​Uniting medicine, drugs and technology

“What’s the difference between me and Angelina Jolie?” With this question Professor Claire Wyman of Erasmus MC and TU Delft started her inaugural speech. “Hard to tell. We’re quite similar. Perhaps my husband is better looking than hers. But many of you probably know in this context the difference I am referring to our chances of getting cancer.”

During an inaugural lecture marathon, the seven professors introduced their contributions to innovations in medical technology from their professional field and the impact of these innovations on health care.

Technological novelties will help understand the human body at the DNA cell level and to research the effect of medicines, lifestyle, and medical treatments in personal, individual cases. The research topics of the new dual professors varied from investigating the possibility of ‘One-Hour Cancer Treatment’ specifically tailored to your DNA to testing medicines on a chip with your own cells.

The double appointments took place during the 6th annual Medical Delta Event. Each year this event attracts around 350 leading scientists, engineers, doctors, entrepreneurs and governmental representatives. It is the second time double professorships were selected. In 2014 the first 11 Medical Delta professors were appointed.

Collaboration between the first group of Medical Delta professors has already resulted in innovations in, for example, the field of minimally-invasive procedures and the development of 3D prints of the human body. Such minimally-invasive procedures result in smaller scars, accelerating patient recovery time and reducing time in a hospital. The development of 3D prints of the human body means that before attempting a complicated procedure, surgeons can first practise the method on a 3D-printed model.

Below are the 2016 Medical Delta Professors and excerpts from three inaugural speeches which Delta found to be especially inspiring.

•Professor Cock van Duijn – Erasmus MC / Leiden University. Precision medicine in Medical Delta: About genes, metabolites and prevention.

•Professor Thomas Hankemeier – Leiden University / Erasmus MC. Big Data in Medical Delta: How metabolomics will change health care.

•Professor Marileen Dogterom – TU Delft / Leiden University. Can we build a synthetic cell? And will this impact personalized medicine?

•Professor Claire Wyman – Erasmus MC / TU Delft. What’s the difference between Angelina Jolie and me? We train scientists to find nanoscale answers.

•Professor Corrie Marijnen – LUMC / TU Delft. HollandPTC: A dream comes true: About protons, patients and preferences.

•Professor Jean-Philippe Pignol – Erasmus MC / TU Delft. Active women with breast cancer: About the one-hour radiation treatment.

•Professor Rob Nelissen – LUMC / TU Delft. Smart Implant Surgery! Medical Delta adds: About patient safety, 3D-printed implants & quality.

The synthetic cell

Professor Marileen Dogterom started her speech with a quote from the famous American physicist Richard Feynman: “What I cannot create, I do not understand”. According to Dogterom, to understand life, one should be able to rebuild it from its building blocks.

“One of my dreams, and that of several of my physics and chemistry colleagues in the Netherlands, is to one day be able to build a true synthetic cell: a simple representation of a living cell, that can perform all essential tasks of life in some rudimentary way: grow, divide, and transmit information to a new generation,” said Dogterom. “This would not only be intellectually rewarding but may also provide us with a platform to simulate disease processes and design drugs against these diseases.”

To illustrate what scientists are capable of today, Dogterom showed a movie of a dividing cell.

“One of the most important things a cell has to do when it divides is to copy the genetic material, the chromosomes and see to it that each of the two daughter cells receives exactly one copy of each chromosome. This cell, just like virtually every cell in your body, can do this with incredible reliability. Understanding cell division is a classic problem in cell biology. However, despite the increasingly fabulous movies that we can make of dividing cells, and despite the tremendous amount of progress that has been made in identifying the molecular players, we still do not understand how the cell division machine works, and what makes it so reliable.”

In the movie we could see the mitotic spindle (coloured in green). This is the machine that generates the physical forces to control the motions of the chromosomes.

“It’s a collection of microtubules. By growing and shrinking, the microtubules exert pushing and pulling forces on the chromosomes, which first help line-up the chromosomes in the middle of the cell and then pull them apart towards the two new daughter cells. Our approach in the lab has been to take this machine apart down to its basic components, the microtubules, and study the forces that these components can generate. In other words, we are reconstructing cellular processes in an artificial environment to study and understand their dynamic properties under well-controlled conditions.”

Centre of the universe

“When I was young I had a dream,” said radiation oncologist Professor Corrie Marijnen. “I wanted to be a nurse to make sick people better. Soon my ambition was bigger: I wanted to be a doctor and help the poor people in Africa. And yes, after medical school I found myself in Africa, doing Caesarean sections, traumatology, and anaesthetics.

“Back in the Netherlands, I decided to start working in radiotherapy. Soon I realized patients were not only in need of a cure, but certainly also needed a lot of care. Also, I became increasingly aware of side effects patients were suffering from. As a consequence, I realised that the words in our lecture room at medical school said it all: the patient is the centre of our universe.

“For me as a radiation oncologist, a dream came true when we started talking about protons. In theory, protons will give far less toxicity, simply explained by the fact that in conventional radiotherapy the X-rays go right through the patients. Protons, however, stop exactly at the tumour and give less dose to the surrounding healthy tissue.

“About eight years ago, the collaboration of the TU Delft, ErasmusMC, and LUMC started to initiate the HollandPTC and I was privileged to become part of this team.

“As you may have noticed, there is a discussion about the true value of the proton therapy. I am strongly convinced protons are beneficial for a certain group of patients, but not for all. Selection of patients is crucial.

“For this, we need the help of prediction models with which we can infer correlations of the radiotherapy dose to a specific organ at risk and patient reported outcomes of long-term toxicity. However, data on patient-reported outcomes are still limited, and we are only able to communicate about risks derived from large randomized trials. You may appreciate that this is insufficient.

“I see it as our duty to collect data on every patient we treat so that, we can continuously update our risk models and adjust for patients characteristics. In this way, we can present individualized risk profiles to our patients, both for cure and toxicity.”

Nanobiologists are the folks that will make a difference

“What’s the difference between me and Angelina Jolie? Our BRCA2 genes,” said Professor Claire Wyman of Erasmus MC and TU Delft.

One topic on which Wyman does research is the BRCA2 gene. More specifically on how a defect in that gene can increase the likelihood of developing breast of ovarian cancer. In normal cells, BRCA2 delivers the proteins that repair breaks in DNA. Chromosome breaks happen all the time in dividing cells. If they are not repaired correctly, the genome becomes unstable. This sets a cell off to potential cancerous transformation.

During her speech, Wyman showed a movie of a cell in which BRCA2 is defective. Using a luminescence technology she could show that the repair proteins never get to the right place; there were no green spots.

Wyman and her colleagues can make movies of single molecules moving around in a cell nucleus. “We can measure how fast the molecules move. We watch the proteins work to find out which steps are different when they don’t work properly. These kinds of experiments require a combination of expertise in many areas; molecular biology, cell biology, advanced instrumentation and microscopy, image analysis development, and mathematical modelling.”

Wyman was one of the initiators of a new nanobiology bachelor program, which started in 2012. “This past October 16 students received their bachelor’s degree. These are the folks who will make a difference in the future of biomedicine.”

For further reading: Medical Delta published a magazine featuring interviews with all seven full professors to mark these second Medical Delta inaugurations.