Mats J. Olsson

The smell of disease

The overall aim of this research line is to assess the different functions of the human sense of smell (olfaction). During the last decade, a number of olfactory functions have been described, several indicating that humans in parallel to animals can extract social information from biological signals of conspecifics, such as kin recognition, emotional contagion, mate choice, and reproductive state (Lundström & Olsson, 2010). Although well founded in animal models, the perception of health, or sickness, of conspecifics has on the other hand been neglected in the field of human olfaction. Mostly anecdotal and observational evidence of how physicians now and through history have been able to diagnose diseases by means of their chemical senses has been reported. In the present research we will test the hypothesis that humans can smell sickness. We will use an experimental model to make people "sick". The endotoxin, when injected into the blood stream, causes a transient systemic inflammation just as when we are attacked by pathogens (virus, bacteria, etc.) We sample the body odors of exposed individuals and compare them to controls (injected with saline). The specific aims are to determine how good we are at this (pilot study indicates that we can do it) and how we perceive the difference between healthy and sick. Moreover, we will investigate which are the chemical, physiological and psychological mechanisms behind this olfactory ability.
Final report

1.    The purpose of the project and possible modifications during the project period

The project has followed the project plan. We want to investigate if the sense of smell could detect the disease at an early stage of an illness with the potential to avoid sick people. If this is the case, then the sense of smell will be additional to the physiological immune system in the human vital quest to stay healthy. Furthermore, we investigate the chemical substances that constitute this disease signal and the brain areas activated by it.

2.    What are the project's three main outcomes?

A series of experiments have proved this thesis. We have for example, in two studies (one published) demonstrated that (1) experimental "sick" body odors (endotoxin-exposed with lipopolysaccharide, LPS, which creates a transient systemic inflammation) within hours of smell become more aversive. A third study showed that (2) also urine from the "sick" smells more aversive. In connection with this, we have investigated the chemical substances that convey this detection. Pyrrole is a candidate for urine. This topic has also been indicated for other diseases. In a fourth study, the analysis shows (3) how the brain responds to odors and facial images of diseased individuals compared to the same individuals as they are healthy. This study was done recently, the results are preliminary but promising.

3.    What new questions does the project generate?

Since humans, early in the disease process, seem to emit a signal illness, the question that arises is how general this signal is; i.e., speaking of perception through the senses. That is, if we know the smell when someone is ill, we can see (we already have preliminary support for, Study 4) and tell that the same individual is sick? Furthermore, if the perception of another's illness may be the basis for an early defense against infection (avoiding the ill individual) the question that arises about the disease signal itself may also affect the immune system of the recipient of the signal. Some studies of exposure to disease relevant images (e.g. individual who sneezes) show that the immune system's activity increases. We want to test this disease relevant (disgusting) odors. Together, this would support the behavioral immune system (I know that you are sick and can avoid you, additionally enables detection is my immune system) that would intervene before the classic immune system which is a new and interesting research track.

4.    The project's international presence

The project is conducted in cooperation with Johan Lundström and Bruce Kimball at the Monell Chemical Senses Center in Phliadelphia. A study has been done under the leadership of Lundström. Kimball will analyze the chemical content of our kroppslukt- and urine tests (gas chromatography-mass spectrometry) in search of volatile biomarkers (smelling or not) for the early inflammatory processes. We found a candidate molecule (Pyrrole) we will try to replicate.
An American graduate student (unpaid RJ) and a German post-doc has been tied to the project.

5.    Research Informative actions outside the scientific community

Association for Psychological Science chose to do a press release on our first publication in Psychological Science. The results have been disseminated via commentary and interviews with me in the media around and outside the Western world. I almost always accept an interview, and the team has been in numerous interviews since (e.g., CNN International the other day, but also the BBC and Radio Free Moscow to mention a few) in which this research has had a major or minor role.

6.    The project's two main publications, and a discussion on this

The most important is the first article (Olsson et al., 2014 Psychological Science) that for the first time showed experimentally that the "disease" smells. Additionally, the study showed for the first time that this can happen after a few hours of immune activation! This indicates that the sense of smell (possibly together with other senses) early can be part of a so-called behavioral immune system that helps the classic immune system to keep us healthy. According to Karolinska Institutet bibliometric citation database this article belongs to the top 5% in its field. A second article and a third article replicated, generalize this finding to the urine odor which is important. But the fourth article may have a greater importance. With fMRI modern technique, we have seen how the brain processes signals disease (of smell but also for the image) and can help us understand the mechanisms behind disease detection (Regenbogen et al, in prep). Of related interest, we have also published a chapter on kroppsluktens meaning (Parma et al., In press) and studies on the anteromedial temporal globe (including the amygdala) involvement in elections perception of odors, which contributes to the understanding of our data.

7.    List of publications and links to their own websites cues.
Gordon, A R, Bruce A. Kimball2,4, Kimmo Sorjonen1, Bianca Karshikoff1,5, John Axelsson1,5, Mats Lekander1,5, Johan N. Lundström1,2,3, and Mats J. Olsson. (in prep.) Sickness-detection via volatile cues in human urine
Gordon, A R, Johan N. Lundström1,2,3, Bruce A. Kimball2,4, Bianka Karshikoff1, Kimmo Sorjonen1, Caroline Olgart Höglund1, Anne Soop1,  John Axelsson1, and Mats Lekander1,5 and Mats J. Olsson1* (In prep.) Human scent as a first-line defense against disease.
Juran, S. A., Lundström, J. N., Geigant, G., Kumlien, E., Fredrikson, M., Åhs F., and Olsson, M. J. (In press). Unilateral resection of the anterior medial temporal lobe impairs odor identification and valence perception. Frontiers in Psychology 6(2015) 1-7.
Olsson MJ, Lundstrom JN, Kimball BA, Gordon AR, Karshikoff B, Hosseini N, Sorjonen K, Olgart Hoglund C, Solares C, Soop A, Axelsson J, Lekander M. The Scent of Disease: Human Body Odor Contains an Early Chemosensory Cue of Sickness. Psychological Science. 2014.
Parma, V., Gordon, A.R., Cecchetto, C., Cavazzana, A., Lundström, J. N. & Olsson, M. J. (In press). Central Processing of Human Body Odors. In (Eds.) Handbook of Odor. London: Springer.
Regenbogen, C., Axelsson, J, Lasselin, J., Porada, D., Peter, M., Lekander, M., Lundström, J.N.,&  Olsson, M.J. (in prep.). Multisensory detection of sickness cues.
web page: http://ki.se/cns/mats-j-olssons-forskargrupp

8.    What is the project's publishing strategy?

Only international scientific journals with peer-review are relevant to our original data. The first article, as mentioned above, published in Psychological Science, a journal with a very good spread and scientific reputation. Additionally, press releases on the journal and the KI website were made. The article is made available through the Journal's auspices with a free link on my website to the article. Everyone who has contacted me has got a pdf of the article. The second study, which replicates the results from the first and a third on the smell of urine are intended to be published in an open access journal (e.g. a journal PLOS) or otherwise, the article will be made available at no cost to the consumer.

9.    How has the project been integrated into the department / equivalent activity?

Very good. At the beginning of the project, Johan Lundström (also at the Monell) placed his main research here at the School of Psychology at the Karolinska Institute. Our groups have in practice become one, with a pooling of resources and completion of relevant competencies as a result. The Section has been very positive to the new research grouping where new dedicated research laboratories have been built and served us.

10.    Have the project's employees participated in national or international conferences? Which?

Association for Chemosensory Sciences, 2014 Bonita Springs; European Chemoreception Research Organization, Istanbul, 2015)

11.    Which spin-off effects, the project has given (e.g. new research collaborations, new research data)?

As mentioned above (see 3.), we are also interested in how disease-related (in this case, nauseating) smells and images may trigger the immune system. Pilot studies already run on this. We have also had formative meetings with a network of researchers at Karolinska Institutet who have a common and generally focus on what one can term as The Parasite Stress Theory (describe how evolution has dealt with the fact that humans evolved in a world of ever-threatening pathogens, especially coming from out-group members) and its influence on the behavior and health. We have on this subject jointly formulated a program application to VR, Vinnova, and RJ. Cooperation with Stockholm University, Jonas Olofsson, Department of Psychology, has begun. A survey to determine how disgusted sensitive individuals is the right body-related substances have been developed. This sensitivity relative to e.g. political opinion is examined.


12.    Other comments

We have conducted a high dose study with LPS in collaboration with Professor Mats Lekander at the Karolinska Institute and the Stress Research Institute. The main objective is to replicate our previous findings and to establish a dose-response curve that further support that we measure something important. At the same time, in collaboration with Professor John Axelsson, we collect body odor sample from naturally sick (colds, influenza) and from a few groups with inflammatory disease judges (seasonal allergy, rheumatoid arthritis) to see if they also smell aversively and if they give off volatile, molecular biomarkers.

We are currently refining our sampling methods of body odor and we are now testing a carbon-based membranes absorb volatile substances effectively; good for both determination of odor and of molecular content using gas chromatography-mass spectrometry.

Grant administrator
The Karolinska Institute Medical University
Reference number
P12-1017:1
Amount
SEK 2,841,000.00
Funding
RJ Projects
Subject
Psychology (excluding Applied Psychology)
Year
2012