Team:Groningen/Template/MODULE/PP/martini/nieuwenhuis

Nearly halfway through our iGEM-adventure of creating an infection-detection-protection dressing for (burn) wounds, we got the opportunity to talk with some experts in the field. Of course, creating a ‘genetically engineered machine’ is what we do, but we want to explore the application further. Having a talk with people who could eventually use our concept in real-life was therefore essential; if there is no need for this type of dressing, then there is no need to develop it!

Marianne Nieuwenhuis is the head of clinical research for the three cooperating burn centres in the Netherlands and is based at the burn centre of the Martini hospital in Groningen. Jakob Hiddingh is also affiliated to the burn centre and is working on clinical research trials. Whenever a researcher is not around, Jakob takes over the responsibilities, making him an expert on the practical side of clinical research trials.

Can you explain something about the burn centres? How do they work? What kind of research should we imagine when you talk about clinical research trials?

‘In the Netherlands there are about 600-800 recordings (annually) of patients in the three burn -centres; Beverwijk, Rotterdam and Groningen. Rotterdam is the largest of these three. The time patients stay at the centre varies from one day to several months. We do research in everything ranging from psychological research to physical issues like itching. On average, patients remain at the centre for 14 days, but as said, this varies a lot depending on the patient and severity of the injury.’

As you may know, we are developing a dressing that is aimed at protecting burn wounds, specifically to detect an infection of S. aureus or P. aeruginosa. Do many problems with infections occur when treating burn wound patients? How do you handle these?

‘There is a clear distinction between an infection and a wound that has some pathogen (harmful bacteria) in it; a colonization. Colonization is when the pathogen is there, but you do not get ill from the presence of these bacteria. When you talk about an infection, many of the classical features occur and these are very harmful for the healing process. In this centre, we typically take a sample of all the wounds once a week to see if there are any harmful bacteria on them. We also take a sample of the throat and nose. ‘

Groningen, and the Netherlands in general, does not have many problematic infections. How is this problem of infection prevention taken care of in the rest of the world?

‘It’s hard to compare numbers because every centre and hospital has its own way of detecting infections. There is a large range of pathogens, but especially S. aureus and P. aeruginosa are the pathogens that cause most problems.’

If we understood well, Flammacerium (a cream-like substance) is used mostly to keep the wound clean and improve wound healing. How does this treatment work and is it used in other parts of the world?

‘Flammacerium consists of two components, the silver sulphadiazine (also known as Flammazine), and cerium nitrate. The silver sulphadiazine keeps the wound clean, but a serious downside is that it induces hypergranulation after a while (the overproduction of tissue). People have been looking for an alternative for quite some time, but so far nothing really superior is on the market yet. We believe that the cerium nitrate does have a positive impact on the treatment of burn wounds, therefore we keep using Flammacerium. In other parts of the world this treatment method is used to a lesser extent.’

For our dressing, we would like to think a step further than only developing it and then putting the prototype in the fridge. What are the main hurdles to be taken when developing this dressing for burn patients?

‘Keep in mind that for every minor step you want to do when dealing with a clinical research trial, you should write a protocol and all actions should be cleared by the medical-ethical commission. In the Netherlands, this is the case for every WMO-research (research involving humans). For the testing of a new product, such as your dressing, you would need to fill out many forms involving a complete description, how it works, what could go wrong, what is the goal and added value etc. etc. .’

As we are speaking about regulation issues regarding new products, what do you think of our idea once it has gone through all the clinical trials and been proven to work, say in 10 years? Do you see the relevance of having such a dressing? Do you foresee any ethical issues that might arise in the practical application of GMO’s in healthcare?

‘The funny thing is, I never heard of synthetic biology before you came along. I did not realize this project would involve any moral dilemmas that needed to be so seriously addressed. I just thought: that’s great, they are “playing around” to make bacteria do a specific task! As long as the added value is clear, in other words, if it helps the patients to get better, there will be not so much resistance against it. It should be very well regulated though, but this is already under debate. I understand that genetically modified organisms are a bit difficult to use and there is some resistance, but to me this project seems very worthwhile.’

Do you have any advice for us that could help us in the development of our dressing?

‘We are enthusiastic about your idea and think that this is an innovative approach to treating wounds. The idea I like so much is that it goes beyond normal theoretical research, but you are actually making it. It is a quite appealing concept. There is also possibly less resistance as you are trying to make a better treatment for patients with burn wounds. You should have a talk with our medical microbiologist and medical director!’