New facility takes up the chase for doped athletes and future drugs

21 October 2020

Mikael Hedeland, Professor at Uppsala University's Faculty of Pharmacy

Mikael Hedeland, Professor at Uppsala University's Faculty of Pharmacy

Using a home-grown filamentous fungus, Mikael Hedeland, professor of analytical pharmaceutical chemistry, managed to expose four medalist guilty of doping at the Olympic Games in Athens. Now he is refining his methods further, opening a facility for mass spectrometry at the Uppsala Biomedical Center.

Would you take a drug that resulted in invincibility in your sport if you knew it would mean your death in five years? "Yes" answered more than half of all elite athletes surveyed in the late 20th century. Today, the proportion who would choose the drug is considerably smaller, a healthy development that can probably be attributed to the increasingly advanced methods of exposing use of performance-enhancing drugs.

“During the Athens Olympics in 2004, there was a lack of effective methods to detect the use of oxandrolone, an anabolic steroid that the body rapidly excretes. In a research project many years later, we worked with Cunninghamella, a filamentous fungus that turned out to break down substances in a similar way to humans and horses. With the help of this fungus, we discovered that oxandrolone leaves another, more long-lived and traceable substance behind, a finding that had major consequences in the world of sports,” says Mikael Hedeland, Professor of analytical pharmaceutical chemistry.

When the results from Uppsala reached the World Anti-Doping Agency, WADA, they chose to bring out 105 urine samples from Greece, then having been stored in the freezer for eight years. With the new analysis method, the agency found degradants from oxandrolone in several samples. A series of retroactive disqualifications were carried out and in four cases medals were recalled, among them a gold in shot put.

Adam Nelson received his gold in 2013
Adam Nelson received his goldmedal in 2013

“It is of course positive if we help to expose cheating, and the story of the Olympic medals always come in handy to start research presentations with as it never fails to arouse interest. But our biggest contribution in this case is that we shed light on Cunninghamella's usefulness in finding degradants, so-called metabolites, from pharmacologically active substances. It is a cheap method that also reduces the need for animal experiments and which, after our study, has become scientifically widespread.”

Mikael Hedeland's group also continue to benefit from Cunninghamella in the work of curbing doping. Recently the team published an article in which they map eight metabolites from a variant of SARM, a form of anabolic compound that accelerates muscle growth, making them useful in the treatment of certain diseases. In competitive sports they have been banned since 2008, but are now being traced in both horses and athletes.

In 2018, Mikael Hedeland was recruited to Uppsala University after a long and successful stay at the Swedish National Veterinary Institute, SVA. Here, the group conducted a multi-year collaboration with Nordic Trotting and Galloping analysing samples from competition horses - the team's many notable efforts include the revelation of the French trainer who gave his horses cobalt. The assignment also provided revenue that helped finance a laboratory with a distinct focus on in vitro methods.

“It was an interesting time that opened several international doors. I have chosen to keep an employment of 20 percent and a doctoral student with a physical placement at SVA, and also continue my scientific collaboration with laboratories at the University of California and Deutche Sporthochschule Köln. In parallel, I see many opportunities for collaborations at Uppsala University, where our technology-intensive environment with a focus on separation science can add significant values.”

Currently, Mikael Hedeland is preparing a facility for mass spectrometry at Uppsala's Biomedical Centre. However, the process has - like much else - been delayed as a result of covid-19, but the ambition is to complete the establishment as soon as possible, thus being able to support other researchers in obtaining data in order to create faster, more selective analytical methods in pharmaceutical research.

“As soon as our facility is installed and ready, it will generate important data, including in the work of identifying and tracking endogenous substances that mark disease. Our analytical pharmaceutical chemistry is primarily an auxiliary science that with high quality analysis data lays the foundation for other groups to solve their challenges, and I am convinced that the competence we add will be of great value to our colleagues at Uppsala University”, says Mikael Hedeland.

Facts

  • Mass spectrometry is a technique in which a mass spectrometer distinguishes ions from each other based on their mass / charge relationship, which enables qualitative and quantitative analyzes in analytical chemistry.
  • The first mass spectrometer was launched in the early 20th century. In 1922, F W Aston received the Nobel Prize in Chemistry for using a mass spectrograph to determine the weight of atoms.
  • Mikael Hedeland's research group also runs projects focusing on Medicines in the environment, Metabolomics and Lipidomics.