Clinical trials recruitment

Recruitment into clinical trials is an extremely problematic question with regards to ethics. Generally, participation in a clinical trial is a (minor) risk for the individual, but an enormous (potential) gain to society. In the past, this dilemma was "solved" by force - running clinical trials on prisoners, the mentally disabled, the poor, residents of third world countries and generally any population that was disenfranchised. This unethical behaviour is now widely condemned and has been illegal now for a long time.

So how then are patients recruited for clinical trials? Essentially the safeguard for ethics is the principle of volunteering with informed consent. In certain specific cases patients may volunteer  for the possibility of personal gain, such as a trial of a novel medication for an untreatable disease, but generally the motivation is, and should be, altruism. Clearly this is a vast improvement, but even this solution is not perfect. How do you do pediatric trials? You need the informed consent of the guardian, since the actual participant cannot give it. Can anyone really be "informed" of the risks without sufficient medical training? What about indirect coercion? It is illegal to force an unproven drug onto patients, but what about the case of a patient who does not have access to the normal standard of care? For them the only option might be the unproven drug, and in fact this does occur widely in the US and the developing world where universal health care is not available.

Finally, there is the issue of payment. It may make sense to pay for participation, but in that case the participant is not a volunteer and it opens the door to financial coercion. Yet if only unpaid volunteers are allowed, large demographic groups become under-represented in studies due to the inability to afford time off and transport costs involved in volunteering. To balance these conflicting interests, the ethical and legal rule in clinical trials is that you cannot pay volunteers, not provide a financial reward. You can, however, compensate them for their time and expenses. 

In other words, this is not how to recruit volunteers:

The UZ Leuven ethics committee really should take a walk around campus and look at the clinical trials recruitment flyers pinned up.

In the news: Flanders Today

Q&A

Professor Adrian Liston

Professor Adrian Liston of life sciences research institute VIB headed the Belgian-Australian research team that discovered the genetics determining the strength of the immune system.

Which missing link in the immune system did you find? 
We focused on the regulatory T cells, which determine how our immune system reacts to possible health threats. In short, these T cells are in charge of the activity of white blood cells – the cells that defend us against viruses. When there are not enough regulatory T cells, our immune system can be overactive and cause allergies or autoimmune diseases such as diabetes and arthritis. In the opposite case, an underactive immune system allows infections and tumours to grow. We have now identified the genetic programme that sets the number of regulatory T cells, which should help us to keep the immune system ideally balanced.

Until now, you have worked with genetically modified mice 
Yes; the next step is to design and test drugs for humans. We are contacting academic research groups and pharmaceutical companies. Basic medicine can be developed in a time span of five years, but the clinical trials to perfect the working of the drugs can take another 10 years. In the near future, our findings will hopefully help, for example, to kill off the remaining cancer cells after chemotherapy. Later, we hope to develop the means to give an 80-year-old back an immune system that is as strong as that of a healthy teenager.

Was the Australian connection coincidental? 
No, I have Australian roots and finished my PhD at the Australian National University in Canberra. During my research there, I collaborated with experts, including the Walter and Eliza Hall Institute in Melbourne. Four Australian scientists from this institute took part in this recent research project. The team in Flanders consisted of seven researchers at the Autoimmune Genetics Laboratory of VIB and the University of Leuven. Our project lasted four years and was funded by the Flemish Agency for Innovation through Science and Technology and the European Research Council. The results were published in the scientific journal Nature Immunology.

Interview by Andy Furniere

(see original in Flanders Today)

Scientists discover molecular pathway that controls the strength of the immune system

Researchers led by Adrian Liston at VIB and the University of Leuven have discovered the genes that control the number of regulatory T cells in the body, a critical determinant for setting the strength of immune responses. This discovery may be an important starting point for the development of new drugs for the treatment of diseases of the immune system. The research has been published by the prestigious journal Nature Immunology.

In ideal circumstances the immune system is in balance, protecting us from infections and keeping us healthy. This balance can be disrupted, causing diseases of the immune system. An underactive immune system allows infections and tumours to grow, while an overactive immune system can drive allergies and autoimmune diseases such as diabetes and arthritis.

Regulatory T cells are a type of white blood cells that are specialised to keep the immune system in balance. To find out how the right level of balance is achieved, Adrian Liston, an expert in autoimmunity, teamed up with an Australian research group headed by Daniel Gray, an expert on cell death at Australia’s Walter and Eliza Hall Institute. In a 4 year research project funded by the IWT (agency for Innovation by Science and Technology) and the European Research Council, the two research groups found a network of genetic control that determined whether regulatory T cells lived or died, setting the level of immune activity in mice. The genes involved are almost unchanged between mice and humans, providing strong hope that the same pathway is active in patients.

“By working out the genetic control mechanism over regulatory T cell numbers we create a real challenge and opportunity for pharmaceutical researchers”, said Professor Liston. “We now have the blueprint for controlling the level of immune activation. The next step is to identify drugs which influence this system so that we can rectify disturbances when they occur. In theory, such drugs could be used to combat everything from cancer (when the immune system needs to be stimulated to clear cancer cells) to allergies and autoimmune diseases (when the immune system needs to be inhibited).”

(klik voor Nederlands)

Relevant scientific publication

The study is published in the leading journal Nature Immunology:

Update on Tuesday, July 16, 2013 at 11:13AM by Adrian Liston

Covered in ScienceDaily and SciCasts. Also now in Greek.

Sex discrimination in academia - Flanders edition

This is a very interesting article about the sex discrimination in academia in Flanders. In Flanders only 11% of professorships are held by women, making Flanders one of the worst regions in the EU for sex equality in academia. The "glass ceiling index" has been calculated for Belgium as a whole at 2.25, meaning that it is 2.25 times harder for a woman to get a professorship than a man - again, almost the worst value in the EU. 

As the largest and oldest university in Belgium, KU Leuven bears a great deal of responsibility for this situation. Despite 600 years of history, KU Leuven has never had a female Rector. Even in Biomedical Sciences, a field dominated by women at the graduate level, only 25% of professors are female, and the situation gets much worse in the traditionally male-dominated areas. Worst of all, despite performing so badly in this area, the university has no systematic policy directives to even start to correct the problem. To try to compete in an international high performance field while ignoring half of the available talent is absurd, to say the least.

Is this a cut-and-dried case of blatant sexism? In consideration, I would suggest probably not. The effect is certainly sexist, women are not getting opportunities given to men. The primary cause, however, is probably not so much sexism as conservatism. Marc Hooghe (KU Leuven) says "What Belgian universities still have is this kind of closed-shop attitude", where old white men pick people who look like themselves for the next generation academia. Alison Woodward (VUB) points out "In Belgium, no one knows about two-thirds of the jobs. How did that guy get it?" and notes that this old boys' club excludes not only women, but also foreigners and ethnic minorities. So rather than just trying to improve parental issues*, perhaps Flemish universities should instead focus on open merit-based hiring. If women are just given a truly equal chance, I have no doubt that soon they will hold at least 50% of positions.

* One of my pet peeves, as the data showing that having a child is detrimental to women but not men is not a cause of discrimination - it is an effect of discrimination. If men actually did half the parenting, then parental issues would have absolutely no effect on sex equality. By all means, try to make child raising easier, just don't think that this alone creates sex equality.

Faculty position opening up in Leuven

See the details on NatureJobs

Autoimmune Genetics Laboratory in the news

De Standaard, 29-11-2012:

(English translation below)

De sfeer is hier collegialer' - Brain Gain

De Australiër Adrian Liston (32) werkt als hoofddocent immunologie voor de KU Leuven en als onderzoeker aan het VIB. ‘Ik had dubbel zoveel kunnen verdienen in de VS of Australië, maar dat is niet doorslaggevend.'

‘Wij zullen hier nog lang blijven, ja. België is een goede plek om aan onderzoek te doen en om onze zoon op te voeden.'

Bent u uiteindelijk tevreden met uw keuze voor België?

‘Het zou duidelijker moeten zijn dat je je werk in het Engels kunt doen. Publicaties, congressen, lessen,... het gebeurt allemaal in technisch Engels in onze branche.'

‘Ook de taal schrikt misschien af. Aan de KU Leuven moet je op papier in het Nederlands lesgeven, dat werkt drempelverhogend. In de praktijk kan je wel in het Engels lesgeven, zeker in de hogere graden. Maar dat weet een buitenlander niet.'

‘Academische vacatures mikken hier nog heel specifiek op de Belgische markt, ze worden vaak zelfs alleen intern uitgeschreven. Universiteiten zijn hier minder internationaal georiënteerd.'

‘Ik heb gestudeerd aan de Australian National University van Canberra en heb daarna een tijd gewerkt aan de University of Washington in Seattle', zegt Adrian Liston. Hij kreeg aanbiedingen uit Canada, Australië, Ierland, het Verenigd Koninkrijk en België.

Waarom is het België geworden?

‘Omdat het Vlaams Instituut voor Biotechnologie (VIB) zeer actief is in het rekruteren van internationale toponderzoekers. Ik was op zoek naar een plek waar ik onderzoek van het hoogste niveau kon doen. België leek me ook een aangenaam land, met een open houding tegenover mensen die Engels spreken. Ik vind hier ook een goed evenwicht tussen werk en vrije tijd.'

Ziet u verschillen in het academisch klimaat in België en pakweg de VS?

‘De sfeer is hier collegialer, omdat academisch onderzoek veel meer een kwestie van samenwerken is. Wie met buitenlandse onderzoeksgroepen samenwerkt, wordt daar financieel voor beloond. In de Verenigde Staten is het eerder belangrijk wat je als individu verwezenlijkt.'

‘Ik had ongeveer dubbel zoveel kunnen verdienen in de VS of in Australië. Het salaris van een senior researcher ligt best laag in België. Maar ik denk niet dat zoiets doorslaggevend is. De meeste academici willen vooral voldoende geld om aan research te doen. En op dat vlak doet België het tegenwoordig net heel goed.'

‘Er wordt ondanks de crisis niet drastisch gesnoeid in onderzoeksfondsen, in tegenstelling tot in Amerika. Als een academicus echt op zoek is naar een exuberant loon, zoekt hij het in de private sector.'

Wat kan een buitenlandse onderzoeker toch tegenhouden om hier te werken?

'Wij zullen hier nog lang blijven, ja. België is een goede plek om aan onderzoek te doen en om onze zoon op te voeden.'

 A rough English translation:

The atmosphere here is more collegial  - Brain Gain

The Australian Adrian Liston (32) works as a professor of immunology at the KU Leuven and a researcher at VIB. "I could earn twice as much in the U.S. or Australia, but that is not important."

"I studied at the Australian National University in Canberra and then worked at the University of Washington in Seattle," says Adrian Liston. He received offers from Canada, Australia, Ireland, the United Kingdom and Belgium.

Why come to Belgium?

"Because the VIB is very active in recruiting international researchers. I was looking for a place where I could do research at the highest level. Belgium seemed a pleasant country, with an open attitude towards people who speak English. Belgium also has a good work-life balance".

Do you see differences in the academic environment in Belgium and the U.S.?

"The atmosphere here is more collegial, which is important because academic research requires people to work together. Here the grant system rewards those who make international collaborations. In the United States the grants focus on individual researchers."

"I had the option to earn about twice as much in the U.S. or Australia. The salary of a senior researcher is relatively low in Belgium. But that was not a decisive issue. Most academics are more interested in knowing there is enough money to do the research they are interested in. And in this respect Belgium is doing well."

"There is no crisis in Belgium, unlike the drastic cuts in research funds in America. If an academic was focused on their personal salary they would move to the private sector."

What stops foreign researchers from coming here?

"Academic vacancies aim there focus very specifically on the Belgian market, they are often only internally issued. Universities are less internationally oriented."

"Also the language might scare off some people. At KU Leuven on paper you need to teach in Dutch. In practice you can teach in English, especially at the higher levels, but foreigners do not necessarily know this."

"It would attract a broader set of international researchers if they know they can work in English. Publications, conferences, seminars... it all happens in technical English in our profession."

Are you finally happy with your choice for Belgium?

"Yes, we will stay here for a long time. Belgium is a good place to do research and to raise our son."

This is more-or-less what I actually said. The one point that I think was left out is that Belgium shouldn't be concerned about the "brain drain". In science it is very important to have a "brain circulation", good ideas come from mixing people with different training and backgrounds, so it is actually a great thing for Belgian science if a lot of Belgians leave and non-Belgians come in. Rather than be concerned about the outflow, try to work more on the inflow, and then everyone wins.

Here is the article which started the issue (22% of Belgian researchers leave Belgian, only 18% of researchers came in from abroad, making a small net brain drain). And here is the opposing interview, from a Belgian researcher working in China.

Planning the paediatrics genetics screen

Only fair to have an age-appropriate represenative at the meeting...

Women in Molecular Immunology

It is easy to discuss equality in science through anecodote. Just by spending most of my waking adult life on university campuses across three continents I am fairly confident in saying that sexual equality is better in biology and medicine than in chemistry or physics, is great at undergraduate level and lagging at professorial level, and is better in Australia than in Belgium. Much better than anecodote, though, is quantitative analysis, which is why I love this website. If you don't publish your research it is a hobby, not science, and a good publication record is the A to Z of career success for a scientist. This website collates data on authorship across time and across disciplines, at a global level, and assesses the participation of women. There are a few caveats: papers are only assessed if they are listed in the JSTOR database, and a gender is only assigned by first name analysis (using the US Social Security database as a reference, so it probably fails for first names not commonly used in the US). Still, it is an absolutely beautiful reference point.

There is an wealth of knowledge in this database, but my interest is in molecular immunology, so how are we performing? Well, the question kind of depends on "compared to what?" In 1991-2010, 29.7% of authors on molecular immunology papers were women. This is an improvement from 1971-1990 (23.9%), and a huge improvement from pre-history (being everything from 1970 and before, at 13.7%). It is also outstanding compared to fields such as mathematics, where women still only account for 10% authors (maths clearly has a problem with women; anyone who says the reverse is kidding themselves). But 29.7% is still a long way from 50%. Even among first authors (typically PhD students or post-docs), only 33.2% of molecular immunology authors were women, and among last authors (typically professors) only a dismal 15.4% were women. 

I've said before what I think the problem is (hint, it is men), but this database gives us a resource to see who is fixing the problem, and how fast, and who is content to live in the stone-age and try to do science with a 50% lobotomy. So many questions arise. Why has virology been more equal than immunology throughout the time period? I would love to see a break-down by country to know if this is a discipline-thing, or is a statistical quirk due to regional differences in sexism correlating by chance with regional differences in research focus.

Oh, and for the trivia-minded, within molecular biology the most equal area of research is heat shock proteins, while the most sexist is prostaglandins. In the entire database, the most female-dominated area of research is gender studies (57.8% female authors), while the most male-dominated area of research is a discipline of mathematics called Riemannian manifolds (99.3% male authors). Check it out.

Autoimmune Genetics Laboratory on the front cover of Cellular and Molecular Life Sciences

Our recent analysis of the function of microRNA-29 in the adaptive immune system was features on the front cover of the latest issue of Cellular and Molecular Life Sciences.

Adrian Liston, Aikaterini S Papadopoulou, Dina Danso-Abeam and James Dooley. ‘MicroRNA-29 in the adaptive immune system: setting the threshold’. 2012. Cellular and Molecular Life Sciences. 69(21) p3533. Pubmed | Direct access 

We also did some science

Lab retreat 2012 photos