Once again, The Telegraph sensationalizes scientific news that doesn’t need it. The work done by Dr. Katrin I. Andreasson’s group at Stanford is exciting enough. The Telegraph doesn’t have to use a title that suggests they have a cure for Alzheimer’s Disease (AD). I’ll admit they didn’t do a terrible job. I’ve got worse examples below. So what’s really going on? The researchers at Stanford found that a particular cell signaling pathway, cyclooxygenase/prostaglandin E2 (COX/PGE2) pathway, was involved with restoring the function of microglial cells.
☼ What are microglial cells?
Glial cells are “support” cells in the brain, as they surround neurons, providing the mylein sheath (think of it as electrical insulation). Microglial cells are scavengers in the brain, like macrophages. In fact microglial cells (like the image below) are more like macrophages than they are like glial cells. It’s thought that microglial cells are less efficient in older animals and therefore cannot clear as much debris from the brain. In particular, beta-amyloid is thought to accumulate in Alzheimer patients eventually causing dementia. If the microglial cells could resume their clean up job then the beta-amyloid wouldn’t accumulate.
I’m not an expert in cell signalling so I’ll just highlight the important bits. Again, since microglial cells are more similar to macrophages than neurons, it was hypothesized that an inflammatory response was involved with microglial function. COX1 and COX2 along with PGE2 are known components of an inflammatory signaling pathway. More importantly, it’s related to aspirin and aspirin was shown to be beneficial to preventing onset of dementia in AD patients. There’s a catch though. There’s always a catch. Aspirin only helps if AD is detected early. That’s one of the biggest stumbling blocks to AD research, early detection (more on that below). The Stanford group found that if you block EP2 signalling (it’s part of the PGE2 pathway), you can restore the function of microglial cells and they can resume clean up on aisle 9.
So how did they do this? They did some in vitro work, i.e., work with macrophage cells in a dish to start identifying part of the cell signalling. They also did work with genetically altered mice, the so-called knock-out mice, to see if blocking certain parts of the pathway restored function of the microglial cells. Combined, their work suggests that blocking EP2 restores microglial function and memory impairment is reduced.
So this is very promising work but it is not a cure for AD. They have to identify an EP2 blocking agent, make sure it works in mice. Make sure it isn’t toxic in mice and one large species. Then they have to do toxicology studies in humans before even thinking of testing on AD patients. Notice how the titles of the articles become less sensational when you compare them?
References:
Has Stanford University found a cure for Alzheimer’s disease? via The Telegraph
There is a report making the rounds on social media that really needs to be explained, because as usual the media hype is distorting the findings. The article in question was published in the Cell Stem Cell journal, and is #OpenAccess (http://goo.gl/pnoiwa). I will explain the background, what these results mean, and more importantly, what they don’t mean.
✤ Traditional chemotherapy is toxic to cells. The only reason traditional chemotherapy works is because it kills cancer cells faster than it kills normal cells. The side effects from chemo often happen because normal cells are also affected. One such side effect is the suppression of the immune system. This happens because chemo damages adult stem cells too, which impairs tissue repair and regeneration.
✤ Blood stem cells (known as hematopoietic stem cells) are responsible for replacing our blood cells; these reside in the bone marrow. In this study, scientists investigated the effect of prolonged fasting on hematopoietic stem cells.
✤ Mice used in this study were fasted for 48 hours, which the scientists defined as prolonged fasting. These mice received no food, only water. They then treated the mice with cyclophosphamide, a common chemotherapy drug. They found that cycles of prolonged fasting reduced the damage caused to hematopoietic stem cells when the mice were treated with cyclophosphamide. They also found that prolonged fasting cycles promoted the regeneration of blood cells through the protection of hematopoietic stem cells.
✤ Next, the scientists tested whether the effects of prolonged fasting were independent of the toxic side effects of chemotherapy. Could prolonged fasting alone stimulate hematopoietic stem cells to self-renew? Indeed, it could.
✤ What is the molecular mechanism for this process? A growth factor known as Insulin-like Growth Factor-1 (IGF-1) seemed to be involved. Growth factors are proteins that control the multiplication of cells. To examine this mechanism, the scientists used mice that were deficient in IGF-1. If you’re curious about how these ‘knockout mice’ are generated, read http://goo.gl/jdbqbk. When these IGF-1 deficient mice were treated with cyclophosphamide, they showed similar results to the prolonged fasting mice; reduced levels of hematopoietic stem cell damage. So getting rid of IGF-1 induced the same protective effects on hematopoietic stem cells.
✤ How does IGF-1 signalling protect hematopoietic stem cells? They found that the activity of an enzyme known as PKA was also reduced in these prolonged fasting/IGF-1 deficient mice. PKA controls the pathway involved in stem cell regeneration. So inhibiting IGF-1 or PKA signalling mimics the effect of prolonged fasting; it promotes the regeneration of hematopoietic stem cells, thereby reducing the immuno-suppressive side effect of chemotherapy.
✤ This is really interesting data – this research has identified one of the signalling pathways in the intricate network of reactions controlling the behaviour of hematopoietic stem cells. The mechanism involves PKA and IGF-1 signalling.
WHAT THE DATA DOESN’T SHOW
What this doesn’t show is that fasting is magically a cure-all for cancer. There isn’t a single study that shows lowered incidence of cancer in human populations that fast regularly. The fasting that these mice underwent also did not include the feasting that goes on every night as seen with human populations either. The scientists also conducted a small Phase I clinical trial in which patients undergoing chemotherapy fasted for 72h – the results are promising; their hematopoietic stem cells were protected when compared with the non-fasting control group. But obviously more data is needed, and it is highly inadvisable to fast before undergoing chemo, without the explicit guidance of a physician.
To summarise, fasting is not a cure for cancer. If anything, fasting does “cure” everything, eventually; this pathway involves a mechanism known as ‘death’.
Image: fasting causes a major reduction in white blood cells followed by their replenishment after refeeding. These effects of prolonged fasting can result in the reversal of chemotherapy-induced immunosuppression.
For those that like science, I’m sure you can appreciate the value of having real scientists on G+ share their knowledge. Zuleyka Zevallos does an excellent job addressing 3 issues that I also work on:
Correlation does not equal causation
Sensationalized headlines are dangerous
Science outreach without jargon is important
The study itself is fascinating and her discussion of it puts a different emphasis on it that helped me gain more from it. I naturally focused on the imaging aspect.
The images that they show are volume differences from one group to another. The very complex part of it, is that you have to use a brain atlas to make sure you are comparing the hippocampus in subject A with the hippocampus in subject B, for example. The atlas is necessary because, as the study demonstrates, not everyone has the same size substructures of the brain. John Csernansky is one of my boss’s collaborators, so I can talk to him about the study.
This is why we stress in our community that posts should summarise the science behind an article in detail. The link should be there for people who want to read further (and if you write a good post, people will be more willing to click on a link!).
I’ve talked about sensationalized headlines and science outreach before:
Why Correlation is not Causation: Cannabis Use & Schizophrenia
As so often happens, a post from Science on Google+, a community I help moderate, has got me thinking about how easy it is for headlines to quickly lead to #ScienceMediaHype . A post with a link to a news story has the headline, “Teen Marijuana Use Linked with Schizophrenia” (http://goo.gl/w09d7L). As a sociologist with an interest in mental health, this sets off alarm bells. The discussion on our community quickly turned into a debate about the correlation presented in the headline. As a few of our community members pointed out, correlation does not equal causation. My post provides a summary of the actual study and I discuss the sociological problems associated with media coverage of mental illness.
Study on Working Memory
The linked article does an okay job of describing the study but the headline and its focus over-extends the study’s findings. This is the problem with media stories: headlines can shape the way the public understands scientific findings. Journalists present quotes from scientists that fit the angle of their story, putting less emphasis on other aspects of the research.
The study is published in Schizophrenia Bulletin. The sample includes 44 healthy controls, 10 people with a history of cannabis use disorder (CUD), 28 schizophrenia participants with no history of substance use, and 15 schizophrenia patients with a CUD history (http://goo.gl/EQQx2K). Ninety percent of the participants who had schizophrenia already had a CUD history prior to their mental illness. Most of the cannabis users were heavy users, smoking cannabis daily or at least weekly, and most also smoked cigarettes heavily, a variable that the researchers wanted to test.
The study actually tests working memory deficiency not the cause-effect relationship between schizophrenia and cannabis use. Participants were given memory activities and then brain imaging was used to see their brain patterns. I’ve included the three images from the study. Neuroscience is not my area of research, but I include the diagrams in case other researchers should be interested.
The researchers note that without substance abuse, schizophrenia inhibits cortical development. They note less is known about how cannabis affects brain symmetry, though it is known to disrupt the hippocampus, which is related to our limbic system. The hippocampus is linked to information retention for both short and long-term memory as well as other functions like spatial navigation.
The study finds that use of cannabis at an early age impacted memory function. The sample had an average age of 24, so patterns associated with longer-term development need further study.
The study observes that cannabis users and the participants living with schizophrenia both have problems with memory tasks. At the same time, the researchers not that the brain asymmetry observed when carrying out memory tasks may be linked to a” neurobiological vulnerability” among schizophrenia sufferers. That is, that the observed pattern may be the outcome of a predisposition to substance abuse. For example, the researchers note that similar brain patterns are found amongst cocaine users. So, to put it another way, schizophrenia users may be drawn to substance abuse. More on this below.
Finally, the authors conclude what many of our community members had been discussing: that there is no direct cause and effect relationship. “Although our data may be compatible with a causal hypothesis, the cross-sectional data do not allow us to test causal relationships or reject alternative explanations. Thus, the shape differences could be explained as either due to the effects of chronic cannabis abuse or the presence of biomarkers that characterize a vulnerability to the effects of cannabis.”
Their research notes that with laws changing, cannabis may be more readily available to youth with a predisposition towards schizophrenia. This makes their research all the more pivotal. This is both in terms of better understanding how brain development is affected by schizophrenia and the social, health and subjective reasons why youth may engage in cannabis use at different stages of their disease.
Research on Correlation
There are many studies that have linked self-reported cannabis use in early adulthood to an increased risk of developing schizophrenia later in life. One of the most widely cited studies involves Swedish conscripts of 1969, with a follow up study confirming the results (http://goo.gl/7uw0hK). Nevertheless, the direct association between cannabis use and schizophrenia is disputed. For example, there is more to be learned about the relationship between the time that someone starts using cannabis and their first schizophrenic episode (http://goo.gl/waOgfR).
There are three hypotheses to explain why young people with schizophrenia use cannabis (http://goo.gl/ZOSk7H).
1) Cannabis triggers the disease in people with a predisposition, as is suggested by the study at hand.
2) People with schizophrenia use cannabis as a way to self-medicate or manage their experience of the disease. The research does not support this strongly, though cannabis use may give sufferers a perception of control over their disease. This is not something to be dismissed and requires further research. One study from 2012 suggests that one component of marijuana, cannabidiol, may be used to treat schizophrenia. This component does not contain THC which is responsible for the intoxication effects of traditional marijuana. Instead, cannabidiol may reduce the symptoms of psychosis, but further research is needed to fully test this treatment (http://goo.gl/NPGKjm).
3) Cannabis use can trigger schizophrenia through confounding variables. This is the prevailing medical view, though the association is not so neatly weaved together.
Problems with Media Coverage of Mental Illness
The article that covered this story went for a shock value headline. Headlines prime audiences about what they should expect from a scientific article. Sensationalised headlines invite personal opinion based on individual experience. This may range from “I smoke pot and I’m fine” to disparaging comments about “crazy” people. This is the problem with the way in which news headlines shape public discussions of science. Should people read an article before discussing the soundbite? Of course. Does this happen in practice? Not as much as it should. The idea that sensational headlines “sell” is flawed. Shock headlines sometimes get people to click on a link. On a social media site like Google+, some people will go off the headline and the text in a post. In fact, most of the social media research shows that people rarely want to click away from the social site they’re currently on (more on this in another post). This is why we stress in our community that posts should summarise the science behind an article in detail. The link should be there for people who want to read further (and if you write a good post, people will be more willing to click on a link!).
While research suggests that people are sceptical of media reports, not everyone is trained to think about research the way scientists do. Paywalls also stop people from reading the study for themselves (as well as the technical language used in academic journals). This is why scientists need to step up and debunk bad science journalism.
Moving Beyond Individual Speculation
The research has established a correlation, but causation is disputed. The evidence strongly suggests that cannabis compounds schizophrenia and the gravity of this finding cannot be reduced. Nevertheless, media stories that run with a causation headline only serve to spread misinformation.
Bad science writing invites cannabis users to say: “I use it and I’m fine!” It also serves to reinforce a cultural stereotype that people with mental illness may have avoided their condition if they’d only stayed away from recreational drugs. In the end, the causation narrative does more damage and serves only to stigmatise both cannabis users and schizophrenic sufferers as deviants. People living with schizophrenia are doubly stigmatised as their cannabis use makes it seem as if they are wilfully contributing to their illness. Research is seeking to better understand why some people with schizophrenia rely on cannabis.
Mental health is a serious matter. It shouldn’t be reduced to an alarmist headline. Mental illness is part of the human condition. Addressing the treatment of schizophrenia requires compassion, not judgement. Most of all it needs solid scientific research, not dismissive condemnation based on personal or social conjecture.
