A golden age for a geneticist

Text: Cecilia Odlind, first published in Medical Science nr. 4, 2017.

Imagine having a regular health check-up, only to be told that you have leukaemia – and without having had any symptoms. This is the experience of 85 per cent of all patients diagnosed with the most common form of leukaemia, chronic lymphatic leukaemia. The next shock is when you are not offered any form of treatment.

“Despite the emergence of a number of promising drugs, there is still no cure. Nor has early treatment been found to improve survivability, so we do not do anything until the symptoms appear. Obviously we monitor the patient's condition”, says Richard Rosenquist Brandell.

Unfortunately it is also difficult to give the patient a prognosis for what the future will be like. A third of those affected will not even go on to require treatment for their disease, while a smaller proportion will die within just a few years.

“The goal of our research is to be able to distinguish between these individuals early on. In order to do this, we are looking for genetic markers in patients’ tumour cells that will indicate how the cancer can be expected to develop. We can then use these to give patients clear information about their individual prognosis, as well as identifying which patients should be monitored particularly closely and how they should best be treated”, says Richard.

Molecular profiling

And researchers are making good progress. Genetic testing, or molecular profiling as it is called, is already being conducted in many leukaemia patients. This represents an important part in the risk assessment and also influences the choice of treatment to some degree. For leukaemia specifically, it is easy to do this using a blood sample; it is harder to take a sample from a solid tumour in the body. However, molecular profiling is increasingly being used for all types of cancer.

“The other cancer forms where most progress has been made include lung cancer, colon cancer and malignant melanoma. These are also the forms for which genetic analysis currently appears to be most relevant, though the situation is changing as additional knowledge is obtained”, he adds.

“All patients should have access to this analysis, which may in the long term influence the choice of treatment and outcome. It is a matter of fairness”, he says.Roughly half of all lung cancer patients, for example, have their tumour genetically analysed. This is good, but according to Richard Rosenquist Brandell, it is still not enough.

This is also the objective of the national Genomic Medicine Sweden project which he is coordinating, and which will see the new genetic mapping techniques introduced in the health service on a nationwide basis. Similar projects are in progress in the UK, France and other European countries.

“An important factor for development in Sweden has been the build-up of advanced genetic diagnostics for hereditary diseases and cancer that has resulted from close collaboration between SciLifeLab* and the health service”, says Richard Rosenquist Brandell.

Our genetic material

The ability to chart our genes has developed at enormous speed in recent years, and as a result we can now analyse all or parts of our genetic material relatively quickly and at a moderate cost. In other words, it is only now that individually-adapted medical treatment, which has been talked about for so long, can be introduced.

“We're there now, at least for cancer, hereditary diseases and infectious diseases, where we are able to individualise treatment and administer the right medicine to the right patient. For the major widespread diseases, however, individual adaptation will have to wait a while”, says Richard.

He believes that we are in the midst of the golden age of clinical genetics.

“It is a technological revolution. I feel incredibly lucky to be able to work on these issues now. Five years ago, I could never have imagined being able to analyse our entire genome in one to two weeks, as we do now, which means that the methods can be used in the health service. I would never have guessed that progress would have been so rapid.

Greater knowledge about how patients can be divided up into different subgroups with different prognoses and treatment needs also means that it will be slightly more difficult to recruit sufficient numbers of individuals in order to conduct well-founded studies.

“Of course, real individual adaptation requires us to identify what medicines are most suited for a certain genetic profile. And we have to be able to get access to these medicines. For now, there are a lot of drugs that are at the research stage, in clinical studies, and which we are not always able to offer to our patients. Closer collaboration with the pharmaceutical industry could accelerate this development”, he says.

Relatively recent phenomenon

Our ability to find out so much about our genetic disposition is therefore a relatively recent phenomenon, and one that also involves a number of ethical challenges. Charting an individual's entire genome may result in finding out more than you had intended. A patient who has come in with a particular condition can find out that he or she is genetically predisposed to some other serious illness. It is not entirely clear as yet how this situation should be dealt with.

“In the USA, they have, for some years, been using a list of 56 genes that have to be reported back to the patient if mutations are detected in any of them, regardless of the question at issue. However, patients can waive their right in advance to any information obtained. In Sweden and Europe we have adopted a more cautious approach”, says Richard.

How can we know, for example, that the patient has been sufficiently informed to know what kind of information they are saying yes or no to? There has been a lot of discussion of the ethical issues, but there is still no statutory regulation on how this should be dealt with.

“However, I hope that the situation will become clearer with the work that will be done at Genomic Medicine Sweden. We are going to have a special legal and ethics group, which will be working on these issues,” he says, adding that this is not something that is in his area of expertise.

The managerial and diplomatic side seen by many of Richard Rosenquist Brandell's colleagues might be really needed in this major project. Trying to secure national access to the technologies used in molecular profiling has its challenges.

“In Sweden we have 21 different county councils. However, it would take far too long to sign agreements with each and every one of them. A major challenge is to bring about more of a national consensus in the health service”, he says.

Suffered from burn-out

There is a detectable impatience about Richard Rosenquist Brandell, who otherwise gives the impression of being very calm and collected. Keeping calm has been the subject of some focus over the past six years after he suffered from burn-out. Since then he has been careful to work from home one day a week.

“I get a tea tray ready and sit down with Bach playing in the background. Then I work at my own speed. I think it is incredibly important not to kill off creativity, which is such an important ingredient in the research profession”, he says.

*SciLifeLab, a collaboration between several universities, is a national molecular biosciences resource focusing on health and environmental research.