- The capacity of genetic engineering is increasing at breakneck speed, which is welcome. But what happens when the technology takes the step into the clinic and society? When should complex biomedical data be communicated to patients? That's where knowledge falls behind.

Mats G Hansson leads the RJ-funded research program Mind the Risk, which investigates ethical and psycho-social aspects of genetic risk information. He describes a reality that is rapidly changing care. With the help of whole-genome sequencing (analysis of the entire genetic mass), it is possible to map the gene set of the human body in a short time and in this way find an inherited tendency to a number of different diseases.

The development took off after the so-called HUGO project at the beginning of this century, where the researchers succeeded in mapping the human gene set, through enormous efforts. Since then, technology has taken several leaps forward. Today, it is possible to buy gene tests online at a price many people can afford.

In many ways, the development is promising, says Mats G Hansson. It opens the way to finding unusual genetically transmitted diseases - and in the best case being able to start treatment against them. It is not difficult to find sunshine stories about how children were saved to life and health in that way.

It also opens the door to individual-based medicines and therapies that the individual patient responds to better. Furthermore, it enables people to gain greater knowledge of their inherited predispositions to various diseases and thus have the opportunity to adapt their lifestyle and diet accordingly, so that the risk of falling ill is reduced.

But the pitfalls are many. The information from the genetic tests is difficult to interpret. In most cases, diseases are not due to a single gene but to a complex of genes, and environmental factors often play a major role. So what does a genetic test bought online actually say?

Sometimes there is also no treatment for the disease for which a genetic predisposition is found. Is there then reason to notify the patient or his next of kin?

At the same time, the genetic technology and the interpretation of the genetic tests are under development. One month you may have a risk gene. Next month, research says the gene is harmless. In addition, the commercial genetic tests are not 100 percent accurate and can give false answers, both positive and negative. The matter is not made easier by the fact that those who happen to carry risk genes can risk social stigmatization. People can be seen as carriers of bad genes.

This plus a number of other difficult choices make the issue of genetic risk information particularly difficult for healthcare professionals to manage.

Mats G Hansson explains:

- Genetic risk information can bring great benefits, but also entails risks. In part, it is about how to design the information. When it is left and how it is done. It is one thing to produce a risk information. But how it lands, how people understand this it is unexplored. There are many questions that are unanswered and they end up with doctors and other healthcare professionals who are not fully prepared.

This was the origin of the research program Mind the Risk, which is unusual, partly because of its scope and because it is early in taking these ethical aspects of genetic risk information so seriously.

- We wanted to investigate this. We wanted to evaluate how the information is given and see how it can be packaged to reduce fear and increase patients' well-being and autonomy. We also wanted to find methods to measure the effect of risk information.

Mats G Hansson is the day-to-day director of the Center for Research and Bioethics at Uppsala University. There is training in medical ethics for healthcare personnel and research in the same field. It is about interdisciplinary applied ethics research and the same can be said about the research program he leads.

- The research must be used in decision-making and in the clinics, says Mats G Hansson.

A large grouping of researchers in different fields and in different countries has come together under the Mind the risk umbrella. Here there are psychologists, biomedical analysts, health scientists, philosophers, political scientists and they come from universities in Sweden, Germany, Great Britain and Italy.

To begin with, a proper concept inventory was made that would form the basis of the empirical investigations. What is risk, value, uncertainty? What is a reasonable approach to the bad news? That work resulted in a theme issue in the Journal of Risk Research in January 2018.

The philosopher Ulrik Kihlbom is a lecturer in medical ethics and led that work. 
- A reasonable goal of genetic risk communication is to get people to think constructively about the message. It is not good for people to become depressed, worried or suppress the information, he says.

One thing that Ulrik Kihlbom investigated is the risk that the patient will regret it. How does healthcare relate to that? Decisional regret is something that many in healthcare are worried about. Kihlbom has interviewed hematologists who inform leukemia patients about the difficult and extremely painful cancer treatments.

- The haematologists are worried that the patients will suppress the information and then become upset - "had I known, I would never have agreed to treatment", says Ulrik Kihlbom.

The researchers have since gone further and continued to empirically investigate how people, patients and healthcare professionals, actually react to risk information. Do they want to know that they have an increased risk of certain diseases? Do they have the ability to assess the risk? If lifestyle changes can keep the disease at bay, are they making those changes?

Jennifer Viberg-Johansson Health scientist Jennifer Viberg Johansson has investigated how people receive and value genetic risk information. She has used the health economic method discrete choice experiment, which is particularly suitable here.

- It is a way of examining preferences in complex election situations. What is most important and how much more important is one parameter than the other? What happens if we change a parameter - I get to know that through regression analyses.

For example, do you want to know that you have an 80 percent risk of getting a fatal disease for which there is no cure? Jennifer Viberg Johansson's surveys show that 53 percent want it.

Furthermore, her studies show that people seem to have an either-or approach to genetic risk. Either you have a risk gene or you don't, and it matters less if the risk is 5 percent or 35 percent.

- People often think in binary terms about such information. It is risk information, i.e. uncertain information. The danger is if people interpret it as 100 percent. This, in turn, can create anxiety, affect sleep and lead to unnecessary and perhaps incorrect life choices.

But if people are told that they have, for example, an increased risk of cardiovascular disease, does that lead them to stop smoking and start exercising? Studies within Mind the Risk carried out at the University of Milan show that this is not the case. Although risk information creates anxiety, it is difficult to change ingrained habits and people tend to live as usual.

- All this complicates the question of how, when and if the information should be given, says Jennifer Viberg Johansson.

Another question that is difficult to deal with ethically is whether the genetic tests show risk genes that were not looked for. Should healthcare tell the patient? It's good to let people know the risks, right?

 - It is not obvious. There may be times when it is not advisable to tell. Here, healthcare must find a way to have informative conversations with the patient before the tests. You definitely shouldn't tell if the patient says they don't want to know, says Jennifer Viberg Johansson.

Much of what the researchers at Mind the Risk have come up with is to raise the difficult questions, turn and twist them. It has conducted patient surveys in several countries to gain a deeper understanding of how people think about health information. However, they avoid giving answers. Instead, they present a palette of ideas and perspectives that those who work in healthcare can make use of.

- We show that there is a gap between technology and people's perceptions. We want to provide a basis for guidance on how to approach this. Much of our research points to that need, says Mats G Hansson.

Text: Thomas Heldmark