Medical science 2016

A magazine from Karolinska Institutet

English Language Edition

2016

Renewal How stem cells heal the body

ALSO: EMPATHY/ ABORTION / RECIPE FOR LIFE

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Contents—2016 4

Meet the Vice-Chancellor

Advances 5 6

The genes that initiate life Resuscitation in record low temperature 7 A close look at the carotid bodies 9 Around the body 10 In short 16 Elusive viruses partly conquered 44 Aim: To do away with peanut allergies

Focus 18 Internet drugs – legal and dangerous 20 Perspective: The Abortion Act 40 years on 38 Curious about empathy

The researchers 8 12 24

43 45 50

A recipe for life Three researchers chasing time Carol Tishelman interview: Seriously good questions about the end of life The moment – “Our research saved him” Psychopaths are not monsters The moment – “Becoming a psychiatrist wasn’t even on the map”

In depth 28 The self-healing body

Also 46 This is where the secret decision is taken 48 High impact publications

24 Fearless.

Carol Tishelman wants us to talk about death.

Freezing cold.

New survival record due to chilling.

33

43

Bit by bit.

Meticulous research led to breakthrough.

6 Repairments.

Molly Stevens regenerates damaged organs.

44 Cure. How to get the body used to intolerances.

Medical Science–2016

3

Vice-Chancellor of Karolinska Institutet

D

EAR READERS, Karolinska Institutet is one of the world’s leading medical universities. Our vision is clear: to significantly contribute to the improvement of human health. The goal for our research is to achieve scientific breakthroughs that change the view of human health and disease, as well as normal vital processes.

Karolinska Institutet acts on a global market, where we not only compete for the best individuals, students, scientists and experts but also provide talent. Critical to our ability to remain competitive is our collaboration at the regional, national and international levels. Together with other stakeholders in the region – universities, county councils and municipalities – our goal is to create an internationally competitive life science cluster with the potential to attract researchers, students and industry. Karolinska Institutet contributes to the regional infrastructure by providing new advanced research laboratories that will be ready for use by 2019. At the national level, Karolinska Institutet supports the establishment of national infrastructures to facilitate and strengthen high quality research. Karolinska Institutet seeks strategic alliances with other internationally leading universities to enhance our ability to carry out large-scale, ambitious and resourceintensive research for the benefit of individuals and society at large.

The former Vice-Chancellor, professor Anders Hamsten, left his position in February as a direct consequence of the university’s lack of control and failure to act on behaviours and environments in a specific area of regenerative medicine. A number of investigations have been launched that we expect to provide answers to what went wrong. In parallel, the institute is taking a number of concrete measures to ensure that our activities remain characterized by their very high quality and ethical approach. However, these extremely serious incidents have not changed the university’s general view that regenerative medicine is an area that holds great promise for the future.

You will note that several articles on this topic are included in this issue.

Research at Karolinska Institutet spans the entire medical field, from basic experimental research to patient-oriented and care sciences. This year’s edition of Medical Science will give you a glimpse of some of the many exciting research projects being conducted at our university in the interests of improving human health.

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Medical Science–2016

Medical Science is an annual English language edition of the Karolinska Institutet popular science magazine Medicinsk Vetenskap. Here you can read selected examples of current research at our university.

Editor-in-chief Christina Bostedt Director of Communications Karolinska Institutet Editors Ola Danielsson Cecilia Odlind Medicinskvetenskap@ki.se Art Direction Daniel Låftman, Content Innovation Contributors Jenny Tollet, Anders Kjellberg, Annika Lund, Frida Wennerholm, Karin Söderlund Leifler, Martin Stenmark, Ann-Cathrine Johnsson, Mattias Ahlm, Fredrik Hedlund, Christopher Hunt, Linda Forsell Cover: Anders Kjellberg Print E-print Translation Språkservice Web ki.se Communications and Public Relations Office, Karolinska Institutet, SE-171 77 Stockholm, Sweden ISSN 1104-3822 Follow us on Facebook!

Facebook.com/ karolinskainstitutetenglish

Photography: Gustav Mårtensson

Karin Dahlman-Wright:

The latest in medical research

Photography: Science Photo

The ignition key of life explained For the first time, an international research team led by Karolinska Institutet has mapped all the genes that are activated in the first few days following the fertilisation of a human egg. A human life begins with a single fertilised ovum. A day after fertilisation there are two cells; after two days there are four; after three days eight, and so on until there are billions of cells at birth. Up to now, the order in which our genes are activated after fertilisation has been a mystery.

There are in total around 23,000 human genes. In the study in question, the

On the way After 8 weeks, most organs are in place and the embryo changes name and is called a foetus.

researchers show that 32 of these genes are switched on two days after fertilisation and that by day three there are 129 activated genes. Seven of the genes discovered and described by the researchers were previously completely unknown.

“These genes are the ignition key needed to start the development from egg to human; it’s like throwing a stone into water and watching the rings spread out on the surface,” says Juha Kere, lead researcher and Professor at the Department of Biosciences and Nutrition. Jenny Tollet Nature Communications, September 2015 Medical Science–2016

5

Advances about the cold

-10

O U T D O O R T E M P E R AT U R E –1 2 ° C

A cool 0 resuscitation against all the odds After being underwater in an icy sea for almost an hour and a half, a girl was able to be resuscitated and made a complete recovery. Researchers are now trying to learn the lessons of the incident.

10 B O DY T E M P E R AT U R E 3 2 ° C B R E AT H I N G

20

Text: Ola Danielsson

6

Medical Science–2016

B O DY T E M P E R AT U R E 1 3 . 8° C N O B R E AT H I N G

temperature was 13.8°C. After connecting the girl up to a heart-lung machine, the medical team started to slowly warm up her body. At 20°C, they noted the occasional breath, and at 32°C, after 20 hours of treatment, she opened her eyes.

After four days the heart-lung machine could be disconnected, but she continued to be looked after in intensive care for almost a month, at which point an intensive rehabilitation programme started. Fifteen months after the accident she had recovered and was able to ride a horse and attend piano lessions just as she had before.

A severe cooling effect reduces oxygen consumption and can, paradoxically, save lives if it happens before the person experiences cardiac arrest. This is particularly so with children who cool down more quickly than adults.

Claesson believes it is important that people outside of health care are aware of this case, including the emergency services.

“The first thing you have to ask yourself is: are you looking for a body or trying to save a life? That’s why it’s important to know that there is hope even if considerable time has elapsed.”

Critical Care Medicine November 2015

Photography: Istockphoto

“AS FAR AS WE KNOW, no-one else has been underwater for so long and survived without serious brain injuries,” says Andreas Claesson, researcher at the Centre for Resuscitation Science, who has worked with colleagues to reconstruct the course of events in a case report.

The seven-year-old girl, who was wearing pink clothes, went out one day in December to look for Father Christmas. Then something went dreadfully wrong.

To their horror, her parents found evidence of sliding in the snow on a slope leading down to the sea. By the time the rescue helicopter arrived it was already dark, but at half past four a small pink dot was seen in the water.

When the girl was winched up to the helicopter, she had been in the icy water for at least 83 minutes.

On arrival at the hospital she was not breathing, had no pulse and her body

30

A close look at the carotid bodies Advances

They keep a check on your breathing Text: Ola Danielsson Illustration: Anders Kjellberg

When?

If the carotid bodies detect a lack of oxygen, they send a signal via the carotid sinus nerve to the respiratory centre of the brain. Within a few seconds, respiratory rates rise automatically and remain at a higher level for 5-10 minutes. The carotid bodies’ response aims to restore the important chemical balance in the blood.

And? A chronic lack of oxygen resulting from lung disease or being at high altitude can lead to over-sensitive carotid bodies, resulting in hyperventilation and effects on the cardiovascular system. Anaesthetics on the other hand can reduce the sensitivity of the carotid bodies, which in the worst case scenario can lead to potentially fatal respiratory arrest. By learning more about the carotid bodies, the researchers hope to be able to counter these conditions.

What?

The carotid bodies are two small cell structures, one in each carotid artery, that act as chemical sensors. Their main task is to monitor the oxygen level of the blood, but they can also react to changes in carbon dioxide levels, pH value, temperature and blood sugar levels.

How? The level of oxygen is picked up by what are known as glomus cells in the carotid bodies, but it is not known how this works. Research is currently underway to find out about whether, for example, the vital mechanism is effected on the cell membrane, in the mitochondria or by means of a change in the balance of reactive oxygen compounds in the cell.

Source:The human carotid body in sensing and signaling of oxygen and inflammation, thesis, 2014, Jessica Kåhlin, Department of Physiology and Pharmacology, Karolinska Institutet.

Medicinsk Medical Vetenskap Science–2016 №1–2015

7

Advances 5 questions to ROMAN ZUBAREV ON THE ORIGINS OF LIFE. Roman Zubarev is Professor of Medical Proteomics in the Department of Medical Biochemistry and Biophysics.

Bringing us into being Roman Zubarev and his research colleagues have discovered the optimum recipe for the start of life.

Text: Annika Lund Photography: Mattias Ahlm

Your group is researching the origin of life. How are you doing that?

“We have been researching the influence of different isotopes on living cells.

Isotopes are slightly heavier or lighter versions of the same atoms, but have a different number of neutrons in the atomic nucleus. We cultivated E. coli bacteria and systematically changed the isotopic composition of carbon, nitrogen, oxygen and hydrogen in the solution that the bacteria were growing in. When we mixed the isotopes in a particular way, the bacteria started to grow more quickly. That was the point at which we achieved what we are calling isotopic resonance. It is a condition that is to do with how the average weights of the atoms relate to each other in accordance with a special calculation model. There is a bit of numerical magic here – the calculation must end in a whole number. Roughly speaking, there is then a lower level of chemical complexity that speeds up the biochemical process.

I see. And what does the best recipe look like?

“For carbon, 9.54 per cent must be of isotope 13C; 10.89 per cent of nitrogen must be of isotope 15N, and 6.6 per cent of oxygen must be of isotope 18O. That results in what we call super resonance 8

Medical Science–2016

An experiment to test how long shrimps can survive in closed systems with water of different isotopic composition.

– the perfect conditions for biochemical processes which can then work much more quickly.

Were these conditions in place on the earth when life began?

“No, we have never had that isotopic composition. That means we don’t have the perfect conditions for life on earth. But we are still in a good position compared to other planets in the solar system because we do have conditions that are good enough. Here, life was able to emerge relatively quickly, even if it took a billion years for it to happen.

Super resonance would have made it happen more quickly.”

What sort of reactions are you getting to your research?

“Many of our colleagues are surprised and think that this is an unexpected new area of research. The bit of numerical magic is seen as pretty amazing and difficult to take in, but that part of our research is statistically highly

significant. Some people with religious beliefs might see this line of thinking as proof that we were meant to be here on earth, that there is a god with a plan for our planet. I’m agnostic myself and have an open mind. But I would perhaps have thought that if a god had created the earth, we would have had super resonance, i.e. the perfect conditions for life.

How can we use this knowledge?

“There are lots of areas where it can be used. In medicine, for example, it might be useful in cancer treatment, where by making the composition of isotopes less favourable for biochemical processes we ought to be able to slow down the growth rate of tumours. In the food industry, on the other hand, improved conditions might make food grow more quickly. I think we are at the start of a new branch of knowledge that could be very useful to us.”

Scientific Report March 2015

Around the body Advances Join Medical Science journal on a journey around the body and find out about the latest research news.

For the first time, a study has shown that a signalling molecule, TGFbeta, can control the development potential of nerve cells over time. For example, the signal controls when a stem cell should stop producing a certain type of nerve cell and make a different one. Increased knowledge of how stem cells develop into nerve cells can lead to new methods of treatment for neurodegenerative diseases.

More help for people with heart failure

New findings on agerelated diabetes

These days we use what are known as beta-blockers to protect a failing heart against the damaging effects of stress hormones when the heart is not able to pump blood around the body. A study now shows that these medicines also reduce mortality in the event of diastolic heart failure, a common but somewhat forgotten form of heart failure where the heart is unable to relax.

As we grow older, we run an increased risk of developing type 2 diabetes, which may be caused by insulinproducing cells wearing out.

A new study has shown that it may instead be the blood vessels that provide the cells with oxygen and nourishment that are not working as they should; when these were replaced in mice with diabetes, production of insulin restarted and the blood sugar balance was restored.

THE HEART

Lengthy exercise switches muscle genes on and off THE MUSCLES

Illustration: Istockphoto. Photography: Istockphoto

A time signal governs the development of brain cells THE BRAIN

In one study, healthy volunteers cycled on one-leg bicycles and the gene expression in the muscles in the exercised leg was compared with that of the unexercised leg. The exercised muscles showed epigenetic changes, which means that certain genes had been switched on and others switched off. The results can help to explain why exercise is so important for the prevention of heart disease, diabetes and obesity.

T H E PA N C R E A S

Gut bacteria affect the brain T H E I N T E ST I N E S

The blood-brain barrier protects the brain from damaging substances in the blood. In a new study, the blood-brain barrier of mice that had been raised in a completely bacteria-free environment had a higher level of permeability. After the mice had been given normal gut bacteria by means of faeces transplantation, permeability was normal.

Sources: The brain: Dias J et al, Neuron, November 2014. The heart: Lund L et al, JAMA, November 2014. The pancreas: Almaca J et al, PNAS, November 2014. The intestines: Braniste V et al, Science Translational Medicine, November 2014. The muscles: Lindholm M et al, Epigenetics, December 2014.

Medical Science–2016

9

Advances In short

“Nobody had expected it and most people just shrugged their shoulders.”

Research news from Karolinska Institutet, downloaded from ki.se

DNA rabbit. Researchers have found a new method for folding DNA origami structures.

Thomas Lindahl on his initial discovery of the way DNA disintegrates and is repaired, made during his time at Karolinska Institutet. The research community gradually realised the significance of the discovery, and in 2015 he was awarded the Nobel Prize in Chemistry.

New method for making nanostructures of DNA that work in the body Physiological. Researchers at Karolinska Institutet have successfully constructed more advanced DNA origami structures that can also tolerate the low concentrations of salt in the body.

The required structure is designed as a polygon object in a 3D program. Software that the researchers have developed together with computer scientists at Aalto University in Helsinki is used to make automatic calculations of what the DNA sequences should look like. When the DNA sequences produced are then combined in a salt solution, they assemble themselves into the correct structure.

“The new technique is simpler to use and also means that we can produce structures that can be folded and which are serviceable in the salt concentrations found in the body,” says Björn Högberg of the Department of Medical Biochemistry and Biophysics that was responsible for the study. “It opens up whole new opportunities for the biological use of DNA nanotechnology.” Nature, July 2015 10

Medical Science–2016

Body control. Researchers at the Department of Neuroscience have managed to create a feeling of being invisible.

Some of the participants in the study were placed in front of an audience of unknown people directly after the test.

“Their heart rate and selfreported stress level during the appearance were lower immediately after they had experienced the invisible body illusion compared with when they felt that they had a physical body. This shows that our experience of the physical nature of the body can change how our brains process social impressions,” says Arvid Guterstam.

The researchers hope that the results can be put to use, perhaps as a possible treatment strategy for social phobias.

Professor Henrik Ehrsson, who led the study, says, “Future studies should also investigate whether the feeling of invisibility also influences moral decisions, as then we would see whether the experience of being invisible makes us lose our sense of right and wrong – something that Plato argued over two thousand years ago.” Scientific Reports, April 2015

Photography: Erik Benson, Staffan Larsson

Creating the illusion of being invisible

Improved survival rates for new heart treatment

Intense. Just a few minutes of high-intensity interval training has the same effect as normal endurance exercise.

Risk reduction. A study by Karolinska Institutet and Lund and Uppsala universities shows that a new anticoagulating treatment for heart attacks has led to fewer complications from bleeding and increased survival rates. The results, from 40,616 heart patients, show that the risk of serious bleeding was reduced by about half for those treated with the new anticoagulant fondaparinux compared to earlier drugs. Hospital mortality rates also fell, from 4 to 2.7 per cent. JAMA, February 2015

Medicine for slowhealing wounds in sight Hope. An international team

of researchers led by Karolinska Institutet has shown that microRNAs are involved in the wound-healing process, a discovery that may in the future lead to new medicines for slow-healing wounds.

According to Ning Xu Landén, who led the research at the Department of Medicine in, Solna, “The results show that miR-132 is important during the transition between the inflammatory phase and the proliferative phase and so functions as a critical regulator for the healing of skin wounds. Because miR-132 has a healing effect, it is of interest as a potential medicine for chronic wounds.” Journal of Clinical

Investigation, June 2015

Photography: Getty images.

Why high-intensity exercise works Effective. High-intensity

training has become popular amongst sportsmen and women and others who exercise, and also for patients with poor muscle function.

Just a few minutes of highintensity interval training

has the same effect as normal endurance exercise. But how can it be so effective?

To investigate what happens in muscle cells, the researchers asked male recreational cyclists to cycle as intensively as possible for 30 seconds, rest for four minutes and then repeat up to six times. After the highintensity exercise, small samples were taken from the muscle tissue in the thighs.

“We were able to show that three minutes of highintensity exercise breaks down calcium channels

in the muscle cells,” says Håkan Westerblad, a professor from the Department of Physiology and Pharmacology who led the study. ”This leads to a lasting change in the way calcium is handled in the cells and that leads to the formation of new mitochondria, which in turn can increase muscular endurance.”

The researchers were also able to see that the breaking down of calcium channels triggered by the high-intensity exercise was due to an increase in free radicals and

25

Percent higher overall test scores when measuring mental function. That was the result in the group of patients given comprehensive advice on healthy eating, exercise, brain training, and management of metabolic and vascular risk factors compared to the group receiving only regular health advice. Lancer March 2015

that the effect was reversed by antioxidants, common ingredients in dietary supplements.

PNAS, November 2015

New medicine for the side effects of treatment for Parkinson’s Discoveries in the lab. Despite

common side effects such as involuntary movements, levodopa remains the most effective drug for the treatment of Parkinson’s disease.

Researchers at Karolinska Institutet working with Lund University have now shown that a drug called eltoprazine currently used for psychiatric disorders can greatly reduce these side effects.

“The drug has already been tested on other patient groups, but this is the first time it has been tested in relation to Parkinson’s disease,” says Per Svenningsson, Professor of Neurology at the Department of Clinical Neuroscience and doctor at Karolinska University Hospital. What’s particularly pleasing is that we have managed to turn discoveries in the laboratory into something of clinical use.”

Brain, February 2015 Medical Science–2016

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Three researchers chasing time

k c i T

Ta c Name: Linus Bengtsson.

Title: Physician and researcher at the Department of Public Health Sciences Researches: How mobile phone data can make disaster aid more effective.

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Medicinsk Vetenskap №2–2015

In the event of acute illness or danger, there can be little or no time.

Meet three researchers who want to use the time before help arrives more effectively.

Text: Ann-Cathrine Johnsson Photography: Mattias Ahlm

ck!

“ Tracking mobile phones could save lives” “In the wake of a disaster, there are always great population movements.

This complicates efforts to quickly get essential help out to those in need.

Shortly after the disastrous earthquake in Haiti in 2010, we started a research project with the aim of monitoring the ongoing displacement taking place. I was able to set up a collaboration with the major mobile phone operator in Haiti, and we were given access to their registered calls in an anonymous format, containing information concerning the location from which each phone call had been made. This allowed us to see the movements of two million mobile phones in Haiti both before and after the earthquake.

When the cholera outbreak hit ten months later, we already had the system in place. It was satisfying to see how the millions of data entries we had on our screens could be transformed into meaningful maps, which were then used directly in the rescue efforts.

I was part of starting up the foundation Flowminder, where we implement these lessons at scale in poor countries, currently in Nepal. I am fascinated by the possibility to help people on such an enormous scale, and I find a special appeal in the real-time element, as it is so far removed from what we normally do within public health, where studies are planned years in advance and the results are presented long afterwards.”

Read more at: www.flowminder.org Medical Science–2016

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Three researchers chasing time

“A matter of life and death how the call is received”

Name: Katarina Bohm.

Title: Associate Professor at the Department of Clinical Research and Education at Södersjukhuset Researches: How acute illness is communicated and identified by the emergency service centre.

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Medical Science–2016

“The emergency service centre is the first link of the healthcare chain if we fall acutely ill, and it therefore constitute an important part of the health services. In order to get the right resources to reach the right person, and at the right time, good communication is required from the first contact. Whether things turn out well depends on both the emergency operator and the caller.

The best scenario is when the patient is able to talk. If you call on behalf of someone else, it is preferable to remain next to the person in question, so that you can describe the circumstances in the best way. As an emergency operator, you gain time by trying to calm individuals under stress or by getting petrified and scared people to act. It is important to keep an open mind and to be a good listener. It is not simply a matter of what is being said, but how. In normal communication, we use all of our senses, but in this case you have to rely only on your hearing.

In my research I have taken a closer look at certain medical situations where time is of the essence, such as stroke, sepsis and cardiac arrest. In order to speed up the assessment and increase the accuracy of the calls, we have initiated a new project to look at whether it is possible, with the help of technology, to transfer images, for example of an injury, from the callers smartphone to the emergency operator. It can also be a question of identifying key words that are often used, so that the operator can quickly ask further questions as soon as these words turn up. Within an international collaboration, we have asked questions to twenty European countries about how their emergency service centre handle calls concerning cardiac arrests. Every country has a different procedure, and we can learn from one another.

Irrespective of what effective technical solutions we have, it all falls apart if we cannot achieve good communication. Increased knowledge in this area can save lives and reduce suffering. That feels inspiring and important.”

“In cardiac arrest, simple methods can save lives” “The first few minutes after a cardiac arrest are absolutely crucial. It is therefore important to find new methods of making sure help arrives on time.

In our research, we have seen that cardiopulmonary resuscitation (CPR) while waiting for an ambulance doubles the chances of survival. We also see a clear association between the number of people trained in CPR and the proportion of resuscitation attempts, and by extension the number of survivors.

In order to get more people to do CPR training, we need to talk about these issues. It is, for example, important that we send out the simple message that the worst thing to do in the event of a cardiac arrest is to do nothing at all. One method that has increased the proportion of patients who receive CPR while awaiting the ambulance is the ‘SMS-lifesaver’ system, where mobile positioning is used to send nearby volunteer lifesavers to patients suffering a cardiac arrest.

In my opinion, schools, workplaces and public institutions should offer their employees CPR training and always have a defibrillator (heart starter) on hand.

As a cardiologist, I have felt frustrated that so many people die in this condition each year in Sweden. It has made me passionate about the fact that, with relatively simple methods, we can save more lives.”

Name: Jacob Hollenberg.

Title: Associate Professor and Director of the Centre for Resuscitation Science at Karolinska Institutet and Cardiologist at Södersjukhuset.

Researches: The benefit of a quick response to patients in life-threatening conditions, such as cardiac arrest. This research involves the entire care chain, from the home to the ambulance and on to the emergency and intensive care units at the hospital.

Medical Science–2016

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Brief facts: Hepatitis viruses A to E are not related, but they can all cause acute and chronic (B and C) liver infections, hepatitis. Chronic hepatitis can lead to cirrhosis and liver cancer. Hepatitis B and C cause almost a million deaths each year. There are vaccines for hepatitis A, B and E. Hepatitis A and E are mainly spread via food and water. Hepatitis B, C and D are transmitted through blood.

Elusive virus partly conquered The liver inflammation caused by a blood-transmitted virus was long a frustration for the research community.

Over the past 50 years, research has revealed how the virus works and come up with both vaccines and medicines.

5th century. First description.

Hippocrates des­ cribes the clinical characteristics of jaundice epide­ mics. There have been epidemics of jaundice, caused by inflammation of the liver, through­ out the ages. It has been particularly common amongst soldiers in battle.

400

Text: Karin Söderlund Leifler

1883. Route of transmission discovered. A smallpox vaccine, produced from human spleen tissue, causes 15 per cent of those vac­ cinated to get jaun­ dice. Researchers draw the conclusion that hepatitis can be transmitted through blood.

1800

1960 1966. The hepatitis B virus is discovered.

Baruch Blomberg discovers the virus that causes hepatitis B, which helps to produce the first vaccine. In 1977, Blumberg is awar­ ded the Nobel Prize in Medicine or Physiology for his research into hepatitis B. 16

Medical Science–2016

1980s. More hepatitis viruses are discovered.

Researchers discover the hepatitis D virus, which is dependent on hepatitis B virus to enable it to mul­ tiply. In 1983 the hepatitis E virus is identified. It is not until 1989 that the virus that causes hepatitis C is uncovered.

1970

1980

1981. Vaccine prevents cancer. The first hepatitis vaccine researchers used came from an unusual source – blood plasma from hepatitis B carriers. A few years later, the vaccine is produced from yeast cells. The hepatitis B vac­ cine was the world’s first cancer vaccine.

1970s. The hepatitis A virus is revealed. The hepa­ titis A virus is discovered in 1973. But the researchers continue to be frustrated by an infectious agent known for some time to be the cause of liver inflammation after a blood transfusion, and it is many years before it is identi­ fied as the hepatitis C virus.

Photography: Istockphoto, Tom Trower (NASA). Illustration: Istockphoto

Timeline Hepatitis

2000s. Improved treatment. Combination therapy is refined with long-acting interferon in combination with the antiviral ribavirin.

Around half of the patients with the most common, and the most severe, form of hepatitis C are cured.

1992. Improved diagnostics. Up until now, the most common way to get infected with hepatitis C has been through a blood transfusion.

Once a blood test is possible, the risk of being infected when undergoing blood transfusion is reduced almost to zero in countries where all blood is tested.

1990

2000

2010

Ola Weiland.

T O D AY

1990s. Treatment to boost the immune system. Interferon alpha, which is found naturally in the body and strengthens the immune system, starts to be used to treat hepatitis C and chronic hepatitis B. Antiviral medicine later becomes part of the treatment.

Future challenges

Paradigm shift in the treatment of hepatitis C 2014 cure for hepatitis C. The breakthrough by scientists on the workings of the hepatitis C virus paves the way for tailor-made, direct-acting antiviral drugs.

Combinations of the new drugs are able to cure chronic infection in over 90 per cent of cases.

Improved treatment for hepatitis D Chronic hepatitis D can be a serious infection and is difficult to treat with present-day medications. Researchers are trying to develop new, more effective drugs.

Photography: Istockphoto, pressbild

Vaccine against hepatitis C The hepatitis C virus is constantly changing and avoids the immune system. Researchers have taken on the challenge of creating a vaccine.

2015

Strengthen the body´s defense Researchers want to develop a therapeutic vaccine that can cure chronic hepatitis B carriers, so that their immune system can keep the virus in check after anti-viral treatment.

Sources: Ola Weiland; cdc.gov (Centers for Disease Control and Prevention); who.int (WHO); hep-index. eu; T Scheel and C Rice, ‘Understanding the hepatitis C virus life cycle paves the way for highly effective therapies’, Nature Medicine 2013; R Palmer Beasley, ‘Development of Hepatitis B Vaccine’, JAMA.

In 2014, people with chronic hepatitis C infection started to be treated with the new direct-acting, antiviral drugs. They reduce treatment time, cure more people and produce fewer side effects. Ola Weiland, consultant and professor at the Department of Medicine, Huddinge, talks of a paradigm shift.

“Suddenly we are able to cure serious liver damage. It is an unparalleled improvement, of a sort we don’t often see in medicine. A few years ago, it was difficult to imagine that we would be able to cure chronic hepatitis with cirrhosis in twelve weeks.”

Clinical studies are now underway to see how things go for the patients. The hepatitis treatment means that the risk for people with cirrhosis of developing liver cancer is reduced from four per cent per year to less than one per cent.

“We try to find out which patients need to be followed up so that tumours are found at an early stage.

This is so that health care services can focus their efforts on those who really need them,” says Weiland.

Currently, however, not all patients have access to the drugs; costs are high and those who are most seriously ill are treated first.

“The costs will go down when more drugs come onto the market and competition increases, which is a process that’s already started.

But while we are unable to provide treatment for everyone, transmission of the virus will continue.”

Medical Science–2016

17

In focus Spice

“A hundred times more potent than cannabis” Smoking mixes, also known as ‘spice’, are consistently at the top of the list for young people who abuse internet drugs. At Karolinska Institutet, researchers are working on identifying new varieties to keep pace with the drug poisoning cases that are now coming in at the rate of up to two per day.

Text: Frida Wennerholm Photography: Mattias Ahlm

T THE OUTSET a specific brand, ‘Spice’ has now become a collective name for herbal smoking blends that contain synthetic cannabinoids. The spice problem was first noticed at the end of 2008, after patients showing symptoms of cannabis use tested negative for cannabis.

People then started to realise that items being sold openly and marketed as legal ‘herbal blends’ on the internet were actually drugs.

The active substance in spice, which is categorised as an internet drug, is 18

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mass-produced in Asia before being sent to Europe in powder form where distributors create smoking mixes that are then sold on.

“The sellers often don’t realise how potent the substances are and how much there is in each smoking

blend,” says Anders Helander, Adjunct Professor at Karolinska Institutet’s Department of Laboratory Medicine.

“People who buy spice have to go online themselves to get information about the product and how much you can smoke without risking an overdose, but such information is unreliable.”

In autumn 2014, there was a sharp increase in cases of poisoning when some unusually strong varieties of spice came onto the market.

“These substances were between 50 and 100 times stronger than THC, the active ingredient of natural cannabis, which means that anyone having a puff would be getting the equivalent of 50-100 puffs of marijuana. The result was lots of overdoses and cases of acute kidney failure, liver problems and respiratory arrest,” says Helander.

One problem is that new varieties of drugs are coming out all the time, so it is problematic to study the consequences or any lasting damage.

“That makes it difficult to say anything about long-term risks,” says Helander.

However, statistics produced by the Swedish National Board of Health and Welfare show that the number of young people aged between 15 and 24 who have been given in-patient care for mental health disorders caused by cannabis or a combination of drugs has doubled since 2005. This diagnosis was given to over 1,800 young people in 2013.

It has previously been shown that young people who use cannabis can have permanent problems with intelligence levels.

“The brain is not fully developed until the age of 25 and cannabis inhibits the neural connections that are supposed to develop while growing up,” says Helander. “Studies from Australia show that those who have used cannabis have a lower IQ. It is very likely that this is also the case for synthetic cannabinoids. They do have the same biological

Internet drugs can be both legal and dangerous The term internet drug refers to synthetic psychoactive substances which can be sold online legally because the authorities have not yet classified them as illegal. The term also covers compounds that have previously been sold and marketed as legal but which have now been classified as drugs and are therefore illegal. Another name often used is ‘new psychoactive substances’, or NPS.

” If you misuse internet drugs, sooner or later you’ll encounter a substance or a product that’s particularly dangerous”

Anders Helander has identified hundreds of new internet drugs in his research, partly so that users who have been poisoned will receive better care.

effects and some of them are also a lot stronger.”

To date there have only been a few individual cases in which spice has been identified as the direct cause of death.

Most drug-related deaths are put down to mixed poisoning, i.e. the user had used a combination of drugs.

“If you misuse spice and other internet drugs, sooner or later you’ll encounter a substance or a product that’s particularly dangerous; it’s like playing chemical Russian roulette,” says Helander.

MOST CASES of poisoning involve men, but the proportion of women is steadily increasing from every fifth case a few years ago to almost a third today. Most users are between 15 and 30, but last year saw positive tests for an 11-year-old and a 71-year-old.

In order to get a better overview of the new internet drugs, for the last six years Anders Helander has been running STRIDA, a national collaborative project involving Karolinska Institutet, Karolinska University Laboratory and the Swedish Poisons Information Centre. Analysis of blood and urine samples from intoxicated patients is combined with clinical information so as to link symptoms with substances.

“This is a unique combination,” says Helander. We work with all the different internet drugs, and when we started we had about two poisoning cases requiring hospitalization a week in Sweden; now we have two a day. But STRIDA probably still only sees about half of all cases.”

The project uses a very sensitive analytical method – high resolution mass spectrometry. The results of the analysis are kept in a data file so that new drugs can also be identified in patient samples at a later date. The project has enabled the researchers to identify hundreds of new internet drugs in Sweden, with the result that the Poisons Information Centre is able to provide doctors and care staff with more accurate advice. In addition, the health and social care sector

gets a greater insight into which internet drugs are circulating in the country.

“We also keep an eye on internet forums and websites. If a new substance turns up we need to get access to reference material so that we are ready with our analysis if poisoning cases start arriving at emergency departments,” says Helander.

Several other countries have shown an interest in STRIDA and are in the

process of starting up similar projects of their own. The reason why spice is often first choice for internet drug purchasers is because the smoking blends are easy and cheap to get hold of; they can be quickly and discreetly sent to your home. The drugs don’t need to be injected either. Another important factor is that they are marketed as being legal.

“The authorities are always one step behind,” says Helander.

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Perspective Abortion

The Swedish Abortion Act came into force 40 years ago, giving women the right to decide for themselves whether they wanted to end a pregnancy in the first eighteen weeks. Since then, abortion procedures have become more effective, safe, accepted and accessible.

Text: Karin Söderlund Leifler Illustration: Neil Webb/The Ispot

T

HE FACT THAT a prestigious university such as Karolinska Institutet is conducting research on abortion is very important from a global perspective according to Kristina Gemzell Danielsson, Professor of Obstetrics and Gynaecology at Karolinska Institutet, Senior Consultant at the Women’s Clinic at Karolinska University Hospital as well as Head of the WHO Collaborating Centre for Research in Human Reproduction.

“It shows that this is an important

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medical issue, and that there is an academic interest in it. What we do matters to women in Sweden, but it also matters to women in low-resource countries, where the consequences of the lack of safe methods are worsening,” she says.

Unsafe abortion methods take the lives of approximately 47,000 women around the world each year, according to the World Health Organization (WHO). This makes unsafe abortions one of the major causes of death among women, globally speaking. Women’s access to and possibilities of having a safe abortion differ enormously bet-

ONE IMPORTANT EXPLANATION for the increased proportion of early abortions is the development of medical abortion. The procedure mimics what happens in the body when the foetus is expelled during a miscarriage. The medical abortion is founded to a great extent in research conducted at Karolinska Institutet. It is based on the realisation that a group of substances called prostaglandins have a number of effects on the body. It was later discovered that prostaglandins could stimulate the uterus to contract and thus be used as an abortion method. The first abortion procedure using prostaglandin is as old

Foto:Ulf Sirbom.

Safe abortion care saves women’s lives

ween different countries. While some countries have legislation that gives a woman the right to decide over her own body and have an abortion during part of the pregnancy, abortion is illegal in many places around the world.

However, abortions are still carried out, and often in an unsafe manner. Globally, approximately 21 million women go through unsafe abortions every year, primarily in countries with fewer resources. According to the WHO, unsafe abortions constitute nearly half of all the abortions carried out in the world.

“We know that it is not possible to reduce the number of abortions by making abortion laws more restrictive or by denying women the possibility of having an abortion. The only thing that happens is that women will still have abortions, but they may be carried out at a later stage and using unsafe methods. The only way to reduce complications and mortality rates in connection to abortions is to increase the access to safe methods and to promote the use of effective contraception,” says Kristina Gemzell Danielsson.

Over the 40 years that have passed since the introduction of the Swedish Abortion Act, the number of abortions in Sweden has remained stable at a relatively even level, between 18 and 21 abortions per 1,000 women of fertile age 15–44 years old). But this is not to say that nothing has changed. The proportion of early abortions, which are carried out in the first nine weeks of pregnancy, has increased from 45 per cent in the early 1980s to 80 per cent today.

” The motto in our research is ‘from bench to bed to roadside’, to give women the possibility of self-treatment.” as the first moon landing and was carried out at Karolinska Institutet in 1969.

“In the 1960s, before the introduction of medical abortions, the average duration of the pregnancy at the time of the abortion was 17 weeks,” says Kristina Gemzell Danielsson.

Her research team has gradually been working on simplifying the procedure.

Now, the substance used is the prostaglandin analogue misoprostol, which was originally developed to prevent ulcers, but which has turned out to have a wide range of applications.

“We have shown that it is possible to use misoprostol not only for abortions, but also to treat an incomplete miscarriage or abortion, to induce labour, to treat bleeding after the birth or to dilate the cervix. We have found that several of the indications counteracted by misoprostol are ones that contribute to maternal mortality,” says Kristina Gemzell Danielsson.

Misoprostol is on WHO’s list of essential medicines for basic medical care, and it can be obtained in most countries.

Medical abortion has been particularly significant in low-resource countries where surgical abortion is both inaccessible, due to a lack of physicians, and risky. The development of the method is propelled by research that looks at how it can be made easier and more accessible, and by extension save lives.

“The motto in our research is ‘from bench to bed to roadside’, to give women the possibility of self-treatment,” says Kristina Gemzell Danielsson.

Her research team recently published two articles in The Lancet, of which one concerned the treatment of an incomplete abortion or an incomplete miscarriage in the Ugandan countryside.

“We showed that misoprostol treatment is as effective as surgical treatment, but easier. We also showed that midwives in the Ugandan countryside, where there are few doctors, could implement this treatment. Since this is a very large problem around the world, this study becomes very important and has contributed to new WHO guidelines,” says Kristina Gemzell Danielsson.

RESEARCH IS ALSO CONDUCTED at home in order to simplify the medical abortion procedure. Today, the woman is recommended to come back for a check-up to ensure that the pregnancy has been terminated. The second study that was published in The Lancet showed that it is possible to switch the check-up for a special pregnancy test, which the woman can take in the comfort of her own home.

“We see that the majority fails to show up for the check-up. These are healthy women who have undergone treatment and see no reason to come back when they are feeling fine. The women greatly appreciated the possibility of evaluating the treatment by taking the test at home and thereby save themselves another trip to the doctor’s. We feel that it is important to have choices, and now you can choose to do this at home if you prefer,” says Kristina Gemzell Danielsson.

Regardless of where you live in the world, an unwanted pregnancy can trigger strong and sometimes contradictory feelings. Several studies have shown that it is the time before the actual abortion that is perceived as the most difficult by the woman seeking an abortion.

“Research has shown that this is not

Facts about Medical abortion A medical abortion is done with a combination of two drugs. The woman is first given a tablet with mifepriston, which in accordance with the Abortion Act must be taken at the hospital/clinic. This drug inhibits the effect of the hormone progesterone and increases the uterus’s sensitivity to prostaglandin analogues such as misoprostol. After one to two days, the woman is given misoprostol, which causes the uterus to contract and dilates the cervix so that the foetus is expelled. A check-up or an at-home test verifies that the abortion is complete.

Sources: Skåne University Hospital, Kristina Gemzell Danielsson.

black and white, but that the experience of a pregnancy as well as an abortion can entail a range of different emotions. The unwanted pregnancy may trigger a crisis, while the abortion, when you have a choice, can be a solution to a problem. And many also feel a sadness that their life situation is not what they would want,” says Kristina Gemzell Danielsson.

Both Swedish and international research has shown that the abortion procedure is seen as a necessity and is perceived as a relief by the majority of women who undergo it.

“In Sweden, we have an abortion law that trusts the woman to be the best judge when it comes to decisions about her body and her life, and she doesn’t have to explain herself. Women’s reasons for having an abortion can be summed up as mainly being founded in a desire for a planned parenthood. Abortion is one of the most common medical procedures.

Nearly half of all women will have an abortion at some point.”

Abortion is an emotionally charged subject, and debates regarding issues relating to abortion will flare up on a regular basis. One issue that midwives, physicians and gynaecologists have raised is the matter of a quality register for abortion procedures. Today, the National Board of Health and Welfare compiles statistics, but only on age intervals and with no possibility of connecting a procedure to the clinic where it was performed. One argument that has been voiced against the registration of personal data has been that it should not be possible to identify the women who have had an abortion.

“In the Swedish healthcare system, we have health and medical records for everything but abortion, including information that could be considered sensitive, for example referring to psychiatric care and substance abuse. It is currently not possible for us to monitor what happens after an abortion in terms of complications and side effects, or whether certain drugs lead to deformations when used during pregnancy.

If we want to find something out, it has to be done in the form of large prospective research studies, where we monitor the women over time, as we currently don’t have any way of conducting studies where we compare records,” says Kristina Gemzell Danielsson.

In countries that unlike Sweden have Medical Science–2016

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Perspective Abortion

1 Abortion is not allowed if the foetus is deemed to be viable outside of the uterus. Today, the limit applied is 21 weeks + 6 days.

2

Facts: Abortion in Sweden

Vecka 3

When? The majority of abortions are carried out early in the pregnancy.

79 per cent of the abortions are carried out up until week 8.

14 per cent are carried out in weeks 9–11, 6 per cent in week 12–17 and one per cent in week 18 or later (when authorisation is required).

How? The method used is influenced by when in the pregnancy the abortion is carried out: In week 6 or earlier, the medical method is used in as much as 97 per cent of abortions. The other 3 per cent are carried out using the surgical method.

However, at week 12 or later, the surgical method is used in most, 91 per cent, of the cases.

Source: National Board of Health and Welfare

quality registers for abortion, such as Denmark, researchers have been able to conduct register studies to look at supposed links between abortion and negative consequences for the woman.

Coherent studies have for example shown that abortion does not increase the risk of mental ill-health or breast cancer. Physicians and researchers have also been involved in the debate regarding the abortion limit for late abortions. Medical developments have made it possible to save a small proportion of children born in week 22. In accordance with the Swedish Abortion Act, the Legal Council of the National Board of Health and Welfare can grant an abortion after week 18 of a pregnancy if there are special grounds to do so, but not if the foetus is deemed to be viable outside of the uterus. Today, the limit applied in terms of viability is 21 weeks + 6 days.

“There is no absolute upper limit in the Swedish Abortion Act, and that

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38 37 36 35 34

33

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79 %

31 30 29 28 27

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25 24 23 22

5

6

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7 10 8

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14 % has been done specifically so that this can be adjusted as new developments occur. When the Abortion Act was adopted, the limit for when in the pregnancy it was possible to save prematurely born children was significantly later, so a higher practical limit was set, which has then been gradually adjusted downwards,” says Kristina Gemzell Danielsson.

STATISTICS SHOW THAT less than one per cent of all abortions in Sweden are done after week 18. Most of these are carried out due to birth defects. One factor that led to Sweden adopting the law of free abortion 40 years ago was that Swedish women would go to Poland, where abortion was allowed.

Since then, the Catholic church has increased its power in Poland.

In the same country that Swedish women would go to for an abortion in the 1960s, abortion is now more or less forbidden. And in many countries, including Sweden, repeated attempts are made to restrict the abortion laws.

“We don’t see an increased op-

”We don’t see an increased opposition to abortion in Europe, but a more strategic one. ” 22

39

12

13

18 14 15 16 17

6%

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1%

position to abortion in Europe, but a more strategic one. Those who oppose abortion are adapting their strategies to what they think is possible, so instead of propagating for a complete abortion ban, they are trying to pass restrictions little by little. Activists in the USA and Europe are coordinating their efforts in a way that we have not seen before, and they operate on the EU level to attempt to pass restrictions to abortion rights,” says Kristina Ljungros, Secretary General of the Swedish Association for Sexuality Education (RFSU).

In Spain last year, the government had to back away from a proposal that would have made the country’s abortion laws some of the most restrictive in Europe. But new proposals to limit the right to abortion were presented only a few months later.

“All restrictions of abortion rights entail a risk of guilting and shaming women, which leads to abortions that are clandestine, delayed and carried out under greater medical risks. For this reason, restricting women’s right to free abortion can have incredibly serious consequences,” says Kristina Ljungros.

Foto:RFSU. Illustration: Niel Webb/The ispot.

How many? In 2013, approximately 36,600 abortions were carried out in Sweden. That figure corresponds to 20.3 abortions per 1,000 women.

GIVING TO KAROLINSKA INSTITUTET

CONTACT US

Our vision, to contribute significantly to improving human health, is what drives research and education at Karolinska Institutet. Thanks to generous gifts from Swedish and international friends, we are continuously breaking new ground. If you share our vision and wish to join us in creating a future with better health and quality of life for everyone, then we welcome your support. Please contact us and let us know how you would like to become involved in helping us achieve tomorrow’s medical breakthroughs.

Charlotte Köhler Lindahl Director, Development Office E-mail: charlotte.kohler.lindahl@ki.se Mobile: +46 (0)737 121 387 ki.se/stodki

Donate online: ki.se/donate

For US citizens: Make your donation via our partner organisation King Baudouin Foundation United States (kbfus.org) and choose KI.

Karolinska Institutet opens research center in Hong Kong Karolinska Institutet has established a research base in Hong Kong – The Ming Wai Lau Center for Regenerative Medicine.

The center will have two nodes, one in Hong Kong and one in Stockholm. The aim is to add to a continued performance of world-leading research in regenerative medicine at Karolinska Institutet. By building a front line technology focused hub, the center can facilitate increased contacts in the area of stem cell research and regenerative medicine between KI and the Hong Kong and Chinese scientific communities. In 2016, KI will recruit assistant professors to the Hong Kong node and announce Lau Fellowships for mid-carrier researchers placed in Stockholm.

ki.se/mwlc

Ming Wai Lau Center for Regenerative Medicine

Interview Carol Tishelman

Carol Tishelman wants us to talk about Everyone faces it.

And yet, we rarely talk about death.

Professor Carol Tishelman wants her research questions to raise issues about everyday existentialism.

Text: Cecilia Odlind Photography: Martin Stenmark

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INNOVATIVE Carol Tishelman is the nurse from the Bronx who became a new thinking professor.

Medicinsk Vetenskap №1–2014

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Interview Carol Tishelman

HAT WILL BE important to you when you are dying? That is a question that more people should ask themselves, according to Carol Tishelman. She is just starting a research programme called “DöBra,*” integrating palliative care, health promotion and public health.

The programme’s goal is to increase awareness of death as a natural part of life, and to help people to give support and stay involved when family, neighbours, friends or co-workers have a lifethreatening disease or are in mourning. ”Those who want to talk about how they want things to be when they are dying should be given a chance to do so. And of course, there are people who don’t want to talk about it at all, and they shouldn’t have to. Some people feel better leaving the details about their dying to others,” she says.

But talking about death with those close to you can prevent many unnecessary problems that may otherwise arise. This might involve issues such as who you want to speak for you at the end of your life, but even about your priorities. For example, is it more important to you to be painfree than to be awake and lucid? Would you rather die in your home or in hospital? Is it important for you to know what happens to your body after you die? These, and other similar questions have been assembled on 37 cards in a Swedish version of the “GoWish” card deck, and is now being tested in collaboration with different patient and pensioner associations.

In addition to stimulating discussion about how we and our family members values around death and dying, another of DöBra’s aims is to achieve more equal palliative care, regardless of diagnosis or where in the country a person lives.

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”Today, the vast majority of patients who receive specialised palliative care at the end-of-life have some form of cancer - despite the fact that cancer is only responsible for a quarter of all deaths.

Access to palliative care is also unevenly distributed geographically. If you compare it to other forms of care, the equality of end-of-life care seems to be lagging behind,” says Carol Tishelman.

But to do something about it, we need to know more about dying. ”We know a great deal about what it’s like to die due to certain forms of cancer, as dying is easier to diagnose and predict in these cases. But by improving our knowledge about what dying is like even with other diseases, and what support is then needed, end-of-life care can be made more equal.”

Whilst palliative care needs to be standardised, it also needs to be better individualised. ”We are all different. Who we are and how we have lived also has an influence on how we want to die.”

This is where the GoWish cards come in again. It is easy to postpone conversations about these difficult subjects with those close to you. When Carol Tishelman’s husband used the cards, she was surprised to see his answers. ”He prioritized in ways that I wouldn’t have predicted. And we have been married to each other for over 40 years! It shows how important it is to talk about these things.”

Name: Carol Tishelman Title: Professor of Innovative Care at the Department of Learning, Informatics, Management and Ethics, and University nurse with special responsibility for strategic health care innovation at Karolinska University Hospital.

Age: 61.

Grew up in: The Bronx, New York, USA. Family: Husband, a daughter and her family (three grandchildren), a son, two stepchildren and their families. And quite a large family in the USA. Motto: Try to improve the world at the same time as I allow myself to be curious about it.

Relaxes by: Reading novels and picking mushrooms in the forest around my husband’s family farm outside of Trosa.

Before he introduced me to the Swedish countryside, I didn’t know I was a nature person, I thought of forests as patches of grass in between highways.

CAROL TISHELMAN HAS had a long career in research. Her overall goal has been to reach an increased understanding of how people experience sickness, particularly cancer, all the way from before diagnosis, for example through screening studies, through diagnosis and up to the end of life. The sick, or potentially sick, individuals are central, but so are their families and healthcare providers. In her work with the experiences of patient groups and the people around them, Carol Tishelman has increasingly realised how we are all part of systems. ”If you want to influence and change things for on the individual level, you also have to understand the overall organisation. This has meant that I’ve spent a great deal of time trying to bridge gaps between research, education and care, get them closer to each other.”

Carol Tishelman’s interest in the overall healthcare system can be useful in her new position - as professor in innovative care. The mandate of this professorship includes finding new and creative ways of working within the health care services. And even if Carol Tishelman does not yet have the answers for how to solve the healthcare challenges of the future, she is interested in the bigger picture, the overall organisation of the health services.

Among other things, this has resulted in a major, ongoing project, where 11,000 registered nurses in Sweden have answered questions regarding their profession. ”With the help of their responses, we hope to understand how we can get more nurses to stay in the profession and more about factors that impact their perception of the working environment. This is important, as we know the link between experiences of the working environment and patient safety is very strong in this professional group. If they feel ok, the care they provide will be good. Besides, it is uneconomical to educate nurses who then leave the profession, so this is something we should avoid as far as possible,” says Carol Tishelman.

The professorship in innovative care is special in that it is funded by an external donation – Investor AB has donated SEK 10 million to the new professorship over a period of five years.

It is unusual for professorships within health care sciences to be funded in this manner. The combination of innovation and health and social care research that

this position involves is also unusual, and this has opened a number of doors that have previously been closed. Carol Tishelman was recently invited to speak with the steering group at Karolinska University Hospital, and she has been asked to speak at a seminar on the future of health care, organized in March 2015 by the business-oriented daily newspaper, Dagens Industri. The Swedish Minister for Health Care will give the opening speech, and Carol Tishelman was asked to conclude proceedings with her thoughts. ”It´s pretty awesome!”

But the task of speaking on behalf of a larger group is also a great responsibility. ”Among other things, I will talk about the outdated hierarchical structure within our health care services.

Why haven’t the roles of doctors, nurses and assistant nurses changed more over time? It seems to be that the closer to the patient you are in the health care chain, the less intelligent you are assumed to be. As a nurse, I have seen proof of the opposite many, many times. I believe it’s time to change these structures, for many different reasons. Even family members and patients should have a different status; they should be seen as stakeholders who can be involved with and even drive changes within the health care system, she says.

The word “innovation” has been used a few too many times, in contexts that are slightly too vague for it to have a clear meaning. What does the word mean to you?

”New thinking. And I believe the way to get there is via more interdisciplinary collaborations and collaborations with new stakeholders,” says Carol Tishelman.

And Carol Tishelman practices what she preaches. Her research group has collaborated with architects and designers, ethnologists, statisticians, life sci-

Carol Tishelman on …

Carol Tishelmans best quality as a researcher is, according to herself, that she is ”curious and persistent like a leech.”

entists, pensioner associations, doctors, midwives, artists – the list goes on and on. Those who know Carol Tishelman and her work see her as a shining example, where energetic outreach is combined with a desire to make an impact, not least in sectors where health care science has not been previously represented. She herself thinks that her unwillingness to automatically follow rules and directions has often led her down new, seemingly inaccessible paths. Growing up in the Bronx makes you thick-skinned. ”It’s like we say: You can take a girl out of the Bronx, but you can’t take the Bronx out of the girl...”

… how she became a successful researcher: When growing up, I had many arguments with my father, for example he thought it was an obvious choice for me to become a doctor and not a nurse. Sometimes, I think that my experience arguing with older men has helped me in the male-dominated world of research.

… the difference between Fred Astaire and Ginger Rogers: Ginger Rogers could do everything that Fred Astaire could do, except backwards and on high heels. And then she was still only considered to be almost as good as him. That’s what it feels like sometimes, being a woman nursing researcher.

Now, for the first time in her life, at the age of 61, Carol Tishelman has a fixed income for the next five years, as well as funding for all of her projects. ”I never intended to be a researcher, I wanted to become a nurse and work closely with people. And I still get to do that, thanks to all the contact with patients and their family members in the type of research I do. The subject of my work is never a parenthesis in people’s lives. That’s a great privilege, says Carol Tishelman.” * In Swedish, DöBra is a play on words, literally meaning ’Dying Well’, but also an idiom roughly equivalent to ’awesome’ in English

... dying as a social function: We are all going to die.

And that means that dying, death, and the feelings they bring about, is something that can unite us across national and class boundaries. Conversations about death can bring us closer together in an increasingly heterogeneous society.

… her way of reasoning: My colleagues have pointed out that I often say: “I’m not sure I agree with myself when I say this, but...” I need to bounce ideas off the people around me in order to figure out my own perspective.

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27

In depth The self-healing body ALREADY IN PLACE. Stem cells can be found in most of the body’s tissues, such as the skin, bone marrow, blood, muscles, teeth, liver, heart and brain.

The pi o ALWAYS READY. Stem cells keep a low profile until they have a job to do, to replace cells that have died or been damaged somewhere in the body.

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OPEN TO DEVELOPMENT. Stem cells have different levels of development potential and may in certain cases need to be reprogrammed in a laboratory.

SEES NEW OPPORTUNITIES. Stem cells are flexible and are keen to help out in place of other cells. When a cell has to be replaced, they develop into that specific type of cell.

Illustration: Anders Kjellberg.

i oneers The best healing is performed by our stem cells.

Now the researchers recruit the body’s own health workers to build up new healthy organs.

Text: Fredrik Hedlund

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In depth The self-healing body

HE HUMAN BODY has an amazing ability to repair itself. Everyone knows that a skin cut quickly heals itself.

The body can even handle quite large wounds with just a little help to hold together the edges of the wound, using a plaster or stitches. A person who breaks their leg can rest assured that they will walk again. However, it is beneficial if the fracture is secured with plaster, for example, so that it heals straight. But the healing itself is automatic.

But this is not always the case. Not all organs and tissues can recreate themselves, or regenerate as it is called. But with some additional help it is possible. This is the foundation of the rapidly growing area of research that doctors refer to as regenerative medicine. That is, helping the body to help itself. And the help comes in the form of stem cells, immature cells, that exist naturally in the skin, in bone marrow or other parts of the body. Stem cell research is still very much under development and no one really knows what paths it will take in the future, but there are currently some main lines of inquiry and a number of smaller side trails.

THE EARLIEST AND so far most wellknown example of stem cell treatment is bone marrow transplantation that was performed for the first time in the world in 1968 and in Sweden in 1976. Bloodforming stem cells were then transplanted to the bone marrow of a patient.

Other stem cells from the bone marrow have also been used in the same way; ”mesenchymal stem cells”, which can develop into bone, cartilage or con30

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BUT CREATING TREATMENTS out of

left-over fertilised eggs has, primarily in the USA, been questioned based on ethical principles. Furthermore, the access to different genetic sets is limited. That is why the possibility of getting closer clinical application increased with the next big step.

In 2006, Japanese researchers were able to demonstrate an entirely new way of creating stem cells. They simply took regular cells and gave them an extra set of four genes that caused them to reverse their development and return to stem cells again. They will then be reminiscent of embryonic stem cells but have a completely different origin.

The researchers called them induced

” A larger patient with acute liver failure needs about 15 billion cells and it is in no way possible to manufacture that quantity.”

pluripotent stem cells, or IPS cells. The first attempts were made with mouse cells, but as early as 2007 they were able to revert human cells and now it is done with normal skin cells as original material. In the beginning, however, the cells that were developed from IPS cells were problematic in that there were cells that had not matured properly and that could cause cancer growth when transplanted. Today this can be managed. But it also seems that the cells change during cultivation. The first clinical study on IPS cells recently had to be aborted due to potentially dangerous cell changes.

The basic principle of helping the body repair itself is to control the stem cells so that they develop into the type of cells necessary to treat a certain disease.

There are currently a large number of research projects to develop cells that can help patients with different types of diseases to repair themselves. Sweden is at the forefront in a global perspective.

This big question for most researchers within this field is where to source the stem cells. For most cases, one of the three versions mesenchymal (a type of mature stem cells), embryonic or induced pluripotent stem cells are available.

BUT NOT FOR EVERYONE . Professor Stephen Strom, at the Department of Laboratory Medicine, Karolinska Institutet, will within the next few months initiate clinical trials where he will treat small children with congenital liver diseases with cells from the inside of the membrane of the foetus. The story behind his discovery is almost as good as the discovery itself. But he prefers to tone this down.

“I was just lucky. There is a saying that it is better to be lucky than to be smart”, he says.

Stephen Strom started his scientific career at the Kansas City University, USA, with an interest in liver cells and how they handle carcinogenic chemicals. In order to study the cells’ behaviour he developed a method for isolating liver cells from donated pieces of liver that could not be transplanted.

Together with an American transplant surgeon he eventually developed the world’s first method of transplanting these cells to patients.

“In collaboration with several different

Photography: Private.

T

nective tissues, etc. Bone marrow stem cells are examples of mature stem cells (see figure) that are very useable but that also have certain limitations. For example, it is not possible to cultivate large amounts of mature stem cells. It is also difficult to separate mature stem cells from other cells; something that is not always appropriate. Mature stem cells are multipotent, which means that they can build many types of cells but not all.

That is why it was a great advance when American researchers in 1998 could show how they had succeeded in creating embryonic stem cells. They can divide an infinite number of times and are pluripotent, which means that they can develop into any cell type found in an adult body. Most embryonic stem cells come from fertilised eggs left over from IVF. The cells are often so foreign to the patients that their immune system reacts and a rejection occurs, though this can be managed with immunosuppressive drugs. Another idea is to build up a large bank of different types of embryonic stem cells so that a sufficient amount of tissue-like cells can be chosen for each patient. This is currently happening in several parts of the world, including Karolinska Institutet.

surgeons, I have performed transplantations on about 25-30 patients, but the big problem is the lack of decent liver cells for transplantation. The surgeons have become better and better at successfully transplanting the left-over pieces that I was previously given. It’s great for the patients, as it is a curing treatment, but their success has had negative consequences on my research”, he says.

He says that when transplanting liver cells in order to treat liver diseases, many cells are required.

“Even a little new-born baby needs several billion cells for a transplantation. A larger patient with acute liver failure needs about 15 billion cells and it is in no way possible to manufacture that quantity, neither with embryonic stem cells nor induced pluripotent stem cells”, he says.

INSTEAD HE WAS LUCKY. In his role as editor of a scientific journal, he was reviewing a manuscript for a scientific paper written by another researcher. The trial involved gene therapy by means of cells from the inside of the membrane of the foetus being transplanted to laboratory animals.

” I discovered that the transplanted cells looked like liver cells.

And I thought, ’oh my god, these membrane cells could become liver cells’. ” “What I discovered on the photographs they sent was that the transplanted cells looked like liver cells. And I thought, oh my god, these membrane cells could become liver cells if we just place them in the liver. I don’t think the other researcher understood this.

He was not working on liver cells”, says Stephen Strom.

He immediately started to transplant human epithelial cells from the amnion membrane – which is a part of the placenta – to mice, and it worked straight away without any processing of the cells.

“We collect the placenta after the live birth of a baby. We isolate cells from the amnion membrane and we transplant them, that’s what we do. We don’t need to treat them, we don’t need to deal with Petri dishes, we don’t need to differen-

tiate them to liver-like cells. We administer a cell infusion straight into the blood system that goes to the liver. The cells will stay there and grow attached to the liver at the same time as they develop into liver-like cells. We let the liver do the work for us”, he says.

The big question is, how is it possible that this just works?

“I don’t know why it works. I can only guess. During foetal development, the placenta functions as the child’s kidneys, liver and lungs, among other things. The placenta tissue is unique in that it has to perform a great number of tasks. We know that it expresses liver genes and since these genes are already active in the cells that we isolate, it may just be just a question of increasing the expression in them. It’s like turning up the volume on something that already exists”, says Stephen Strom.

He has not had any immunological problems either, even though he has transplanted human cells to mice; something that is due to the special contents of the placenta.

“The placenta is the organ that allows the child to be born without the mother’s immune system rejecting it.

Illustration: Anders Kjellberg, Istockphoto.

Facts: 3 x stem cells Stem cells are the source of all cells in the body.

Here are the three types researchers use.

3

2 1

Embryonic stem cells Source: The immature embryo.

Advantage: Great potential, can form almost all types of cells in the body (pluripotency).

Disadvantage: Hard to access, must be extracted from an embryo the first week after the ovum is fertilised.

IPS stem cells Source: Common skin cells that are reprogrammed to become stem cells in a laboratory.

Advantage: Unlimited access. Researchers can tailor-make stem cells for research. Pluripotent.

Disadvantage: Still a risk factor of using them in treatments, may have undesirable qualities.

Mature stem cells Source: Body tissue from both children and adults.

Advantage: Relatively easy to access.

Disadvantage: Can only be developed into certain cells in certain tissue (multipotency).

Example: Mesenchymal stem cells that can develop bones, cartilage and fat.

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In depth The self-healing body

The placenta contains human leukocyte antigen G (HLA-G), which tells the mother’s immune system not to attach the tissue. Without this factor we would still be laying eggs”, he says.

That is why he is fairly sure that it will be possible to transplant the membrane cells without having to subdue the patient’s immune system.

“Contrary to liver cells, where we have to put the patient on immunosuppressive drugs when we’re transplanting the cells, we can probably transplant these cells without having to do that. That would be an absolutely crucial step forward for cell transplantation”, he says.

He agrees that this sounds almost too good to be true, but at the same time he has produced results that indicate that 32

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what he says is correct. What is really fascinating is that previously, these stem cells would just be thrown out.

“There is a saying that you shouldn’t throw the baby out with the bath water, but that is exactly what we were doing.

We used to throw out the placenta, so we were throwing away a rich source of stem cells”, he says.

” There is a saying that you shouldn’t throw the baby out with the bath water, but that is exactly what we were doing.”

ANOTHER TRIAL TREATMENT is “Boost Brittle Bones Before Birth”, BOOSTB4, which will start in January 2016 at Karolinska Institutet. The project involves children suffering from congenital osteoporosis, osteogenesis imperfecta, who are to be treated with stem cells. The children have a genetic defect in their production of collagen. ”Collagen works as reinforcement rods in the bones. The mutation results in the

Illustration: Anders Kjellberg.

Retinal pigment epithelium cells are one of the easiest cell types to create from stem cells, read more on page 36.

WHETHER HIS RESEARCH findings are too good to be true or not will soon be revealed. Stephen Strom has been given ethical approval to treat the first ten patients and is now just waiting for a last formal approval that the method of sourcing cells is adhering to all applicable rules.

“Hopefully we’ll have a complete approval by the end of the year and we could start then or at the beginning of next year with clinical transplantation of these cells”, he says.

The patients that he is considering for treatment are children born with a defect in one single gene that causes a critical liver dysfunction, something that results in these children often having to go through a liver transplant very early in life. It could be about them being unable to metabolise the nitrogen in the proteins in their food or that they cannot handle bilirubin, which is a breakdown product of the red blood cells; something that could result in jaundice and brain damage.

“We add a cell that can express the gene that is missing in these patients.

If you can just get enough of these cells into the liver you can treat the disease without having to perform a whole organ transplantation”, says Stephen Strom.

Then of course it remains to be seen how long the treatment will last. It is evident that it will not last forever. In the mouse model, the cells hold up until the middle of the mice’s lives, but whether this means that the cells in humans will last until the middle of the patient’s life or just within a similar time span is something no one knows.

“We don’t know if we have to transplant new cells every year, every other year, every fifth year or less frequently.

But even if we have to add new cells fairly often, this is trivial compared to an organ transplantation. This is like coming in for a vaccination or an infusion”, says Stephen Strom.

MOLLY STEVENS

Photography: Linda Forsell.

Professor at Imperial College London and at the Department of Biochemistry and Biophysics.

Motivation: “Seeing my research ideas reach clinical application and understanding how the body works.”

“We are designing biomaterials to help regenerate the heart” How can your research help the body to regenerate tissue?

“We are designing new bio-inspired materials to regenerate bones and cartilage and support heart cells and even certain applications in neurotechnology. We use different polymers that we conjugate or functionalize with bioactive substances such as peptides or parts of proteins that controls their interactions with the tissue and help create newly engineered tissue.”

Can you give any examples?

“There are several exciting examples created in my labs. We have developed a gel that can be injected in cartilage that solidifies post-injection. We have also designed electrically conductive materials on which we can cultivate heart cells, which has great potential as a materials-based approach that could control cardiac arrhythmia. We also have a type of patch that interacts very well with heart cells, so we are envisioning its attachment to the outside of the heart to help prevent scar tissue after a heart attack. We can also implant porous scaffolds in bone that allow blood vessel in-growth and directs bone regeneration.”

You have also developed a method of regenerating bones inside the body, please tell us how.

“The surface of all large bones in the body comprises a thin layer of stem cells. We, along with our collaborators, have developed a technique where we access that layer and inject a liquid that makes the stem cells start producing large volumes of new bone tissue. We can then remove the newly formed bone material and use it to repair damaged bone somewhere else in the patient while the part of the bone we used for cultivation returns to a healthy state.

We can now also cultivate cartilage in a similar way.”

As told to: Fredrik Hedlund.

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Please tell us about your current research.

“We have created more than 60 human embryonic stem cell lines at Karolinska Institutet. They are very capable cells that can be used to create many different cell types. These can in turn be used for many types of therapies in the future.”

How long until clinical treatment with embryonic stem cells is possible?

“Fairly soon. There is a group in Lund that is already treating OUTI patients with Parkinson’s HOVATTA disease with the aid of Senior professor at brain cells from aborted the Department of Clinical Sciences, Intervention and foetuses, but embryonic Technology. stem cells are a much bet-

Motivation: Establishing cell lines that can be used to treat diseases that are currently incurable.

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ter source and we are fairly close to getting them. At the moment we are developing, in collaboration with Anders Kvanta from St. Erik Eye Hospital, retinal pigment epithelium cells that can be transplanted to the eye in order to cure age-related macular degeneration, the most common form of blindness in developed countries. We have also received an EU grant to develop a treatment of the disease ALS but that is a bit further down the road.”

What is left to do before you have cells ready for clinical treatment?

“We already have the cells but they are not processed in accordance with good manufacturing practice, which is a very demanding procedure required by the authorities. This is a good thing, of course, as the quality and purity of the cells must be perfect before we start treating patients.

But it’s expensive, so at the moment we’re looking for new funding.”

As told to: Fredrik Hedlund.

Photography: Christopher Hunt.

“We’re close to a treatment now”

The self-healing body In depth collagen not working as it should. It interrupts the bone formation and leads to the cardinal symptom fractured bones,” says Cecilia Götherström, researcher at the Department of Clinical Science, Intervention and Technology at Karolinska Institutet and leader of the study.

The disease has different degrees of severity, where the most severely ill die before or just after birth, while those who survive can have anything from a mild form that is barely noticeable to suffering more than 30 fractures a year. The disease is extremely rare and only one or two children are born with this condition in Sweden each year. It is discovered in the ultrasound examination taken by all pregnant women; the foetuses with this disease are smaller than normal and have short, bent bones as well as fractures.

In the study in question, the researchers will treat 30 children with stem cells from the livers of aborted foetuses that will then develop into bone cells that produce collagen.

“We have seen that the cells from foetuses develop bones better than stem cells from adults and there is data that shows that when transplanting cells prior to birth, it is better to use foetal stem cells instead of cells from adults.

We don’t know why, but it could be that they hit the right spot in another way”, says Cecilia Götherström.

The study will evaluate how safe the stem cell treatment is and how well it works, and also how early treatment should be initiated for the best results.

Half of the children shall receive stem cell transplantation while in the womb and the other half will receive the first transplantation after delivery.

Photography: Jacob Sjöman, Getty images.

NEW TRANSPLANTATIONS WILL

then be done every six months in order to increase the effect. A setup that is based on experience.

“We think that the sooner you treat, the better the result, and likewise with performing the treatment several times.

We have previously transplanted stem cells to a child prior to birth and she is 13 years old now. We have evaluated her progress all these years, and she has also received top-ups as we have seen that the effect seems to wane”, says Cecilia Götherström.

The method for transplanting stem cells to a foetus inside the mother’s

womb was developed by Magnus Westgren, professor at the Department of Clinical Science, Intervention and Technology at Karolinska Institutet. It may seem like an incredibly advanced treatment, but it is not, according to Cecilia Götherström.

“It’s an established technique that we use. It’s the same method as used when giving blood transfusions to the foetus during pregnancy. Foetal therapy centres that can administer blood transfusions can also do this”, she says.

As the disease is so uncommon, the study is a European collaboration project that includes research centres in Britain, the Netherlands and Germany, as well as Lund University. The number of Swedish children in the study will also be quite small.

“We have counted on a maximum of three. We would also like to recruit

By matching stem cells that are to be transplanted to the patient, rejection can be avoided.

children from Norway, Denmark, Finland and Latvia for example”, says Cecilia Götherström.

The study will run for five years and when it is completed the researchers will be able to say something about which theory is the best. The children will be monitored until ten years of age for security reasons. But this is not about any kind of miracle treatment.

“It’s important to remember that this is not a curing treatment, instead the aim is to change a severe variant of the disease to a milder one. For a patient that otherwise would have suffered ten fractures a year, we may be able to help cut that figure in half. But even that would mean a large improvement in quality of life. These patients will normally only become one metre tall. After that, they stop growing. The first patient is still growing and is almost 1.2 metres tall now”, she says.

USING STEM CELLS from aborted foetuses and injecting them into other ill foetuses is naturally a sensitive issue and not something Cecilia Götherström sees as a permanent solution, but this study

The world is building stem cell banks Transplanting cells from a randomly chosen donor to a patient with an intact immune system almost always entails the cells being rejected unless the patient receives life-long treatment. The ideal situation would be access to cells with the exact same genome as the patient, but at present, this is practically impossible.

If cells can be matched to the patient in terms of crucial immunological markers, the risk of rejection is minimised. Important parameters would then be the blood type and the human leukocyte antigens, HLA. Cells with blood type AB0 work for all patients, and calculations made for different populations show that between 50 and 150 cell lines with different HLA sets would be sufficient to match cells for between 50 and 90 per cent of the population.

This is the reason why researchers from countries around the world, including Sweden, are building up stem cell banks in order to facilitate the quick production of suitable cells for individual patients.

Source: Barry J et al. Curr Stem Cell Rep 2015;1:110–7.

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In depth The self-healing body focuses mostly on demonstrating that it works and that it is safe.

“I’m sure it’s possible to find more optimised methods of doing this. If it turns out that the treatment works, we’ll have to think about how to solve the issue of access to stem cells. This is just the first study so there’s lots more that we can do in the future”, she says.

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cells from embryonic stem cells and at the end of last year, Japanese researchers injected a patient with cells from induced pluripotent stem cells.

However, Anders Kvanta and Outi Hovatta claim to have significantly better cells with a higher degree of purity; something they can back up with the good results achieved with their rabbit model.

“We’ve managed to make the pigment epithelial cells lie perfectly in single cell layers, and once there they protect dying visual cells. We’ve got the cell layers to last for eight months, which is sensational as they are human cells transplanted to a rabbit”, says Anders Kvanta.

His plan is now to be able to conduct human trials with these cells in about a year and a half to two years. But this is just the first step in the process of actually being able to improve the patients’ vision. For this it is also necessary to transplant photoreceptor cells; a feat which no-one has yet achieved.

“What we hope for with the transplantation of pigment epithelium cells is that we’ll see a type of halting effect where vision is stabilised and does not deteriorate. We are working on photoreceptor cells as well but we haven’t got as far in that area”, he says.

He says that the eye is a great organ to work with when it comes to replacing dead cells. There are methods for depicting what happens inside the eye, which also allegedly is less sensitive to cells foreign to the body, even though this is something that still needs to be completely proven. Anders Kvanta will use embryonic stem cells as a starting point for the pigment epithelium cells

that he intends to transplant. Another possibility is using induced pluripotent stem cells as a starting point for these cells. However, these have so far shown changes that risk causing tumours after transplantation. With a better technique of developing the cells, this risk has been decreased, but in principal he sees a safety advantage with the eye.

“The likely situation, if a tumour forms, is that is forms directly in the eye.

And then it would be easier for us to see it. We have fairly few cells in the eye and we have very good control over the area we’re injecting the cells into”, he says.

The final goal is to restore vision in older people who have suffered from macular degeneration. That this is achievable is something he has no doubts about.

“Absolutely. Considering how fast the development has been so far. In ten years we’ve gone from just having a vague notion of how this could be used to actually testing it on patients. In another ten years we’ll have got much further and in 20 years we may have a vison-improving treatment. Fairly soon it will be possible to combine the treatment with photoreceptors”, says Anders Kvanta.

THE OTHER RESEARCHERS also see the future potential in the treatments they work with. But Stephen Strom still wants to add a caveat.

“I’m very positive about the possibilities my research brings but I’m also a realist. I mean, we’ve already cured all diseases in mice – diabetes, cancer, cardiovascular diseases. But there’s a fairly big step from our subjects with tails to all of us without tails”, he says.

Photography: Johanna Hanno, Istock Photos.

IF STEPHEN STROM and Cecilia Götherström are going to treat small children and even unborn foetuses, Anders Kvanta, Senior Consultant at St. Erik Eye Hospital and Adjunct Professor at Karolinska Institutet, has an entirely different patient group in mind – elderly.

The most common cause of loss of central visual acuity and reading vision in older people in the Western world is the age-related widespread disease macular degeneration. The eye disease is a result of the supporting cells behind the retina, the ”retinal pigment epithelium” cells, slowly die, which means that the retinal cells that support vision – the rods and cones – also die. The disease has two forms; a wet and a dry form. The wet form can nowadays be halted with drugs but 90 per cent of the patients have the dry version, which so far has no effective treatment.

“That’s why the idea of trying to replace the dead cells by transplanting new healthy cells has come up”, says Anders Kvanta.

The idea is in the first stage to transplant new pigment epithelial cells that are to build up the support tissue and then try to repair dying visual cells. Anders Kvanta collaborates with Outi Hovatta, Professor in Obstetrics and Gynaecology, and Fredrik Lanner, researcher at Karolinska Institutet who produces cells from embryonic stem cells.

“The natural thing is to start with these pigment epithelial cells as they are central to the emergence of the disease. Furthermore, stem cells are very susceptible to becoming this particular type of cell. Of all the cell types in the body, the retinal pigment epithelial cell is one of the easiest to create from stem cells”, says Anders Kvanta.

This is one of several reasons why the method is at an advanced stage. As early as 2012, American researchers tried injecting patients’ pigment epithelium

Macular degeneration may result in blurred or no vision in the center of the visual field and is a leading cause of vision loss among older people.

“We have a model of the brain”

ANNA FALK

Photography: Christopher Hunt.

Researcher at Karolinska Institutet.

Motivation: “Curiosity, understanding the role of stem cells in a healthy and a diseased brain.”

You can revert common skin cells to “induced pluripotent stem cells”. How? “We start by cultivating cells from a bit of skin. We then supply the skin cells with four special reprogramming genes that initiate the reverse development from an adult cells to a stem cells.”

What can the cells be used for?

“I use reverted skin cells from persons with diseases such as autism and schizophrenia in order to make and cultivate brain cells. We can then study how these patients’ brain cells differ from brain cells from a healthy person. Thus we make models in petri dishes from patients with a brain disease, which we call “patients in a dish”. For example, we’ve made a 3D model of an Alzheimer’s brain. We then used a gel where we plated the nerve cells in a three-dimensional pattern where the behaviour of the nerve cells was similar to how they behave in the real brain. It’s also possible to cultivate little spheres in a liquid medium. With the right nutrition, they develop into small brain-like balls called organoids. They can then be used to study the development of both the healthy and the diseased brain.”

Are there other areas of use?

“It is also possible to cultivate brain cells for transplantation to patients with a neurological illness or brain damage.

Those studies are now being conducted on laboratory animals.”

As told to: Fredrik Hedlund

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37

Curious about Empathy

People flee across oceans and nations in the hope of a better life. But can we take in their suffering? Researchers explain why it may not be self-evident to us to empathise with others.

Text: Ola Danielsson

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Photography: Getty Images.

The dream of boundless empathy

DO YOU SEE THE PEOPLE? The ability to feel empathy for the suffering of others may weaken when we think in terms of groups.

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Curious about Empathy

EING ABLE TO EMPATHISE with others is a fundamental human ability.

When we share the suffering of others we also have a wish for the suffering to end. It is therefore not strange that catastrophes such as the ongoing migrant crisis give rise to great action and a willingness to help.

However, some researchers have likened empathy with a “delicate flower” that is easily destroyed by other psychological forces. In the worst case scenario, people in distress are not met by a helping hand but by direct hostility, such as when refugee accommodation is set on fire. For the most part, xenophobic rhetoric does not primarily reach out to empathy but to another human instinct: protecting one’s own group.

Andreas Olsson, researcher at the Department of Clinical Neuroscience, conducts research into how people learn from each other in social situations – an area of research in which both empathic ability and group psychology have proven to be key features.

Both exist within all of us and the combination has been important for the creation of a safe social environment.

“Identifying with a group comes very naturally to us. In evolutionary terms it has been crucial to be part of a group in order to collaborate and defend oneself against external threats.

But this tendency is also currently a big problem in society”, he says.

Research shows that we in many ways discriminate in favour of members belonging to what researchers call “the in-group”, the group that an indi-

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IN A CLASSIC EXPERIMENT the empathy researcher Tania Singer, professor at the Max Planck Society, let football supporters witness other fans being subjected to painful electric shocks. They felt the strongest feelings of empathy when the pain was inflicted on someone supporting the same team as them. When the electric shocks were aimed at fans of rivalling teams, the levels of empathy decreased. At the same time, the researchers noted decreased activity in the anterior insula, a part of the brain connected to empathy. It was even the case that the brain reward system became very active – they enjoyed seeing others in pain!

Empathy transforming into pure schadenfreude can also be seen in game-based experiments where cheaters are given electric shocks as punishment. It sounds terrible. But it seems it is predominantly one half of the human population who have cause to feel ashamed on this account; schadenfreude is a phenomenon more commonly observed in men.

Andreas Olsson says that group divisions are hard to shift once they have been established. It makes it harder than you might think, to succeed with measures to reach increased understanding between groups. As an example he mentions integration projects where children got to visit marginalised environments.

“It is not enough to let groups meet; a few days later they have as little understanding of each other as they did before meeting. It is necessary to actively try to see things from other people’s perspective. Another factor which has proven to be significant is working towards common goals, such as playing in the same football team”,

says Andreas Olsson.

Not to mention the situation in war, where empathy for other groups seems to have been lost entirely.

“In war, the enemy becomes an extreme out-group who are completely dehumanised. Another explanation is that people who experience a great deal of suffering become desensitised and lose the ability to take in other people’s feelings”, he says.

Andreas Olsson is actually not that keen on the word empathy as it involves several abilities that are not really represented in the term. A primitive part is copying the feelings of others, like when a baby hears another baby crying and becomes upset as well – which happens even though they have not yet developed a concept of anyone other than themselves. Emotions are among the most contagious things in existence, but it is simply not enough that two people have the same emotions at the same time. We only become empathetic when we have an understanding for the other person’s perspective and when the feeling is separated from the self so that we share someone else’s feelings.

EMPATHY CAN ALSO be separated from its more sophisticated cousin compassion, which can be described as feeling for someone without sharing that person’s feelings. Studies using brain imaging reveal that compassionate persons do not find themselves in a similar condition to the person suffering; instead, other areas of the brain are activated – areas connected to positive emotions. It is then about something entirely different than schadenfreude, sympathetic persons usually describe their feelings for the other person as warmth and concern.

Like other qualities, the empathetic ability varies in the population. Certain research suggest that women are generally more empathetic than men.

The difference is greatest early in life, in children, and it decreases once we grow older. But variations within the groups are wide; many men are more sensitive than the average woman.

“At one extreme, there are people with high empathetic sensitivity who are very negatively affected by the suffering of others. At the other there are, for example, people with psychopathic

Photography: Privat.

B

vidual perceives as their own. The outsiders, in “the out-group”, are people we often feel less empathy for, and we more easily associate them with unpleasant experiences. The psychological positioning happens rapidly and subconsciously and is frequently affected by factors such as ethnicity or social class. But even arbitrary group divisions, such as when we are randomly placed in different groups at school or at work, can affect our empathy.

character traits who find it hard to be affected by other people’s feelings”, says Andreas Olsson.

But empathy is not just about caring about others. Other people’s experiences are also a useful compass for the individual.

“There is a lot of research into what happens when we learn from our own experiences. Yet, we also very much learn from other people, and it is then important how we perceive the other person’s perspective. But how that happens and what role empathy plays is something we do not know much about, which is quite strange really”, says Andreas Olsson.

With his research he is trying to answer a fundamental question – how do we learn what to be afraid of? He is especially interested in what we do when we learn from the experiences of others, i.e. something that can involve more or less empathy.

“In evolutionary terms it has been crucial to be part of a group in order to collaborate and defend oneself against external threats.”

In his experiments, he often has a research subject watch a series of images such as faces or abstract figures.

In connection with certain images, an unpleasant electric shock is given, so that the person learns after a while which stimuli are “dangerous” and reacts to these with fear. Sometimes the events are witnessed by a second research subject, who then learned the same thing, indirectly, through the reactions of the other person.

“A reoccurring pattern is that the perceived group affiliation of the participants affect the results. For example, the observer does not learn as easily if the person receiving the electric shocks has another skin colour”, says Andreas Olsson.

Animals also have a moral compass Photography: Ulf Sirborn, Istockphoto.

Many mammals show signs of empathy. Here are three examples that have caught the researchers’ interest: Rats will rescue their distressed pals from drowning — even when they’re offered chocolate instead. Rats demonstrate helping behavior toward a soaked conspecific, Animal Cognition, May 2015 Chimpanzees often try to comfort other chimpanzees that have been subjected to an attack. Consolation as possible expression of sympathetic concern among chimpanzees PNAS July 2010 Dogs who see a crying human do not wag their tail as usual but instead get closer to them by sniffing, licking and pressing their nose against the person who feels sad. Empathetic-like responding by domestic dogs (canis familiaris) to distress in humans, Animal Cognition, May 2012

IN A NEW STUDY, Andreas Olsson divided observers from an electric shock experiment into different groups. Some of them were instructed to try to understand the other person’s experience of the painful electric shocks. Other participants were told that the person was just pretending to be tortured by the shocks, which were actually barely noticeable. A third group received no instructions at all.

A further division was made based on the participants’ general empathetic ability. It turned out that the ability to learn from the other person’s experiences was directly connected to the level of empathy – those who were the most empathetic during the experiment developed the strongest fear of the images that were “dangerous”.

“This indicates that we do more than just observe regularities when we learn from others; the more we step into the perspective of others, the stronger the impression from their experiences,” says Andreas Olsson.

BUT HOW IS IT even possible to share the experiences of someone else? That is a question that Predrag Petrovic, a researcher at the Department of Clinical Neuroscience, has attempted to answer with his research. He explains that when we see another person experiencing something, such as pain, it is partly the same parts of the brain that get activated as when we are subjected to the same thing ourselves. It suggests that empathetic pain literally is a form of pain. But this could be a misconjecture.

“The fact that empathetic pain and individual pain involve the same areas of the brain does not necessarily mean that they are one and the same. It could be entirely different functions that happen to exist in the same place in the brain”, says Predrag Petrovic.

In order to settle the question, Predrag Petrovic and his co-workers have designed an ingenious experiment. More than a hundred research subjects were placed in functional MRI scanners and received a painful treatment. At the same time, they observed another person in the room who was being subjected to pain and were asked to try and describe the other person’s pain.

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Curious about Empathy TEST YOUR PREJUDICES

PREDRAG PETROVIC HAS previously demonstrated that pain relief through placebo has a biological basis in that the body’s own morphine system, the opioid receptors, are activated. In order to see whether the empathic pain is dependent on the same mechanism, half of the research subjects were given a substance that blocked the opioid receptors. It then became evident that empathy was normalised – when the pain relief subsided, the other person’s pain was also perceived as more unpleasant again.

According to Predrag Petrovic, the results tell us that empathy can be understood as a simulation of other people’s experiences, where the same networks in the brain are active, as if the experience was our own. Such an overlap between brains comes with some strange consequences.

“It could be the case that a common painkiller not only reduces our own pain but also has the side effect of decreasing empathy for the suffering of others. But this must be examined in more studies”, says Predrag Petrovic.

IN HIS RESEARCH , Andreas Olsson often studies people’s reactions to images. A current image that caused an explosive emotional effect is that of Alan Kurdi, the three-year old boy wearing a red jumper and trainers who was found washed up on a Turkish beach.

A few days after the publication of that photo, the company SIFO, commissioned by the newspaper Svenska Dagbladet, conducted a survey on the Swedish people’s opinion on immigration policy. The results showed that the number of Swedes who thought that rules and legislations should be amended in favour of receiving more refugees had increased from 17 to 25 per cent. The biggest change was that fewer people were unsure, i.e. more people had taken a stance. It is a statistically ensured difference compared to the days before the publication and an 42

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Do you empathise with the people in the photo? That does not necessarily mean that the desire to help increases, according to the researchers.

unusually quick turn in opinions.

“It shows the enormous forces we are dealing with”, according to Predrag Petrovic, who says that he was one of those deeply affected by the photo.

Empathy is an important moral compass but common sense can sometime point in the opposite direction.

For example, research show that the larger the number of people who need help, the more indifferent we become. When researchers at Linköping University showed research subjects images of children in need, both the emotional response and the willingness to donate money were greatest when an individual child was shown.

The generosity decreased as soon as there were two children and continued to decrease the larger the need for help became. The participants were also more willing to make a moral decision to save the life of an individual identifiable person than to try to save 40 anonymous people.

With this counterintuitive logic, the immense power of the individual image of Alan Kurdi becomes perfectly reasonable. But does this kind of empathy shock make people automatically reach out a helping hand? Not necessarily, according to Andreas Olsson.

“Many people identified strongly with that image. But this does not mean that there is an increase in the motivation to help as a matter of course. Many people may have felt a pure sense of discomfort, which is more likely to make people look away or turn off the TV in order to avoid feeling the pain of others”, he says.

We all carry thoughts and emotions that are outside of our conscious control. Within Project Implicit, researchers have developed tests that measure our subconscious attitudes on everything from ethnic groups to political questions and pets. Try it yourself at www.projectimplicit.net

Book tip: Train your compassion Buddhist monks who have actively worked on their compassion are on to something important. When most people react negatively to the suffering of others, the monks react more constructively, with warmth and compassion. What is their secret?

In the e-book Compassion. Bridging Practice and Science Tania Singer and Matthias Bolz, both researchers at the Max Planck Society, present different ways to train your compassionate abilities. Through text, audio and films the Buddhist view on compassion is put forward, as well as secular and research-based training programmes that can be used within schools, psychotherapy or in palliative care. www.compassion-training.org ANDREAS OLSSON DOES NOT think that his view on morals has changed through his research as he has learnt about people’s empathy or lack thereof. On the contrary, he is careful to differentiate between scientific facts and moral or political views. However, he believes that we all have a lot to learn from the research.

“It is very important for politicians and others to learn from the research.

To understand, for example, that it is natural for people to divide into groups that are hard to change. But just because something is natural it does not mean that we must accept the negative consequences or use it as a model for society”, he says.

Photography: Getty Images.

After having been given a placebo, i.e. a chemically ineffective pill that was presented as a painkiller, their own pain decreased as expected. But so did the research subject’s empathy for the other person in the room.

At the same time there was visibly decreased activity in the areas of the brain connected to empathetic pain.

The moment As told to: Anders Nilsson Photography: Martin Stenmark

“It’s when you meet the patient that the circle closes” Research breakthroughs are not just about new discoveries. Anna Martling tells us how a long period spent on development meant that she was able to offer a patient life-saving treatment.

Name: Anna Martling Title: Professor of surgery specialising in colorectal cancer at Karolinska Institutet and senior consultant surgeon at Center of Digestive Diseases, Karolinska University Hospital.

“It was just after the turn of the millennium. The patient was about 25 and was preparing to die. He had rectal cancer which was very advanced and was spreading. The hospital where he lived had explained to him that there was no hope; the tumour was growing so aggressively that there was no longer any chance that it could be cured by an operation.

By some roundabout route he arrived at Karolinska University Hospital. He was now sitting in my office and I told him that we could offer him treatment that might lead to a long-term cure. Our research group had been engaged for some time in developing surgical technology. We had learned how to perform more and more extensive interventions and to combine this with the correct dosage of radiation and chemotherapy. The treatment he needed had gradually emerged from our research over many years and we were now able to offer it in a clinical setting.

When we talk about breakthroughs in research, it is often the scientific discoveries we are referring to. But for me, the major breakthrough is when I, as a doctor, after completing a research study, can sit down with a patient and make something better because of our research; when I can offer a patient improved treatment that I know will increase their chances of a cure. That’s the moment when I feel most satisfaction as a researcher. That’s when the circle closes.

We operated on the young man. It’s a tough operation – we removed not only the rectum but also all the nearby organs: the bladder, the prostate and the perineum. But the man survived and recovered well.

He’s now living a good life and is cured from the disease. He has a partner and has gone back to his physically-demanding job. And the treatment that had only just been developed when he had it just under ten years ago is now offered widely throughout the world.

Medicinsk Medical Vetenskap Science–2016 №2–2012

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Advances 3 items on peanut allergy

How to get the body tolerant Food allergies are common, but there is still no curative treatment. An attempt is currently underway to cure 20 young people with severe peanut allergies.

Text: Frida Wennerholm

5 OUT OF EVERY 100 children between 4 and 18 are allergic to peanuts or other nuts.

long period along with medicine that suppresses the allergic reaction. “When we eat something our bodies are allergic to, a special type of allergy antibody, immunoglobulin E (IgE), prompts certain cells to release histamine, causing an allergic reaction,” says Nilsson.

“The medicine blocks the IgE antibodies and prevents the allergic reaction, which means that the patient is able to be gradually used to peanuts and weaned off their allergy without any great

risk of allergic side effects. Lastly, the medicine dosage is scaled down when the body has got used to the peanuts.“ To check whether it is safe to start treatment, researchers test a patient’s current allergy status by taking a blood test and adding peanut. This makes it possible to gauge how the cells involved in the allergy will react in the case of this one patient.

“We are very optimistic about this experimental treatment,” says Nilsson. We have already cured one girl of a severe milk and egg allergy.”

Risk of anaphylactic shock “It’s important to taste food to be identified in advance A life-threatening allergic response is called anaphylaxis or anaphylactic shock, a condition that can be caused by substances contained in peanuts or a wasp sting, for example. In a new study, researchers at the Centre for Allergy Research are trying to identify new biomarkers – measurable substances – for anaphylaxis, so that those at risk of anaphylactic shock can be identified in advance. Find out more: http://ki.se/en/research/theanaphylaxis-project 44

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at an early age to avoid developing allergies to it” Magnus Wickman, doctor and professor at the Institute of Environmental Medicine, commenting on a British study which shows that babies that eat peanut snacks during their first 11 months of life are much less likely to develop a peanut allergy. Source: Svenska Dagbladet (national daily paper)

Photography: Istockphoto

PEANUT ALLERGIES ARE the most common of all food allergies and the cause of most emergency admissions to hospital. Caroline Nilsson, a paediatrician at Södersjukhuset hospital and researcher at the Department of Clinical Research and Education, Södersjukhuset, has been researching allergies for many years and is leading a new study aiming to find a future cure for peanut allergies.

“Around half of those who arrive at our emergency department with allergic reactions have eaten peanuts.

Curative treatment would make a huge difference.”

The study, which is scheduled to finish in 2016, involves 20 young people with severe peanut allergies. During the treatment, the participants are allowed to eat small amounts of peanuts over a

4 questions Advances Text: Ann-Cathrine Johnsson Photography: Mattias Ahlm

“Psychopaths are not monsters” The researcher Karolina Sörman, who has explored psychopathy in depth, thinks the subject is often described in stereotypical terms and would like a more nuanced picture.

How accurate is the general picture of psychopaths?

“Psychopaths are often described as cold-blooded, evil monsters or as people you might find heading up any company. Both these stereotypical portrayals are too simplified. It’s possible to have certain psychopathic traits, such as being manipulative, fearless or selfaggrandising, without being classified as “a psychopath” according to established criteria for psychopathy. A real psychopath, on the other hand, is characterized by elevated levels of several of these characteristics, in combination with deviant anti-social behaviour such as poor impulse control and in some cases criminality and violence. This combination of deviant character traits and behaviours means that the person often has great difficulty relating to other people. For example, individuals with psychopathy don’t seem to react in the same way as most people to fear and punishment, which can lead to reckless behaviour. In the absence of studies in Sweden, it remains unknown what proportion of Swedes could be classified as psychopaths, but according to a British study the figure is less than one per cent of the population.”

What did you conclude in your thesis?

“Until date, psychopathic traits have mainly been investigated in criminal populations. We have evaluated alternative models and assessment tools developed in the US that can also be used with non-criminal groups. These models have not been tested in Sweden, but we could see that they were considered to

be in line with perceptions of psychopathy among individuals working in the Swedish judicial system. We could also see that assessments of psychopathy are not always entirely reliable in clinical situations, i.e. two clinicians assessing the same person sometimes arrive at different conclusions. More research is needed on this subject.”

Has your outlook on people changed since you researched psychopathy?

“I’ve gained a greater understanding of the complex interplay between character traits and behaviours. Having explicit psychopathic traits can lead to a range of problems, but can also be advantageous in specific circumstances.

Another thing that has struck me is that as humans we are constantly reflec-

KAROLINA SÖRMAN is a neurobiologist and postdoctoral researcher at the Centre for Psychiatry Re­ search at the Department of Clinical Neuro­ science.

Researcher Karolina Sörman says that we need to distinguish between psychopathic traits, which many people may have to some degree, and psychopathy, which is a personality disorder.

ting ourselves in other people. There is always a recipient who will be charmed and perhaps feel special in the company of a person with explicit psychopathic traits, who may often have an air of grandeur and self-importance.”

Did you meet many people with psychopathic traits during your work?

What was it like?

“I have met some individuals who were very contradictory in that they seemed to function normally and could sometimes even be charming, but they had a fundamental lack of insight into what they had done to other people.

There are probably biological explanations for it, but we need more neurobiological research to get a better understanding of people with psychopathy.”

Medical Science–2016

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Nobel The photo

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Tabling a decision This is the table where the decision on who is to be awarded the Nobel Prize in Physiology or Medicine is taken. Come along into the Assembly Hall.

The number of years that the discussions leading up to the selection of Nobel laureates are kept secret before being made public. n.

Text: Ola Danielsson Photography: Martin Stenmark

No eating or drinking is allowed in the Assembly Hall.

Where?

The Assembly Hall is in the Nobel Forum, which was designed by architect Johan Celsing. The room was designed specifically to accommodate the meetings of the Nobel Assembly.

The large round table where the Nobel Assembly gathers is 6.2 metres in diameter.

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Medical Science–2016

The youngest member is 46 and the oldest 67.

Who? The Secretary of the Nobel Assembly is currently professor Thomas Perlmann. It is his role to lead the group of 50 professors in the Nobel Assembly at Karolinska Institutet as they decide who is to be awarded the Nobel Prize in physiology or medicine.

39 of the members are men

In attendance. All 50 professors in the Nobel Assembly are called to the meetings. There is room for 20 of them around the table and the others have to sit on the chairs around the walls.

11 are women

Worn out. The chairs were reupholstered in identical, newlywoven fabric in 2015.

How? Difficult to shake.

The carpet is 7 metres by 7 metres in size and was woven in one piece by Kasthall.

Each meeting lasts between two and two and a half hours, sometimes more. The laureate is decided at a special decision-making meeting the same day as the decision is made public.

Medical Science–2016

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Top publications

The number of suicide attempts by young people can be greatly reduced IN SWEDEN, THE NUMBER OF suicides has been decreasing for some time for both men and women. This isn’t the case, however, for suicides of young people aged 15 to 24, where the number has remained fairly constant. At the global level, suicide is the second most common cause of death in the 15-29 age group; only road accidents cause more deaths in this age group. At the same time, there has been a lack of knowledge about the best strategy for preventing suicidal behaviour in young people.

New research involving over 11,000 pupils from almost 170 schools in ten EU countries has now provided strong endorsement of a method by which pupils learn to recognise mental health problems in themselves and their friends while being trained to understand, interpret and manage difficult emotions.

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One year after the end of the Awareness programme, developed by researchers at Karolinska Institutet and Columbia University in the US, the figures for suicide attempts and serious suicidal thoughts were only half those of the control group. The method involved training for the pupils plus guided role-play where they could examine their feelings and learn strategies to cope with difficult life situations that can lead to suicidal behaviour. The training took a total of five hours over four weeks.

“The current study provides muchneeded evidence of the effectiveness of a universal, school-based public health initiative aimed at pupils,” says Danuta Wasserman, Professor at the Department of Learning, Informatics, Management and Ethics and Head

of the National Centre for Suicide Research and Prevention of Ill-Health, both at Karolinska Institutet, who led the study. “The study shows that it is possible to successfully address mental health promotion and suicide prevention in schools.

We can now move on from passively noting the statistics that demonstrate the gravity of the problem to widespread active testing of the Awareness Programme in Swedish schools.

We also want to develop the method into an online facility, perhaps a mobile app, so that we can reach lots of young people.”

‘School-based suicide prevention programmes: the SEYLE cluster-randomised, controlled trial’ Wasserman D, Hoven CW, Wasserman C, Wall M, Eisenberg R, Hadlaczky G, Kelleher I, Sarchiapone M, Apter A, Balazs J, Bobes J, Brunner R, Corcoran P, Cosman D, Guillemin F, Haring C, Iosue M, Kaess M, Kahn JP, Keeley H, Musa G, Nemes B, Postuvan V, Saiz P, ReiterTheil S, Varnik A, Varnik P, Carli V, The Lancet, January 2015

Illustration: Istcokphoto. Photography: David Gimlin.

A selection of the most recent publications from Karolinska Institutet in the world´s leading scientific journals

Suicide is the second most common cause of death amongst young people aged 15 to 29.

But, a study shows, it is possible to prevent it.

Current blood management practice is safe

Photography: Istockphoto, Åsa Petré. , Frida Hansson.

Transfusion of stored blood is safe IN SWEDEN AND most of the Western world, blood is allowed to be stored for up to six weeks before being used for transfusions. So there was much concern and uncertainty at health clinics around the world when a study published in 2008 claimed that cardiac surgery patients who had been given blood that had been stored for two weeks or more had a higher mortality rate.

To fully investigate possible adverse effects on health of stored blood, researchers from Karolinska Institutet carried out the biggest study in the field to date. By linking a series of records, they were able to involve almost 50,000 patients who had had a blood transfusion in conjunction with heart surgery in Sweden over a 16-year period. This included patients who had had transfusions of blood that had been stored for up to 42 days. There was no link between the storage time and the outcome for the patients.

“Thanks to our unique Swedish records, we have been able to clearly demonstrate that current blood management practice is safe,” says Gustaf Edgren, doctor and researcher at the Department of Medical Epidemiology and Biostatistics, who led the study.

‘Red cell concentrate storage and survival after cardiac surgery’ Sartipy U, Holzmann MJ, Hjalgrim H, Edgren G JAMA, October 2015

The immune system is shaped more by environment than genes RECENT RESEARCH AT Karolinska Institutet and Stanford University, USA has shown that our environment affects our immune system more than has previously been thought. By analysing 105 sets of twins, researchers have been able to show that individual variations in the different components of the immune system are a consequence of environmental factors, for example bacterial flora or diet, rather than heritable factors. The influence of the environment also increases over time. Genetically-identical single-egg twins become more and more dissimilar the older they get.

“The study means a breakthrough in our overall understanding of the factors that affect the human immune system,” says Petter Brodin at the Department of Medicine in Solna. “The results also mean that the focus in recent years on genetic predisposition and its influence on the functioning of the immune system and the risk of disease now needs to be complemented by more studies of the influence of non-heritable factors.”

Brodin hopes that one long-term result might be that it will become easier to predict which individuals are at higher risk of being affected by immune-mediated disorders and infectious diseases.

Variation in the human immune system is largely driven by non-heritable influences Brodin P, Jojic V, Gao T, Bhattacharya S, Lopez Angel CJ, Furman D, Shen-Orr S, Dekker CL, Swan GE, Butte AJ, Maecker HT, Davis MM Cell, February 2015.

Over time, the immune sytems of identical twins become more unalike.

LIST

More of the year’s publications Bariatric surgery affects risk of pregnancy complications Outcomes of pregnancy after bariatric surgery Johansson K, Cnattingius S, Näslund I, Roos N, Trolle Lagerros Y, Granath F, Stephansson O, Neovius M NEJM, February 2015 Most heart muscle cells are formed during childhood Dynamics of cell generation and turnover in the human heart Bergmann O, Zdunek S, Felker A, Salehpour M, Alkass K, Bernard S, Sjostrom SL, Szewczykowska M, Jackowska T, dos Remedios C, Malm T, Andra M, Jashari R, Nyengaard JR, Possnert G, Jovinge S, Druid H, Frisén J Cell, June 2015 Parental age difference increases risk of autism Autism risk associated with parental age and with increasing difference in age between parents Sandin S, Schendel D, Magnusson P, Hultman C, Surén P, Susser E, Grønborg T, Gissler M, Gunnes N, Gross R, Henning M, Bresnahan M, Sourander A, Hornig M, Carter K, Francis R, Parner E, Leonard H, Rosano. M, Stoltenberg C, Reichenberg A Molecular Psychiatry, June 2015 Complex grammar of the genomic language DNA-dependent formation of transcription factor pairs alters binding specificity Jolma A, Yin Y, Nitta KR, Dave K, Popov A, Taipale M, Enge M, Kivioja T, Morgunova E, Taipale J Nature, November 2015 Why combined therapies increase prostate cancer survival Castration radiosensitizes prostate cancer tissue by impairing DNA doublestrand break repair Tarish FL, Schultz N, Tanoglidi A, Hamberg H, Letocha H, Karaszi K, Hamdy FC, Granfors T, Helleday T Science Translational Medicine November, 2015 Medical Science–2016

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The moment

“Becoming a psychiatrist wasn’t even on the map” Meeting a patient with delusions made Karl Deisseroth want to understand brain dynamics better.

Since then he has developed several ground-breaking methods.

“The man was staring at me. He had a schizoaffective disorder and suffered from severe delusion. At this occasion it included me – he was screaming at me; he was loud and Name: Karl Deisseroth. upset! It was the early 1990s, I was studying Title: Professor of Bioengat Stanford School of Medicine and had just ineering and of Psychiastarted my mandatory internship in psychiatry and Behavioral try. I came there without particularly high Sciences at Stanford expectation because I already knew what University, USA. specialisation I wanted to pursue: neurosurCurrently: Guest professor gery. It was the most challenging thing I could at Karolinska Institutet where there are now imagine. Becoming a psychiatrist wasn’t even research environments on the map for me. for both optogenetics But meeting the patients in psychiatry and transparency technimade me revaluate everything. Particularly que – two new areas of the meeting with this man. The situation research developed by provoked strong feelings and new thoughts Deisseroth. within me. It was awful to see how much he suffered and how little the health care system could do for him. He had been ill for many years, all possible treatments had been tested, none of them helped.

I was also struck by the realisation that TRANSPARENCY this man’s brain actually didn’t have any TECHNIQUE IN BRIEF damage. I knew that no test – neither Dead tissue is processed so that it becomes transparent. This EEG, MRI, PET nor any other techniallowsthe researchers to examine que – would show anything other than entire organs, such as the brain, his brain being totally normal. without having to cut through the tissue.

Still he lived in his own deluded world. It was something else, something more subtle that was wrong: the system dynamics. It fascinated me and became crucial to my career choice. As a neuroscientist I have focussed on the dynamics of the brain.

The questions that arose at that meeting eventually also led to the methods and techniques that I have developed: optogenetics and the transparency technique.

And as a clinician I obviously never became a neurosurgeon but a psychiatrist.”

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Medical Science–2016

As told to: Anders Nilsson Photo: Christopher Hunt

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