JR: You received the Bayer Early Excellence in Science Award in 2012, which is a prestigious award for a young scientist. Could you explain the nature of your work for which you received the award?
CO: The prize was for my work on tryptophan degradation in cancer cells. It was previously known that tryptophan degradation can act as an immunosuppressive mechanism and it was also known that some tumors contain a certain tryptophan degrading enzyme called IDO. I was interested in studying brain tumor cells because I treat brain tumor patients in my work as a physician. When we examined brain tumor cells, we found that they degrade significant amounts of tryptophan but that this was surprisingly unrelated to the IDO enzyme. We then decided to look into a different enzyme known as TDO which metabolizes tryptophan in other tissues such as the liver. It turned out that the brain tumor cells contained high levels of TDO and that metabolites of tryptophan activated the transcription factor AHR (aryl hydrocarbon receptor) in the tumor cells*. JR: How does the activation of AHR by tryptophan metabolites affect the tumor cells? CO: This pathway has two very detrimental effects: The tryptophan metabolites increase the growth of the brain tumor cells, while at the same time allowing the tumor cells to evade the immune system. On the other hand, blocking this pathway in human brain tumor cells suppressed the growth of tumors in mice derived from these human cells. JR: You studied this mechanism on a cellular level but do you have reasons to believe that it is also active in tumors of patients? CO: When we looked at brain tissue samples from patients with malignant brain tumors (glioblastoma), we found evidence of increased AHR activity. The patients with the highest activity levels had the most aggressive form of the tumor. Currently, we know that this metabolic pathway is a predictor of poor survival, but of course our hope is that by targeting this pathway, we might one day be able to improve the survival of patients. JR: In a previous conversation, you discussed the challenges of being a practicing physician and a scientist at the same time. All clinical work has its challenges, but in your case it must be especially tough since you primarily see patients who have malignant brain tumors. It is a fatal condition for which we currently do not have any curative therapies. How do you deal with this emotional burden? CO: One of the things that I am very grateful for is that when I go to the lab, I get regular breaks from my work as a physician. If I had to see patients with a terminal disease every day, it would be very hard on me psychologically. I have to give my patients terrible news about the extent of their disease or a relapse of their cancer. My job is to comfort them and try to give them strength, even though I often feel powerless. I have to keep my own emotions to myself and take my misery home with me. But the time I spend with my family at night or the time I spend in the lab during the following days allows me to recharge before my next neuro-oncology clinic. JR: You just mentioned your family. An important ongoing discussion is that women in science struggle with the balance between work demands and the demands of their families. The number of women in science has substantially increased over the past years, but there is still a big gender divide when it comes to leadership positions. There isn’t so much of a gender gap at the training stages such as during graduate school or postdoctoral fellowships , but comparatively few women advance to becoming group leaders, professors or directors of academic institutions. What has your experience been in this regard? CO: Female group leaders are still a minority in Germany. The German Cancer Research Center (DKFZ) is putting a lot of effort into changing this. I benefited from one of the measures introduced by the Center, an initiative to create tenure track group leader positions for women scientists with children. These positions have a duration of ten years instead of the standard five year duration.
Female group leaders are still a minority in Germany.JR: Tenure-track positions require that young group leaders establish cutting-edge, independent research programs with international visibility and publish high impact papers before they can advance to a tenured position. In the US, tenure track positions for junior faculty are usually slotted for six years, and it can be very challenging to develop an independent program and publish several papers during such a short time period. Molecular and cellular research projects are very time-consuming, and unforeseeable scientific obstacles often delay projects for a year or two. Major personal life events such as pregnancy, maternity leave, paternity leave or illnesses can also make it difficult to meet the tenure requirements. This is why some American universities allow “stopping of the tenure clock”, so they can extend the tenure track position beyond six years. Achieving tenure in only five years seems very tough, and any unforeseeable event could potentially derail a young scientist’s career. Aren’t women scientists especially vulnerable in a rather short five year tenure track position because of pregnancy, maternity and the fact that mothers are often expected to shoulder the bulk of the demands of parenthood? CO: This is why I applaud the efforts of the DKFZ to be pro-active and offer ten year positions to women scientists who are mothers. I had applied for a standard five year position as a junior group leader because I did not even realize that there were other options. It was Professor Otmar Wiestler, the director of the DKFZ, who explained the Center’s vision to invest in the long-term scientific success of women and their leadership roles in science. He suggested that I instead accept a ten year position instead of the one I had applied for. JR: How did you feel about the offer? CO: At first I had some mixed feelings. I was happy that the DKFZ was so interested in increasing women in leadership roles and the Center was aware of the hurdles women face. However, I was also concerned about receiving privileged treatment. I want to be judged based on my scientific merit and not because I am a mother. Professor Wiestler then explained to me that offering the position to me was based on my scientific accomplishments. The ten year duration was merely an additional support structure. It is intended to level the playing field between male and female scientists so that women are not disadvantaged and held back by the demands of motherhood. This is why I gratefully accepted the great opportunity. I do not intend to use up all of the ten years. I am hoping that my group will develop a solid research program within five years but it is nice to know that I have some extra time as a fall back. I want to spend time with my husband and my children and knowing that I have some additional buffer time takes off some of the pressure.
I want to be judged based on my scientific merit and not because I am a mother.JR: You see patients, you run a research lab and you have two kids. How do you manage raising your kids with your demanding work schedule? CO: My husband is extremely supportive of my career and my parents also help out a lot. We carefully coordinate our work schedules. When I have to work late either in the lab or because of my clinical work, I know that my husband is there to care of the kids. I do not have to rush when I am seeing a patient or performing experiments because of my husband’s help, and this gives me a lot of peace of mind. JR: You mentioned how grateful you are for the support you receive from the DKFZ which enables you to be a physician-scientist and a mother. But you also mentioned that female group leaders are still comparatively rare in Germany. Is the mindset still evolving to improve the prospects for women in science? CO: To illustrate the issues women still face in Germany, I can mention the example of a female physician scientist whose clinical rotations during her residency training were changed because she got married. She was told that would not need these rotations because married women have children and then drop out from their careers. Nobody bothered to check with her first or ask her about her own career plans. In another instance, a female scientist was asked not to have a second child when she returned back to her research project after the maternity leave for her first child. Her mentor told her that having another child would distract her from her research. JR: These are very troublesome incidents. Instead of building support structures to help mothers, some people seem to discourage female physicians or scientists from having children. Is this a generational issue? CO: On the whole, these incidences are becoming rare and such remarks are made by relics who belong to a culture of the past. There is a gradual increase in the number of women in leadership positions who themselves have struggled with motherhood. There is also an increasing number of male scientists who are actively involved in caring for their families. These colleagues and mentors recognize the importance of building support structures which allow women to become successful scientists. JR: Is your outlook optimistic in regards to closing the gender gap in leadership positions? CO: It will take time, but I am optimistic that the overall shift in the scientific culture and the specific initiatives such as those of the DKFZ will ultimately succeed. JR: Let us end on this positive note. Thank you very much for your time and I wish you all the best for your future career as an outstanding researcher in the field of cancer cell metabolism.
* Readers interested in learning more about TDO and Dr. Opitz’s original research can read her article published in the journal Nature: Opitz, Christiane A., et al. “An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor.” Nature 478.7368 (2011): 197-203.