• Influenza, or flu, outbreaks are recurrent and every year pose  a significant risk to global health
• Influenza affects millions: each year 3m to 5m cases of severe disease and 500,000 deaths
• Pandemics occur about three times a century
• The 1918 flu pandemic killed 21m . . . Total deaths in World War I was 17m
• Effective treatment of patients with respiratory illness depend on accurate and timely diagnosis
• Early diagnosis of influenza can reduce the inappropriate use of antibiotics and provide the option of using antiviral therapy
• Rapid Influenza Diagnostic Tests (RIDTs) are useful in determining whether outbreaks of respiratory disease might be due to influenza
• RIDTs vary in their sensitivity, specificity, complexity, and time to produce results
• There is a pressing need for faster, cheaper, and easier-to-use flu tests with higher levels of sensitivity and specificity than those currently available
• The large, fast-growing, global and under-served RIDT market drives a host of initiatives
• Various development challenges pose significant threats

 
What challenges face developers of cheap, easy-to-use, rapid and accurate diagnostic tests for influenza, or flu, which improve on tests currently available?
 

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Influenza

Influenza is a highly contagious respiratory illness caused by a virus, and occurs in distinct outbreaks of varying extent every year. Its epidemiologic pattern reflects the changing nature of the antigenic properties of influenza viruses. The viruses subsequent spread depends upon multiple factors, including transmissibility and the susceptibility of the population. Influenza A viruses, in particular, have a remarkable ability to undergo periodic changes in the antigenic characteristics of their envelope glycoproteins; the hemagglutinin and the neuraminidase. Anyone can get influenza. It is usually spread by the coughs and sneezes of an infected person. You can also catch flu by touching an infected person (e.g. shaking hands). Adults are contagious one to two days before getting symptoms and up to seven days after becoming ill, which means that you can spread the influenza virus before you even know you are infected. Influenza presents as a sudden onset of high fever, myalgia, headache and severe malaise, cough (usually dry), sore throat, and runny nose. There are several treatment options, which aim to ease symptoms until the infection goes, and aims to prevent complications. Most healthy people recover within one to two weeks without requiring any medical treatment. However, influenza can cause severe illness or death especially in people at high risk such as the very young, the elderly, and people suffering from medical conditions such as lung diseases, diabetes, cancer, kidney or heart problems.

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Costly killer

Influenza is a cruel, costly killer with a history of pandemics. It causes millions of upper respiratory tract infections every year as it spreads around the world in seasonal epidemics, and poses on-going risks to health. The most vulnerable are the young, the old and those with chronic medical conditions such as heart disease, respiratory problems and diabetes. Each year, on average 5% to 20% of populations in wealthy countries get influenza. In the US it causes more than 200,000 hospitalizations and 36,000 deaths annually, and each year costs the American economy between US$71 to US$167bn.
 

History of pandemics

The 1918-19 “Spanish Flu” pandemic caused 21m deaths, and was one of three 20th century influenza pandemics. At least four pandemics occurred in the 19th century, and the first pandemic of the 21st century was the 2009 “Swine Flu”. Its virulence and global human impact was less deadly than originally feared, but it still resulted in 18,449 laboratory confirmed deaths. If you account for people who died as a result of complications precipitated by the Swine Flu, the actual death toll is significantly higher. Mindful of the potential accelerated spread of a pandemic subtype of the influenza virus, the World Health Organization (WHO), and national governments continuously monitor influenza viruses. Assessment of pathogenicity and virulence is the key to taking appropriate healthcare actions in the event of an outbreak.

However, without widespread access to improved diagnostic tests, each year millions will not receive timely anti-viral medication, tens of thousands of influenza sufferers will develop complications, and thousands will die unnecessarily, as the growing interconnections and complexity of the world present an increasing challenge to influenza prevention and control.
 

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The influenza viruses

Influenza is a single-stranded, helically shaped, RNA virus of the orthomyxovirus family. Influenza viruses are divided into two groups: A and B. Influenza A has two subtypes which are important for humans: A(H3N2) and A(H1N1). The former is currently associated with most deaths. Influenza viruses are defined by two different protein components, known as antigens, on the surface of the virus. They are haemagglutinin (H) and neuraminidase (N) components. Influenza viruses circulate in all parts of the world, and mutate at a low level, referred to as "genetic drift", which allows influenza to continuously evolve and escape from the pressures of population immunity. This means that each individual is always susceptible to infections with new strains of the virus. "Genetic shift" occurs when a strain of influenza A virus completely replaces one or more of its gene segments with the homologous segments from another influenza A strain, a process known as reassortment. If the new segments are from an animal influenza virus to which humans have had no exposure and no immunity, pandemics may ensue.

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Gold standard diagnosis rarely used

The gold standard method for the detection of influenza viruses is rarely performed, as patients with suspected influenza are most likely to be seen by a primary care doctor with limited resources, and the gold standard test requires sophisticated laboratory infrastructure, and takes at least 48 hours. Even the faster Reverse Transcription-Polymerase Chain Reaction (RT-PCR) test, which is a relatively new type of molecular assay that uses isothermal amplification of viral cells, has a turnaround time of four to six hours. It is also expensive, and therefore not commonly used.

The slowness and expense of traditional influenza tests led to the development of an array of commercially available Rapid Influenza Diagnostic Tests (RIDTs), which screen for influenza viruses, and provide results within as little as 15 minutes after sample collection and processing. Such tests are largely immunoassays that can identify the presence of influenza A and B viral nucleoprotein antigens in respiratory specimens and display the results in a qualitative way (positive or negative). About 10 such tests have FDA approval and are available in the US. About 20 have been determined suitable for the European market. All are growing in their usage. However, the RIDTs vary in their sensitivity, specificity, complexity, and in the time needed to produce results.
  

Tests rule in Influenza but do not rule it out
 

According to the Centers for Disease Control and Prevention (CDC) the commercially available RIDTs in America have a sensitivity ranging from 50% to 70%. This means that in up to 50% of influenza cases, test results will still be negative. A study showed that tests for the N1H1 virus, a subtype of influenza A that was the most common cause of the Swine Flu in 2009, and is associated with the 1918 Spanish Flu pandemic, have a sensitivity ranging from 32% to 50% depending on the brand of test. A 2012 meta-analysis of the accuracy of RIDTs reported an average sensitivity for detecting influenza in adults of only 54%. Sensitivity in children is somewhat higher since they tend to shed a greater quantity of virus. Thus some 30% to 50% of flu samples that would register positive by the gold standard viral culture test may give a false negative when using a RIDT, and some may indicate a false positive when a person is not infected with influenza. Thus, RIDTs that are currently available allow Influenza to be ruled in but not ruled out. More sensitive tests are needed.
 

New flu tests

There are a number of innovative nano-scale molecular diagnostic influenza tests in development, which are expected to deliver more accurate validations than existing antigen-based molecular tests. The new tests use a platform, comprised of an extremely thin layer of material, which detects the presence of influenza proteins in saliva or blood. This is attached to an electronic chip, which transforms the platform into a sensor. This is an essential part of the measuring device as it converts the input signal to the quantity suitable for measurement and interpretation. The presence of influenza proteins in saliva or blood triggers an electrical signal in the chip, which is then communicated to a mobile phone.
 
Here Roger Kornberg, Professor of Medicine at Stanford University and 2006 Nobel Laureate for Chemistry describes how advances in molecular science are enabling the replacement of traditional in vitro diagnostics with rapid, virtually instantaneous point-of-care diagnostics without resort to complex processes or elaborate infrastructure.  Antiviral drugs for influenza are available in some countries and may reduce severe complications and deaths. Ideally they need to be administered early (within 48 hours of onset of symptoms) in the disease.  An almost instantaneous point-of-care test will enable better access to appropriate treatment particularly in primary care:
 

 

Challenges

Notwithstanding all the recent scientific advances, new and innovative influenza detection tests will need to overcome significant challenges to outperform current RIDTs. In addition to the usual challenges associated with sensitivity and specificity, new developers have to be aware of recent changes in immunochromatographic antigen detection testing for influenza viruses, and the rapid development of commercially available nucleic acid amplification tests. Also, there are the usual development challenges associated with miniaturization, fabrication, scaling, marketing, and regulation. Effective from 13 February 2017, the FDA reclassified antigen based rapid influenza detection tests from class I into class II devices. Class II devices are higher risk than Class I, and require greater regulatory controls to provide reasonable assurance of the device’s safety and effectiveness. This was provoked by the potential for the devices to fail to detect newer versions of the influenza virus. For instance, a novel variant of influenza A,H7N9, has emerged in Asia, and H5N1 is also re-emergent.
 
Another challenge, especially for start-ups with limited resources, is the fluctuating nature of the influenza virus itself. A bad year for patients, when influenza causes millions of people to become ill, is a good year for manufacturers of RIDTs. Conversely, a good year for patients, when influenza affects a lower percentage of the population, is a bad year for manufacturers who suffer from unsold inventory, and reduced revenues. Thus, the vagaries of the flu virus not only have the potential to kill millions of people, they also pose a significant threat to start-ups dedicated to developing RIDTs.
 

Takeaways

Despite all the challenges, there is a significant commercial opportunity in the current under-served global RIDT market for improved tests. Each year, in the US, more than 1bn people visit primary care doctors, and in the UK, the NHS, deals with over 1m patients every 36 hours. The global in vitro diagnostics market was valued at US$60bn in 2016. Between 2016 and 2021, the market is expected to grow at a CAGR of 5.5% to reach US$79bn by 2021. Over the same period, the global point-of-care diagnostics sub-market is expected to grow at a CAGR of 10% to reach US$37bn by 2021. Large corporates, small start-ups, and university research laboratories have spotted the opportunity, and started developing new and innovative RIDTs. Given that each-year influenza causes widespread morbidity as well as mortality, it should be a matter of priority to support all efforts to develop swift and reliable RIDTs. A significant step forward would be a RIDT with greater sensitivity and usability such that the test could be administered and a result given within a 10-minute primary care consultation.

• People are using A&E departments as convenient drop-in clinics for minor ailments because they cannot get GP appointments
• In January 2017 the British Red Cross said A&E was struggling with a "humanitarian crisis" to keep up with a rush of patients over  the winter
• UK’s Prime Minister suggests that all GP surgeries should open from 8am to 8pm, 7 days a week 
• Primary care in England is in crisis, fuelled by a large and increasing demand and a shrinking supply of GPs
• 75% of GPs across 540 general practices over the age of 55 are nearing retirement, and newly trained GPs are seeking employment abroad
• By 2020 there could be a shortfall of 10,000 GPs in England
• Curing the primary care crisis would relieve pressure on A&E departments
• A simple, cheap and easy-to-use online dashboard could help relieve the primary healthcare crisis

 

• Obesity is one of the most serious global public health challenges of the 21^st century and a major cause of type-2 diabetes (T2DM), a life-threatening illness, which costs billions
• 60% of adults in the UK are either overweight or obese, 74% in the US
• Low calorie diets and exercise are difficult to sustain and therefore tend to fail as treatment options 
• Conventional treatments for T2DM have failed to dent the vast and escalating burden of the condition, so interest is increasing in alternative treatment options
• Bariatric (stomach reduction) surgery is a therapy for obesity, which has been shown to “cure” T2DM
• In 2016, 45 international health organizations called for bariatric surgery as a treatment for T2DM
• Is bariatric surgery the biggest step forward in T2DM treatment in 100 years?

Weight loss surgery to treat T2DM

• Tobacco is a legacy recreational drug that causes cancers, and kills over 6m people each year
• No new food, drink, recreational or over the counter drug with a similar adverse health profile would ever be approved in the modern world
• Smoking causes 150 extra mutations in every lung cell
• New research demonstrates that smoking causes cancers in organs not exposed to smoke such as the bladder, kidney and pancreas
• Smoking triggers cell mutations that can cause cancer years after quitting
• Anti-smoking campaigns have decreased the prevalence of smoking, but incidence rates have increased because of population growth
• Identifying all the cancer genes will eventually improve treatments

Tobacco is the only legal drug that kills millions when used exactly as intended by manufacturers. New research into the root causes of cancer demonstrates how tobacco smoke mutates DNA, and gives rise to more than 17 types of cancers, and surprisingly, causes cancers in organs not directly exposed to tobacco smoke.
 

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Cell mutation and the body’s natural resistance

 
A mutation occurs when a DNA gene is damaged or changed in such a way as to alter the genetic message carried by that gene. The more mutations a cell acquires, the more likely it is to turn cancerous.

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Decreased prevalence, but increased incidence of smoking

Globally, smoking prevalence - the percentage of the population that smokes regularly - has decreased, but the number of cigarette smokers worldwide has increased due to population growth. Today, over 1bn people worldwide smoke tobacco, which each year causes nearly 6m early deaths, many different cancers, pain, misery and grief; not to mention the huge costs to healthcare systems and the loss of productivity.  If current trends continue tobacco use will cause more than 8m deaths annually by 2030. On average, smokers die 10 years earlier than nonsmokers.
 

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Cancer and the body’s natural resistance

Cancer is a condition where cells in a specific part of the body mutate and reproduce uncontrollably. There are over 200 different types of cancer. Cancerous cells can invade and destroy surrounding healthy tissue and organs. Cancer sometimes begins in one part of the body before spreading to other areas. This process is known a metastasis. The body has a capacity to naturally resist cancer, through tumor suppressor genes, which function to restrain inappropriate mutations, and stimulate cell death to keep our cells in proper balance.New therapies that boost the body’s own immune system to fight cancer are believed to be a game-changer in cancer treatment.

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Cancer and the causes of cancer

Whitfield Growdon, a surgical oncologists from Harvard University Medical School and the Massachusetts General Hospital in Boston, describes cancer and the causes of cancer:
 

What is cancer?



What causes cancer?

 

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Epidemiology of smoking

Today, it is widely accepted that tobacco use is the single most important preventable health risk in the developed world, and an important cause of premature death worldwide. The research of the British epidemiologists Richard Doll and Tony Bradford Hill, more than anyone else, is responsible for the link between tobacco use and lung cancer. Following reports of several case-controlled studies in the early 1950’s Doll and Hill published findings of a larger case-controlled study in 1954 in the British Medical Journal, which suggested that smoking was, "a cause, and an important cause" of lung cancer. This was followed by the publication of further research findings in 1956. Doll and Hill’s latter study confirmed their earlier case-controlled findings: that there is a higher mortality rate among smokers than in non-smokers, and a clear dose-response relationship between the quantity of tobacco used, and the death rate from lung cancer. Data also indicated a significant progressive reduction in mortality rates with the length of time following the cessation of smoking.

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US Surgeon General Report of smoking and lung cancer

The research of Doll and Hill, along with other cohort studies published in the 1950s, formed the basis for the game-changing 1964 report of the US Surgeon General, which concluded that, "Cigarette smoking is causally related to lung cancer in men; the magnitude of the effect of cigarette smoking far outweighs all other factors". This led to groundbreaking research on tobacco use, and investments by governments and nonprofit organizations to reduce tobacco prevalence and cigarette consumption, which in some developed countries has been successful. In 2003, the Framework Convention on Tobacco Control was adopted by the World Health Organization, and has since been ratified by 180 countries.  
 

The best and the worst countries for smoking related lung cancer
 

Between 1980 and 2012 age-standardized smoking prevalence decreased by 42% for women and 25% for men worldwide. Canada, Iceland, Mexico, and Norway have reduced smoking by more than half in both men and women since 1980. The greatest health risks for both men and women are likely to occur in countries where smoking is pervasive and where smokers consume a large quantity of cigarettes. These countries include China, Ireland, Italy, Japan, Kuwait, South Korea, the Philippines, Uruguay, Switzerland, and several countries in Eastern Europe. The number of cigarettes smoked worldwide has grown to more than 6 trillion. In 75 countries: smokers consume an average of more than 20 cigarettes a day.
 

Smoking-related deaths in the UK and US

19% (10m) of adults in the UK, and 17% (40m), of adults in the US are current cigarette smokers, a figure, which has more than halved since the mid 1970s. Results from a 50-year study shows that half to two thirds of all lifelong cigarette smokers will be eventually killed by their habit. Death is usually due to lung cancer, chronic obstructive lung disease and coronary heart disease. Many who suffer from these diseases experience years of ill health and subsequent loss of productivity. Every year, around 96,000 people in the UK, and 480,000 people in the US, die from diseases caused by smoking. This equates to 226 and 1,300 smoking-related deaths every day in the UK and US respectively.
 

Costs

In addition to death and sickness, tobacco use also imposes a significant economic burden on society. These include direct medical costs of treating tobacco-induced illnesses, indirect costs including loss of productivity, fire damage and environmental harm from cigarette litter and destructive farming practices. Cigarettes sales contribute significant tax revenues to national coffers; the industry employs tens of thousands of people who also pay taxes. Notwithstanding, the total burden caused by tobacco products outweighs any economic benefit from their manufacture and sale.
 

Direct link between the number of cigarettes smoked and cancers

Scientists from the Wellcome Trust Sanger Institute near Cambridge, UK, the Los Alamos National Laboratory in New Mexico, and others have discovered a direct link between the number of cigarettes smoked and the number of mutations in the tumor DNA, and that smoking also causes cancers in organs not exposed to tobacco smoke.

Research published in the Journal Science in 2016 analyzed more than 5,000 cancer tumors from smokers and nonsmokers, and concluded that if you smoke even a few cigarettes a day you will erode the genetic material of most of the cells in your body, and thereby be at a significantly greater risk of cancer. "Before now, we had a large body of epidemiological evidence linking smoking with cancer, but now we can actually observe and quantify the molecular changes in the DNA due to cigarette smoking," says Ludmil Alexandrov, a theoretical biologist at Los Alamos National Labroratory and an author of the study.
 
The discovery means that people who smoke a pack of cigarettes a day for a year, develop on average, 150 extra mutations in every lung cell, and nearly 100 more mutations than usual in each cell of the voice box, 39 mutations for the pharynx, 23 mutations for mouth, 18 mutations for bladder, and 6 mutations in every cell of the liver.
 

Smoking causes cancers not exposed to smoke
 

Scientists were surprised to find that tobacco smoke caused mutations in tissues that are not directly exposed to smoke. While more than 70 of the 7,000 chemicals in tobacco smoke have long been known to raise the risk of at least 17 forms of cancer, the precise molecular mechanisms through which these chemicals mutate DNA, and give rise to tumours in different tissues have never been altogether clear, until now. The study showed that some chemicals from tobacco smoke damage DNA directly, but others found their way to different organs and tissues, and ramp up the natural speed at which mutations built up in the tissues in more subtle ways, often by disrupting the way cells function. The more mutations a cell acquires, the more likely it is to turn cancerous.
 

Why some smokers get cancer and others do not

“It won’t happen to me. . . . My grandfather started smoking when he was 11, smoked 20 a day, and lived ‘til he was 90”. We have all heard this before. But we now know why some smokers get cancer and others do not. it is because of the way mutations arise. When a person smokes, the chemicals they inhale create mutations at random points in the genome. Many of these changes will be harmless, but others will not be so benign. The more smoke a person is exposed to, the greater the chance that the accumulating mutations will hit specific spots in the DNA that turn cells cancerous. Even decades after people stop smoking, former smokers are at a long-term increased risk of developing cancers.“You can really think of it as playing Russian roulette,” says Alexandrov.
 

Takeaways

Until now, it has not been fully understood how smoking increases the risk of developing cancer in parts of the body that do not come into direct contact with smoke.
 
Sir Mark Walport, director of the Wellcome Trust, says that the findings from the research described above: “will feed into knowledge, methods and practice in patient care.” Dr Peter Campbell, from the Wellcome Trust Sanger Institute says: “The knowledge we extract over the next few years will have major implications for treatment. By identifying all the cancer genes we will be able to develop new drugs that target the specific mutated genes, and work out which patients will benefit from these novel treatments.”

The Mexican Connection
A Special Report 

• People are eating themselves to death and our healthcare systems and governments are failing to stop it
• Obesity and type-2 diabetes (diabesity) kills thousands unnecessarily, and threatens the stability of healthcare systems around the world
• In the UK there is mounting frustration with the diabetes establishment’s failure to make inroads into the prevention and management of diabesity
• Mexico is re-engineering the way primary care delivers its services in order to prevent and reduce the burden of diabesity
• There are lessons from Mexico for healthcare systems challenged by the diabesity epidemic

• 16% of Mexico’s population has type-2 diabetes (T2DM) and each year it kills 70,000
• Mexican mothers feed their children sugary beverages from birth and create soda addicts
• In 2014 a national sugar tax on fizzy drinks was introduced, but sales on untaxed sugary beverages increased
• The Carlos Slim Foundation (CSF) takes fundamental action to dent Mexico’s T2DM epidemic
• The CSF collaborates with MIT’s Broad Institute to conduct the largest and most comprehensive genomic study on T2DM in Mexican populations
• Three years later CSF announces the discovery of the first common genetic variant shown to predispose Mexicans to T2DM
• Findings could lead to improved diagnostics and new therapies for T2DM, say experts
• The Broad Institute and the CSF make their genomic studies and other data freely available to scientists worldwide
• Organizations with bureaucratic walls that restrict the free-flow and sharing of knowhow and information significantly impede the advancement of our understanding and management of globally important chronic conditions such as T2DM

Each year, T2DM related complications kill 70,000 Mexicans. In 2015, there were 11m people with diabetes in Mexico - almost 12% of its adult population - projected to rise to some 16m by 2035. Mexico has one of the world’s highest rates of childhood obesity, a significant contributory risk factor of T2DM. The prevalence of overweight or obese children and adolescents between 5 and 19 years is 35%. This is believed to be the result of mother’s feeding their babies sugary drinks: partly because of the lack of clean water, and partly cultural since many Mexicans consider chubby babies to be good. According to Dr. Salvador Villalpando, a childhood obesity specialist at the Federico Gomez Children's Hospital in Mexico City, “about 10% of Mexican children are fed soda from birth to six months, and by the time they reach two it's about 80%." Mexico has become the No. 1 per capita consumer of sugary beverages, with the average person drinking more than 46 gallons per year: nearly 50% more than the average American.
 
Over the last 20 years, the prevalence of T2DM in Mexico, a country with a population of 122 million, has increased rapidly. The Mexican health system is struggling to effectively adapt to the diabetes burden facing the nation. Healthcare spending represents approximately 6% of GDP and is divided near equally between the public and private sectors. The former, supports mostly low-income non-salaried workers, accounting for about 60% of those in work: some 30m. The latter, is an employer-based scheme linked to salaried workers.

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Sugar tax

So acute is the problem of T2DM in Mexico that in January 2014, the government introduced a 10% tax on sugar-sweetened beverages. Research published in the British Medical Journal in 2016 suggests that the tax resulted in a 6% reduction in the purchases of taxed beverages in the first year, increasing to 12% by the end of the second year. The study also reported increases in purchases of untaxed beverages. Findings are disputed by the drinks industry. “Fizzy drinks only account for 5.6% of Mexico's average calorie consumption so can only be a small part of the solution to obesity and diabetes,” says Jorge Terrazas of Anprac; Mexico's bottled drinks industry body.
  

Carlos Slim Foundation and diabetes

The obesity epidemic, aging population and escalating health costs have increasingly strained resources and exacerbated Mexico’s diabetes burden, which the CSF is intent to reduce. In 2010 the Foundation formed an association with MIT’s Broad Institute. With an investment of US$74m it formed the Slim Initiative in Genomic Medicine for the Americas (SIGMA). It was a natural fit because Slim knows just how big data strategies transformed retail businesses and also cancer research and therapies; and the Broad Institute specialises in developing big genomic data sets and making them available to molecular scientists in premier research centres throughout world in order to transform medicine. From its inception SIGMA set out to systematically identify genes underlying diabetes.
 
The development of T2DM depends on complex inheritance-environment interactions along with certain lifestyle behaviors. Previous HealthPad Commentaries have described such complexities. One described the lifetime research endeavors of Professor Sir Steve Bloom, Head of Diabetes, Endocrinology and Metabolism at Imperial College London, on obesity and the gut-brain relationship.
 
SIGMA believed that having access to genomic research undertaken by a network of world class scientists holds out the possibility of discovering fundamental aspects of the biological mechanisms linked to T2DM. And this could form the basis for more effective diagnostics and new and improved therapies for the condition. Until recently, only a select group of specialists had full access to such data. The CSF was also mindful that their relationship with the Broad Institute would help build Mexico’s capacity in genomic medicine.
 

T2DM risk gene found in Latin Americans

A major focus of SIGMA’s 2010 research agenda was to identify the genetic risk factors that contribute to the significantly higher incidence rate of T2DM in Mexico compared with the rest of the world. SIGMA conducted the largest and most comprehensive genomic study to date on T2DM in Mexican populations, which involved scientists at 125 institutions in 40 countries, and resulted in the discovery of the first common genetic variant shown to predispose Latin American’s to T2DM.

Findings show that people who carry the higher risk version of the gene are 25% more likely to have diabetes than those who do not. People who inherit copies of the gene from both parents are 50% more likely to have diabetes. The higher risk-form of the gene is present in half of the people with recent Native American ancestry, including Latin Americans. The elevated frequency of this risk gene in Latin Americans could account for, as much as 20% of the populations’ increased prevalence of T2DM. The gene variant also is found in about 20% of East Asians, but is rare in populations from Europe and Africa.
 

Doing science with one eye closed

"Most genomic research has focused on European or European-derived populations, which is like doing science with one eye closed,” says Eric Lander, Professor of Biology at MIT and President and Founding Director of the Broad Institute, who went on to say, “There are many discoveries that can only be made by studying non-European populations." José Florez, a principal investigator of the SIGMA study adds, “By expanding our search to include samples from Mexico and Latin America, we’ve found one of the strongest genetic risk factors discovered to date, which could illuminate new pathways to target with drugs and a deeper understanding of T2DM.”
 

The impact of evolutionary science on healthcare systems

Roger Kornberg, Professor of Medicine at Stanford University who won the 2006 Nobel Prize in chemistry, "for his studies of the molecular basis of eukaryotic transcription", describes how human genome sequencing and genomic research fundamentally changed the way healthcare is organized and delivered. “Genomic sequencing enables us to identify every component of the body responsible for all life processes. In particular, it enables the identification of components, which are either defective or whose activity we may wish to edit in order to improve a medical condition,” says Kornberg.
 

 

Website helps translating genomic discoveries into therapies

Three years following their discoveries; the CSF launched SIGMA 2 with a mandate to complete its genetic analysis of T2DM, improve diagnostics, and develop therapeutic roadmaps to guide the development of new treatments. SIGMA 2 also planned to ramp up scientific capabilities in both the US, and Mexico by developing a unique resource. In 2016 SIGMA 2 created a website of open-access genetic data on T2DM. The site contains data available from all the SIGMA studies, plus information on major international data networks, including more than 100,000 DNA samples, and the complete results of 28 large genome association studies. Scientists throughout the world have free access to these data.
 

The importance of the open exchange of information

The new web portal represents a breakthrough, because it allows scientists throughout the world access to genetic information, and this is expected to accelerate progress of our understanding and treating diabetes. “The open exchange of information is essential for scientific progress, but it is not always easily achievable. This site not only helps us to overcome this barrier – by allowing access to patient data from around the world – but also will allow directing scientists to the most prevalent genetic risk factors among the populations of Latin America and others who have been underrepresented in large-scale genomic studies,” says Lander who believes that, "It is essential that the benefits of the genomic revolution are accessible to people throughout the Americas and the world."

“The SIGMA project has been a story of total success. Our extraordinary partners, both in Mexico and the US, have made it possible to make historic advances in the understanding of the basic causes of T2DM. We hope that through our contributions we will be able to improve the ways in which the disease is detected, prevented and treated,” says Roberto Tapia-Conyer, CEO of the CSF.
 

Takeaways

 
So, for an investment of US$25m a year for three years SIGMA made a significant discovery, which could beneficially affect the diagnostics and treatment of T2DM, and it also enhanced Mexico’s capacity for genomic research. Such success was due, in part, to the leadership of a 77-year-old Mexican businessman intent on solving problems, who thought globally, partnered with world-class institutions, understood and supported the potential of big data strategies and genomic research, and stood shoulder-to-shoulder with Eric Lander against healthcare organizations, which build and defend bureaucratic walls that significantly restrict the open access of knowhow and data.
 

• Diabetes UK’s (DUK) 2016 State of the Nation Report calls for diabetes education to be improved
• Effective education can reduce the vast and escalating burden of diabetes and is significantly cheaper than treatment
• Traditional diabetes education is failing miserably
• DUK’s education only reaches a small percentage of people with diabetes
• Self-management is the only realistic way forward to better diabetes management, but will require a transformation of the current patient-educator relationship
• Could DUK play a leading role in this transformation?

1. The majority of the charity’s education and support services only appear to reach a small percentage of the total number of people either at risk of T2DM or those living with diabetes. We have drawn attention to the fact that a large percentage of people with T2DM are over weight and 40% of obese people reside in deprived areas of the UK. To be effective diabetes education must have the Heineken effect.
2. For the past decade at least, the DUK has tended to report the costs and distribution of its education and support services. More relevant would be for the charity to report costs and the effects its services have had on reducing the burden of diabetes, slowing complications, improving efficiencies, and enhancing patient outcomes.

• Healthcare systems throughout the world are in constant crisis
• Attempts to introduce digital infrastructure to improve the quality of care, efficiency, and patient outcomes have failed
• Modern healthcare systems were built on the idea that doctors provide healthcare with meaning and power, but this is changing
• Advances in genetics and molecular science are rapidly eating away at doctors’ discretion and power
• People are loosing their free will and increasingly being driven by big data strategies
• An important new book suggests that a biotech-savvy elite will edit people's genomes and control health and healthcare with powerful algorithms, and that people will merge with computers
• Homo sapiens will evolve into Homo Deus

 

• It is one of the most serious global health challenges of the 21^st century
• It causes high incidence of morbidity, disability and premature mortality
• It affects 30% of children and 62% of adults in the UK
• It costs the UK £47bn a year
• For 40 years official statistics have under-reported its main cause
• Doctors have neither been able to reduce nor prevent it
• Behavioural scientists are well positioned to reduce it

Prof. Karol Sikora - Cancer linked to obesity


Dr Seth Rankin - Can being overweight lead to health problems?

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