Tagged: genomics



  • In 2003 the US first discovered the genome and became the preeminent nation in genomics
  • This could change
  • World power and influence have moved East
  • China has invested heavily in genomic technologies and established itself as a significant competitive force in precision medicine
  • Ownership of intellectual property and knowhow is key to driving national wealth 

The global competition to translate genomic data into personal medical therapies



Professor Dame Sally Davies, England’s Chief Medical Officer, is right. (Genomics) “has the potential to change medicine forever. . . . The age of precision medicine is now, and the NHS must act fast to keep its place at the forefront of global science.”
It is doubtful whether the UK will be able to maintain its place as a global frontrunner in genomics and personalized medicine. It is even doubtful whether the US, the first nation to discover the genome, and which became preeminent in genomic research, will be able to maintain its position. China, with its well-funded strategy to become the world’s leader in genomics and targeted therapies, is likely to usurp the UK and the US in the next decade.
This Commentary is in 2 parts. Part 1 provides a brief description of the global scientific competition between nation states to turn genomic data into medical benefits. China’s rise, which is described, could have significant implications for the future ownership of medical innovations, data protection, and bio-security. Part 2, which follows in 2 weeks, describes some of the ethical, privacy, human capital and economic challenges associated with transforming genomic data into effective personal therapies.
Turning genomic data into medical benefits
Turning genomic data into medical benefits is very demanding. It requires a committed government willing and able to spend billions, a deep understanding of the relationship between genes and physiological traits, next generation sequencing technologies, artificial intelligence (AI) systems to identify patterns in petabytes (1 petabyte is equivalent to 1m gigabytes) of complex data, world-class bio-informaticians, who are in short supply; comprehensive and sophisticated bio depositories, a living bio bank, a secure data center, digitization synthesis and editing platforms, and petabytes of both genomic, clinical, and personal data. Before describing how the UK, US and China are endeavoring to transform genomic data into personal medicine, let us refresh our understanding of genomics.

Genomics, the Human Genomic Project and epigenetics
It is widely understood that your genes are responsible for passing specific features or diseases from one generation to the next via DNA, and genetics is the study of the way this is done. However, it is less widely known that your genes are influenced by environmental and other factors. Scientists have demonstrated that inherited genes are not static, and lifestyles and environmental factors can precipitate a chemical reaction within your body that could permanently alter the way your genes react. This environmentally triggered gene expression, or epigenetic imprint, can be bad, such as a disease; or good, such as a tolerant predisposition. Epigenetics is still developing as an area of research, but it has demonstrated that preventing and managing disease is as much to do with lifestyles and the environment, as it is to do with inherited genes and drugs. If environmental exposure can trigger a chemical change in your genes that results in the onset of disease, then scientists might be able to pharmacologically manipulate the same mechanisms in order to reverse the disease.
DNA is constantly subject to mutations, which can lead to missing or malformed proteins, and that can lead to disease. You all start your lives with some mutations, which are inherited from your parents, and are called germ-line mutations. However, you can also acquire mutations during your lifetime. Some happen during cell division, when DNA gets duplicated, other mutations are caused when environmental factors including, UV radiation, chemicals, and viruses damage DNA.

You have a complete set of genes in almost every healthy cell in your body. One set of all these genes, (plus the DNA between them), is called a genome. The genome is the collection of 20,000 genes, including 3.2bn letters of DNA, which make up an individual. We all share about 99.8% of the genome. The secrets of your individuality, and also of the diseases you are prone to, lie in the other 0.2%, which is about 3 or 4m letters of DNA. The genome is known as ‘the blueprint’ of life’, and genomics is the study of the whole genome, and how it works. Whole genome sequencing (WGS) is the process of determining the complete DNA sequence of an organism's genome at a point in time.
‘The Human Genome Project’ officially began in 1990 as an international research effort to determine a complete and accurate sequence of the 3bn DNA base pairs, which make up the human genome, and to find all of the estimated 20 to 25,000 human genes. The project was completed in April 2003. This first sequencing of the human genome took 13 years and cost some US$3bn. Today, it takes a couple of days to sequence a genome, and costs range from US$260 for targeted sequencing to some US$4,000 for WGS. Despite the rapidly improving capacity to read, sequence and edit the information contained in the human genome, we still do not understand most of the genome’s functions and how they impact our physiology and health.

Roger Kornberg explains the importance of genomics
Roger Kornberg, Professor of Structural Biology at Stanford University, and 2006 Nobel Laureate for Chemistry, explains the significance of sequencing the human genome, “The determination of the human genome sequence and the associated activity called genomics; and the purposes for which they may be put for medical uses, takes several forms. The knowledge of the sequence enables us to identify every component of the body responsible for all of the processes of life. In particular, to identify any component that is either defective or whose activity we may adjust to address a problem or a condition. So the human genome sequence makes available to us the entire array of potential targets for drug development. . . . . The second way in which the sequence and the associated science of genomics play an important role is in regard to individual variations. Not every human genome sequence is the same. There is a wide variation, which in the first instance is manifest in our different appearances and capabilities. But it goes far deeper because it is also reflected in our different responses to invasion by microorganisms, to the development of cancer and to our susceptibility to disease in general. It will ultimately be possible, by analyzing individual genome sequences to construct a profile of such susceptibilities for every individual, a profile of the response to pharmaceuticals for every individual, and thus to tailor medicines to the needs of individuals.” See video below.
UK’s endeavors to transform genomic data into personal therapies

In 2013 the UK government set up Genomics England, a company charged with sequencing 100,000 whole genomes by 2017. In 2014, the government announced a £78m deal with Illumina, a US sequencing company, to provide Genomics England with next generation whole genome sequencing services. At the same time the Wellcome Trust invested £27m in a state-of-the-art sequencing hub to enable Genomics England to become part of the Wellcome Trust’s Genome Campus in Hinxton, near Cambridge, England. In 2015, the UK government pledged £215m to Genomics England.
DNA testing and cancer
DNA sequencing is simply the process of reading the code that is in any organism . . . It’s essentially a technology that allows us to extract DNA from a cell, or many cells, pass it through a sophisticated machine and read out the sequence for that organism or individual,” says David Bowtell, Professor and Head of the Cancer Genomics and Genetics Program at the Peter MacCallum Cancer Centre, Melbourne, Australia; see video below. “DNA testing has becomeincreasingly widespread because advances in technology have made the opportunity to sequence the DNA of individuals affordable and rapid  . . . DNA testing in the context of cancer can be useful to identify a genetic risk of cancer, and to help clinicians make therapeutic decisions for someone who has cancer,” says Bowtell, see video below.

What is DNA sequencing?

What are the advanteges of a person having a DNA test?

Need for National Genome Board
Despite significant investments by the UK government, Professor Davies, England’s Chief Medical Officer, complained in her 2017 Annual Report that genomic testing in the UK is like a “cottage industry” and recommended setting up a new National Genome Board tasked with making whole genome sequencing (WGS) standard practice in the NHS across cancer care, as well as some other areas of medicine, within the next 5 years.
USA’s endeavors to transform genomic data into personal therapies

In early 2015 President Obama announced plans to launch a $215m public-private precision medicine initiative, which involved the health records and DNA of 1m people, to leverage advances in genomics with the intention of accelerating biomedical discoveries in the hope of yielding more personalized medical treatments for patients. A White House spokesperson described this as “a game changer that holds the potential to revolutionize how we approach health in the US and around the world.

Data management challenges
The American plan did not seek to create a single bio-bank, but instead chose a distributive approach that combines data from over 200 large on-going health studies, which together involves some 2m people. The ability of computer systems or software to exchange and make use of information stored in such diverse medical records, and numerous gene databases presents a significant challenge for the US plan. According to Bowtell, “Data sharing is widespread in an ethically appropriate way between research institutions and clinical groups. The main obstacles to more effective sharing of information are the very substantial informatics challenges. Often health systems have their own particular ways of coding information, which are not cross compatible between different jurisdictions. Hospitals are limited in their ability to capture information because it takes time and effort. Often information that could be useful to researchers, and ultimately to patients, is lost, just because the data are not being systematically collected.” See video below.
China’s endeavors to transform genomic data into personal therapies

In 2016, the Chinese government launched a US$9bn-15-year endeavor aimed at turning China into a global scientific leader by harnessing computing and AI technologies for interpreting genomic and health data.  This positions China to eclipse similar UK and US initiatives.

Virtuous circle
Transforming genomic data to medical therapies is more than a numbers race. Chinese scientists are gaining access to ever growing amounts of human genomic data, and developing the machine-learning capabilities required to transform these data into sophisticated diagnostics and therapeutics, which are expected to drive the economy of the future.  The more genomic data a nation has the better its potential clinical outcomes. The better a nation’s clinical outcomes the more data a nation can collect. The more data a nation collects the more talent a nation attracts. The more talent a nation attracts the better its clinical outcomes.

The Beijing Genomics Institute
In 2010 China became the global leader in DNA sequencing because of one company: the Beijing Genomics Institute (BGI), which was created in 1999 as a non-governmental independent research institute, then affiliated to the Chinese Academy of Sciences, in order to participate in the Human Genome Project as China's representative. In 2010, BGI received US$1.5bn from the China Development Bank, and established branches in the US and Europe. In 2011 BGI employed 4,000 scientists and technicians. While BGI has had a chequered history, today it is one of the world’s most comprehensive and sophisticated bio depositories.

The China National GeneBank
In 2016 BGI-Shenzhen established the China National GeneBank (CNGB) on a 47,500sq.m site. This is the first national gene bank to integrate a large-scale bio-repository and a genomic database, with a goal of enabling breakthroughs in human health research. The gene-bank is supported by BGI’s high-throughput sequencing and bio-informatics capacity, and will not only provide a repository for biological collection, but more importantly, it is expected to develop a novel platform to further understand genomic mechanisms of life. During the first phase of its development the CNGB will have saved more than 10m bio-samples, and have storage capacity for 20 petabytes (20m gigabytes) of data, which are expected to increase to 500 petabytes in the second phase of its development. The CNGB represents the new generation of a genetic resource repository, bioinformatics database, knowledge database and a tool library, “to systematically store, read, understand, write, and apply genetic data,” says Mei Yonghong, its Director.

Whole-genome sequencing for $100
The CNGB could also help to bring down the cost of genomic sequencing. It is currently possible to sequence an individual's entire genome for under US$1,000, but the CNGB aims to reduce the price to US$152. Meanwhile, researchers at Complete Genomicsa US company acquired by BGI in 2013, which has developed and commercialized a DNA sequencing platform for human genome sequencing and analysis, are pushing the technology further to enable whole-genome sequencing for US$100 per sample. China's share of the world's sequencing-capacity is estimated to be between 20% and 30%, which is lower than when BGI was in its heyday, but expected to increase fast. “Sequencing capacity is rising rapidly everywhere, but it's rising more rapidly in China than anywhere else,” says Richard Daly, CEO, DNAnexus, a US company, which supplies cloud platforms for large-scale genomics data.

The intersection of genomics and AI
Making sense of 1m human genomes is a major challenge, says Professor Jian Wang, former BGI President and co-founder, who has started another company called iCarbonX. Also based in Shenzhen, the company is at the intersection of genomics and AI. iCarbonX has raised more than US$600m, and plans to collect genomic data from more than 1m people, and complement these data with other biological information including changes in levels of proteins and metabolites. This is expected to allow iCarbonX to develop a new digital ecosystem, comprised of billions of connections between huge amounts of individuals’ biological, medical, behavioural and psychological data in order to understand how their genes interact and mutate, how diseases and aging manifest themselves in cells over time, how everyday lifestyle choices affect morbidity, and how these personal susceptibilities play a role in a wide range of treatments.

iCarbonX is expected to gather data from brain imaging, biosensors, and smart toilets, which will allow real-time monitoring of urine and faeces. The Company’s goal is to be able to study the evolution of our genome as we age and design personalized health predictions such as susceptibilities to diseases and tailored treatment options. iCarbonX’s endeavours are expected to dwarf efforts by other US Internet giants at the intersection of genomics and AI.

Ethical challenges

China’s single-minded objective to turn its knowhow and experience of genome sequencing into personal targeted medical therapies has made it a significant global competitive force in life sciences. However, precision medicine’s potential to revolutionize advances in how we treat diseases confers on it moral and ethical obligations. For personal therapies to be effective, it is important that genomic data are complemented with clinical and other personal data. This combination of data is as personal as personal information gets. There could be potential harm to the tested individual and family if genomic information from testing is misused. Reconciling therapy and privacy is important, because privacy issues concerning patients' genomic data can slow or derail the progression of novel personal therapies to prevent and manage intractable diseases. The stakes are high in terms of biosecurity, as genomic research is both therapeutic and a strategic element of national security. While it is crucial to leverage genomic data for future health, economic and biodefense capital, these data will also have to be appropriately managed and protected. Part 2 of this Commentary dives into these challenges a little deeper, and describes some of China’s competitive advantages in the race to become the world’s preeminent nation in genomics and precision medicine. 

Despite the endeavours of the UK and US to remain at the forefront of the international competition to transform genomic data into personalized medical therapies for some of the worlds most common and intractable diseases, it seems reasonable to assume that China is on the cusp of becoming the most dominant nation in novel personalized treatments. Notwithstanding, China’s determination to assume the global frontrunner position in genomic science might have blunted its concerns for some of the ethical issues, which surround the life sciences. To the extent that this might be the case the future of humanity might well differ significantly from the generally accepted western vision. 
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  • Competition is intensifying among scientists to develop and use gene editing and immunotherapy to defeat intractable diseases
  • Chinese scientists were the first to inject people with cells modified by the CRISPR–Cas9 gene-editing technique
  • Several studies have extracted a patient’s own immune cells, modified them using gene-editing techniques, and re-infused them into the patient to seek and destroy cancer cells
  • A new prêt à l'emploi gene editing treatment disables the gene that causes donor immune cells to attack their host
  • The technique harvests immune cells from a donor, modifies and multiplies them so that they may be used quickly, easily and cheaply on different patients
  • Commercial, technical, regulatory and ethical barriers to gene editing differ in different geographies 

Gene editing battles

Gene editing and immunotherapy are developing at a pace. They have been innovative and effective in the fight against melanoma, lung cancer, lymphomas and some leukaemias, and promise much more. Somatic gene therapy changes, fixes and replaces genes at the tissue or cellular levels to treat a patient, and the changes are not passed on to the patient’s offspring. Germ line gene therapy inserts genes into reproductive cells and embryos to correct genetic defects that could be passed on to future generations.  Although there are still many unanswered clinical, commercial and ethical questions surrounding gene therapy, its future is assured and will be shaped by unexpected new market entrants and competition between Chinese and Western scientists, which is gaining momentum.
14 February 2017

On the 14th February 2017 an influential US science advisory group formed by the National Academy of Sciences and the National Academy of Medicine gave support to the modification of human embryos to prevent “serious diseases and disabilities” in cases where there are no other “reasonable alternatives”. This is one step closer to making the once unthinkable heritable changes in the human genome. The Report, however, insisted that before humanity intervenes in its own evolution, there should be a wide-ranging public debate, since the technology is associated with a number of unresolved ethical challenges. The French oppose gene editing, the Dutch and the Swedes support it, and a recent Nature editorial suggested that the EU is, “habitually paralysed whenever genetic modification is discussed”. In the meantime, clinical studies, which involve gene-editing are advancing at a pace in China, while the rest of the world appears to be embroiled in intellectual property and ethical debates, and playing catch-up.
15 February 2017

On the 15th February 2017, after a long, high-profile, heated and costly intellectual property action, judges at the US Patent and Trademark Office ruled in favor of Professor Feng Zhang and the Broad Institute of MIT and Harvard, over patents issued to them associated with the ownership of the gene-editing technology CRISPR-Cas9: a cheap and easy-to-use, all-purpose gene-editing tool, with huge therapeutic and commercial potential.
The proceedings were brought by University College Berkeley who claimed that the CRISPR technology had been invented by Professor Jennifer Doudna of the University, and Professor Emmanuelle Charpentier, now at the Max Planck Institute for Infection Biology in Berlin, and described in a paper they published in the journal Science in 2012. Berkeley argued that after the 2012 publication, an “obvious” development of the technology was to edit eukaryotic cells, which Berkeley claimed is all that Zhang did, and therefore his patents are without merit.

The Broad Institute countered, suggesting that Zhang made a significant inventive leap in applying CRISPR knowledge to edit complex organisms such as human cells, that there was no overlap with the University of California’s research outcomes, and that the patents were therefore deserved. The judges agreed, and ruled that the 10 CRISPR-Cas9 patents awarded to Zhang and the Broad Institute are sufficiently different from patents applied for by Berkeley, so that they can stand. 
The scientific community

Interestingly, before the 15th February 2017 ruling, the scientific community had appeared to side with Berkeley. In 2015 Doudna, and Charpentier were awarded US$3m and US$0.5m respectively for the prestigious Breakthrough Prize in life sciences and the Gruber Genetics Prize. In 2017 they were awarded the Japan Prize of US$0.45m for, “extending the boundaries of life sciences”. Doudna and Charpentier have each founded companies to commercially exploit their discovery: respectively Intellia Therapeutic, and CRISPR Therapeutics.
16 February 2017

A day after the patent ruling, Doudna said: “The Broad Institute is happy that their patent didn’t get thrown out, but we are pleased that our patent based on earlier work can now proceed to be issued”. According to Doudna, her patents are applicable to all cells, whereas Zhang’s patents are much more narrowly indicated. “They (Zhang and the Broad Institute) will have patents on green tennis balls. We will get patents on all tennis balls,” says Doudna.
Gene biology

Gene therapy has evolved from the science of genetics, which is an understanding of how heredity works. According to scientists life begins in a cell that is the basic building block of all multicellular organisms, which are made up of trillions of cells, each performing a specific function. Pairs of chromosomes comprising a single molecule of DNA reside in a cell’s nucleus. These contain the blueprint of life: genes, which determine inherited characteristics. Each gene has millions of sequences organised into segments of the chromosome and DNA. These contain hereditary information, which determine an organism’s growth and characteristics, and genes produce proteins that are responsible for most of the body’s chemical functions and biological reactions.

Roger Kornberg, an American structural biologist who won the 2006 Nobel Prize in Chemistry "for his studies of the molecular basis of eukaryotic transcription", describes the Impact of human genome determination on pharmaceuticals:
China’s first
While American scientists were fighting over intellectual property associated with CRISPR-Cas9, and American national scientific and medical academies were making lukewarm pronouncements about gene editing, Chinese scientists  had edited the genomes of human embryos in an attempt to modify the gene responsible for β-thalassemia and HIV, and are planning further clinical studies. In October 2016, Nature reported that a team of scientists, led by oncologist Lu You, at Ghengdu’s Sichuan University in China established a world first by using CRISPR-Cas9 technology to genetically modify a human patient’s immune cells, and re-infused them into the patient with aggressive lung cancer, with the expectation that the edited cells would seek, attack and destroy the cancer. Lu is recruiting more lung cancer patients to treat in this way, and he is planning further clinical studies that use similar ex vivo CRISPR-Cas9 approaches to treat bladder, kidney and prostate cancers
The Parker Institute for Cancer Immunotherapy
Conscious of the Chinese scientists’ achievements, Carl June, Professor of Pathology and Laboratory Medicine at the University of Pennsylvania and director of the new Parker Institute for Cancer Immunotherapy, believes America has the scientific infrastructure and support to accelerate gene editing and immunotherapies. Gene editing was first used therapeutically in humans at the University of Pennsylvania in 2014, when scientists modified the CCR5 gene (a co-receptor for HIV entry) on T-cells, which were injected in patients with AIDS to tackle HIV replication. Twelve patients with chronic HIV infection received autologous cells carrying a modified CCR5 gene, and HIV DNA levels were decreased in most patients.
Medical science and the music industry

The Parker Institute was founded in 2016 with a US$250m donation from Sean Parker, founder of Napster, an online music site, and former chairman of Facebook. This represents the largest single contribution ever made to the field of immunotherapy. The Institute unites 6 American medical schools and cancer centres with the aim of accelerating cures for cancer through immunotherapy approaches. 

Parker, who is 37, believes that medical research could learn from the music industry, which has been transformed by music sharing services such as Spotify. According to Parker, more scientists sharing intellectual property might transform immunotherapy research. He also suggests that T-cells, which have had significant success as a treatment for leukaemia, are similar to computers because they can be re-programed to become more effective at fighting certain cancers. The studies proposed by June and colleagues focus on removing T-cells, from a patient’s blood, modifying them in a laboratory to express chemeric antigen receptors that will attack cancer cells, and then re-infusing them into the patient to destroy cancer. This approach, however, is expensive, and in very young children it is not always possible to extract enough immune cells for the technique to work.

Prêt à l'emploi therapy

Waseem Qasim, Professor of Cell & Gene Therapy at University College London and Consultant in Paediatric immunology at Great Ormond Street Hospital, has overcome some of the challenges raised by June and his research. In 2015 Qasim and his team successfully used a prêt à l'emploi gene editing technique on a very young leukaemia patient. The technique, developed by the Paris-based pharmaceutical company Cellectis, disables the gene that causes donor-immune cells to attack their host. This was a world-first to treat leukaemia with genetically engineered immune cells from another person. Today, the young leukaemia patient is in remission. A second child, treated similarly by Qasim in December 2015, also shows no signs of the leukaemia returning. The cases were reported in 2017 in the journal Science Translational Medicine.
Universal cells to treat anyone cost effectively

The principal attraction of the prêt à l'emploi gene editing technique is that it can be used to create batches of cells to treat anyone. Blood is collected from a donor, and then turned into “hundreds” of doses that can then be stored frozen. At a later point in time the modified cells can be taken out of storage, and easily re-infused into different patients to become exemplars of a new generation of “living drugs” that seek and destroy specific cancer cells. The cost to manufacture a batch of prêt à l'emploi cells is estimated to be about US$4,000 compared to some US$50,000 using the more conventional method of altering a patient’s cells and returning them to the same patient. Qasim’s clinical successes raise the possibility of relatively cheap cellular therapy using supplies of universal cells that could be dripped into patients' veins on a moment’s notice.
CRISPR-Cas9 provides a relatively cheap and easy-to-use means to get an all-purpose gene-editing technology into clinics throughout the world. Clinical studies using the technology have shown a lot of promise especially in blood cancers. These studies are accelerating, and prêt à l'emploi gene editing techniques as an immunotherapy suggest a new and efficacious therapeutic pathway. Notwithstanding the clinical successes, there remain significant clinical, commercial and ethical challenges, but expect these to be approached differently in different parts of the world. And expect these differences to impact on the outcome of the scientific race, which is gaining momentum.
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  • 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
Slim lessons in diabetes understanding and management

What can a self-made 77-year-old son of Catholic Lebanese immigrants to Mexico contribute to our understanding and management of T2DM?
77-year-old Carlos Slim built a business empire, which today is worth the equivalent to 6% of Mexico’s GDP. His company Grupo Carso is influential in every sector of the Mexican economy, and he is currently the chairman and CEO of telecom giants Telmex and América Móvil. Slim believes that businessmen should do more than just give‍ money, and says they "should participate in solving problems".

An important aspect of reducing the significant burden of chronic health conditions such as T2DM, is to reduce the bureaucracies of key organizations, which impede the sharing of important knowhow that help our understanding and management of these globally important disease.
Slim has turned his attention to Mexico’s vast and escalating diabetes epidemic, which devastates the lives of millions, and significantly dents the Mexican economy. Recently, the Carlos Slim Foundation (CSF) started applying the knowhow and skills used to build world-class companies to tackle the Mexican diabetes burden, and in less than three years, discovered a gene, which contributes to the significantly higher incidence rate of T2DM in Latin Americans. The CSF intends to build on this to develop new treatments.

Diabetes in Mexico

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.

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.

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.
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  • 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
Future healthcare shock
This book should be compulsory reading for everyone interested in health and healthcare, especially those grappling with strategic challenges. Homo Deus: A brief history of tomorrow, by Yuval Harari, a world bestselling author, published in 2016 is not for tacticians responding to their in-trays, but for healthcare strategists planning for the future.

The book is published a year after an OECD report concluded that NHS England is one of the worst healthcare systems in the developed world; hospitals are so short-staffed and under-equipped that people are dying needlessly. The quality of care across key health areas is “poor to mediocre”, obesity levels are “dire”, and the NHS struggles to get even the “basics” right. The UK came 21st out of 23 countries on cervical cancer survival, 20th on breast and bowel cancer survival and 19th on stroke.

Harari pulls together history, philosophy, theology, computer science and biology to produce an important and thought provoking thesis, which has significant implications for the future of health and healthcare. Homo Deus, more than the 2015 OECD Report will make you think.
Healthcare’s legacy systems an obstacle for change

While a large and growing universe of consumers regularly use smartphones, cloud computing, and global connectivity to provide them with efficient, high quality, 24-hour banking, education, entertainment, shopping, and dating, healthcare systems have failed to introduce digital support strategies to enhance the quality of care, increase efficiency, and improve patient outcomes.


The answer is partly due to entrenched legacy systems, and partly because digital support infrastructure is typically beyond the core mission of most healthcare systems. Devi Shetty, cardiac surgeon, founder and CEO of Narayana Health, and philanthropist, laments how digital technologies have, “penetrated every industry in the world except healthcare”, and suggests doctors and the medical community are the biggest obstaclesto change.
Doctors’ traditional raison d'être is being replaced by algorithms

Notwithstanding, modern medicine has conquered killer infectious diseases, and has successfully transformed them, “from an incomprehensible force of nature into a manageable challenge . . . For the first time in history, more people die today from old age than from infectious diseases,” says Harari.
Further, modern healthcare systems were built on the assumption that individual doctors provided healthcare systems with meaning and power. Doctors are free to use their superior knowledge and experience to diagnose and treat patients; their decisions can mean life or death. This endowed doctors and healthcare systems with their monopoly of power and their raison d'être. But such power and influence is receding, and rapidly being replaced by biotechnology and algorithms.

Healthcare systems in crisis

This radical change adds to the crisis of healthcare systems, which lack cash, and have a shrinking pool of doctors treating a large and growing number of patients, an increasing proportion of whom are presenting with complicated co-morbidities. Aging equipment in healthcare systems is neither being replaced nor updated, and additionally, there is a dearth of digital infrastructure to support patient care.
A symptom of this crisis is the large and increasing rates of misdiagnosis: 15% of all medical cases in developed countries are misdiagnosed, and according to The Journal of Clinical Oncology, a staggering 44% of some types of cancers are misdiagnosed, resulting in millions of people suffering unnecessarily, thousands dying needlessly, and billions of dollars being wasted. Doing more of the same will not dent this crisis.
Computers replacing doctors
As the demand for healthcare increases, healthcare costs escalate, and the supply of doctor’s decrease, so big data strategies and complex algorithms, which in seconds are capable of analysing and transforming terabytes of electronic healthcare data into clinically relevant medical opinions, are being introduced.
Such digital infrastructure erodes the status of doctors who no longer are expected solely to rely on their individual knowledge and experience to diagnose and treat patients. Today, doctors have access to powerful cognitive computing systems that understand, reason, learn, and do more than we ever thought possible. Such computers provide doctors almost instantaneous clinical recommendations deduced from the collective knowledge gathered from thousands of healthcare systems, billions of patient records, and millions of treatments other doctors have prescribed to people presenting similar symptoms and disease states. Unlike doctors, these computers never wear out, and can work 24-7, 365 days a year.
The train has left the station

One example is IBM’s Watson, which is able to read 40 million medical documents in 15 seconds, understand complex medical questions, and identify and present evidence based solutions and treatment options. Despite the resistance of doctors and the medical establishment the substitution of biotechnology and algorithms for doctors is occurring in healthcare systems throughout the world, and cannot be stopped. “The train is again pulling out of the station . . . . Those who miss it will never get a second chance”. For healthcare systems to survive and prosper in the 21st century is to understand and embrace “the powers of biotechnology and algorithms”. People and organizations that fail to do this will not survive, says Harari.
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 genomics have 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.

The new world of ‘dataism’

Harari’s “new world” describes some of the implications of Kornberg’s discoveries, and suggests that evolutionary science is rapidly eroding doctors’ discretion and freewill, which are the foundation stones of modern healthcare systems and central to a doctors’ modus vivendi. Because evolutionary science has been programmed by millennia of development, our actions tend to be either predetermined or random. This results in the uncoupling of intelligence from consciousness and the “new world” as data-driven transformation, which Harari suggests is just beginning, and there is little chance of stopping it.
Over the past 50 years scientific successes have built complex networks that increasingly treat human beings as units of information, rather than individuals with free will. We have built big-data processing networks, which know our feelings better than we know them ourselves. Evolutionary science teaches us that, in one sense, we do not have the degree of free will we once thought. In fact, we are better understood as data-processing machines: algorithms. By manipulating data, scientists such as Kornberg, have demonstrated that we can exercise mastery over creation and destruction. The challenge is that other algorithms we have built and embedded in big data networks owned by organizations can manipulate data far more efficiently than we can as individuals. This is what Harari means by the “uncoupling” of intelligence and consciousness.
We are giving away our most valuable assets for nothing

Harari is not a technological determinist: he describes possibilities rather than make predictions. His thesis suggests that because of the dearth of leadership in the modern world, and the fact that our individual free-will is being replaced by data processors, we become dough for the Silicon Valley “Gods” to shape.
Just as African chiefs in the 19th Century gave away vast swathes of valuable land, rich in minerals, to imperialist businessmen such as Cecil Rhodes, for a handful of beads; so today, we are giving away our most valuable possessions  - vast amounts of personal data - to the new “Gods” of Silicon Valley: Amazon, Facebook, and Google for free. Amazon uses these data to tell us what books we like, and Facebook and Google use them to tell us which partner is best suited for us. Increasingly, big-data and powerful computers, rather than the individual opinion of doctors, drive the most important decisions we take about our health and wellbeing. Healthcare systems will cede jobs and decisions to machines and algorithms, says Harari.

For the time being, because of the entrenched legacy systems, health providers will continue to pay homage to our individuality and unique needs. However, in order to treat people effectively healthcare systems will need to “break us up into biochemical subsystems”, and permanently monitor each subgroup with powerful algorithms. Healthcare systems that do not understand and embrace this new world will perish. Only a relatively few early adopters will reap the rewards of the new technologies. The new elite will commandeer evolution with ‘intelligent’ design, edit peoples’ genomes, and eventually merge individuals with machines. Thus, according to Harari, a new elite caste of Homo sapiens will evolve into Homo Deus. In this brave new world, only the new “Gods”, with access to the ultimate source of health and wellbeing will survive, while the rest of mankind will be left behind.

Harari does not believe this new health world is inevitable, but implies that, in the absence of effective leadership, it is most likely to happen.

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