2017 BIS annual meeting, November 24
Denise Fitzgerald (UK) on neuroimmunology
Becoming a Scientist
Virus Fighter
Build a virus or fight a pandemic!
Maya's Marvellous Medicine
Battle Robots of the Blood
Just for Kids! All about Coronavirus
The smallest viruses can be just a few nanometres wide and contain two genes. Viroids can get even smaller. Recently, however, giant viruses have been found, 1000-fold larger and with more genetic content than some bacteria.
This raises a fascinating question as to the origin of viruses. The first model is that viruses were spawned out from some proto-bacteria-like cells. A bit of bacterial DNA, like a plasmid, that was able to survive cell-free and move from cell to cell. In this view, viruses don't really belong on the tree of life, and giant viruses are just abnormally large viruses that have captured more and more DNA from hosts.
Giant viruses raise a second model. What if the tree of life had an original fourth strand (bacteria, eukaryotes, Archaea and proto-viruses). The first three strands are still with us today, while the proto-viruses have devolved from a free-living cell to a dependent virus. Under this alternative view, giant viruses are ancient relics closest to the original proto-viruses, with the smaller viruses having gone further down the evolutionary pathway of becoming highly efficient replicators.
A paper published in Science this week argues for the first model, with evidence that some key machinery in giant viruses is directly stolen from other lineages of the tree of life. But the argument is not closed, and as more and more giant viruses are found, I look forward to seeing which direction the evidence moves.
Our very own Susan Schlenner was just announced as a winner of the BOF-ZAP competition for a prestigious research professorship at the University of Leuven!
This is a time when the international nature of science is under threat - from Brexit, Trump and war, the movement of scientists is being restricted, and with it the scientific advantages of 'brain circulation'.
Just how international an endeavour is science? At the moment, our lab has 21 researchers: 12 are international (from 12 different countries) and 9 are Belgian.
Over the past 8 years, our lab has trained 113 young scientists. 52 have been Belgian, 61 have been international (31 from the EU, 30 from outside the EU, from 32 nationalities). Belgium has benefited from this international talent, our researchers benefited from being trained here, and the country of origin benefits from the additional training they receive. Immigration is a win-win!
While I am discussing demographics, it is worth noting that 65% of my trainees have been women, so if any departments are struggling to hire female Professors just ask - there are lots of amazing women coming out of my lab.
The intersection of science and the public is always a delicate balance. Medicial research is explicitly performed for the public benefit, and good communication of the results to the public aids in further investment. Difficulties arise due to the discrepancy between scientific publication (with all the caveats, nuance and steady progress) and a brand of journalism that tends to be excessively focused on sensationalism.
One of the areas where this balance is most difficult to achieve is in any medical research related to food. People are interested in food, and a story that one of our favourite foods is either going to kill us or save us always makes headlines. The area abounds with popular myths that go so far beyond the supported science that they have lost all connection with reality.
Take the issue of artifical sweetners and pancreatic cancer. Aspartame is often the boogeyman of the artifical sweetner world. Aspartame is one of the most studied food additives and to date there is no robust link to cancer, and yet aspartame is oft campaigned against in the public sphere. Indeed, the public pressure against aspartame is such that major food companies have started to phase it out, replacing it with much less studied compounds, such as stevia. By contrast, stevia is the darling child of food advocates in the public sphere. It is touted for a myriad of benefits, including as a potential inhibitor of pancreatic cancer. So what is this based on? Next to nothing, actually. There are a handful of studies using pancreatic cancer cell lines, and adding stevia to them while they grow in a dish inhibits them a bit. As for data on stevia being anti-cancer in an actual organism, the only experiment is one where stevia paste was applied to the skin, which was then treated with a carcinogen. The mice were protected from developing skin cancer, but that is likely because the stevia paste acts as a barrier, like sunscreen. In other words, there is zero evidence that stevia in the diet is actually anti-cancer in function.
In a recent study we directly tested whether aspartame or stevia had any influence, either positive or negative, over pancreatic cancer development, growth or lethality. We used mice, rather than just cells grown in a dish, and we gave the artificial sweetners in the drinking water in doses that are similar to popular beverages. We found.... nothing. No effect, either positive or negative. Aspartame won't kill you, stevia won't protect you. Sorry Daily Mail.
Read more: Dooley, Lagou, Dresselaers, van Dongen, Himmelreich and Liston. "No effect of dietary aspartame or stevia on pancreatic acinar carcinoma development, growth or induced mortality in a murine model". 2017, Frontiers in Oncology.
In Flanders Today, by Andy Furniere
Two sides of the same coin
Last November, animal rights organisation Gaia released undercover footage recorded at the Free University of Brussels’ (VUB) animal unit in Jette. Throughout the seven-minute video, shot by an undercover researcher, the unit’s staff handle mice and rats roughly, as other seemingly stressed rodents jump or run around their cages incessantly.
In the clip, the investigator, whose identity remains unknown, says that the animals were suffering needlessly in overcrowded cages and from painful deaths. There is a distinct lack of care by the scientists, we hear, many of whom are unaware of even the most basic regulations concerning the treatment of lab animals.
The undercover footage has again intensified the animal testing debate among activists, researchers and policymakers. The government of the Brussels-Capital Region quickly responded to the video, while the government of Flanders announced investments in the development of alternative methods, aspiring to play a leading role on the European stage.
According to Gaia’s president, Michel Vandenbosch, the investigation shows there is a need for stricter monitoring, but also for a radical change of mentality among scientists. “We need a new generation of researchers who don’t just reduce test animals to research tools,” he says, “but also possess the empathy to fully realise that these are living, sentient and vulnerable beings.”
‘We are not monsters’
But at least one scientist believes most researchers already have the greatest respect for lab animals. Dr Adrian Liston of KU Leuven has been an animal rights advocate his entire adult life, he says.
When he first entered medical research, he considered participating in a research project that did not use animals so that his dual passions did not come into conflict, but decided against it.
“I could not bear being a hypocrite, willing to take advantage of the outcome of animal testing but not to get my own hands dirty,” he says. “Animal research is the bedrock of medical research. We need to accept that our advances depend on the work done on animals.”
Liston serves as the director of Crispr Core, a genome engineering facility at KU Leuven, and doubles as a researcher at the Flemish life sciences research institute VIB. He argues that the Gaia video is misleading. “We are not monsters,” he says.
The scientist does concede, however, that there should be more communication between activists and researchers and points out that lab test subjects already have the strongest legal and ethical protection of all animals. “In order to even start researching on mice,” he says, “I have to take countless training courses and fill in hundreds of pages of animal health assessments.”
(Un)announced inspections
The mice he uses, he continues, are kept in conditions that would be luxurious for wild mice. “They have daily health checks by trained staff, and the use of each individual mouse is assessed by an external ethics panel.”
Gaia, however, believes that the current legislation is not strict enough. It does not prohibit scientists from, for example, carrying out tests on animals that are anaesthetised.
According to Vandenbosch, of the 240,000 lab animals used in Flanders in 2015 – more than half rodents – about one in five experienced considerable discomfort. “In other words, one in five suffered.”
In the video, Gaia also denounced inspections announced ahead of time; VUB researchers knew about an inspection at the animal unit about a week before it took place. According to the undercover inspector, this gave them enough time to quickly make all the necessary adjustments and cover up bad practices.
Statistics from Flanders do suggest that unannounced inspections are important. Every year, at least one-third of the 120 recognised labs undergoes inspection. Last year, of the 42 that were inspected, 28 were found to be in breach of regulations. In 27 of the cases, the labs were given a warning, while one lab received a fine.
Changes underway
Gaia’s campaign met with widespread attention in the media and led to swift political response. Brussels state secretary for animal welfare Bianca Debaets promised more unannounced inspections.
She also ordered an investigation into the VUB’s animal unit and asked its research staff to halt any new tests on animals over a three-month period. She called for an action plan to improve the situation in the lab.
The plan, which includes more extensive internal monitoring, has already been approved by Debaets. “But we also expect a structural plan to improve the situation in the long term,” she say.
In response, VUB has announced the construction of a new animal unit by the end of 2018, at a cost €7 million.
In the political discussion that followed, Debaets proposed a national register that would list all programmes in Belgium that use lab animals. The register, run by all three regions, would indicate exactly what kind of work is performed at each facility.
This, Debaets says, would facilitate co-operation, not only reducing the number of required lab animals but improving transparency around animal research.
Joining forces
Brussels opposition party N-VA, however, questioned the need for a register, pointing out that much of the info is already available. The party asked that Debaets invests in the development of alternatives for animal testing instead.
In response, the state secretary pointed out that she’s been providing a €30,000 annual subsidy to Vera Rogiers, a professor of toxicology at VUB, since 2015. Flemish animal welfare minister Ben Weyts has also recently allocated €350,000 for finding alternative testing methods.
One-third of the money will go to Vito, the Flemish institute for technological research, to develop an alternative to the Draize test. The obligatory test is used to measure chemical toxicity in the human eye and involves dropping the test substance into the eye of a live rabbit.
“Every year in the EU, no fewer than 50 million animals are subjected to such a test,” said Weyts in a statement.
The price to pay
The other €250,000 will go to the creation of an online platform that brings together all European research into alternative testing methods. “There are many alternatives, like in-vitro tests and computer models,” said Weyts. “We will bring together the fragmented expertise and make it accessible to researchers.”
The platform is a Flemish initiative but will be managed by the European Union Reference Laboratory for Alternatives to Animal Testing, encouraging the participation of other European countries. The Netherlands has already expressed interest in the project.
“I’ve also been in talks with partners in the animal-research sector and suggested that they financially contribute to specific projects that relate to alternative testing methods,” Weyts says.
For now, there is no plan to fund a Belgian centre, a project that was approved in 2009 but has not been realised. “Money that goes to the founding of new structures cannot go to research,” says the minister.
Gaia has demanded that the government of Flanders go a step further by investing even more into alternative testing methods and by setting up a detailed action plan on animal research in general. “What we need is a coherent strategy based on a clear vision, one that has concrete goals,” says Vandenbosch.
The animal rights activist also suggests that politicians demand a gradual reduction in the overall number of animals used for medical tests, like mice, by defining limits on specific research domains.
Safeguarding progress
“Experts predict that toxicity testing, for example, could soon be carried out without using animals,” says Vandenbosch. “This would also lead to more reliable results.”
This approach is in line with a proposal submitted by the Groen party in both the Brussels and Flemish parliaments. Debaets and Weyts, however, don’t agree with such rigid limitations.
Liston, meanwhile, says that using animals in research should only be limited if other methods are available. Only this approach, he adds, will safeguard medical progress.
“We are constantly refining our methods, from more in-vitro screenings to fewer animal tests,” he says, “for ethical and legal reasons, but also because in-vitro tests are faster, cheaper and less complicated.”
He also believes that even as animal research becomes a niche market, there will always be a need for it. “Before we can administer medication that could have serious side effects in humans,” he says, “we will always have to test it on animals first.”
Verrassing: onze woonplaats en de mensen met wie we samenleven hebben meer impact op ons immuunsysteem dan onze genen.
Sommige mensen worden gemakkelijk ziek, anderen niet. Sommige ziektes manifesteren zich vooral in de winter of treffen eerder vrouwen. Die verscheidenheid van ziektepatronen kan deels verklaard worden door variaties in de werking van ons afweersysteem. Een reeks artikelen in het vakblad Cell wierp licht op die variaties. Daarbij vertrokken de auteurs van de productie van cytokines: belangrijke signaalmoleculen die ervoor zorgen dat het afweersysteem adequaat reageert op bedreigingen.
Zo hebben bepaalde cytokines een piekproductie in de winter, andere in de zomer. Dat kan mee verklaren waarom griep vooral een winterziekte is. Sommige cytokines reageren goed op virussen maar minder op bacteriën, waardoor sommige mensen gevoeliger zijn voor verkoudheden. De opvallend verschillende reactie van mannen en vrouwen op bepaalde aandoeningen heeft niet voornamelijk met hormonen te maken, maar met verschillen in de cytokineproductie in vetcellen: vrouwen hebben een andere vetsamenstelling dan mannen.
Verrassend was ook de vaststelling dat bepaalde facetten van het immuunsysteem niet verouderen – veel verouderingsziektes gaan gepaard met zware ontstekingen. Een en ander sluit aan bij de bevindingen van immunoloog Adrian Liston van de Leuvense tak aan hetVlaams Instituut voor Biotechnologie en enkele collega’s, die een stand van zaken van het onderzoek presenteerden in Trends in Immunology .
Hun voornaamste conclusie was dat onze woonplaats en de mensen met wie we samenleven een veel grotere impact op ons immuunsysteem hebben dan onze genen. De immuunsystemen van samenwonenden lijken sterker op elkaar dan puur statistisch verwacht kon worden. In feite is dat goed nieuws: je leefomgeving veranderen is gemakkelijker dan je genen veranderen.
Knack - 01 Feb. 2017
Recently I was interviewed by Vinoy Vijayan for his excellent Science Minds podcast.
You can download the interview here, if you are interested in a discussion on science careers, different pathways to take in science, mentorship and diversity in science.