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Monday
Feb272017

The perils of food science

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. 

Saturday
Feb112017

Animal rights and wrongs: Flanders debates ethics of animal testing

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.”

Wednesday
Feb012017

Ieder zijn afweer

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

Tuesday
Jan312017

Interview with Science Minds

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.

Saturday
Jan282017

Diabetes: the fragile beta cell model

In the current issue of Trends in Molecular Medicine, we put forward the evidence for and against the beta cell fragility model, where innate defects in beta cell survival drive both type 1 and type 2 diabetes.  

Read: Liston, Todd and Lagou (2017). "Beta cell fragility as a common underlying risk factor in type 1 and type 2 diabetes". Trends in Molecular Medicine. 

 

Wednesday
Jan182017

New insights in genetic defect allow prevention of fatal illnesses in children

A team of scientists led by prof. Adrian Liston (VIB–KU Leuven) and prof. Isabelle Meyts (UZ Leuven – KU Leuven) were able to characterize a new genetic immunodeficiency resulting from a mutation in a gene named STAT2. This mutation causes patients to be extremely vulnerable to normally mild childhood illnesses such as rotavirus and enterovirus. Prof. Liston’s comprehensive analysis of the genetic defect allows clinicians to provide children with the proper therapies before illnesses prove fatal. The findings of the research have been published in the Journal of Allergy and Clinical Immunology.

Recent advancements in technologies and tools now make it possible for researchers to identify extremely subtle defects of the human immune system. In the past, many patients with “hidden” immunodeficiencies, or defects that were not obvious from the outset, often become extremely ill or die before their genetic disorders are diagnosed. Prof. Liston and his lab were able to identify a gene mutation causing an immunodeficiency that can be fatal during childhood, enabling children to be diagnosed, monitored and preemptively treated for the disorder.

Immunodeficiency disorders are not rare

Ranging from disorders as severe as the well-known “bubble boy” to nearly impossible-to-detect ‘hidden’ defects, immunodeficiencies are more common than scientists previously thought. Immunologists and geneticists have only just begun to scratch the surface when it comes to defining these latter types of immune disorders, which can be specific enough to make sufferers highly susceptible to just one or two types of diseases.

Prof. Adrian Liston (VIB-KU Leuven): “I wouldn’t be surprised if, when we finally do complete the identification of all genetic immunodeficiencies, we discover that up to 1 in 100 children are affected. The ‘hidden’ ones are especially insidious, because they do not present as obviously as other genetic immune disorders. In our study, one of the patients did unfortunately die before a diagnosis could be made. The other patient is alive and well, and now that she has been diagnosed, she is being carefully watched. We can do something about most immunodeficiencies – if only we can identify them.”

Severe common illnesses may signal immune disorder

Prof. Meyts, lead clinician for the patients, stresses the importance of assessing the severity of childhood illnesses on the part of parents, suggesting that parents look for helpful information online and raise the possibility of a potential genetic immunodeficiency with a pediatrician.

Prof. Isabelle Meyts (UZ Leuven – KU Leuven): "When an otherwise healthy child experiences extremely severe infection with a common pathogen, like influenza or the chickenpox virus, or whenever a child is particularly vulnerable to infection with a single pathogen, an underlying defect in the immune system is likely. Likewise, a family history of a child succumbing to infection should alert the family and the clinician. Identifying the causative gene defect allows for genetic counseling of the family and for preventive measures to be taken."

Unraveling ‘hidden’ immunodeficiencies

The potential future avenues for this research are numerous and extremely relevant to current medicine. Prof. Liston’s lab has developed a unique immune phenotyping platform and gene discovery program that can help identify previously unknown immune system defects and inflammatory diseases, leading to novel new treatments that can be administered in a timely way.

Prof. Adrian Liston: “We seek to identify every possible cause of genetic immunodeficiency so that every child displaying warning signs can be tested and treated before it is too late.”

Saturday
Jan142017

Journal club: A new hint to the evolution of the nucleus?

One of the fundamental divisons of life is between prokaryotes and eukaryotes. Prokaryotes, including both Archaea and bacteria, have a very simple cell, with no major subcellular compartments. Eukaryotes, essentially all over living things (plants, animals, fungi, amoeba, etc), have much more complex cells, with a nucleus and dedicated organelles (mitochondria, chloroplasts, etc).

Exactly how eukaryotes evolves from prokaryotes is one of the biggest questions in evolution. It is clear that some organelles, such as mitochondria and chloroplasts, evolved by endosymbosis. Essentially, one bacteria swallowed another, which survived inside and took on specialised functions. The nucleus has been a bigger mystery, with no clear preceeding structure in prokaryotes to build upon. Until now. In the lastest issue of Science, Chaikeeratisak et al discover a nucleus-like structure in bacteria. Interestingly, the structure is not part of the bacteria's normal lifecycle, instead it is assembled by a virus, bacteriophage 201φ2-1, as a structure for DNA replication and transcription, after which the RNA is sent to the cytoplasm of the bacteria for translation, exactly as occurs in eukaryotes.

There are many fascinating angles to this paper. Why does bacteriophage 201φ2-1 assemble this structure? Is it to protect the phage genome from bacteria attack by restriction enzymes and the like? Most importantly, could similar viruses have been the origin of the eukaryotic nucleus? One can easily imagine an ancestral prokaryote becoming permanently infected by such a virus, and rapidly evolving useful functions for a nucleus of its own. 

 

Read the paper: Vorrapon Chaikeeratisak, Katrina Nguyen, Kanika Khanna, Axel F. Brilot, Marcella L. Erb, Joanna K. C. Coker, Anastasia Vavilina, Gerald L. Newton, Robert Buschauer, Kit Pogliano, Elizabeth Villa, David A. Agard and Joe Pogliano. 'Assembly of a nucleus-like structure during viral replication in bacteria'. Science  13 Jan 2017: Vol. 355, Issue 6321, pp. 194-197

Friday
Jan132017

To post-doc or not?

This Nature Biotechnology paper has an interesting analysis of American biomed PhDs who chose to post-doc or not. Essentially, doing a post-doc is essential for an academic position, but it actually lowers net salary outside of academia. How well this translates to other countries is not clear - American post-docs are paid much lower salaries than some other countries, but it is worth a read.
This was my favourite paragraph:
"Ex-postdocs continued to earn less on average than non-postdocs ten or more years postPhD. In-fact, ex-postdocs gave up 17–21% of their present value of income over the first 15 years of their careers. This suggests that postdoctoral education is inconsistent with a model of human capital investment. Instead, it indicates that postdoc positions work as tournaments, where individuals compete for an increasingly limited number of tenured/TT jobs by signaling their ability and commitment through long hours in laboratories and years spent underpaid."
Sounds about right. Except that it forgets to mention some of the great things about doing a post-doc. You can easily relocate and live for a few years pretty much anywhere in the world. It is like starting your PhD over again, except you are actually competent at your job, you don't have to write a thesis, and you can leave whenever you feel like. You meet great people that are in research for the love of it, and you will keep some of the most valuable contacts you ever make for the rest of your career. 
Sunday
Jan082017

Science career advice, age 5

Want to be a scientist?
Like to solve problems?
Good at maths?
Patience?
Like to experiment?
Want to be a doctor?
Like to help people?
Not afraid of blood?
Good listener?
Like to study?
Want to be a professor?
Like to read?
Like to teach?
Patience?
Good memory?
Thursday
Jan052017

Effecting change as an animal rights advocate

I have been an animal rights advocate for my entire adult life. I am also a medical researcher, specialising in the translation of advances from mouse immunology to patients. I am a vegetarian, for ethical reasons, and yet I am director of the mouse genetic engineering service at KUL. How can one be an advocate for both animal rights and for the use of animals in medical research?

Few would argue against medical research. Who wants a life that is nasty, brutish and short? When I first entered medical research I considered starting in a research project that did not use animals, so that my dual passions did not come into conflict. In the end, however, I decided to work on a mouse model of Multiple Sclerosis – scenes of which would certainly be confronting if shown to the public out of context. I did so because I could not bear to be a hypocrite, willing to take advantage of the outcomes of laboratory animal use, but not willing to get my own hands dirty. Since then, advances in Multiple Sclerosis research in mice have resulted in better treatments for patients, with new medications capable of adding decades of healthy life to the millions of sufferers. Who would be willing to deny their loved ones access to these medicines, despite the work being based on animal models?

At the same time, few would argue against animals having rights. We no longer throw cats from the belfry in Ypres, or other such wanton brutality that was once commonplace. Cruelty against pets is now criminal and farms are inspected for the treatment of livestock. The most intensive protections for animals are reserved for animals in medical research. In order to even start research on mice I have taken countless training courses and filled in hundreds of pages of animal health assessments. My mice are kept in conditions that would be luxurious for wild mice, and have daily health checks by trained staff. The use of each individual mouse is assessed by an external ethics panel, including an ethicist and a veterinary surgeon. I assure you that nothing as brutal as a mouse trap or rat poison would pass muster, let alone the conditions that wild mice endure daily!

Animal research is the bedrock of medical research. Even as we continue to refine, reduce and replace animals in research, we need to accept that all of our advances rest upon work done in animals. At the same time, and rightfully so, laboratory animals have the strongest legal and ethical protections of any animals in our society.

This is not to say that animal use in medical research cannot be improved. Not all researchers have a full awareness of the responsibility that comes with animal research, and violations of animal rights do occur. But the worst thing that we can do would be to reverse progress with a knee-jerk reaction. Attempts to reduce animal research by increasing bureaucratic burden simply de-emphasize the most important regulations. An extra tax on animal use in medical research will need to be paid by reducing the number of trained staff caring for the animals. Public condemnation of animal researchers in the media shuts down dialog. We need to increase, not decrease, communication between animal rights advocates and medical research advocates. Animal rights groups that demand absolutes only make progress more difficult for moderates. Those of us willing to proceed with mutual respect know that the only way to continue the steady improvements in laboratory animal conditions is to increase openness and transparency. If you are an animal rights advocate that actually wants to effect change, I encourage you to work with, instead of against, medical researchers. We will listen.