Good examples

Cancer scientist with one foot in the lab and the other in the clinic

Eva Hellström Lindberg

When Eva Hellström Lindberg was a newly appointed doctor, she met a number of patients with a mysterious blood disease that had no name at the time. It wakened her curiosity and became the start of her research career. Today she is a professor, and after many years of research and international collaboration the disease now has a name. New treatment models have been developed and major advances have been made to help a vulnerable patient group.

It is Monday afternoon and Eva Hellström Lindberg has as usual gathered her research group at HERM, Center for Haematology and Regenerative Medicine at Karolinska institutet Huddinge.

HERM is a research center where clinical and experimental researchers collaborate to find new angles for scientific problems in different areas. The main focus is the patient.

– I started working as a doctor early. Already after eight semesters of med school, I was fascinated by patient work, but not only seeing and caring for patients but also trying to understand them and make things better. My main driving force is probably my curiosity.

Eva Hellström Lindberg leads a translational research group studying genetic, epigenetic and cellular causes of disease emergence. The group has a particular focus on MDS, myelodysplastic syndrome, a collective name for a group of tumor diseases that originates from the bone marrow stem cells.

Every Wednesday morning, Eva also meets the clinical team to discuss difficult cases and review new referrals on patients with MDS.

– I am the head of a very exciting and wide ranging activity where the work in the lab is closely intertwined with the work in the clinic. It only takes a few minutes to go to our medical service center.

Eva Hellström Lindberg is a professor of haematology at the Department of Medicine at Karolinska Institutet, as well as a senior physician at the Haematological Center at Karolinska University Hospital. Over the years, she has had several heavy executive and leadership roles and has been internationally acclaimed for her research on MDS.

In 1992 she defended her thesis on the disease at Karolinska institutet.

– I am good at asking research questions and gathering competent people around me who are experts in areas where I am not. I could not do what I do on my own, I am highly dependent on my group and a well functioning network. Getting opportunities to change things and participate in an international process that drives development is extremely stimulating.

Recently she received another recognition as she, as one of four Swedish researchers, was appointed Wallenberg Clinical Scholar in 2018. This means that she will receive 15 million SEK for a five-year period, with the possibility of renewal.

– It really made me very happy and proud. It also brings a sense of relief because the grant means that I can think more long-term and saves me the worst worry for funding, says Eva Hellström Lindberg.

Joint detective work

Just over 30 years ago when Eva Hellström Lindberg was a relatively new doctor and researcher, she met several patients with strange blood values at the haematology center at Huddinge Hospital. The patients felt tired, faint and out of breath. "It's probably just age" said several of them and continued to fight until the body eventually had enough.

– At that time, not much was known about this blood disease, more than that there was something wrong with the bone marrow. I was curious to find out more and it was the start of my research career.

Eva Hellström Lindberg was not alone in her interest in this patient group. Elsewhere in the world, other researchers had begun discussing the disease that eventually became known as MDS, myelodysplastic syndrome.

– The first classification was made in 1982, but it took a few years before knowledge reached the hospitals in Sweden.

Then, 30 years ago, the disease was a life threatening condition. MDS is characterized by anemia and patients have a constant need for blood transfusions. Many died of bleeding and infections or from the excess iron caused by frequent transfusions.

– I saw a pattern and started collecting data about these patients. A group of interested people was formed in Sweden and eventually we created a network in the Nordic region. Over time, we also started clinical studies to find out more about background causes and disease mechanisms and new treatments.

Development of new methods

Since patients with MDS have severe blood deficiency, regular blood transfusions are required. Some but not all are helped by the drug erythropoietin. There are also patients at high risk of developing acute leukemia, and for them, allogeneic stem cell transplantation is the only possible treatment. However, until recently, stem cell transplantation has been limited to younger patient groups and since MDS patients are generally older (the median age is 74 years), many of them have not been given treatment.

– We have therefore not been able to transplant so many people over the years. In addition, a high proportion of those undergoing treatment have recurrencised. So historically, we have not been able to cure more than a third of the patients we have transplanted.

Much has happened in recent years. Eva Hellström Lindberg talks about knowledge and technology development and how close collaboration between healthcare and academy, but also with research groups around the world, has led to new and more effective treatments.

– Today, we can transplant patients up to the age of 70-75. My research team has also introduced a treatment with the hormone erythropoetin that inhibits the disease and postpones the need for multiple transfusions for several years. Today, we can also medicate the excess iron so that patients are not injured by frequent transfusions. We also work intensively to minimize the risk of relapse.

Eva Hellström Lindberg's research team has developed new methods to look at what is called MRD, minimal residual. Through MRD analyses the risk of relapse after stem cell transplantation can be determined and the continued treatment can be better controlled.

– Another important part of our research is the big biobank we started many years ago, and in which we register about 80-90 new patients each year. It is an extremely important source for follow up, clinical studies and treatment research.

Registered patients are also included in a major international multicenter study. In total, there are about 6,000 participants with MDS, of which 1,000 are Swedish patients. The aim is to look at gene expression and gene changes with sequencing methods and develop a new diagnostic system.

– We work closely with major centers around the world and together we try to understand this disease better.

A third research trail is to map a subset of MDS called refractory anemia with ringsideroblasts. The disease leads to severe blood deficiency and high levels of iron accumulate in the mitochondria of the cell.

– There are several different subgroups of the disease, and I have chosen to focus on one of them characterized by a special mutation called SF3B1. We had been working for a long time to find the gene mutation that gives rise to the misplaced iron, and in 2011, we were suddenly successful. It accelerated the entire MDS research field.

The results were published in the prestigious scientific journals Nature and the New England Journal of Medicine. Eva Hellström Lindberg explains that the gene is so important because it affects splicing, a biological process that clears so-called "junk DNA" before genetic information is passed on to protein coding

– The knowledge can be used to find gene mutations and better understand the causes behind anemia and to find new treatment models. I usually explain to my patients that the end result is similar to the barcode you find on the ICA products. When the barcode is scanned, all necessary information about the item can be read.

Advice for young researchers

Eva Hellström Lindberg has a combinatory professorship, which means that she devotes about 30 percent of her time to the clinic and patient work, and 70 percent of the time to research and education.

– Every Monday, I meet seven to eight patients and I am extremely pleased to be both a doctor and a scientist. I get to work with what I like most and it is amazingly satisfying when knowledge leads us to new treatment opportunities for our patients.

If she is to give advice to young medical students who are curious about research, the main suggestion is to look for a strong and open environment with a wide and broad range of skills and where everyone is helping each other.

– It is also necessary to be committed and ambitious and willing to work hard. It usually takes longer to become a specialist and you should be prepared. Then I think that a strong will is required and that one is passionate about what one does. It is amazing fun to be a doctor and scientist in an expansive world where lots of things happen all the time. Personally, I do not think there is a better job.

Combining the medical profession with a research career also has other benefits, she believes.

– It is tough to be a researcher only and to depend on funding. Combining the roles will allow you to work more at the clinic during periods when it is more difficult to get research funding. After all, everyone needs to pay their rent and put food on the table.

Eva Hellström Lindberg also highlights the Swedish Research Council's major focus on clinical treatment research as a good example of measures that favour Sweden's position as a strong research country.

– It has had an impact on the quality of the research projects. The investment is excellent and I think more funding agencies, such as the Cancer Fund and the Heart-Lung Foundation, should adopt the Swedish Research Council's model to further strengthen clinical research in Sweden.

She dreams about developing a method that can cure the majority of patients with MDS.

– And then it would be great to develop a completely new treatment for MDS patients with the SF3B1 mutations. It is not unreasonable to get there. In the best of worlds, I'd love to be in for that breakthrough before retiring in just over seven years.