet

One of the most notable differences between the two events, however, was that this second protest was certainly smaller and also much quieter. I suppose it’s true that scientists – and yes, the marchers were mainly scientists and their relatives, partners and close friends – are a little bit shy and socially awkward. Amongst the stewards, one was trying to get the following chant off the ground, with little success, “Scientists are good at generating questions, not so good at slogans”…

french embassy

Here’s a blurry Li in the foreground, with a sharp French embassy in the background. Walking by I couldn’t help but send what’s known as a “Stoßgebet” in German to the high heavens; roughly translates as a quick (secular) prayer. For now we can breathe a brief sigh of relief after the first round of the presidential elections. Hopefully Europe, science and European Research Council funding will be able to continue to prosper.

knowledge trumps ignorance

Speaking of Trump, the March for Science event emanated from Washington DC, where it started as a protest against fake news, alternative facts and a world in which experts are regarded as worthy of derision. Honestly, as with the Women’s March, I don’t know and can’t tell how much impact marches like these actually have in politics, but as a start there was significant media coverage. Even Buzzfeed compiled its list of top banners and slogans (some scientists do have a sense of humour). My personal favourite was this one, of course.

big brains

I do know that within three months I went to two marches, the first two of my life. Ideally, I won’t have to go to any more and will be able to spend my Saturdays in the lab, where a diligent PhD student should be (and where I know some of my colleagues were). Lastly, let’s give reason, described by Wikipedia as being “the capacity for consciously making sense of things, applying logic, establishing and verifying facts, and changing or justifying practices, institutions, and beliefs based on new or existing information”, a big thumbs up.

reason

Behrens lab retreat 2016

Imagine spending a weekend in these idyllic surroundings in the Peak District with nothing to do but talk about and discuss science.

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The Peak Mermaid Inn – taken at sunrise on November 13th 2016

Well, that’s exactly what we, the Behrens lab, did last weekend. We invited a keynote speaker, Roland Rad, and Dieter Saur’s group from the Technical University of Munich to join us. Each of us gave a talk about the most interesting or exciting aspects of our projects and in between we drank copious amounts of coffee. In the evenings we cooked enough food to feed a small regiment, drank beer, played pool, darts or table football, all punctuated by heated debates about science. Although this wasn’t a relaxing weekend by normal standards, it was motivating and inspiring and a good reminder of why I enjoy being a scientist: a combination of rational and logical thinking, curiosity and the drive to learn new things for their own sake, all shared with people who, by and large, know more than I do and think differently.

Of the talks I just want to highlight one in particular, because my project also uses one of the techniques mentioned. Dieter Saur is a medical doctor and has his own lab group, which studies mainly gastrointestinal diseases, including pancreatic cancer. In a recently published paper (Schönhuber et al, 2014) they describe an experimental system in mice called the “dual recombinase system“. This is a genetic system that allows the study of complex diseases such as cancer. Until recently it was only possible to simultaneously switch on a gene that drives tumour progression and switch off a gene that prevents tumour formation in a cell type or organ of interest (e.g. in the pancreas). Using the dual recombinase system it is possible to make genetic alterations sequentially. For example, in the beginning of a mouse’s development one can activate a potent tumour driver called Ras and delete an important tumour suppressor called p53. And then, once a tumour has formed, one can additionally delete genes that may be important to maintain the established tumour. Alternatively, the dual system also makes it possible to make genetic changes to the normal cells surrounding the (pancreatic) tumour. If all goes well then I will be able to use these tools to conduct experiments like this in the next year or so.

15044797_10154563370871405_2126581266_o zip-line

Oh and admittedly we did have an activity scheduled that was slightly less scientific: we got all geared up and went on a GoApe outing. Secured by a harness and after some rigorous safety instructions we got to fly down zip lines, balance over gaping abysses and jump over the void below.


Lastly, the following week saw Queen Mary University London and Barts host the 11th UK cancer stem cell symposium. There were several interesting talks, including by group leaders at the Crick Institute, but the most unusual talk was given by a philosopher called Lucie Laplane. She did her PhD in philosophy and combined this with a research master’s in stem cell biology. Putting the two fields together she came up with a classification of (cancer) stem cells using definitions and guidelines borrowed from philosophy, applied to biology. [In general, researchers agree that stem cells are cells that can self-renew (i.e. generate new copies of themselves) and can produce differentiated/specialised daughter cells.] The most important point was how to pin down what kind of characteristic “stemness” is or what makes a stem cell a stem cell:

csc-table

Framework for defining (cancer) stem cells – copied from Lucie Laplane’s talk at the symposium

For instance, in some cases a stem cell might always be a stem cell no matter what the environment is like (i.e. categorical); other stem cells may be dispositional in nature, meaning that they always have the potential to act as a stem cell but only do so in a permissive environment. Alternatively, being a stem cell might not be property of a single cell at all but rather an attribute of an entire organ (i.e. systemic). Laplane argued that the way we define (cancer) stem cells has a huge impact on how we try to treat diseases such as cancer. For example, if cancer stem cells are “systemic” then even the best therapies targeted against these cells will fail because the system/the tumour will make new cancer stem cells from other tumour cells. Hans Clevers, one of the Gods in the stem cell field, wrote a glowing review of the book here.

References:

Laplane, Lucie. Cancer Stem Cells: Philosophy and Therapies. Harvard University Press, 2016.

Schonhuber N, Seidler B, Schuck K, Veltkamp C, Schachtler C, Zukowska M, Eser S, Feyerabend TB, Paul MC, Eser P, Klein S, Lowy AM, Banerjee R, Yang F, Lee C-L, Moding EJ, Kirsch DG, Scheideler A, Alessi DR, Varela I, Bradley A, Kind A, Schnieke AE, Rodewald H-R, Rad R, Schmid RM, Schneider G, Saur D (2014) A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer. Nat Med 20: 1340-1347

Max Perutz Science Writing Award 2016

I remember, a couple of years ago, seeing an advert by the Medical Research Council (MRC) for a science writing competition and subsequently being bitterly disappointed when I found out it was only for PhD students. Luckily, it’s an annual competition and even more fortunately, The Francis Crick Institute is partly funded by the MRC so that I was eligible to enter.

Now – spoiler alert – before this post ends with an absolute anti-climax, I’ll tell you straight away that I didn’t win. However, I enjoyed answering the question why my research matters in the 800-word essayNot all cancer cells are equal“. The judges used three main criteria to evaluate the essays: 1) Does the essay convincingly explain why the research matters? 2) Is it easy to understand for a public audience? 3) Is the essay well written?

Although I didn’t win, I was shortlisted together with thirteen other entrants and got to attend a science writing masterclass led by Jon Copley, the co-founder of SciConnect, a company that provides science communication training to scientists. The News and Features producer at the MRC was live-tweeting from this course – how cool is that?

The class was really helpful. For instance, I learnt that when writing short to medium length articles (up to 1000 words maximum) the most common structure is the “inverted triangle”. The most important information goes first, i.e. my research matters because it may lead to the development of new anti-cancer drugs. This is different from a research article because there the discussion and conclusion are arguably the most important and come last. I think most essays, including mine, had introductions that were too long. Another handy tip was to think about when/at what age I last shared a class with my target audience. For these essays we could probably assume that interested readers would have had a science education until GCSE level – so we were supposed to write in a way that a fifteen year old might understand.

inverted-triangle

Inverted triangle essay structure for short to medium length articles – copied directly from Wikipedia

When I looked around the room during the writing class – and you might notice it in the photo – I realised that everyone else was probably British and definitely white. At first I was a little bit confused by this since, surely, there is no correlation between skin colour and English writing skills; of last year’s six Man Booker Prize nominees only two were white. But it all made sense when I looked up the MRC’s PhD student funding policy: students need to be eligible to reside in the UK without restrictions and therefore this skews the demographic. [Why higher education in the UK is not more widely accessed is a whole different kettle of fish.]

all-shortlisters

The fourteen shortlisters together with two of the judges, Chris van Tulleken and Donald Brydon, and Robin Perutz, the son of Max Perutz – image copied directly from the MRC website

To round off the day we were all invited to the ceremony at the Royal Institution that evening. In addition to the actual prize-giving, both Donald Drydon, chairman of the MRC, and Robin Perutz, Max Perutz’s son, gave good speeches. The former emphasised that science communication with the public is more important than ever for securing support and funding, since Brexit probably means there will be less money from the government.

Your ability to explain your science allows us, as a country, to carry on being curious. – Donald Brydon

Robin Perutz told a story, also very topical, about how his father and mother met due to an organisation called the Society for the Protection of Science and Learning (SPSL, founded in 1933), which had the mandate of supporting refugee scientists in the UK. Among others, the SPSL helped sixteen future Nobel Prize winners, among which were Max Perutz, Max Born and Hans Krebs. Other prominent academics included Nikolaus Pevsner and Karl Popper. Robin Perutz, currently a professor of inorganic chemistry at the University of York, explained that his lab is taking/has taken in a scientist from Syria who is being funded by the Council for At-Risk Academics (Cara). And it turns out that Cara is none other than SPSL under a new name.

Lastly, we received a copy of The Oxford Book of Modern Science Writing. Who can say no to a book. Overall, from the actual essay writing to the writing class and the ceremony this was an enjoyable experience, which I would highly recommend. Thanks to all the judges and the MRC staff who organised the award. Congratulations to the winners and other almost winners!

modern-science-writing


Now that I think about it, I’ve actually already written a few things relating to Max Perutz, including about his biography, his optimism in research and a symposium in honour of his 100th birthday. It seems I’m quite the fan.

Not all cancer cells are equal

This is the essay I submitted to the Max Perutz Writing Award 2016.

Look at yourself in the nearest mirror and, if you aren’t too squeamish, visualise the inside of your body. It’s obvious that not all your cells are the same. We are made of many different tissues that perform different tasks: skin cells protect us from the environment, white blood cells defend us against infections, nerve cells allow us to move and think. Cancer – the uncontrolled growth of cells – can arise from virtually any type of tissue. We hear about new treatments for skin cancers, about raising money for childhood leukaemias, about inoperable brain tumours. We know that there are different types of cancer.

But an individual tumour in a tissue is also complex. Researchers realised decades ago that, like our healthy bodies, tumours aren’t simply lumps of identical cells; that within each tumour there are different cell types. For instance, some tumour cells divide indefinitely to keep the cancer alive, others invade into surrounding tissue and spread to other sites of the body, while yet others stimulate blood vessels to grow. Some cancer cells even combine several of these properties.

In our laboratory we study the pancreas, an organ of the digestive system, which aids digestion and controls metabolism throughout the body by secreting hormones such as insulin. In particular, we investigate variations among cell types in the most common kind of pancreatic cancer called pancreatic ductal adenocarcinoma (PDAC for short). PDACs are among the most deadly cancers with only about three per cent of patients diagnosed with PDAC in the UK surviving for longer than five years. One of the reasons for this gruelling statistic is that PDACs are often diagnosed late, when the cancer cells have already spread to and wreaked havoc in other internal organs. Previously, several labs, including ours, noticed that some PDAC cells are more aggressive than others, more capable of re-growing new tumours from scratch. Now, we aim to understand what makes the more aggressive PDAC cells different from the rest of the cancer cells and how they contribute to the deadliness of this cancer. With that knowledge in hand, the broader aim will be to find anti-cancer drugs to target and kill the most dangerous cells that lie at the heart of PDAC.

A previous PhD student in our lab discovered that the more aggressive PDAC cells make and display large amounts of a certain protein – let’s call it protein X – on their cell surfaces. We say that the more aggressive cells are “marked” by protein X. This realisation was my gateway into finding out exactly how these two cell types, the more and less aggressive cells, differ.

First, I wanted to know whether protein X not only marks the more aggressive cells but whether it is directly responsible for making those cells more dangerous. Therefore I experimentally reduced or elevated the levels of protein X in PDAC cells we grow in the lab. Then I assessed whether the PDAC cells grew more or fewer, larger or smaller “organoids”, miniature replicas of pancreatic tumours. Astonishingly, the cancer cells actually grew less well when I removed most of protein X, or they divided and proliferated much more when they had more of protein X. This is a good indication that, in future, drugs might be delivered directly to protein X to eliminate the aggressive cells or convert them into tamer cells.

In the meantime, I am on the lookout for other characteristics that might distinguish between the more and less aggressive cells. From one of my experiments I have data hinting that the two cell types might in fact have different physical properties. However, until I’ve repeated these experiments I can’t be certain that this difference in appearance contributes to the more aggressive cells’ behaviour. But it is thinkable, for example, that the more aggressive cells can attach to other cells or blood vessels more easily, aiding their movement to the lungs or liver. These secondary tumours, also known as metastases, are the tumours that PDAC patients usually die from. Next, I need to determine whether there is a direct connection between protein X and the variations among the physical properties of the PDAC cells.

We really want to pin down the differences between the more and less aggressive cells so that hopefully researchers and pharmaceutical companies will be able to design and develop more effective drugs to tackle PDAC. In a few years, once we know more precisely what protein X is doing in the more aggressive cells, our findings might matter a great deal to patients. For the moment I am simply trying to find out more about how PDAC cells work and I know that can sound theoretical. However, I am certain that knowing why and how some cancer cells, clearly, are more equal than others will help patients in the future.

 

New Scientist Live

This weekend the ExCeL centre in London hosted an event called New Scientist Live, which was aimed at the general public and invited speakers across various fields, including Brain & Body, Technology, Earth and Cosmos. Additionally, there were stands and interactive stations run by various scientific institutions from across the UK and Europe, including The Francis Crick Institute, the Royal Society of Biology and the European Space Agency, to name a few.

But, to be honest, I was already sold when I saw the giant bacterium (precise species is still a matter of debate; could be E. coli) hanging from the ceiling:

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Apart from this excellent demonstration of how cool cells are I want to write about two highlights.

  1. The talk by Molly Crockett on “What makes us moral?”
    Molly Crockett has a lab at the Department of Experimental Psychology, University of Oxford (but will be moving to Yale next year) where she and her research group study the neuroscience of “morality”. Dr Crockett’s talk was all-round excellent: from the clarity of her speaking, to the information on the slides, the science simplified enough to be understandable, yet retaining the references on the slides so that one can look up the original research (Crockett et al., 2014 and 2015, both open access!). The main finding of the 2014 paper was that people tend to be “hyperaltruistic”: when deciding whether to inflict painful electric shocks to oneself or another anonymous human being, the person deciding needed to be offered/paid more money to hurt another person. People also decided more slowly when the effects were to be felt by the other person rather than oneself. Importantly, and Dr Crockett emphasised this in her talk, these studies were conducted with real people and real electric shocks so that the results from their experiments might give us information about real life situations, as opposed to hypothetical ethical dilemmas. Possibly one of the most famous of these dilemmas is one in which a person needs to decide whether to save five people by actively sacrificing one, or to passively let five people die:moral-dilemmaIn the 2015 paper the authors then go on to test whether various drugs  – the antidepressant Citalopram, a selective serotonin re-uptake inhibitor and Levodopa, a dopamine precursor – can alter this moral decision making. Interestingly, the antidepressant reduced the overall number of electric shocks the deciders were giving out, both to themselves and to others. The hyperaltruism was preserved since deciders still gave fewer shocks to the receivers for the same amount of money. Levodopa, on the other hand abolished this hyperaltruistic effect:

    crockett-2015

    Bar charts showing the effects of citalopram and levodopa on harm aversion – copied directly from Crockett et al., 2015

    Obviously the talk and the papers go into much more detail, especially with the statistics used to evaluate these admittedly small effects. Lastly, it’s important to note that, as Dr Crockett pointed out, none of this means that researchers are working on, or should be working on, developing a “morality drug”…

  2. The science magazine Nautilus published by the MIT Press.
    Nautilus starts where the New Scientist stops, namely, where things get really interesting. To me, the New Scientist poses similar questions to the ones I might ask, but often fails to really answer them or provide a satisfactory explanation as to why there is no answer (yet). When I do read its articles they often leave me with more questions than before, which, of course, isn’t a bad thing. However, after reading a few articles of Nautilus it seems that this magazine is more thought-provoking: the articles are longer and maybe more on the creative side, but retain the references at the end, and the style of writing is more enjoyable to me. For instance, an article called “The Wisdom of the Aging Brain” by Anil Ananthaswamy discusses the possibility that there are neural circuits, or certain regions of the brain, that, with training and age, allow us to become wiser.
    So if any of my few readers is feeling particularly generous today then why not consider getting me the Sep/Oct edition…?

References:

Crockett MJ, Kurth-Nelson Z, Siegel JZ, Dayan P, Dolan RJ (2014) Harm to others outweighs harm to self in moral decision making. Proceedings of the National Academy of Sciences 111: 17320-17325

Crockett Molly J, Siegel Jenifer Z, Kurth-Nelson Z, Ousdal Olga T, Story G, Frieband C, Grosse-Rueskamp Johanna M, Dayan P, Dolan Raymond J (2015) Dissociable Effects of Serotonin and Dopamine on the Valuation of Harm in Moral Decision Making. Current Biology 25: 1852-1859