It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Thieves across U.S. mistake hemp fields for marijuana Thieves have mistaken hundreds of thousands of acres of newly legal hemp plants for their close cousin -- marijuana -- across the country this year. Across the country, newly legal hemp plants are being mistaken for their close cousin, marijuana -- and they're attracting thieves.
Putin dismisses Trump impeachment, urges talks for missile treaty In his annual Christmastime address on Thursday, Russian President Vladimir Putin dismissed the impeachment of U.S. President Donald Trump, saying the historic step was predicated on "invented reasons."
UPI.COM
Long work hours at the office linked to both regular and hidden high blood pressure
Office workers who spend long hours on the job are more likely to have high blood pressure, including a type that can go undetected during a routine medical appointment, according to a new study published today in the American Heart Association's journal Hypertension.
High blood pressure affects nearly half of Americans ages 18 and older and is a primary factor in more than 82,000 deaths per year. Approximately 15-30% of U.S. adults have a type of the condition called masked hypertension, meaning their high blood pressure readings are normal during health care visits but elevated when measured elsewhere.
The new study, conducted by a Canadian research team, enlisted more than 3,500 white-collar employees at three public institutions in Quebec. These institutions generally provide insurance services to the general population. Compared with colleagues who worked fewer than 35 hours a week:
Working 49 or more hours each week was linked to a 70% greater likelihood of having masked hypertension and 66% greater likelihood of having sustained hypertension- elevated blood pressure readings in and out of a clinical setting.
Working between 41 and 48 hours each week was linked to a 54% greater likelihood of having masked hypertension and 42% greater likelihood of having sustained hypertension.
The findings accounted for variables such as job strain, age, sex, education level, occupation, smoking status, body mass index and other health factors.
"Both masked and sustained high blood pressure are linked to higher cardiovascular disease risk," said lead study lead author Xavier Trudel, Ph.D., assistant professor in the social and preventive medicine department at Laval University in Quebec, Canada.
"The observed associations accounted for job strain, a work stressor defined as a combination of high work demands and low decision-making authority. However, other related stressors might have an impact," Trudel said. "Future research could examine whether family responsibilities—such as a worker's number of children, household duties and childcare role—might interact with work circumstances to explain high blood pressure."
The five-year study involved three waves of testing—in years one, three and five. To simulate in-clinic blood pressure readings, a trained assistant provided participants with a wearable monitor to check each participant's resting blood pressure three times in one morning. For the rest of the workday, the participant wore the blood pressure monitoring device, which took readings every 15 minutes—collecting a minimum of 20 additional measures for one day. Average resting readings at or above 140/90 mmHg, and average working readings at or above 135/85, were considered high.
In all, almost 19% of the workers had sustained hypertension, which included employees who were already taking high blood pressure medications. More than 13% of the workers had masked hypertension and not receiving treatment for high blood pressure. "The link between long working hours and high blood pressure in the study was about the same for men as for women," Trudel said.
The study "did not include blue-collar workers (employees who are paid by the hour and perform manual labor work in positions such agriculture, manufacturing, construction, mining, maintenance or hospitality service), therefore, these findings may not reflect the impact on blood pressure of shift-work or positions with higher physical demands," the authors said. Other limitations include the study's measurement of blood pressure only during daytime hours, and the omission of hours worked outside participants' primary job.
The authors noted several strengths of the study, including its many volunteers, accounting for multiple factors that can impact blood pressure, repeated testing over several years, the use of wearable monitors instead of relying on workers' reports of their blood pressure readings; and the use of the same monitors for all blood pressure measurements.
"People should be aware that long work hours might affect their heart health, and if they're working long hours, they should ask their doctors about checking their blood pressure over time with a wearable monitor," Trudel said. "Masked hypertension can affect someone for a long period of time and is associated, in the long term, with an increased risk of developing cardiovascular disease. We have previously shown that over five years, about 1 out of 5 people with masked hypertension never showed high blood pressure in a clinical setting, potentially delaying diagnosis and treatment."
ANIMAL EXPERIMENTATION
Mice subjected to shift work schedule start developing diabetes
CAPITALISM KILLS
by Sun Yat-sen University, China
Credit: CC0 Public Domain
Exposing mice to a light-dark cycle meant to mimic the schedule of human shift workers changes insulin sensitivity and glucose tolerance in the animals, according to a study published December 18, 2019 in the open-access journal PLOS ONE by Bo Zhang of Southern Medical University, China, and colleagues.
Biological clocks, synchronized with environmental light and dark cycles, are responsible for not only mediating the timing of sleep and hunger cues, but regulating glucose homeostasis and metabolism. Studies have previously shown that mutations in key clock genes can lead mice to rapidly develop metabolic disorder and obesity.
In the new work, researchers exposed female mice to a constantly shifting light-dark cycle. For four days out of each week, 12 hours of light and 12 hours of dark were aligned to the mice's previous schedule. For three subsequent days, the schedule jumped forward by eight hours, with darkness beginning partway through the normal light period. After four weeks of this alternating schedule, the researchers measured the glucose tolerance, insulin tolerance, and insulin secretion of the mice at multiple time points throughout the day, as well as food intake and physical activity. Control mice were kept on a static 12-hour light-dark cycle for the whole four weeks.
The current study was limited by the fact that only female mice were studied and sleep data was not collected. However, should the glucose tolerance patterns seen in these mice occur also in human shift workers, this could lead to a mismatch between glucose uptake rhythms and meal timing, with glucose intolerance occurring during meals. Changes to both insulin sensitivity and glucose tolerance could put shift workers at greater risk of developing Type II diabetes.
Zhand adds: "The effect of circadian disruption induced by light at night on glucose metabolism in shiftwork population and even in general population is a serious concern
More information: Li-Xin Zhong et al. Circadian misalignment alters insulin sensitivity during the light phase and shifts glucose tolerance rhythms in female mice, PLOS ONE (2019). DOI: 10.1371/journal.pone.0225813
A drug that provides the benefits obtained from medicinal cannabis without the "high" or other side effects may help to unlock a new treatment for Parkinson's disease.
The drug—HU-308—lessens devastating involuntary movements called dyskinesias, a side effect from years of treatment for Parkinson's disease.
The research, published today in Neurobiology of Disease, has been conducted by the Centre for Neuroscience and Regenerative Medicine (CNRM) at the University of Technology Sydney (UTS) and the Applied Medical Research Institute of St Vincent's Hospital Sydney.
The study shows that in mice HU-308 is as effective as amantadine, the only available treatment for dyskinesias. Furthermore, the combination of HU-308 with amantadine is more effective than either drug used alone.
Professor Bryce Vissel, director of the CNRM and senior author of the study, said the findings present the possibility of new options for Parkinson's patients.
"Our study suggests that a derivative of HU-308, either alone or in combination with amantadine, may be a more effective treatment for dyskinesias and a much better option than using an unproven potentially harmful substance like cannabis," Professor Vissel said.
"Currently there is limited evidence about the effectiveness of medicinal cannabis. One problem is that no cannabis preparation is the same and cannabis has numerous effects, some of which may not be beneficial in Parkinson's disease."
Cannabis works on several receptors in the brain—CB1 and CB2. The psychoactive effect is caused mostly because of receptor CB1.
Professor Vissel said the HU-308 drug explored by his team works only on receptor CB2, allowing medicinal benefits to be administered without causing psychoactive effects like drowsiness or highness.
Lead author Dr. Peggy Rentsch said it is unclear whether medicinal cannabis itself can help Parkinson's patients.
"Medicinal cannabis contains different compounds, some of which make you high and which can impact a person's normal day-to-day activities," Dr. Rentsch said.
"Our research suggests HU-308 is an important prototype drug which we believe won't interfere with patients' day-to-day activities. They should maintain normal levels of mental sharpness on a treatment like this."
Professor Vissel and his team are investigating ways to block inflammation of the brain to maintain and restore memory and slow the progression for both Parkinson's disease and Alzheimer's disease.
"HU-308 works by reducing inflammation in the brain, affecting the neurons and immune cells.
"In neurological disorders, the immune cells in the brain can lose supportive function with adverse stimuli—including but not limited to trauma or obesity—and become 'activated.' Scientists at the CNRM believe that, after this activation, the immune cells backfire, kill the brain's neurons, destroy them—and become dysfunctional.
"By reducing inflammation in the brain—such as with HU-308—these immune cells can support normal neural function again, rather than inhibiting it."
Study collaborator Dr. Sandy Stayte said: "The fact that amantadine has its own set of side effects, may not work in the long term, and is still the only drug available on the market that is approved for dyskinesias makes our study really exciting.
"First, our study shows HU-308 is equally affective so a drug like HU-308 will be useful for those people who can't take amantadine. Second, for those who can tolerate amantadine, taking the combination may have even greater benefits than taking either drug alone. That means we may end up with a much more powerful treatment than currently available by ultimately prescribing both."
The paper "Targeting the cannabinoid receptor CB2 in a mouse model of l-dopa induced Dyskinesia" is published in the journal Neurobiology of Disease.
New cannabinoid research shows potential for targeted drug therapy
Researchers from the University of Aberdeen have identified parts of a gene that could open the door to treatment with medical cannabis for millions of people.
Although promising, the potential of cannabinoids in treating disease, addiction and obesity has been hampered due to the unpredictability of adverse side-effects which can include depression and psychosis. At present there is no way to predict which people will experience these side-effects, but Dr. Alasdair MacKenzie and his team, including leading cannabis researcher Professor Roger Pertwee, are working towards making these predictions.
In a study published in Psychoneuroendocrinology, Dr. MacKenzie and Dr. Elizabeth Hay from the School of Medicine, Medical Science and Nutrition at the University, used revolutionary DNA sequencing, CRISPR technology to study specific areas of the gene that make cannabis receptors in the brain. According to their research, these previously ignored gene regions may hold the key to understanding why people respond differently to some drugs and could help inform treatments tailored to the individual.
Dr. MacKenzie explains: "We found that there was a genetic switch within the cannabis receptor in humans and mice and which had remained almost unchanged for hundreds of millions of years. This switch controlled the expression of the receptor in a part of the brain that modulates mood. We found that when we disrupted this switch in mice, alcohol intake and anxiety levels were reduced, as were the effects of cannabinoids.
"This means that we are helping to establish a functional role for this switch which may help us understand how it responds to cannabinoids. Going forward, this will contribute to unlocking the potential of medicinal cannabis."
Targeted drug therapy could dramatically increase the effectiveness of medicinal cannabis by eliminating the risk of harmful side-effects and this research has moved a step closer to that.
In a related study the team that were also able to identify a genetic change in the switch which occurred in about 20% of people. In a second paper published in Human Mutation, the team concluded that this may increase susceptibility to side effects in these individuals.
Dr. MacKenzie explains: "Cannabinoids are amazing source of drug therapies however the side effects that some people suffer hampers the development of these drugs. We need to know why people respond differently to drugs? Why do some people suffer depression and psychosis when taking cannabis when others don't? By identifying the people who could suffer from these adverse effects we could try to develop personalized medicine."
"It is hoped that this "gene switch" based approach may accelerate the development of more effective "personalized" cannabinoid-based drug treatments to treat obesity, addiction and mood disorders more safely. "
Professor Pertwee who is an internationally recognised leader in the therapeutic potential of cannabinoids added: "By starting to look at the effects of genetic changes on the switches that turn genes on and off in specific cells and at specific times, instead of changes in the genes themselves, we can begin to understand how drug side effects arise in different patient groups and focus treatment using these drugs on those who would most benefit. "
More information: Elizabeth . Hay et al. Disruption of an enhancer associated with addictive behaviour within the cannabinoid receptor-1 gene suggests a possible role in alcohol intake, cannabinoid response and anxiety-related behaviour, Psychoneuroendocrinology (2019). DOI: 10.1016/j.psyneuen.2019.104407
Elizabeth A. Hay et al. Disease‐associated polymorphisms within the conserved ECR1 enhancer differentially regulate the tissue‐specific activity of the cannabinoid‐1 receptor gene promoter; implications for cannabinoid pharmacogenetics, Human Mutation (2019). DOI: 10.1002/HUMU.23931 Journal information: Psychoneuroendocrinology
Vancouver’s Right-Wing Municipal Party Just Moved Even Further to the Far-Right
NPA supporters jump ship after far-right activists take over the party, despite the NPA’s long history of pushing right-wing policies
December 16, 2019
People are abandoning Vancouver’s right-wing political party amid accusations that the party has shifted even further to the far-right.
Last week, Rebecca Bligh, a city councillor with the Non-Partisan Association party, announced her resignation from the NPA after the party elected a new executive with extreme, far-right views.
In a statement posted on Facebook, Bligh complained that the new party executive included “anti-SOGI” activists who oppose LGBTQ rights.
After considerable discussions with my family, I made the personal decision to resign from the NPA Party and remain on Vancouver City Council as an independent. My full statement is attached. https://t.co/EvqAxbuA0E
Christopher Wilson, another newly elected NPA board member, is a former Rebel Media personality. In 2017, he made national headlines after Catherine McKenna, then the federal environment minister, confronted him about referring to her with a sexist nickname.
A number of current NPA councillors and former NPA candidates also criticized the party’s new board, including 2018 mayoral candidate Ken Sim, 2018 council candidate Justin P. Goodrich, ex-councillor George Affleck and sitting councillor Sarah Kirkby-Yung.
But party insiders who complain the NPA is losing its “progressive” identity might be overlooking the party’s long history of promoting hard right-wing policies:
1. The NPA provoked the second longest strike in Vancouver’s history
Former NPA mayor Sam Sullivan oversaw an 88-day strike of Vancouver’s civic workers in 2007. At the time, CUPE leaders accused Sullivan of refusing to negotiate on pay increases and job security for workers, resulting in widespread disruptions to city services.
2. The NPA voted against a tax increase designed to help ease the city’s opioid crisis
In 2016, Council voted to increase property taxes by 0.5% (around $4 for condo owners, $11 for single family homes) to help pay for resources to deal with the city’s fentanyl and opioid crisis.
Voting against that measure, NPA councillor Melissa De Genova said “it’s easy for us to make that decision, $4 more, $10 more, hundreds of dollars more — it all depends on your property value.”
4. NPA councillors voted against the creation of an empty-homes tax
NPA councillors voted against the introduction of the city’s Empty Homes Tax and regulations on short-term rentals. The measures were introduced in an effort to tackle global real estate speculation. However, Affleck called the measures “tax cash-grabs to increase bottom line revenue for the city.”
5. The NPA forced out its own sitting mayor because he supported harm reduction
NPA officials contested the nomination of long-serving NPA mayor Philip Owen after he sought a fourth term in the 2002 election over his pursuit of a harm-reduction strategy to tackle the city’s overdose crisis.
Owen lost the nomination, and the NPA’s candidate went on to lose the election.
6. An NPA councillor voted against the city’s reconciliation efforts
NPA councillor Colleen Hardwick recently voted against Vancouver’s City of Reconciliation report.
Hardwick told the Vancouver Sun: “Are we a local government? Or are we a values-based organization. I just wish there was more education and a little less ideology.”
Natural causes are the key driver of change in Athabasca Delta flood patterns, research shows by Matthew Grant, University of Waterloo THE CHEMICAL PROCESS OF DILUTION [EP] "It's clear from our research that lakes in the Athabasca Delta have been largely influenced by shifting river paths within the delta," said Mitchell Kay, a Ph.D. candidate at Waterloo and lead author of the studies. "Our findings also identify that concentrations of metals supplied by the Athabasca River have remained unchanged during the past 150 years."
About 80 per cent of the Peace-Athabasca Delta is
contained within Wood Buffalo National Park,
one of Canada’s 20 UNESCO World Heritage Sites.
Credit: Mackenzie Schultz
Natural environmental processes—not upstream energy projects—are the primary cause of changing flood patterns in Alberta's Athabasca Delta, new research shows.
The research also shows there is no evidence to support the perception that energy projects have increased the amount of metal pollutants in the delta ecosystem.
Two recent studies, led by researchers at the University of Waterloo and Wilfrid Laurier University, found that natural changes to the river paths alongside climate impacts remain the dominant influences in the Athabasca Delta. In this area, recent lake drying and an increased perception of pollution have been widely attributed to the WAC Bennett Dam and oil sands developments, which are located upstream.
"It's clear from our research that lakes in the Athabasca Delta have been largely influenced by shifting river paths within the delta," said Mitchell Kay, a Ph.D. candidate at Waterloo and lead author of the studies. "Our findings also identify that concentrations of metals supplied by the Athabasca River have remained unchanged during the past 150 years."
"These findings provide important information to the Government of Canada, First Nations, and UNESCO, who are currently reviewing the World Heritage status of Wood Buffalo National Park, which houses a large portion of the delta."
About 80 percent of the Peace-Athabasca Delta is contained within Wood Buffalo National Park, one of Canada's 20 UNESCO World Heritage Sites. There are ongoing discussions between the Government of Canada, UNESCO and First Nations in the area about the conservation status of the park and whether it should be downgraded to a "World Heritage in Danger" site.
The studies analyzed cores of sediment that has settled at the bottom of floodplain lakes across the Athabasca Delta, providing a record of the flooding and metal concentrations over the past 150 years.
These records show that the major change to flooding patterns in the delta occurred after 1982, with some areas of the delta experiencing a marked increase in flooding, while other areas flooded less. The researchers attribute this change to a natural erosion event that occurred in 1982 when the Embarras River broke through its bank, substantially shifting the direction of river flow within the delta. This event is known as The Embarras Breakthrough.
"While there is broad consensus that the lake and river water levels have been declining in recent years, there is considerable controversy over the cause," said Roland Hall, a biology professor at Waterloo who has been studying the region for 20 years. "Our research clearly shows drying in much of the Athabasca Delta began in 1982, which corresponds to the Embarras Breakthrough event, not to operation of the WAC Bennett Dam, which began in 1968."
Further analysis of the sediment showed that metals of concern, found abundantly in the bitumen mined upstream of the delta, have remained within the natural range of concentrations that have existed for at least the past 150 years.
The study established baseline levels of six different metals of concern prior to oil sands development, and found no evidence supporting the common perception that pollution from the oil sands industry has reached the downstream Athabasca Delta.
This research was completed by Kay, Hall, collaborator Brent Wolfe of Wilfrid Laurier University, and members of their research teams, and published in the journals Environmental Research Communications and Science of the Total Environment.
More information: M L Kay et al. Bi-directional hydrological changes in perched basins of the Athabasca Delta (Canada) in recent decades caused by natural processes, Environmental Research Communications (2019). DOI: 10.1088/2515-7620/ab37e7
M.L. Kay et al. Evaluating temporal patterns of metals concentrations in floodplain lakes of the Athabasca Delta (Canada) relative to pre-industrial baselines, Science of The Total Environment (2019). DOI: 10.1016/j.scitotenv.2019.135309
Studies find Alberta oil sands development not a major source of long-distance air and water pollution by University of Waterloo
(Phys.org)—Oil sands development in northern Alberta isn’t polluting the nearby Peace-Athabasca Delta via the air and water to the extent many may believe, two recently published University of Waterloo research studies have found.
The research revealed that Alberta oil sands emissions haven’t increased the amount of metal and organic contaminants travelling via the atmosphere to the delta, located 200 km north of the oil sands industry. And it determined that oil sands mining activity hasn’t measurably increased the delivery of organic contaminants to shallow delta lakes via the Athabasca River.
The findings by researchers at the University of Waterloo and Wilfrid Laurier University counter the belief that human health, wildlife, and ecosystems are suffering as a result of long-distance transport of contaminants from the oil sands development.
“This evidence is essential in guiding responsible development of the oil sands while recognizing its true impact and benefits,” says Terry McMahon, dean of science. “It demonstrates the value that comprehensive research and the generation of knowledge can have on future decisions that affect our health, economy, and environment.”
Earlier in September, the study "“Has Alberta oil sands development increased far-field delivery of airborne contaminants to the Peace-Athabasca Delta?"”examining the transport of metal contaminants from the oil sands by air was published in Science of the Total Environment. It shows that key metals of concern including lead, antimony, arsenic, and mercury declined during the period when Alberta oil sands production was increasing dramatically. For these studies, researchers used lake sediment records spanning the past 200 years to provide critical knowledge of baseline, pre-development levels of metal and organic contaminant deposition, and to measure changes over time since the onset of oil sands development.
“The results of this study are significant in providing the knowledge needed for meaningful debates about the environmental exposure and effects of oil production at the world’s second-largest proven reserve,” says Roland Hall, principal investigator on the study and professor in the Department of Biology. “Indeed, our data show that toxic metals like arsenic and lead travelling via the atmosphere have declined dramatically in recent decades despite the growth of Alberta’s oil sands industry. And, we were unable to detect an increase in organic contaminants transported by the Athabasca River above natural levels delivered by floodwaters.”
The study may provide a foundation to map the footprint of emissions travelling via the air and water from oil sands operations over space and time, which could be a valuable contribution to Environment Canada’s new oil sands monitoring program.
This Landsat-8 image covers a distance of over 350 km from top to bottom, all within Canada's Alberta province.
To the north, blue lake waters are visible, interspersed with rivers and creeks. This area makes up the world's largest freshwater inland river delta, where the Peace and Athabasca rivers converge on the Slave River and Lake Athabasca (the water body in the upper right).
Lake Claire to the left is also part of this delta system, and lies within the Wood Buffalo National Park – Canada's largest.
The lower half of the image is part of a wider area known as the Athabasca oil sands, which has the world's largest known reservoir of crude bitumen, which can be upgraded to crude oil using technology that extracts the oil from the soil using chemicals.
Boreal forests and peat bogs in this area are being destroyed by open-pit mining and hydraulic fracturing – 'fracking' – for heavy crude oil.
Boreal forests cover nearly half of the province, but about 20% has been disturbed by open-pit mining, some of which are visible in the lower-right. In addition to deforestation, these activities cause pollution and push wildlife from their preferred habitats.
This image, also featured on the Earth from Space video programme, is just one of more than 130 satellite images on display at the Palazzo delle Esposizioni in Rome, Italy, until 2 November.
As part of the 'My Planet from Space: Fragility and Beauty' exhibition, the collection takes you on a journey to some of the most beautiful and remote places on Earth, demonstrating the fragility of our planet and the challenges posed by human activities and climate change.
New insights into our multi-millenia battle with malaria
Humans have long been thwarted by 'the fever'. References to malaria's infamous febricity are found across antiquity, from writings by the four thousand-year-old Vedic sages of ancient India to the Greek physician Hippocrates. But the disease, caused by a group of parasites belonging to the Plasmodium genus, has troubled our ancestors and close relatives for much longer. A range of malaria species infect apes, monkeys and birds across the tropical world and we now know that about 50,000 years ago the ancestors of Plasmodium falciparum, the parasite responsible for most of the current human burden of the disease, transformed from infecting gorillas to parasites that can infect us.
This means that throughout our history, wherever the ecological conditions have been able to support the mosquitoes that transmit the disease (including the marshes of Kent well into the 19th Century) we've been accompanied by the blood parasite which many believe to be one of the largest killers of people in human history. Reports of malaria killing half of the people who have ever lived are likely to be wide of the mark, however.
Given this shared history, you might expect humans to have evolved ways to neutralise the devastating impact of malaria. In evolutionary terms, the stakes are high—falciparum malaria is most deadly in young children—so there is a clear advantage to adapting to beat the parasite. And, because evolution works with new mutations in DNA that cause genes to work in new and different ways, adaptations that gave our ancestors one up against the parasites should be found across the human genome.
One such adaptation was discovered in the 1950 when Anthony Allison observed that there tended to be more people with sickle cell trait in malarial areas than places without the disease. Perhaps, he thought, because sickle cell trait affects the function of people's blood cells, it afforded some sort of protection against malaria parasites, which thrive by infecting their host's blood cells. This idea was a development of the 'Malaria Hypothesis', invented in 1948 by famed geneticist JBS Haldane, which proposed that certain human traits, particularly those involving blood groups, rise to high frequencies in some populations because they protect people from malaria. The relationship between sickle cell and malaria was soon confirmed when children in Uganda with sickle cell trait were shown to have fewer malaria parasites in their blood than those without the trait. Sickle cell trait is now known to be caused by a single letter change in the genetic code and is the canonical example of human evolution to infectious disease.
Epidemiological research over the intervening years has provided further evidence of human adaptation to malaria. But to go further and investigate the impact of malaria on our DNA requires large well curated datasets of DNA from across the tropics. And, because much of the burden of malaria is in Africa, whose populations are among the most genetically diverse on earth, we also need to think carefully about the statistical approaches that can tease out the real genetic signals from background variation.
Addressing old problems with new data
Big datasets and statistical methods have recently become available thanks to large long-term international collaborative efforts. One such collaboration is the Malaria Genomic Epidemiology Network (MalariaGEN), a global network of malaria researchers that have worked together over the last 20 years to build the largest dataset of human genomes yet assembled for malaria research.
In a new paper using data from over 17,000 people from nine African countries, Vietnam and Papua New Guinea, we explored the extent to which adaptation to malaria has left footprints in the human genome. We used a method called Genome Wide Association Study (GWAS) which compares the DNA of people who have suffered from severe malaria with a control set of people who did not have the disease. The concept of a GWAS is straightforward: you scan these two groups of genomes to look for systematic differences in the genetic code between the malaria cases and the population controls. In practice though this is incredibly difficult as there are many places in the genome where these two groups might differ for reasons that have nothing to do with malaria. Nevertheless, with appropriate care, it is possible to identify regions of the genome where such differences occur, and these provide evidence of association with malaria susceptibility and hint that they might have played a role in evolution against malaria.
Blood cell evolution
Our GWAS found five regions of the genome with convincing evidence of association with malaria. Encouragingly, four of these regions contained genes involved with blood cell formation and function, which one might expect given that this is where the parasites attack. The most compelling case for genetic association with malaria is the gene controlling sickle cell trait, mentioned above. Individuals with this trait were up to ten times less likely to get malaria than those without. We found further evidence of protection from malaria at the gene that controls the main human ABO blood groups. Our analysis supports previous work that has shown that being blood group O in Africa offers some protection from severe malaria. But this association is complex, and strangely, you are at a greater risk of contracting severe malaria in Papua New Guinea with this blood group. Our analysis also corroborated our recent discovery that the individual's carrying the Dantu blood group are protected from malaria. This blood group is rare however, and currently mainly found in people from East Africa, particularly Kenya.
Whilst we are confident that all five of these regions are associated with malaria, together they only account for about 10% of the genetic contribution to malaria susceptibility. Given the size of the dataset this a conundrum: it suggests that although we know that there are more genetic variants that influence an individual's malaria susceptibility, we don't know what they are. One possibility is that malaria susceptibility is controlled by many genetic variants spread across the whole genome, each with a small individual effect. This so-called polygenic model of adaptation is increasingly being used to explain predisposition to a number of diseases, and although our method is less good at picking up these types of signal, it's an avenue for future work. Another possibility is that variation in especially complex regions of the genome, that are hard to access using our current data, is involved. Finally, it's also possible that the parasite has itself evolved to overcome human adaptation in an evolutionary arms race. Parasites and humans may have been adapted to each other in slightly different ways in different parts of the world, so the mutations that help against the parasite in East Africa might not be so helpful in West Africa. Future work is planned to explore the fascinating idea of human-parasite coevolution.
So, have the loci we've discovered been driven to high frequency by natural selection, as Haldane suggested? Well yes and no. We found that these variants are systematically more likely to be found in individuals from sub-Saharan Africa than from regions where malaria has been less prevalent, showing how the genomes of Africans have been shaped through millennia of onslaught from the malaria parasite. But the variants themselves are quite different to each other, with some being very rare except in specific geographical locations, and some found at high frequency all over the globe. This suggests that further factors might be at play. Our paper highlights the potential advances in understanding that large, coordinated data sharing networks can provide in the battle against this most ancient foe.
The full paper, 'Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania,' can be read in Nature Communications.
