Researcher Interview: Mike Musker By Jason Murphy Meet Mike Musker. A former mental health nurse who took the path less traveled. Musker is now a scientist with some excellent research underway. He works with the South Australian Health and Medical Research Institute, and his research – including one major project near completion and another about to start - is definitively biological in approach. The nearly-finished study looked at 23 ME/CFS cases versus 12 controls and sampled their blood in a very unusual way. “We wanted to look at what’s happening in people’s blood in relation to ME/CFS,” Musker says. “Looking for biological causes, the biological basis of it.” The sampling process was intensive. Patients were invited into the lab in the morning and seated in an enormous luxury recliner where they could read, snooze, and watch TV for eight hours. During that period, their blood was taken repeatedly, using a machine called an Edwards VAMP. The rarely-used but highly-promising device permits frequent blood tests without draining a patient completely, by returning blood that would otherwise be wasted to the patient after the sample is drawn. Each sample is just four milliliters. “I placed a cannula in their arms at 9am and we took the first sample at 9am and we took a sample every seven minutes until 5pm. That was 69 samples across the day. We were then able to see the differences in the cytokines across the day.” Musker is an unusual scientist who follows the blood from the body to the bench. His background as a nurse means he was the one who drew the samples, and also the one who analysed them in the lab. “I’m a jack of all trades, I do everything!” he says. The study was designed to test the hypothesis that tiny signaling molecules called cytokines are different in people with chronic fatigue syndrome compared to controls. The analysis so far suggests real differences – but not the exact ones researchers were expecting. It tracked three molecules of interest – interleukin-6, interleukin-1-beta, and leptin. The first two, Musker explains, are inflammatory markers. “They were lower in people with ME/CFS,” he says, referring to interleukin-6 and interleukin-1-beta. “In fact, they were hardly noticeable, whereas in the controls they were a reasonable value that we could read. That was quite clear. That would indicate to me that people with chronic fatigue syndrome, their inflammatory system might not be responding like a normal person would. In other words, it’s almost switched off. But if you are constantly under that adrenaline, your body stops listening to that message and you get chronic stress, I wonder if that’s what’s happening with chronic fatigue syndrome. That’s a theory I’m going to put forward.” The third molecule that was supposed to be of interest surprised the researchers, who had previously tracked its fluctuations in depression. Instead of varying, it remained very, very stable. “All 35 people, their leptin levels barely changed across the day. A third of the people had really high leptin levels, a third had medium, a third had low, but they were all stable across the day.” This is an important part of science – hypotheses that don’t work out. The discovery leptin is stable in ME/CFS patients during the day can help other researchers place their findings in context. For example, University of Alabama at Birmingham researcher Jarred Younger has a well-known piece of research called the “good-day, bad-day study” where he monitors immune markers in female patients over 25 days to see what varies. He has found higher leptin is associated with higher levels of fatigue. The intriguing information that leptin is very stable within the day helps refine the kind of questions researchers should be asking. Contrasting high fatigue times with low fatigue times is an excellent approach for unpicking the mystery of ME/CFS, so it is wonderful news the next study Musker is involved in will do just that. “We are going to take 40 people with ME/CFS, and 20 controls. We are going to wait until they have a crash and take their blood, even if I have to go out to their home and take it. And then I want to take it when they are feeling better .... And we are going to measure 72 cytokines this time.” Once again, Musker will draw the blood, put the samples on dry ice, drive them back to the lab, then “spin it and put it in test tubes.” The study has been delayed by COVID-19, but the hope is the experimental design will reveal key molecules of interest that are signatures of a crash in ME/CFS patients. If so it would contribute enormously to the growing understanding of the molecular basis of the illness. Musker is very enthusiastic when he talks about this project and sends a message of optimism to the ME/CFS community. “I would encourage people to be hopeful for the future,” he says. “Don’t give up hope, and as funds come in we can hopefully do some good research and get some positive solutions.” He’s practical, optimistic, and also, thanks to the Mason Foundation, well-funded. Mike Musker is one reason to be optimistic about science eventually coming to grips with this terrible disease and even, hopefully, generating treatments. About Jason Murphy: Jason Murphy is a freelance journalist and economist who began his career in the Federal Department of Treasury before moving onto journalism. Now Jason's work can be found all over the internet in the Australian Financial Review, News.com.au, The Advertiser and many other Australian news outlets. Jason excels in taking complex information and breaking it down for readers to give a better understanding of intricate systems to the public.