Genomics England and their quest to revolutionise the NHS

Genomics England was born on the 65th birthday of the UK’s National Health Service (NHS). The NHS is a peerless service and institution in the world; a nationalised, comprehensive and universal healthcare system and one the greatest social reforms of the post-war era. Initially the brainchild of visionary MP Aneurin Bevan, it was built around 3 core socialist principles: To meet the needs of all citizens, to be based on clinical need not social nor financial standing and to be free at the point of delivery. 

In 2013, then Prime Minister, David Cameron set forth a mandate to place the NHS at the forefront of global healthcare by establishing the world’s first national genome project, the forerunner to the application of genomic medicine universally across every one of the UK’s 65 million residents. To this end, Genomics England was established as a company under the management of the Department of Health.

Cameron had been inspired toward this paradigm shift following the death of his son, Ivan, aged 6, four years earlier. Ivan had been born with cerebral palsy and a form of severe epilepsy called Ohtahara Syndrome both rare, incurable genetic disorders.

Rt. Hon. Jeremy Hunt, Secretary of State for Health and Social Care said at the time: “The NHS has a long track record as a leader in medical science advances and it must continue to push the boundaries by unlocking the power of DNA data. The UK will become the first ever country to introduce this technology in its mainstream health system – leading the global race for better tests, better drugs and above all better, more personalised care to save lives. Genomics England will provide the investment and leadership needed to dramatically increase the use of this technology and drive down costs.”

Genomics England is funded by the Department of Health & Social Care. and any surplus will be invested back into improving healthcare. Initially its focus is the completion of the UK 100, 000 Genome Project (UK100KGP), which seeks to sequence the genomes of patients with cancer and rare disease and their healthy relatives. At its inception it seemed immensely ambitious, the kind of enterprise which had never been attempted before. Five years on, it still does.

Chaired by Sir John Chisholm, former chair of the Medical Research Council, who said: “This project represents a great opportunity to translate our world class genomic science into world leadership in genomic medicine. Genomics England will create a dataset of anonymised whole genome sequences matched with clinical data at a scale unique in the world. Participating patients will have the opportunity to benefit from clinical insights derived from the sequencing of their genome while at the same time contributing to knowledge which will be valuable to the whole patient community. It is from that knowledge that world leading therapeutic products and processes will become available to all patients.”

The Department of Health & Social Care chose to establish Genomics England, which frankly, should be called Genomics Great Britain, as a subsidiary limited company because, to have established it as an agency or a public body, would have required primary legislation such as an act of Parliament.

How & Why?

Genomics England was created with four core aims: to bring benefits to all patients, to create an ethical and transparent programme, and to enable new scientific discovery and medical insights and to kickstart the development of a UK genomics industry.

The 100K Genomes Project is not about sequencing 100,000 different patients but 100,000 different genomes. Specifically, the study looksed at; two genomes from every cancer patient with one coming from them and one coming from their cancer, three genomes from each rare disease family with one from the afflicted individual and two more from close blood relatives such as parents. So the actual numbers are around 75,000 people sequenced of whom around 40,000 are patients.

The number was chosen based on experience from the 2010 Sanger Institute study known as the UK10K which sequenced 4,000 healthy individuals and 6,000 with extreme or undiagnosed health problems. The project succeeded in building the foundations for future genomic studies. It built databases of gene interactions and pathogenicity as well as identifying inumerable variants and giving a clearer understanding of the challenges which would face the world’s first national genomic medicine system. This has gone on to form the blueprint for all subsequent large scale genome studies.

Founded by members of the UK10K, including the Primary Investigator, Prof. Richard Durbin, Congenica developed their clinical genomics decision support platform Sapientia out of that research and work done by Prof. Matt Hurles on the Deciphering Developmental Disorders Project, which identified 80,000 genomic variants from exome sequencing and microarray analysis.

In the intervening years, the cost of sequencing has fallen and knowledge about rare variants has increased, thus 100,000 genomes was selected, as the right balance between cost and benefit for NHS patients, with which to build a clinical and research legacy.

Transformation

The 100,000 Genomes Project is not simply a research project. It is a transformation project using genomic medicine to change how NHS patients are treated.  It is transforming healthcare from the modern model in a paradigm shift as big as the introduction of radiology or penicillin. It is transforming the research and findings of the UK10K into actionable results for the populace. These facts alone will transform the NHS and thusly transform Britain into the world leader for life sciences and healthcare but also the owner of the only socially accountable, universal healthcare system anywhere in the world.

Rare diseases aren’t as rare as is commonly conceived, affecting, as they do, 1 in 17 worldwide, over 6% of the global population - half a billion people. In 2014, 163, 444 people in the UK died of cancer, in 2015, 359,960 new cases were reported and the UK has a further 3.5million rare disease sufferers. The legacies of UK100KGP will be most acutely felt by some of the youngest and oldest patients on the NHS. This is because, the risks of cancer increase significantly as you get older and as a nation we are living longer with every generation. In the case of the youngest, it is here that genomics has the greatest life saving potential as 80% of rare diseases manifest in children and, tragically, most of them won’t live to see their 5thfifth birthday.

As the UK100KGP draws to a close in the first half of this year and the company prepares to change its focus to a more traditional business model, it will trade on access to the anonymised data held in the Genomics England Secure Data Centre with research organisations and commercial entities. To aid in this shift, they recently announced the appointment of a new CEO. Taking over from former Chairman, Sir John Chisholm, is Prof. John Mattick, previously of the Australian based Garvan institute of Medical Research, is focusing on this next stage in the life cycle of Genomics England.

Innovative Britain

Britain has always led the world in scientific breakthroughs and DNA was no exception. Crick and Watson won the Nobel Prize for discovering the double helix structure of DNA alongside the too-oft ignored Rosaline Franklin. It was a British scientist, Fred Sanger, who discovered how to sequence it, winning two Nobel Prizes in the process. Now there is the very real opportunity to turn these discoveries into a life-saving reality for NHS patients. A pedigree and mentality of innovation and an understanding of the public good overriding the profit motive have long personified British innovation and the genomic revolution is no different.

Within genomics, researchers and clinicians need as much data as possible and there is no shortage of it. Each person’s genome contains 3.2billion individual letters, nucleotides, within which a single change could result in a devastating pathogenicity. The NHS has lots of supporting data too, this data includes test results, scans, medicines administered, the age at which a person developed particular symptoms and so on. They continue to collect it so they can keep monitoring how a condition progresses over time. This information is important because even small differences in symptoms between individuals might be crucial in finding the changes in their genomes and helping to decide the best treatments.
 

Beginning with a Bake-Off

In the Spring of 2014 Genomics England began taking its first steps towards their bold vision with what was branded the, ‘Genomics England Bake-Off’. This initial phase, named in reference to the popular BBC cookery competition, saw 28 companies compete to find the variants within 15 trios. These companies ranged from industry giants such as Illumina to start-ups, then, still in their infancy such as Congenica.

Of these competitors, 10 were selected in October of that year based upon their ability to quickly and accurately identify the variants known to be in the trios. This pool would reduce further as the four most exciting and effective prospects were given a grant to further develop their ground breaking software platforms. They became Genomics England’s Clinical Interpretation Partners, a validation against their peers thatwhich gave enormous credibility to their tools.

Amongst these companies was Cambridge based, Congenica, and their clinical genomics decision support platform Sapientia. Founded by key members of the 10KGP and DDD, Congenica grew quickly drawing expertise from the private and public sectors and spearheading innovation. Previous diagnostic methods had often been phenotype driven discovery of genetic causes in cases of monogenic disorders but now doctors and clinicians were able to demonstrate the power of their unbiased genotype driven approach and were able to apply this further to identify subsets of patients with similar disorders.

Counting 6 of the world’s leading genome scientists amongst their founders, Congenica came into being after they were inspired to attempt to eliminate the arduous diagnostic odyssey experienced by the majority of rare and inherited genetic disease patients. Using traditional testing methods and consulting strategies, it can take 7 cliniciandoctors 5 years to reach a diagnosis but with Sapientia they had found a way to reduce this to 1 clinician doctor and just 5 days on average. A life changing, and often life saving, difference for patients and their families. Sapientia forms part of the front-line services delivering robust and reliable diagnoses in a rapid manner reducing the anxiety of patients, empowering doctors and reducing costs for healthcare providers.

Implementation

Within the Genomics England ecosystem the aim is to analyse and constantly refine the clinical interpretation of the 100,000 genomes dataset. Clinical interpretation is the next step for the data after the whole genome sequencing, annotation and integration of existing phenotypic data is completed. Through data linkage, this dataset will develop into a rich resource of longitudinal life-course data that is continually augmented and refreshed over time. The goal is to create a truly unique resource in its number of subjects and its breadth of variables.

Genomics enables healthcare professionals to collect associated data in the form of secondary and tertiary findings. These findings may not have direct relevance for the health condition under investigation but, may affect:; medication options, reproductive choices or future medical conditions which are yet to manifest. Implicit in this too is the potential impact one person’s data may have on the patient population as a whole as with every bit of data added to our collective knowledgebases, the more powerful the science becomes.

The raw sequence data from one genome is about 200GB. This mountain of data needs to be interrogated, annotated and presented in a way that is helpful to doctors and clinicians. Here lie Sapientia’s greatest strengths, as this mass of genomic data is uploaded into the system’s ISO-certified, secure, cloud based environment and the variants within it automatically presented in an intuitive integrated genome browser with pedigrees, pathogenicities and known HPO terms all displayed alongside them. From here specialists can further annotate or interrogate the genes in question, can seamlessly search for supporting publications and hold asynchronous multi-disciplinary meetings.

Field programmable gate arrays and automated secondary and tertiary bioinformatics pipelines ensure that the process is a fast as possible and Sapientia is currently the only platform available able to return results against both the established GRCh37 and the most recent GRCh38 reference genomes.

To make genomics a reality for the NHS it has to be of high quality, fast and affordable with results that are readily understood and these values are encapsulated in the Sapientia platform.

Deployment

Now, two years on, Congenica are involved in a number of ground breaking research projects, including…  with major organisations such as Science Foundation Ireland and their joint effort to add the diagnosis of somatic epilepsy to their list of abilities. Sapientia is deployed across Europe, in the United States with such high profile clients as the New York Genome Center and in China through the partnership with Chinese sequencing giant, Beijing Genomics Institute.

In the UK, it was at Manchester’s Centre for Genomic Medicine that Sapientia saw its first live deployment within the NHS. In their Ophthalmology lab in particular they were able to go from offering genetic testing in around 10% of cases to offering it universally.

Now, as the UK100,000K GP enters its final stages, Sapientia is deployed and routinely used in the majority of  6 of the NHS’s 13 Genomic Medicine Centres, where it has been simple to integrate into existing systems, has returned thousands of actionable clinical results and made a tangible difference in treatment or diagnosis to over 450 individual patients. whose cases would have seen little or no progress otherwise.

Legacy

This common approach ensures consistency and coherence across the NHS to gain maximum benefits from the application of genomic technologies, curation of knowledge, and is laying the foundations for the future. The UK is increasingly recognised worldwide as a leader in genomics and the unique structure of the NHS is allowing for these advances to be delivered at scale and pace for patient benefit. The 100,000 Genomes Project is cementing the NHS’s position as one of the most advanced healthcare systems in the world, and is providing the foundation for a new era of personalised medicine, and this in turn will contribute towards the delivery of high quality care for all, now and for future generations.

The list of additional findings for will also change over time asbecause new evidence becomes available about the role of genes in disease. Any findings will be fed back to the NHS, to confirm the result. The structure of the NHS makes it much easier to know much more about the patient in question; details like their symptoms and when they first started, along with physiological measurements, such as heart rate or blood pressure.  Another set of information which may be important in interpreting genomic data comes from their past medical records. The way in which the NHS is able to link a whole lifetime of medical records with a person’s genome data on a large scale is unique.

It is not just patients and the NHS that stand to benefit from the 100,000 Genomes Project. There will be numerous knock-on advantages for the country. Benefits such as new medicines and diagnostic tests some of the companies that may develop will be unexpected, built on new, as yet undiscovered technologies that will emerge over the next five years. The UK, which not only leads the world in life sciences but has the unique benefit of the NHS, is the best place in the world to initiate the practical use of genome sequencing and interpretation for patient benefit. Their vision was one where Britain is the leader in a new industry where genomics is used to help patients get better, more personalised care and treatment.

Genomic England’s legacy will be a genomics service ready for adoption by the NHS, high ethical standards and public support for genomics, new medicines, treatments and diagnostics and a country which hosts the world’s leading genomic companies. It is a bold ambition with benefits for all.

A New Method for Neonatal and Prenatal Diagnosis

There are over half a billion people living with rare diseases - one in every 17 people , or 7% of the world’s population. It feels counter-intuitive, half a billion of anything being rare, but there are more than 7,000 rare diseases classified worldwide, 80% of them with a genetic basis that can be attributed to changes (mutations) in one or more genes.

Rare diseases can manifest in adulthood, but the majority of them present in childhood, particularly in newborns. Twenty percent of infant deaths are a result of such conditions, so the work performed in Neonatal Intensive Care Units (NICUs) and Pediatric Intensive Care Units (PICUs) is some of the most urgent and vital that takes place.

The NICU is a specialized care environment for premature babies or those presenting symptoms. Here they have access to cutting edge diagnostic tools; from MRI and CAT scans to whole genome sequencing, which is used in the rarest and most severe cases, where time is of the essence or no other diagnostic methods are possible. The PICU offers a similar care environment to children over 6 months of age and also offers complex operations and post-operative care.

In many of these cases the genetic variant responsible is so rare and undocumented that doctors might be seeing it for the very first time. These disorders can be difficult to diagnose, as they have many symptoms that are shared by other conditions. These may be phenocopies, in which patients manifest the same clinical symptoms but the underlying genetic causes are different, or they may simply be unique cases in which doctors or clinicians are faced with a variant that has never been seen or documented before. Take, for example, cases of epilepsy caused by different mutations in the SCN1A gene, in which the phenotypes and seizures on the surface appear identical, but can have drastically diverse consequences for prognosis, medication and future pregnancies.

With traditional methods, this could set the child on a diagnostic odyssey of many years as each suspected condition was methodically eliminated, but with clinical genomics, answers can be received, and treatment delivered, in a matter of days.

Clinical genomics is the act of taking an individual’s entire DNA code, all 3.2 billion letters of it, sequencing it (converting it into electronic data) and comparing it to a human reference genome, in order to identify variants and mutations that may be causing a disease or condition. This sequence data is a huge amount of information for doctors and clinicians to work through, and this is where interpretation software platforms such as SapientiaTM, from Cambridge based Congenica, are proving invaluable.

Sapientia takes this sequence and displays it to the doctors and clinicians in an intuitive graphical browser. Here, the whole sequence, or specific genes, can be examined and the potential effects of any variants scrutinised. By placing a huge amount of computing power at the doctors’ and clinicians’ backs and a vast array of medical insight at their fingertips, Sapientia empowers them to make actionable, clinically relevant decisions quickly and confidently.

With a diagnosis the family will have realistic prognostic expectations, clear information on reproductive options and definite focus for management of the condition. In cases where treatment is possible, the more timely the intervention, the more likely it will be that doctors will be able to alleviate symptoms, halt further damage to the child’s health or at the very least direct care towards palliative options.

Bringing the Right People to the Right Information

All parents are offered a screening test on the birth of their child, using a drop of blood taken from the newborn’s heel moments after birth. For some conditions, doctors know that an early intervention can drastically change potential prognosis for the newborn, and in these cases the blood sample will be used for whole genome sequencing (WGS). This sample is then sequenced, processed and introduced into Sapientia. Sapientia enables easy viewing the child’s individual genomic data, including the genes, phenotypes and pedigrees, as well as those of their parents or other family members who have submitted samples.

The presented data is then carefully examined by registered Clinical Scientists who identify variants and assign pathogenicity (their likelihood to cause or affect a known disease or disorder) using the worldwide standardised Human Phenotype Ontology (HPO) terms. These assignments are backed up by expert annotation and supported by literature from the world’s leading academic journals and periodicals.

This information is then displayed graphically in a genome browser for members of the healthcare team. The system then enables leading specialists from around the world to consult on the case. This enormously expands the catchment of experts who are able to share their findings and results, making it easy for the multi-disciplinary teams to add or review annotations, cross reference findings, view pedigrees and trios and form the most effective actionable clinical reports.

Multi-disciplinary teams such as these are integral to synergistic healthcare. In addition to the expected doctors and specialists, you also find physiotherapists, psychologists, dieticians and even play specialists.

Then there are the parents themselves who have a crucial part to play in the form of caregivers. Even if the child is sedated, parental contact is incredibly important; the familiar heartbeat of a mother, skin to skin contact, the recognisable tones of voice or innate scent of their skin are all proven to aid bonding and reduce stress in the child.

A matter of time

In NICU or PICU the child’s condition can deteriorate very quickly. In many cases the illness could have already progressed under the surface and only recently started showing symptoms, meaning the risks from the condition may already have matured and become more dangerous.

The application of genomics into clinical practice allows faster and more accurate diagnoses leading to the most targeted and effective medical treatments to be applied, management steps to be taken, and irreversible neurological and developmental problems potentially averted.

Using traditional medical methods, investigative testing and systematic elimination of potential diseases, the average diagnostic odyssey faced by any patient, adult or child, consists of an average of 7.3 clinicians taking 4.8 years of tests to deliver an actionable, clinical diagnosis. It is a tragic truth that the multitude of these children will not see their fifth birthday. Sapientia has the power to greatly curtail that diagnostic odyssey to an average of only one clinician and just five days. The impact is unequivocal.

Sapientia is helping to save the most vulnerable of lives by providing clinically actionable information, which can be carried out within the critically tight window available to these doctors and clinicians on the NICU and PICU wards.

Congenica was founded, and Sapientia developed, with the aim of integrating genomics into healthcare in a way that would provide tangible benefits where patients need them most. Genomics is giving doctors the greatest insight into the patient that they have ever had. It may not be perfect quite yet, but the future may see a form of medical ability unlike anything previously seen outside of science fiction.

Exomiser - Using model organisms for deeper genomic insights

Every one of us possesses variants throughout our genetic code. Millions of them. Most are harmless, some may even be beneficial, but a tragic fraction carry the devastating consequences of rare and potentially deadly diseases. It is the identification of these dangerous, pathogenic variants that is the basis for genomic medicine.

Whereas as a genome contains all of the genetic material of an organism - 3.2 billion letters, or ‘base pairs’, in a human - an exome is the part formed by exons. These are the parts of the genome that are actually transcribed into RNA, and thus proteins. The typical exome sequence of any individual is just 2% of the genome and commonly contains more than 30,000 variants. When an exome is sequenced and analysed we identify thousands of exomic variants relative to the human reference (or ‘normal’) genome.

The challenge therefore becomes sorting through them and deciding which variant is a harmless one, and which one is causing the disease.

SIFTing for a solution

One solution for this has come in the form of the Java based, open-source tool, Exomiser, which uses algorithms to annotate and prioritise variants from whole-exome sequencing. The program was developed in 2014 by the Monarch Initiative, a cross institutional collaboration between the UK’s Wellcome Trust Sanger Institute, Berlin’s Charite Universitatsmedizin and a number of leading American and British Universities.

Exomiser compares genetic variants with Human Phenotype Ontology (HPO) terms. HPO terms are standardised descriptions of how genetic variants may manifest in a patient, as well as those of common model organisms, such as mice or zebrafish. For example, the HPO term HP0004925 codes for Chronic Lactic Acidosis, or chronic build up of lactic acid in the muscles. By using these standardised terms, symptoms between patients, and even between model organisms can be compared.

Genetic research has highlighted a huge number of associations between specific genes and their phenotypic symptoms. For example, the BBS5 gene, which is required for the healthy development of cilia, and its role in Bardet-Biedl Syndrome. By using model organisms alongside humans, we can add almost 30,000 more genes with known phenotype associations to the dataset, allowing for faster and more accurate identification of causative genes.

Exomiser also uses ‘semantic comparison methodology’, which compares genes based on the similarity of their function rather than their position in the genome sequence. Exomiser uses two pre-computed scores taken from the Sorting Intolerant from Tolerant (SIFT) and Polymorphism Phenotyping version 2 (PolyPhen-2) databases, which both predict how amino acid substitution affects protein function.

Exomiser then assigns a Phenotypic Relevance Score by cross referencing any variants found in the patient against the effects of that gene in model organisms, as well as other humans. Based upon the variant’s known pathogenicity and the likelihood of it being linked to the patients’ recorded phenotypes. Together these form the basis of Exomiser’s final hiPHIVE Score in which it designates the variant’s potential pathogenicity.

The Exomiser suite assigns further scores to support its final hiPHIVE score. The first of these is the ‘variant score’, which is based on allele frequency - the frequency that a variant is seen in the population. Next comes a ‘gene phenotype score’ that decides how critical the gene in question is to the patient’s recorded HPO terms, for example if an individual carries a mutation in both the BRCA1 and BRCA2 genes, the risk of breast cancer leaps up to as much as 90% in later life. Finally, a ‘gene variant score’ is applied to the most potentially dangerous possible genes. The various scores are brought together to form a gene combined score upon which it is ultimately ranked.

This score and its related phenotypic information is then checked against the Online Mendelian Inheritance of Man (OMIM) and Orphanet databases, which catalogue human genes linked to disorders and disease.

The Challenge of Genomic Data

Despite the great strides that scientists have been making in recent years, only around 35% of the human coding genes have been sequenced and identified. Exomiser adds tens of thousands of genes from model organisms used throughout research, and uses HPO terms to bring uniformity to their descriptions. It then uses this data to boost the identification rates of various phenotypes and their causative genes.

The technology can work across exome sequences, gene panels and even be used on the vastly larger and less widely understood whole genome sequences, though it may still struggle with elements such as structural or copy number variants. Exomiser is more than capable of supporting a clinical scientist to drill swiftly down through the millions of possibilities to find the variant that is causing a disease.

Exomiser performs best in situations where a patient’s phenotypes (or ‘symptoms’) have been well defined throughout their health record. Whilst Exomiser can be run in isolation on any computer, it is at its most streamlined when optimised into a wider suite of tools, ideally integrated into a comprehensive clinical genomics analysis platform such as SapientiaTM, from Cambridge based Sanger spin out Congenica.

Such platforms enable clinicians to apply Exomiser alongside numerous other open source and proprietary solutions to their clinical or research investigations. Bringing with it, in the case of Sapientia, the platform’s own extensive knowledge base on top of sources such as OMIM or Orphanet integrations, putting more diagnostic power at the clinician’s fingertips than any other solution.

Ever since the first successful identification of a disease causing variant from Whole Exome Sequencing (WES) in 2010 the industry as a whole has made impressive advances. The extra diagnostic power that Exomiser can bring to a clinician can be the critical element by essentially doubling the number of gene associations available. It can save time and money for institutes and experts and provide the diagnoses and treatment possibilities for which rare disease patients are so desperate, and in the long-run, save lives.

The rise of life science in China

From BRIC to broke

For many, if not all, national governments the health and wellbeing of the population is paramount to maintaining a successful nation. Nowhere is this truer than in the cases of emergent and second world economies. On the modern planet the focus has shifted in recent years away from established first world healthcare systems such as are found in America or Europe to look at those of the fastest growing emergent economies; Brazil, Russia, India and China.

Widely known as ‘BRIC’, a name coined by Goldman Sachs Asset Management Chairman Jim O’Neil in 2001, these four states have either outpaced or were expected to outpace normal growth patterns and break through the glass ceiling between first and second world nations. Unfortunately, the road wasn’t without its pitfalls; Brazil fell to corruption and overspending on the 2014 World Cup and 2016 Olympics which were held in the country, Russia has suffered a number of international sanctions since its aggressive actions concerning the Crimea and the Ukraine and India struggled to modernise and stabilise its economy. Investment assets in these countries have now lost 88% of their 2010 value. Only China remains.

Reforms in the far eastern state started in earnest in 1976 following the death of brutal communist dictator Mao Zedong. China of the 80’s and 90’s was built by Deng XiaoPing who understood the importance of infrastructure on the nation. It was this era that saw the birth of the China we know today and that made the ‘Chinese economic miracle’ possible at all. The next key date was the 2008 Olympic games. The ruling Communist party used this as an opportunity to bulldoze and modernise massive swathes of the country in the name of progress and solidify China’s place on the world stage.

Rise of the middle-class

The core demographic group in any such transition and the metric to measure its success is by the growth and expansion of the middle class. They are the indicator of true global economic progress. The middle class is defined by the Organisation for Economic Co-operation and Development (OECD) as those earning between 75% and 125% of the median income in that country. This could however mean that almost $20,000 in Norway and $120 in Liberia would, in both cases place you in the middle class, but everything is relative.

The middle class underpin the growing economy by providing stable demand and stable growth. However, with this comes increasing expectations of provision and opportunities domestically. In China there has been an overt trade-off between the populace and the party which centres on the exchange of economic growth at the cost of political and human rights. Whilst this group may accept that, they expect a higher level of services such as healthcare and education now.

Twenty years ago China lacked any kind of effective primary care system. Mao’s chaotic and brutal reign had driven the nation back into a primitive agrarian state. Now, as demand and a sense of entitlement to such services increases, the Party has promised healthcare for all by 2020. Whilst building structures and upgrading facilities are very much within the Chinese comfort zone they also have a drastic shortage of GP’s and those they do have differ wildly in their levels of education as only two universities in China offer training comparable to that of western countries.

There is also the problem of scale. China is a vast country containing 1/6th of the global population. To be able to implement a western style, patient centric healthcare system they will need to be training or retraining around 50,000 GP’s per year for the indefinite future.

This is why China is turning its attention to precision medicine and genomic technologies.

Genomic China

The spring of 2015 saw China’s central government announced 60 billion Yuan (£6 billion) budget to be spent over the next 15 years with the goal of creating a functioning precision medicine system that will sequence genomes, develop new and generic drugs and gather variant and other clinical data.

Precision medicine harnesses these huge amounts of clinical data to tailor bespoke medical solutions for each patient. Some of this money is also being driven into education and research with the nation's leading universities, Fudan in Shanghai and Tsinghua in Beijing setting up their own precision medical centres. Nationally they are also engaging in their own mass sequencing effort in the form of the 100K Wellness Project. Most trial and discovery efforts are focused on a number of cancers, in particular lung cancer, with confidence based on the large population to drive mutation and variant identification and lead breakthroughs.

“Life sciences are coveted areas for nation-states. The jobs created in these sectors tend to be high wage and knowledge intensive. Countries with vibrant domestic life science players often have analog industries, such as; agricultural science, engineered materials or food production that are equally advanced. These applications and other respective technologies represent major progress in quality of life.” Said Benjamin Shobert, Senior Associate for the National Bureau of Asian Research.

Massive challenge, mammoth market

Despite the multifarious challenges of doing business in a state such as China with its; authoritarian government, planned economy, manipulated currency and utter disregard for international intellectual property rights, is the potential size of the market. London based consultancy, Global Data predicted a market worth as much $315 billion a year. A figure too compelling to allow the possible negatives to discourage most companies.

That figure looks at the sector as a whole though it may be prudent to break the market down somewhat. China already has some large sequencing companies with the Beijing Genomics Institute being the biggest. For them and other Chinese companies their first outlay will be the sequencing machines themselves. As is the case across the industry, these came from California based Illumina who hold the biggest market share globally. This, however, is a single purchase transaction and not a scalable or sustainable revenue stream.

These sequencers will inundate the budding sector with data and processing that will be the next stage of the challenge. Companies such as, Cambridge based, Congenica, who have developed advanced software called Sapientia, to interrogate, classify and annotate clinical genomic data for either diagnosis or research, are able to empower Chinese clinics here. Also, the constant stream of data means that this revenue stream is strong and sustainable. Even more so if robust contracts and partnerships can be signed.

The last aspect of the market is in drug discovery and trials. This is where the biggest windfalls are and the biggest threats. The windfalls are obvious, in the world’s most populous nation, trials and development are much more straightforward than in heavily regulated western countries and the numbers mean any marketable drug will quickly become a high earner. However, at the same time the state is under pressure to fight the rising cost of healthcare in a relatively impoverished country. To this end the government dictates five drugs for major ailments each year which they then demand the price is reduced by 50% and in some cases, patents are not renewed or respected and the drugs given to Chinese companies to make their own generic versions to sell at a fraction of the cost.

“China is the next big wave, it's only a matter of time before it will certainly be the world’s number one pharma market and probably the world’s biggest data producer. You can dip your toe in via partnerships but sophisticated companies need true collaborations where they can build their own R&D facilities and build a true presence.” Advised Greg B Scott, President and Founder of ChinaBio.

The future

Moving forward companies may find themselves attracted by the huge potential market and data set but must be careful of the various Sino-centric business considerations which they will not have faced in other territories.

The state-planned forms of capitalism mean heavy regulation, frequent intervention, a high level of interference and the constant threat of widespread prying into normally confidential aspects of a company.

“What China needs is innovation. It is happening slowly but it it is driven by returnees or through technology brought into the country and then either directly copied or reverse engineered. There is no conceptual reality or legal reality for intellectual property and Chinese enterprises have increasingly turned to buying out competitors to move away from their predatory reputation. There is also the problem of corruption in the country. President Xi is outwardly appearing to address the issue but in fact it is still deeply entrenched in all aspects of the society. Corruption is not unique to China but its level of general practice is high.” Said Greg B Scott, President of ChinaBio.

The biggest threat to most experts is that of stability. Whilst the middle class is growing and China’s population are enjoying more opportunities and income than ever before, a number of spectres sit on the horizon. The housing crisis driven by unsustainable building and pricing alongside rising food and fuel prices threaten to disenfranchise many, shrinking western markets undermine the manufacturing sector and restrictive uncreative teaching methods leave most graduates without the entrepreneurial skills to start their own enterprises and those same graduates are facing a job market with fewer and fewer opportunities every year.

The Eurasia Group, a consultancy which works to aid investors and business decision makers in understanding the impact of political changes on opportunities in foreign markets wrote: “China’s rebalancing agenda is not merely about economics but, ultimately, the political viability of the Chinese system. Beijing has delivered economic prosperity to many Chinese but those very successes have yielded numerous problems for example; the income gap and the accountability gap are both unsustainable, or, disenchanted graduates working long hours and earning low wages and not being able to get on the housing ladder, marry or start a family. All of which are markedly significant milestones to the Chinese.”

These problems may seem familiar to readers in the UK or US, student debts are extremely high, house prices are unattainable, wages are depressed and jobs at a shortage. Yet China remains stable, more stable than a number of European democracies, but dissent and protest are increasing. There are growing demands for political transparency and engagement. Sadly, government repression is increasing too, censorship is an enormous industry and violence is increasingly used to break up grassroots movements.

China is an autocratic state and a frequent and severe human rights abuser yet it is still relatively open, free and stable for an autocracy. If it is going to stay that way or even improve the Party needs to make careful, considered but significant changes to the way the country works but most importantly, they need to keep investing and keep progressing. The market isn’t getting smaller and it needs to be served, as the expectations of the Chinese increase so do the business opportunities.

Healthcare and data security

Data has become a core element of modern life. For individuals, businesses and governments the management, application and protection of this data is a critical concern. Extensive legislation is required to protect these core groups and their subgroups. Legislation which protects the privacy and security of data, safeguarding individuals from identity theft, companies from fraud and governments from asymmetrical warfare.

Cybercrime has been growing exponentially with the expansion of the digital lives of people and businesses. As more information is digitised and more transactions take place in the virtual realm the draw to criminals increases. Cyber crime does not only seek financial quarry, data is also a highly prized target.

There are two crucial pieces of legislation to protect business and their customers in the digital environment. They are primarily concerned with data privacy and data security and seek to empower companies to take control of these aspects themselves through codes of practice, frameworks for implementation and structure to their modernisation.

These legislations are called ISO27001 in the UK and EU and the Health Insurance Portability and Accountability Act (HIPAA) in the United States.

Why they are needed

The world has seen a number of increasingly audacious and damaging cyberattacks in recent years. Some have been financially motivated, some informationally and others goaled with disrupting a site or service to the point of unusability.

Medical data is extremely appealing to hackers. Healthcare records can be easily used to make false identities or, in countries with private healthcare systems, to fraudulently acquire medication or make false insurance claims. Medical data theft is often not immediately identified, as a credit card may be, thus giving criminals potentially years of exploitable information. In 2014, Reuters reported stolen Medicare credentials were discovered for sale on the dark web for twenty times the value of the same individuals credit card information.

IBM undertake a report each year on the vulnerability of various industries and the number of cyberattacks they have suffered. In 2017 healthcare took the top spot from financial services. American providers have already seen 100 million records stolen in just the first six months of 2017 with at least 45 million of these being stolen in a single attack. Meanwhile EU countries had as many as 2 billion records hacked or stolen during 2016 according to a Europol report.

Legislation in general

Both pieces of legislation, despite some deviations, aim to set out the best practices and methods for information and data security. Those deviations mostly centre upon the provision of medical insurance and the associated industries and businesses within the privatised American healthcare system. These factors are not relevant to the British National Health Service (NHS) for which funding is drawn directly from the income of every British national, akin to a tax, called National Insurance. The EU is a disparate patchwork of national health provision and privatised healthcare and partnerships between both.

The societal and commercial realities of the two regions are behind legislative differences. For example; privacy is considered a fundamental right in Europe, equivalent to a constitutional right in America, hence, it is not uncommon to see debates around privacy in Europe evoke similar levels of emotion to those around gun control do in the US.

ISO27001

Published by the Geneva based, Organisation for Standardisation (ISO) in 2005, the legislation drew on the previous model; British Standard 7799, which was created by Britain’s Department for Trade and Industry in 1995.

The digital revolution gathered pace throughout the 1990’s and the 2000’s bringing with it web 2.0, the internet became ubiquitous and an ever increasing number of people, businesses and information moved online it became apparent that companies needed a unified information security and management system (ISMS). This legislation is not prescriptive but instead gives guidelines and minimum standards by which companies should protect their customers and themselves.

The legislation was updated again in 2013 to keep pace with the rapidly advancing digital environment allowing for more flexibility in implementing tailored suites of ISMS apparatus and introducing objective audits to be undertaken annually backed by independent auditors.

ISO27001 requires that all organisations who deal with a customer’s personal data in any way must have a process in place to systematically examine their information security risks and take account of any threats to or vulnerabilities in their defences and what the potential fall-out of any failings could be.

To these ends they are required to design and implement a coherent and comprehensive suite of ISMS controls and to adopt an overarching management process to ensure that these controls continue to evolve to be prepared for future changes or challenges either in the company, market or legislation.

ISO is an independent organisation and its standards are often seen as an unbiased measurement of the broad ISMS climate across the EU and the wider world. The legislation is compliant with all other related laws such as the UK’s 1998 Data Protection Act and the coming General Data Protection Regulation (GDPR), which aims to harmonise all policies across Britain and the EU by 2018.

GDPR will also add teeth to the legislation by giving EU bureaucrats the powers to punish infractions with enormous fines of up to €20 million or 4% of a company's global annual turnover.

The legislation is considered a useful tool for businesses as it reduces their customer and supplier audit trail, thus curtailing third party scrutiny and compliance can reduce liability should any security incidents take place.

HIPAA

Coming into force in 1996 and bearing far stricter rules and regulations than ISO27001, the act focused on a goal of assuring individuals that their protected health information (PHI) was safe and secure across the various practitioners, institutions and businesses that make up America’s diverse but fiscally demanding marketplace.

HIPAA operates at a federal level meaning that all states and agencies must adhere to its rules before adhering to the their own, multifarious state legislations, creating what is known as a sectoral approach. The act is backed-up by The Office of Civil Rights (OCR) which is part of the US Department of Health & Human Services (HHS) and is empowered to issue fines of up to $1.5 million per infraction and, in extreme cases, pass custodial sentences of up to 10 years.

America’s healthcare system is dominated by private health insurance, be it personal or employer provided, though 27 million people, just over 10% of the working age population have no insurance. Whilst this number has fallen due to the 2010 Affordable Care Act (ACA), colloquially known as Obamacare, universal healthcare is still remote.

The largest sector of the American healthcare system are the Health Management Organisations (HMO). These large companies contain health insurers, medical institutions and healthcare practitioners. They are the biggest slice of the market and a key factor in the need for HIPAA in the first place as they are constantly transferring PHI data.

The highest risk sector is that of billing and payment as HMO’s often use 3rd party healthcare clearing-houses to pursue reimbursement which creates many threats around anonymisation and pseudonymisation of the PHI.

The Transatlantic Divide

Whilst the two pieces of legislation have the same goals, and generally similar implementation, there are a number of differences. These differences are rooted in the societal and commercial realities of the two regions though it is critical to remember that the two acts are not in competition, they complement each other and are fundamentally the same.

The biggest of these is the matter of consent. In Britain and Europe a company may only use your data for purposes expressly specified when the data is collected. However in the US your data becomes the property of the company in question with which they can do anything they like.

This attitude extends to terms and conditions too. In America you can still be faced by multiple pages of obfuscating legalese when agreeing to use a product or service yet in Britain or the EU that text must be short clear and easy to understand.

The most important aspect, and the one with the most stringent regulations under ISO27001, is that of data sovereignty. Within Europe all personal data must be retained in the country from which it was gathered. Meaning, for example, that Belgian WGS data must be kept not only in Europe but specifically in Belgium.

ISO is sometimes seen as lacking bite due to its inability to prosecute though that will change with the introduction of GDPR in 2018. HIPAA regulations also aren’t without their criticism as the length of time it takes to make changes to its prescriptive and exacting standards can lead to a lack of flexibility and an inability to react to unexpected threats.

The two pieces of legislation share the central goal of protecting both the service user and their data but also the service or company itself. Both systems require careful and in depth audits to maintain standards and, concerns about privacy or reimbursement aside, they are commensurate and effective legislations.

What Sapientia does to protect your data

Throughout Congenica, and their gold standard clinical genome analysis platform Sapientia, patient privacy and data security are paramount concerns. The company and the product both go above and beyond what is demanded by either piece of legislation.

All data is anonymised and pseudonymised making it impossible to attach them to any individual. Further to this, data is encrypted at all times, be it in transit or at rest. User account access controls are in place across the company to carefully restrict and log who sees and uses various parts of the system and everything is locked behind elaborate password systems.

Congenica boasts an excellent and highly informed quality assurance (QA) team led by a knowledgeable and experienced QA manager. Together with the in-house ISMS team, they ensure that the methods and systems are strong all year round by regularly and methodically reviewing, not just when audits are due.

There are exacting requirements in place too for the disposal or destruction of any hard-copies, machines or peripherals which may contain or had contained personal or private data to ensure nothing is leaked in this way.

Aside from this Congenica employs outside agents to undertake penetration testing or other ‘whitehat hacking’ which means engaging somebody to attack your system, searching for weakspots or faults and reporting back to the ISMS team. Adhering to the rules in place and having a good understanding of what may be on the horizon are key to future proofing.

Conclusion

The two acts exist to help the industry, to protect patients and to build the foundations for future legislation in a domain that is still very much in its infancy. At their cores they are essentially the same, different methods and routes to reaching the same destination.

Repercussions can be far reaching, having direct effects but also damaging your brand in the eyes of peers, potential partners or investors and consumers.

ISO is not a ‘point in time’ audit but an expression of ongoing commitment and improvement towards a greater and ever growing goals. Is overall audit of ISMS as a whole rather than an inspection of the technical goals underpinning the ISMS.

There are potential weaknesses in both legislations. In the case of 27001 it is the fact that an organisation is left to decide what level of security it needs. The level of risk which is acceptable to the organisations is a management decision and this brings into focus a reliance of management being fully aware of their risks and fully willing to budget for protecting against them.

HIPAA is more prescriptive but that defends against companies with too much risk appetite as the mandatory demands reduce the need for risk management and security expertise. Though as has been mentioned before, the slow rate of change in the act leaves it at risk of being compromised.

With the EU about to get the power to punish companies, with fines far higher than those for any other industry and far outstripping HIPAA’s punitive teeth, a more confrontational environment may be created which could hinder trade and innovation across all industries, not just healthcare.

Congenica does far more than either legislation requires. This is the result of a strong risk assessment and a culture of constant monitoring and improvement within a company. Congenica understands the precious nature of the data with which they have been entrusted with and treat it as such.

What is Clinical Genomics?

Clinical Genomics is a modern approach to practising medicine in which healthcare professionals use information on the genetic makeup of a patient to diagnose, treat and prevent disease.

Diseases can be caused by a single DNA mutation, for example, cystic fibrosis, or by much larger chromosomal changes, such as in cases of Down’s syndrome. Genetic data can also help us to understand the causes of more complex diseases, such as Alzheimer’s disease or rheumatoid arthritis. Complex diseases are caused by a combination of multiple genetic changes within the patient but are also influenced by their environmental and lifestyle factors.

Identifying the genetic changes that occur in a wide-range of diseases offers opportunities to develop new treatments which are targeted at specific mutations. Genetic data can also be used to facilitate the provision of medication which avoids unwanted side effects and increases the chances of success.

The term ‘Precision Medicine’ has been coined to represent the need to gain better insights into the biological, environmental, and behavioural influences upon these diseases and to better serve patients.

Background and Driving Forces

The use of genetics in the clinic dates back to the early 1960s with the introduction of screening tests for newborn babies. Prenatal screening for cystic fibrosis and Down’s syndrome has since become a matter of course. In the UK, and increasingly around the world, clinical genetics is a recognised medical speciality with formalised training and a clear career pathway for doctors who diagnose and manage families with genetic disorders.

In recent years, technology has evolved to the point where it is no longer limited to detecting single mutations. DNA sequencing is a technology that enables us to identify all potential variations in a person’s genetic makeup, this is important when studying complex diseases in which there may be many genetic changes that preside over the risk of developing a disease.

The cost of DNA sequencing has been rapidly decreasing, this combined with innovative advances in software and storage solutions for genetic data have increased the accessibility of DNA sequencing for use in clinical settings.

Now that genetic data can be readily generated, clinical scientists need to accurately identify the genetic mutation or mutations that cause disease and to understand the consequences of those mutations upon the human body. Understanding which biological processes are disrupted by genetic mutations is vital to establishing new treatments, clinical trials or drug development thus ensuring the benefits are felt by patients and society as a whole.

Current State

Today, the potential benefits of using genetic data are widely acknowledged by scientists, clinicians, healthcare professionals and even politicians. There are numerous centres, from small private clinics to nationwide initiatives, intent on developing new processes to accelerate the implementation of clinical genomics in the healthcare, research and pharmaceutical sectors.

One particularly prominent example has been Genomics England and their 100K Genome Project, which aims to gather 100,000 genomic sequences from National Health Services (NHS) patients in the UK, providing genetic insights into diseases and their diagnoses. In some cases the diseases in question are so rare that no diagnosis was previously available or, even, possible as they were only recorded in an individual or single family.

Integration of clinical genomics into healthcare comes with challenges, particularly in understanding the vast and complex data that clinicians must now interpret and understand. However, there are new technologies being developed to help with this challenge, and this is where companies such as Congenica are leading the way.

Congenica have developed Sapientia™, a software platform that integrates human DNA data with clinical information and symptoms, and references them against vast private and public databases of genetics, helping clinicians understand the mass of data provided, and helping them to provide actionable interpretations of inherited diseases.

Previously, it took 7.3 clinicians working over a period of 4.8 years to reach a clear diagnosis for a patient with a rare disease in the UK. With Sapientia, however, it can be as little as 1 clinician and just 5 days to reach the same conclusion. A seismic shift in patient experience.

Challenges currently facing Genomic Data Interpretation

The cost and time required for sequencing a whole genome has plummeted in recent years, giving clinicians access to vast amounts of genetic information. Accurately identifying which are the disease-causing mutations within this data can be extremely challenging, but is of the utmost importance for diagnoses and the development of new treatments. Software advances have been helping clinicians by integrating multiple sources of information, including clinical traits and symptoms. Sapientia, for example, provides an actionable list of all the mutations that are likely to cause disease from any mass of data.

As more genomic data becomes available and the ability to interpret it is made possible by such software platforms, it is imperative to ensure data privacy when sharing and collaborating. Data must be anonymised to ensure that it does not contain any personal patient information, and data transfer and storage must adhere to the highest levels of security.

At the same time, it is important for clinicians and scientists to be able to share their discoveries and insights, so that they can make the best decisions based on all the knowledge available. Sapientia, for example, provides a collaborative software environment, where clinical geneticists can share DNA mutations and literature insights. This allows clinicians, across multiple organizations in different parts of the world to, more quickly, identify disease-causing mutations in patients and administer effective therapies.

Looking to the Future

As knowledge in genomics keeps expanding and healthcare practitioners continue to adopt new technologies, the medical community is working towards a future where diagnosing, managing and treating inherited disorders and complex diseases becomes the norm. To achieve this clinicians, doctors, private businesses and even politicians across all medical sectors from primary care to commercial drug discovery need to keep driving forward to push the boundaries of genomic medicine.

The world that Congenica envisions is one where the sequencing of an individual’s genome is part of routine medical practice and where the highest level of healthcare is available to all. A world where having a genome sequenced is as routine as MRI or CT scans. A world in which we understand diseases which, currently, we can’t even name. Genomics is the key to unlocking a world previously thought impossible and in understanding the very building blocks are lives are built upon. It is the medical revolution of our time.

Do algorithms dream of genomic sheep?

Genomics has been the catalyst in the information revolution that is sweeping across healthcare and bringing the dream of personalised medicine closer to a reality. Now, the debate is shifting towards how the potential of complex computing to enable clinicians, doctors and scientists to truly capitalise on the data goldmine that genomics is.

The first thing to address is the terminology. Artificial intelligence and machine learning are two of the hottest buzzwords around this field at the moment and, though they mean quite different things, they are often used interchangeably.

Artificial intelligence is not as dramatic as Hollywood portrays. In many ways it has already become something we take for granted; Google Translate, facial recognition or voice operated devices such as Alexa or Siri. These are systems programmed to mimic or complement human thinking. Although they cannot understand nuance, they are flexible programmes capable of solving a wide range of retrieval questions, essentially locating and connecting you with the information for which you are looking. For example: ‘Siri, what’s the best use for artificial intelligence?’

Machine learning on the other hand is giving a computer a mass of data and allowing it to generate and alter its own algorithms to come up with solutions or patterns. It can design and modify itself - learning for lack of a better word - without being explicitly programmed.

Breaking Down the Data

The traditional approach to solving problems with AI is to give the computer a set of rules to work within, a task to achieve, and then apply brute computing force to the problem, like trying to crack a pin number by trying every possible combination.

With machine learning we give the computer the data and a goal and it defines its own rules and algorithms to reach a result. For example, a wealth of data about people who have suffered heart attacks is fed into the system and its algorithms quickly work through the data, so, when it has seen a million patients it is able to make predictions about groups or individuals who may be at various levels of risk of heart attack. It can’t however ask why any ‘why’ or ‘how’ questions and its answers will always be numerical and statistical in nature.

Computing as it is commonly used operates by a user giving a specific instruction and the machine returning a specific bit of data, for example, what was the average age of our heart attack patients? Here the computer would give a single answer and finish. With machine learning it would be simultaneously asking that and more questions; where did they live? Did they smoke? Was this their first medical contact? It can then cross reference the data. It is from these steps where its advantage comes.

The Limitations of Technology

However, therein lies the great strength and weakness of machine learning. It is excellent at tasks such as pattern recognition or crunching huge amounts of data to reduce it down to the critical decision points. However, it can’t second guess itself and it can’t choose to ‘think’ differently. Machine learning is tied to algorithms; it can only speak in maths and can’t ask deeper, expansive questions, and it can only be as good as the data it is given.

Machine learning is nothing more than a statistic driven technology, but it is a very fast one, capable of carrying out a wide range of complex processes by learning from their inputs rather than reading from sets of pre-programmed rules.

That line between machine learning and statistics is blurry at best with some experts preferring the name ‘statistical learning’. The field itself grew out of the artificial intelligence community of the late 90’s and has mostly focused on the analysis of large, heterogeneous data sets.

Artificial Intelligence & Machine Learning in Genomics & The World

It is estimated that 90% of all the world’s digital data is less than five years old. Across genomics people are talking about the vast amount of information currently being generated through sequencing; machine learning could be the key to transforming this from a daunting burden into a data goldmine.

Machine learning methods have already been applied to a number of problems faced in genomics such as annotating genomic sequence elements, identifying splice sites, promoters, enhancers and positioned nucleosomes. Sapientia, for example, is a clinical genome analysis platform created by Cambridge based Congenica, which uses the Scale Invariant Feature Transform (SIFT) algorithm that can resolve the probable pathogenicity of an amino acid change based upon multi-species alignment to identify how impactful that mutation could become.

“Sapientia puts more information in front of the user than any other platform. Machine learning can’t take clinicians all the way to fully automated diagnosis because you always need the applications of human experience, for example, corner cases. The ‘state of the art’ for this is the empowerment of the experts by organising that data into one place in an easily comprehensible fashion. That is essentially how we got diagnosis times down from 5 years to 5 days. All forms of AI or machine learning are about multiplying human effort rather than replacing it.” Said Alan Martin, Head of Innovation at Congenica.

The promise of machine learning for genomics is enormous if it could be fulfilled. It could mean near perfect diagnoses, optimised medication and treatment choices, accurately predicted readmissions, identified high risk patients and general empowerment of the personalisation of medicine whilst all the time seeing costs minimised.

The biggest machine learning projects in the world are still in their early stages, especially those that look to eventually use real artificial intelligence. The biggest and best funded of these is London-based Google DeepMind Health. The Alphabet backed technology is currently working with Moorfields Eye Hospital in developing methods to tackle macular degeneration in ageing eyes and with University College London Hospitals to detect differences in healthy and cancerous tissues and aiding accuracy in radiation therapies.

Machine learning will undoubtedly become a key appliance in a genetic clinician’s toolbox but it will be limited in scope, best used in niche and specialised areas where specific questions can be answered, or in studies that have a large data set. These situations offer the optimal set-up, with questions and data specific enough to create actionable interpretations. In comparison to feeding a computer information on patients that have suffered heart attacks, it would be akin to giving a computer data on all deaths in the last year and asking, ‘what happened?’

Legal ramifications may also affect adoption of machine learning, in particular for the healthcare industry in which the use of ‘black box’ style algorithms (where inputs go into the programme and outputs are produced with little explanation of how it ventured from point A to point B) may not be acceptable as the law demands increasing transparency.

Sebastian Thrun, former director of the Artificial Intelligence lab at Stanford University, said: “AI and ML are about magnifying human ability. The industrial revolution amplified the power of human muscle. When you use a phone you amplify the human voice. You cannot shout from New York to California. This cognitive revolution will allow computers to amplify the capacity of the human mind in the same manner.”

The Second Greening of America

“Everything is organic and locally grown; I keep all the jars sealed and the strains separated. People are pretty on about that. Most of the strains are between $7 and $10 a gram. The big buds sell as are, I really don’t like to break them up, they’re so beautiful. I’ve got indigoes and oranges and a whole range of body and head hits. It’s a serious thing man”

Brian sells marijuana. A resident of the San Francisco Bay Area, he has sold the drug for decades but does not think of himself as a ‘drug dealer’. “I just supply people with a product they want. Now that weed is kinda legal and the dispensaries have opened, the supply chain has really opened up. Too much is hydroponic though man, people want their weed natural, like, straight from the earth man. Nothing really changed for me though, my customers or suppliers. This has been the cannabis capital of the states for decades man. Its part of Cali.”

The marijuana industry is currently offering major challenge to much of the received wisdom regarding the American economy. California is not the only state to allow some form of legal marijuana but it is the current success story. A title all the more significant due to the state’s enormous debt. Various industries have sprung up around drug and are quickly changing the business and artistic landscape and the changing attitude to drug classification is in fact supporting harder drug legislation and making streets safer.

Despite the various legislations, marijuana is still considered a controlled substance by the federal government at a national level. Even within the legalized states limits are placed on the number of plants which an individual can cultivate – six – and how much an individual can possess – up to 1 ounce in a single container.

Pale green – State with legal medical marijuana

Sludge green – State with decriminalized marijuana possession law

Dark green – States with both medical and decriminalized marijuana laws

Purple – States with full Marijuana legalization

However, a walk around the streets of any part of the Bay Area, from El Cerrito to Embarcadero you will smell the recognizable sweet scent of weed smoke. This is one of the downsides which isn’t being addressed at the moment. Many conservative local and state level lobby groups have claimed that medical marijuana dispensaries are magnets for crime and that a relaxed attitude to soft drugs leads to harder ones – the old ‘gateway’ argument.

Holland has already disproved that theory. When the government decriminalized the drug in 1972 it was part of a policy to treat ‘soft drugs’ – mostly those of natural origin but excluding opiates – separately from ‘hard drugs’. The former is treated as a social issue and legislated against to protect consumers, minimize nuisance and eliminate the black market. This freed up resources for the police to enforce a zero tolerance policy on hard drug trafficking and supply which was praised by Interpol.

Following the voicing of political concerns in America a number of studies took place. In 2010 a Denver Police Department investigation found that crime had fallen by 8.2% in areas around medical marijuana dispensaries. Another investigation in Colorado Springs produced similar results noting significant drops in petty street crime such as vandalism and theft from vehicles. A UCLA study in 2011 found that crime rates had dropped across the most at-risk group, 15-24 year old males. Using ‘routine activity theory’ the researchers found that the delineation within drug legislation and increased sense of ‘guardianship’ had changed the attitudes towards ‘crimes’ and people’s neighborhoods. Some researchers further speculate that it is due to the removal of the gangs from the drugs supply though the report did not officially comment on this.

Only licensed marijuana dispensaries can sell the drug and then only to people who have a valid Medical Marijuana Card but these are readily available to anyone for just $30. Along with this has come a growth in ‘head shops’ which specialize in elaborate pipes and bongs. These shops have sprung up rapidly over the last decade. Mostly owned by independent traders they make most of their profits from the various paraphernalia – the biggest earner and most exciting medium is glassware.

These pipes range in price from $10 to and incredible $30,000. The vast majority are made by individuals or small collectives within whom competition has seen art override simple functionality. Austin’s Salt and Berkeley’s Revere are two examples of the apex of the movement. Their creations are barely recognizable as smoking devices.

“We’re master craftsmen. There is art, great art, in lot of my pieces and across the community but there is also massive skill too.” Dustin Revere told me at his studio. “The whole glass pipe thing is an element of the marijuana scene in the same way that breaking or graffiti is part of the hip hop scene but at the same time it’s an exciting thing in its own right.”

Many studios offer classes and there are other public funded organizations, such as The Crucible in Oakland, teaching young people the skills to one day go into these and other businesses themselves. These are no meager skills too, glassblowing and working is very technical affair with rules and safety at its heart, yet for many young people it is revelation. Suddenly they have skills and are able to create not only beautiful things but saleable, useable products. The documentary Degenerate Art is a fascinating look into this creative and industrial medium.

“It’s a big eye opener to a lot of these younger kids. They see the flames and hot glass and they get scared but when they start doing it they can get creative, make sculptures or jewelry or pipes or anything. It gives them power.” Lance Wright from Newtonian Glass said.

California has many highly respected universities where students pay an average of $32,000 a year for an average of four years to get their degrees. Yet some of the country’s leading glass artists trained for as little as $6,000 and many more of the mediums leaders are self taught.

The current economic crisis is deeply felt amongst America’s recent university graduates with an estimated 1.5 million of the country’s 5.4 million ‘long-term’ unemployed are graduates burdened with debts.

The negative narratives of crime and the positive of business and artistic access, whether you agree with them are not, are the reigning ones. There are increasingly environmental questions surrounding the industry. The legislation on the multitudinous marijuana farms isn’t clear but a story in the LA Times declared, late last year, that marijuana farms were siphoning 18 million gallons of water every year.

There are further allegations of farmers illegally cutting down trees and even grading rugged areas flat causing disruption to water run-off from the state’s sparse rainfall. The effects have even been felt as far away as Yosemite National Park where pesticides and rodenticides have found there way into the food chain, allegedly from Californian marijuana farms.

There is more to marijuana than just smoking though. Its prohibition essentially goes back to face off within American industry at during the interwar years. When Rudolph Diesel invented his engine in 1896 it was planned to run on hemp derivatives. Hemp had also been used for paper across America. The story goes that between Gulf Oil and William Randall Hearst’s lumber and paper interests the once common plant was vilified and criminalized.

Hemp, the non psychoactive train of marijuana is one of the most useful and hardy plant on the planet. Studies have shown that due to the low requirements for herbicides and pesticides hemp paper could be a carbon negative cash crop. The plant has been proved to remove radioactivity from the soil and can stop tumor growth in cancer. As a fibre it can make everything from clothes to car dashboards. As a food stuff it is unrivaled and far less environmentally devastating than soy beans.

Maybe the key to surviving the economic crisis and progress in general is to live in a land of sensi.

Copyright 2013

Designing away from the derivative

No medium is as beholden to its sound design and production as video games. It is an industry which, despite being worth $84.1 billion last year, is never given recognition, be it creatively, contextually or in the sense of its world building and immersiveness.

Video games are not a passive medium like movies or tv. They require a world to be built to then be inhabited by the player. Every footstep, every door opening, the weather effects or the visceral blast of an explosion, everything is carefully crafted.

Few games outside of the $100 million production values of Rockstar's Grand Theft Auto series can afford to license real world songs so it is made from scratch and, Clint Mansell's of the world aside, it is already surpassing its more established celluloid counterpart.

The 2012 Grammy's saw a games first nomination at an unequivocally mainstream event. “To be nominated alongside John Williams and Hans Zimmer is something I genuinely never thought would happen”, Austin Wintory told Wired magazine, adding, “its a long way from Streets of Rage 2.”

Wintory's work on Journey, a mesmeric and ambient game for Sony's various consoles. It would eventually lose out to Trent Reznor's 'Girl with a Dragon Tattoo' soundtrack but, regardless, it was another step on the medium's own journey to true appreciation.

Unlike film, video games don't find themselves as crushingly tied to preconceptions. For every Jack Wall, Mass Effect soundtrack with its huge orchestral strings, sci-fi theremins and Solaris ambience, which cost Canadian developer Bioware almost as much as their entire physics engine, there are indie darlings embracing obsolete technologies and out moded methods to recreate the ear-worms of the 80's and 90's.

Of those earworms, it is Streets of Rage 2 (1992) for the Sega Megadrive which is considered the high water mark both contemporaneously and historically. Yuzo Koshiro was the Bowie of 16bit beats. Working as he was at the time with already outdated technology, an NEC PC-8801, utilised; PSG sound-chips, SID chips and waveform generators to create a retro-futuristic soundtrack that still elevates the game today.

Ed McMillan and Tommy Refennes 2008 release, Super Meat Boy, could have come directly from the realms of Super Nintendo or Sega Megadrive and utilises the same technology, or at least digital emulations of it. Re-embracing the SID chips, FM synthboards, Music Macro Language and Midi interfaces to lead a lo-fi, low bit renaissance. Unlike film the finished product doesn't feel dated as a game's mechanics, controls and visual ambience work to create a polished whole.

In the case of this pixellated, punishing, platforming tale of a skinless boy and the bandage based soul mate, it is not just the tight controls and rapid response gameplay of yore but vibrant, pulsing, catchy soundtrack complete with chip-based synthesis of electric guitar solos and driving riffs, which make it so compulsive.

The most common Chiptune video game music is Koji Kondo's Super Mario Bros. theme from their 1985 NES console debut. It's distinctive sound was generated accidentally as the console's chips couldn't accurately capture the steel drum calypso sound Kondo wanted.

The theme was to be scrapped before the father of the series and its lead designer, Shigeru Miyamoto personally stepped in and decreed it to be used as the canonical theme. Thirty years on and it sounds as fresh as ever and is still the most recognisable piece of game music in the world, the second being the Tetris theme.

Modern sampling and synthesizer technology grew in complexity and abundance throughout the 90's and 2000's as games grew in stature and scope so did their soundtracks. They became grand and cinematic in many cases, mimicked the dance electronic music of the time or slipped into art-house inflected minimalism. Dynamic masterpieces such Harry Gregson-Williams' scores for Hideo Kojima's behemoth of a game series, Metal Gear has given the game's worlds contextual consistency across time periods and locales. The third instalment, Snake Eater's Bond-esque theme, is superior to any 007's recent themes.

Speaking at the awards, “it's been a long time coming,” the 28 year old Denver native, Wintory, went on, “I almost feel ashamed that so much great stuff has been done over the last decade that for reasons unknown has never got the recognition it deserves from the music industries.”

Role playing game Rogue Legacy boasts a 16 bit soundtrack filled with sinister synthesised strings adding a level for tension and foreboding otherwise impossible due to the game's cutesy graphics and 80's schlock-fest Hotline Miami embraces 80's syths and modern Chiptune to create a sense of place and depth as effective as those created through similar techniques in Nicholas Winding Refn's 2011 film Drive.

Regardless of how any individual may view the games industry or the old SID driven styles of music and sound design, their growing significance in and around creative industry sectors point to more opportunities and branches for all and the cross-overs into mainstream popular music with acts like Crystal Castles, The Prodigy and Daft Punk shows that the beeps and bloops are back and this time, here to stay.

Copyright 2012

If Mayans could accurately predict the future…We’d probably still have Mayans.

Once more, the world is facing down a date which some amongst our population have decided is to be the day of our destruction. This isn’t a new thing. It’s not so long ago that we were all being told that at midnight of 31st December 1999 all of the world’s computers would have a collective, digital brain-fart and reset their clocks to 1900 rather than 2000 which would result in planes dropping from the sky, nuclear missiles being launched and all of our bank accounts being reset. Spoiler alert – it didn’t.

In fact Wikipedia lists 83 individual, failed apocalypse prophecies and 9 more, including next week, which have yet to happen. Predictably various Christian sects and American evangelical churches are the worst offenders, being responsible for almost two thirds of the tales of impending woe and destruction, but always offering salvation for supplication.

However, some predictors may surprise you; for example, Issac Newton was part of the Y2K brigade. Botticelli claimed that the year 1500 would be our last. John Wesley, founder of the Methodist Church had us penciled in for holy destruction in 1836.

These names though are the respectable side of apocalyptic predictions. There are some more sinister names upon the list. Charles Manson is one that jumps out. In the late 60’s Manson was enjoying a literal orgy or drugs and sex with his followers before he discovered the hidden messages in The Beatles’ White Album. He called his vision of apocalypse ‘Helter Skelter’, after one of the songs. He saw a race war between black and white Americans destroying the country. But he was going to lead his followers to safety in the ‘bottomless pit’ which he believed was somewhere in Death Valley. As the last years of the 60’s unfolded tensions rose with the assignations of powerful black leaders such as Martin Luther King. Yet he grew inpatient and ordered the Tait – La Bianca murders as a way to kickstart the end. In fact, when the Manson family was arrested it was for stealing dune buggies to search for the pit and the arson of some construction machinery they had found. They would only be linked to the murder when family member Susan ‘Sadie’ Atkins confessed to a cell mate.

The 70’s would give the world the largest mass cult suicide at Jonestown, Guyana which left 914 people dead and would make offers of Kool-Aid slightly sinister – the drink actually laced with poison was ‘Flavor Aid’. Lead by yond and charismatic preacher Jim Jones the cult went through a number of transformations as it moved around northern California but Jones outspoken support of communist regimes in North Korea and the Soviet Union had marked his card. Rumours grew and grew about strange practices with Jones’ church and threats made against people who spoke out or wished to leave. Despite holding some sway in local politics Jones became increasingly paranoid and moved his followers to the Guyanan jungle.

Jones would become convinced of plots to kill him, of secret spies lurking in the jungle and of an impending nuclear war. Back in America the cause of the Jonestown families had been taken up by Congressman Leo Ryan. Ryan organized a trip to Jonestown with concerned relatives. When they arrived things seemed in order but gradually people passed them notes in secret asking for help. The next day some people wanted to leave. Jones, clearly angered let them but refused to allow their children of family to go with them. Eventually Ryan gave in and took the few people to the airstrip. Within 45 minutes he and all the members of Jonestown would be dead. They drank cyanide on his orders; the arrival of Ryan was the last portent of the apocalypse. There is an audio recording of the final hour of Jonestown and images from the helicopter which went to investigate two days later why no-one had come home.

The worst offenders of all though were the Bible Student Movement, a milenialist and restorationist Christian sect which is behind organizations such as Jehovahs Witnesses and the Watchtower. They predicted 9 separate apocalypses between 1874 and 1925.

So, we probably won’t see our poles switch suddenly, super volcanoes burst forth or a massive food inundate the world but what are the more serious potential extinction events on our horizon which we are merrily not thinking about. The obvious ones are over population den climate change, both are undeniable. The old classic, nuclear war, is never far away – August 29th 1997 anyone? Or the biggest elephant in the room, peak oil.

The most serious predictions all put the end far off. In 5 billion years our sun will begin to go into its red giant phase which will destroy this solar system. The Big Rip Theory claims that in 22 billion years the universe’s continual expansion will begin to tear it apart. I don’t even know how to say 10600 years but that is when scientists believe the ‘heat death of the universe’ will occur, total and utter game over.

So what does all of this rambling prove? Nothing more than that there have always been those who call out ‘the end is nigh’ on grey and cold mornings or those so riddled with their own madness and arrogance that they lead the weak willed to their own mini apocalypses but, as with most great threats and evils, it comes not from the supernatural or the cosmos but from us. We are the apocalypse.

Maybe that is why our culture enjoys the macabre spectacle of apocalyptic movies and literature more and more. As our news becomes darker than our films where else is there for the consciousness to go than to imagined doom?

If the Mayans could predict the future to such a degree then why weren’t they prepared for Cortez? Why didn’t they see the plants that would give them antibiotics? Why didn’t they work steel or make black powder? I know the hippies like to think of them as some peaceful, pious to their gods and naively welcoming – you can thank Niel Young and Crazy Horse for that one – but they were aggressive and war like, heart munching, chocolate smoking warriors.

For me all the evidence points in one direction - that the Mayans had a finite counting system or a finite amount of rock to write it on and we are all just distracting ourselves again.

Copyright 2012

History Through Music – Part 2: Christmas Canceled – Macka B, 2000

“It’s Christmas!” Slade’s opening shout will usually start ringing out in the UK’s shops sometime in November, here is the States I’ve heard Jingle Bell Rock about a million times already – though I will never be able to shake the association with John McClane and ‘terrorists with smaller feet than my sister’.

All rambling aside, the factual roots of Christmas have been long lost in most parts of our society, if we ever knew what it was in the first place, but most of all in our mass media. Music litters itself with clichés and movies seldom refer to anything other than 19th century machinations such as Santa, reindeer, pine trees and child abducting snowmen.

To offer some alternative, here are the wikibombed lyrics to British born reggae artist and activist Macka B’s song for a more ‘conscious’ take on it all.

Christmas has been canceled it's been postponed
No longer celebrated inna we home.
Pagan things we try to leave them alone
Incorporated into Christianity by Rome
We're using our brain we're breaking the chain
We're not playing the Christmas game what a shame (2x)

All the drunkenness and the overeating.
Is it the birth of Christ they're celebrating?
Mostly non Christians are partaking
Fi some it's just an excuse fi money making
They say peace and goodwill to all men
So how come they're putting up the prices then?
Targeting the parents through the children
Well them nah ketch I and I again no way me friend

A long time the 25th of December
has been a special date in the pagans calendar
Long, long before the birth of Christ
It was a day for partying and celebrating and to rejoice
From Nimrod to Saturn to Mithra
These Gods were always honoured on that day in December
Worshiping of sun Gods and idols
Why you think Christmas is never mentioned in the Bible

You see the tree and the ivy and the mistletoe
All of these were pagan things a long time ago
People have them in their house and they don't know what they mean
They just come see them so they just join in
Santa Claus what a fraud never once come a me yard
A me parents have to work, work so hard
Christmas put people under pressures
Don't you see that Santa and Satan have got the same letters

Christmas has been canceled it's been postponed
No longer celebrated inna we home.
Pagan things we try to leave them alone
Incorporated into Christianity by Rome
We're using our brain we're breaking the chain
We're not playing the Christmas game what a shame (2x)

History through Music Part 1: We Didn’t Start the Fire – Billy Joel, 1989

It only takes five letters of this song’s title for Google instant to suggest Billy Joel’s 1989 hit single. The song’s lyrics cover forty years of history and reference over 100 significant events and figures..

Billy Joel, a self confessed ‘history nut’, once wanted to become a history teacher and said in an interview at the time of the single’s release that the idea had come to him when talking to a young fan who told him ‘you were born in the fifties, nothing happened in the fifties’.

Joel told author Bill DeMain: “I had turned forty. It was 1989 and I said; "Okay, what's happened in my life?" I wrote down the year 1949. Okay, Harry Truman was president. Popular singer of the day, Doris Day. China went Communist. Another popular singer, Johnnie Ray. Big Broadway show, South Pacific. Journalist, Walter Winchell. Athlete, Joe DiMaggio. Then I went on to 1950.”

Despite the song’s success at the time and longevity to this day, Joel added: “It's one of the worst melodies I've ever written. I kind of like the lyric though”.

Here’s the lyrics all wikibombed up courtesy of ItinerantChild.com:

Harry Truman, Doris Day, Red China, Johnnie Ray 
South Pacific, Walter Winchell, Joe DiMaggio 

Joe McCarthy, Richard Nixon, Studebaker, television 
North Korea, South Korea, Marilyn Monroe 

Rosenbergs, H-Bomb, Sugar Ray, Panmunjom 
Brando, "The King and I", and "The Catcher in the Rye" 

Eisenhower, vaccine, England's got a new queen 
Marciano, Liberace, Santayana goodbye

CHORUS
We didn't start the fire
It was always burning
Since the world's been turning
We didn't start the fire
No we didn't light it
But we tried to fight it

Josef Stalin, Malenkov, Nasser and Prokofiev 
Rockefeller, Campanella, Communist Bloc 

Roy Cohn, Juan Peron, Toscanini, Dacron
Dien Bien Phu Falls, Rock Around the Clock 

Einstein, James Dean, Brooklyn's got a winning team
Davy Crockett, Peter Pan, Elvis Presley, Disneyland 

Bardot, Budapest, Alabama, Khrushchev
Princess Grace, Peyton Place, Trouble in the Suez 

[Chorus]

Little Rock, Pasternak, Mickey Mantle, Kerouac
Sputnik, Zhou Enlai, Bridge On The River Kwai 

Lebanon, Charles de Gaulle, California Baseball, 
Starkweather homicide, Children of Thalidomide

Buddy Holly, Ben Hur, Space Monkey, Mafia
Hula Hoops, Castro, Edsel is a no-go

U2, Syngman Rhee, payola and Kennedy
Chubby Checker, Psycho, Belgians in the Congo 

[Chorus]

Hemingway, Eichmann, Stranger in a Strange Land,
Dylan, Berlin, Bay of Pigs and Beijing 

Lawrence of Arabia, British Beatlemania
Ole Miss, John Glenn, Liston beats Patterson 

Pope Paul, Malcolm X, British Politician sex
J.F.K. blown away, what else do I have to say

[Chorus]

Birth control, Ho Chi Minh, Richard Nixon back again
Moonshot, Woodstock, Watergate, punk rock

Begin, Reagan, Palestine, Terror on the airline
Ayatollah's in Iran, Russians in Afghanistan

Wheel of Fortune, Sally Ride, heavy metal suicide
Foreign debts, homeless Vets, AIDS, Crack, Bernie Goetz

Hypodermics on the shores, China's under martial law
Rock and Roller cola wars, I can't take it anymore

We didn't start the fire
It was always burning since the world's been turning.
We didn't start the fire
But when we are gone
It will still burn on, and on, and on, and on...


 

Greenlight

The video games industry simultaneously parallels precedes and succeeds other media industries. Video games are still enjoying AAA super blockbuster status. Landmark games such as GTA4 cost ＄100 million to make and has grossed 1.3billion at the end of the last financial year. Even annual releases such as Call of Duty have seen their last release make that amount in a single fiscal cycle! Few movies can boast that. Yes, guff like Avatar made 2.7billion but how much of that was forced purchases of plastic migraine spectacles? There is also time investment, on average Gta4 sees 40 hours of use, Cod 9 hours offline yet 62 online. That is value for money and an emotional connection which movies dream of.

Yet the industry also manages to have a huge and vibrant indie scene. Similarly to the music industry, there are bedroom developers constantly producing and pushing boundaries creatively, organically innovating as musicians and artists do. However, services like Valve’s Steam and Kickstarter, and to a lesser extent X-Box Live Arcade (XBLA) and Playstation Network (PSN), have provided a level of support and exposure which is the envy of the creative industries.

The biggest indie hits of recent times include Super Meat Boy – which was also the subject of the 2012 Documentary ‘Indie Game: The Movie’, ‘creativity tool’ Minecraft and the viciously difficult Trials HD.

Whilst the big blockbuster games have generally concentrated on shooting at people in a variety of green and brown locations there has also been a strong focus on story driven, multiple mechanic games such as the Mass Effect, Assassin’s Creed or GTA series’. Vast, living worlds have been opened up to us. Games created by teams of hundreds, sometimes thousand, few true Hollywood budgets. Companies such as Rockstar could be said to have single handedly placed video games within the ‘art’ arena by truly changing them from products to experiences.

How can the indie developers compete with this kind of commercial muscle? We have seen the strangle hold the big studios and blockbuster movies have on our cinema screens in recent decades. However, Super Meat Boy took just 18 months to reach 1 million sales. The game tells the story of Meat Boy, a boy with no skin, and his quest t be reunited with his beloved Bandage Girl, a girl made of bandages but to do so he must make his way through 300 levels of precision jumping and platforming puzzles a la 1983’s defining Super Mario Brothers.

This may seem a flippant novelty yet the games’ sales attest to their playability. It has a single game mechanic and does it perfectly. Trials HD was another huge hit focused on a single mechanic. In this case you must get your motocross bike over a series of increasingly difficult obstacles much like the 80’s TV show Kick Start. It is fiendishly difficult.

We now have two generations of people who have grown up with video games as a home entertainment staple either in the form of consoles or a pc. Yet these two generations experienced very different games during their youth. No-one born in after 1975 will forget first playing Super Mario Brothers 3 or Streetfighter 2 on the SNES or Sonic on the Megadrive. Those consoles are infact the medium’s fourth incarnation and, whilst there is no denying the impact of Pac-Man, Asteroids or Elite, it was in that fourth generation that games began to take the form we know today.

Those late 80’s and 90’s children will have had a different experience. Consoles had seen a quantum leap in technology. The Sony Playstaion was launched in 1994 and would become the dominant force in consoles until the end of the decade. Games were much deeper now featuring better graphics and multiple features and mechanics in a single game. Many of the biggest IP’s we know today started then; Resident Evil – in particular RE2 – were remarkable experiences at the time, Metal Gear Solid took cinematic grandiosity and narrative to its heart. The scene featuring a telepathic boss is one of my personal gaming highlights of all time. The enemy, ‘Psycho Mantis’ could predict and avoid all of your attacks, turn the screen black as if changing the channel and read your memory card commenting on other games you’d played…unless that is, you unplugged the controller from port one and put it into port two. Frankly, genius.

The question of who is buying these indie games is a valid one. Is it just the first generation of gamers who are nostalgic for the skill focused frustration inducing games of their youth? Are the second generation finding something new there despite the low res. graphics and lack of storyline? It is a question which only time will answer.

So far I’ve only talked about console games but the biggest and most exciting things have been happening on the PC and, here, they are not so new. Whilst console gamers were looking at their selection of 6th generation machines and wondering if someone was intentionally making them so ugly, PC gamers were experiencing a depth and immersion with which the consoles were only just being able to cope with. It was a tradition inherited from the Amiga which, when combined with X-Copy, gave gamers access to hundreds of titles and new concepts. A very brief scan of the internet will show you how enduringly loved titles such as UFO, Civilisation, Syndicate, Dungeon Keeper, Fallout, Diablo and one of the most influential titles of all time Halflife are.

Steam uses a system called Greenlight to vet which indie games will be sold through the platform. The current crop is being voted on at the moment and it offers a broad cross-section of developments. There are, of course, innumerable multiplayer shooters in the mode of the globally popular Team Fortress and Counterstrike games and as just as many fantasy rpgs. But these genres have been prominent, along with the management Sims, since the early 90’s – Doom and Sim City spring instantly to mind.

So if we take the Greenlight submissions as an indicator of the indie scene what does it tell us? There is a lot of interest in producing and consuming these products, that is abundantly clear simply from the numbers of games listed and the level of traffic on their comment sections. A lot of clones or ‘homages’ turn up. Clearly, the gamer community wants titles like Wipeout and Dungeon Keeper back as they were but with better graphics. There is also a big focus on open ended Rogue-like games and old fashioned turn based strategy games. Cthulu also appears…a lot.

The Steam community reserves its ire, and there is a lot of ire, especially for Flash games, iOS ports and disturbing Japanese style dating games often set in high schools populated by a mix of giant eyed young girls, chronically anxious boys and demonic tentacle monsters with questionable views on personal space.

There are some very odd games available which illustrates the indie’s creative freedom and juxtaposes the arbitrary and polished mainstream titles with their array of muscular, square jawed heroes and short brown hair. Some like Legend of the Knightwasher are clearly deliberately odd – a washing machine which is sent back through time, gains sentience and goes on to become the mightiest knight in the realm. Or Dusty’s Revenge with its kung fu rabbit protagonist.

Many are ‘simulators’ be it managing a call centre in Smooth Operators, a prison in Prison Architect or you own mental illness in Depression Quest there is one for everybody…in theory at least. However the PC market has a variety of titles which see you farm, drive public transport or even hgv’s in real time. Games have always boasted the USP of being able to place you into a reality or role outside of your usual realm of experience. It’s the Total Recall syndrome; we want to be the freedom fighter, the super hero or even the anti hero with out real risk but vicariously driving slowly along European highways or up and down your field in a tractor at 5mph, seriously?

Will Wright’s Sim series had seen people taking control of cities, ant colonies, skyscrapers and the planet’s biosphere but it was the Sims which first showed the world that a branch of the gaming community wanted to come home from work and do the same things with their digital Sims. It could be argued that this trend started with 1984’s Paperboy but my paper-round was never so dangerous and I would have certainly got in trouble for breaking that many windows.

Mobile and ‘casual’ gaming have shown the market that there is a new group of gamers out there content to ply games without any risk or challenge. The insidious but hugely popular Farmville is an example – there is no peril, goal or obstacle. These are software toys which can never be won or lost.

If anything, most indie games show the opposite trends. They are getting more and more difficult. As the mainstream offers regenerating health-bars and infinite retries more and more indie titles offer permadeath. The mainstream will probably reach photorealism with the next generation of consoles, expected in Q3 this year, but many indie games often offer low res visuals and in some cases have gone all the way back to 8 bit. Others, like BallPoint Universe, have come up with creative solutions to the issue.

The graphics question is an interesting one. Do they really matter to the gamer? Current indie game sales would suggest not but a large portion of those buy the games have grown up with such graphics. Is it just nostalgia that will pass or is it really all about the gameplay?

As the major consoles reach photo-realism, what will this mean for gameplay? Combined with Oculus Rift could future could games cause PTSD? At what point does our brain start thinking its real?

The next generation of consoles could well see the industry plateau for a long time. Extra memory can be added externally and extra functionality downloaded with patches. This would mean great things for developers as history has shown us that the longer a generation lasts the better the games are. Now Valve are looking at launching their own ‘Steambox’ called Piston to bring PC games to you TV. This is the move that should really be worrying the big two. Steam’s marketplace has a vast turnover in comparison to either the Sony or Microsoft setups and has a very active community due to its careful curation and constant special offers.

Regardless, whilst people are developing not just great traditional games but interesting new IP’s and mechanics it shows the industries vibrancy. Platforms such as steam do offer a great outlet and exposure to some games there are hundreds more out there if you look for them. There are exciting esoteric projects like Soundself, loving reboots like War for the Overworld and many potential new IP’s for franchise.

Overall, there is much more happening of interest and consequence on Steam, Xbla and innumerable little websites than you’ll find in the next installment of Call of MedalField.

Copyright 2012

No reason

Half a dozen chairs stand on a dirt track in the desert. A car comes into shot; it drives slowly up the track, knocking the chairs to pieces with the slightest touch. We see it is approaching a small group of people. The car stops and a man in sheriff’s uniform climbs out of the boot holding a glass of water. He gives a speech, the concluding each line with the statement; ‘no reason’. “In The Pianist by Polanski, how come this guy has to hide and live like a bum when he plays the piano so well? No reason.” After several of these he pours his water on the ground and gets back in the car boot.

That is the opening to Rubber, a very odd horror movie about a telekinetic tyre – I know, but bear with me – and another of the unknown gems which would probably never get seen without services like Netflix. Along with Ink and Lunopolis it is something I would never had watched had it not just been there and for having done so, as with all forms of art, life is richer for having done. These are tiny independent films which never really get seen outside of festivals but they certainly deserve to be in an age where ‘inspired by the Hasbro toy’ is becoming an alarming alternative to ‘based on true events’ in opening credits. Battleship – enough said.

Where did these services come from? It seemed like all of a sudden they were everywhere, like FaceBook. At their hearts these virtual video stores are the bastard children of internet piracy. Put simply someone in a suit realized that those adverts weren’t fooling anyone and the only way for the movie industry to survive torrents was to offer a service which is easier than piracy. Itunes took baby steps in that direction but balked at really lowering prices and increasing accessibility. With a subscription setup like Netflix you may as well watch that random movie that piqued your interest, you have nothing to lose. I can’t get my money back because I don’t like something on iTunes, by charging per download and at a price point which is where our high street shops were at anyway before we left them to die. At least then we could lend them to our mates or sell them on without little text boxes popping up asking for passwords.

Regardless, services such as Netfilx, Lovefilm and now Amazon have enjoyed huge success over recent years and the pressure to avoid ‘tape left in car syndrome’ has given filmmakers the exposure they always hoped to find on youtube. There was a time when everyone thought they could put a short film on Youtube and be annoying the world with high-pitched blatherings by the end of the week but it all became so much noise. Why? Because there is no curation. Deep within Youtube there are great documentaries, short films, fascinating stock footage and beautiful works of art and music but I challenge you to find more than one an hour beneath the lolcats, whining teenagers and people falling off things.

It is also the element of surprise and discovery which has been reintroduced to media through these services. We are assured in the role the service plays, that by its own standards and the user’s ‘taste profile’, and we can take riskless chances. The way we as a society have consumed media before the digital revolution was always a pro-active choice within a limited range. The cinema, Blockbusters or Pirate Bay, we always met half way at best. Yes, there have been surprise hits such as Iron Sky but this trade on their kitsch appeal using snappy taglines ahead of deep plot-lines. “In 1945 the Nazi’s went to the moon – in 2010, they’re coming back.” The film was funded on the back of a teaser trailer and that line alone. This isn’t a new thing either Troma made a genre out of it in the 80’s with movies including ‘Surf Nazi’s must Die’ and ‘Killer Condom’, however, their titles were their only strength.

Trailers and movie marketer’s clear contempt for the public intelligence have been undermining the multiplex for years particularly with trailers. Take as an example the current remake of Carrie. The trailer contains, Carrie discovering her powers, being bullied in the shower, being invited to the prom, confronting her mother, killing her mother, the pigs blood, the burning hall, and John Travolta’s (or whoever’s) car crash. That is the whole plot. Why bother going now?

The remake itself, as the majority of Hollywood’s output over the past decade, has become homogenized and committee designed to an aimless gloss. The Stephen King novel is a character piece. It follows the same lines as most of his books – an individual who is different in some way but doesn’t want to be, yet society’s wider fears, prejudices and venom are directed at resulting in some form of cataclysm which is again played out on a personal level.

The original movie is an uncomfortable watch to say the least. Sissy Spacek is perfectly cast. She is awkward both in appearance and character but she is also able to portray Carrie’s sweeter side – the girl who just wants to be normal. Chloe Morretz is a strong actress but she is too attractive and energetic to be believable in her pariah’s role. The inner cruelty of the mother’s preaching is also lost. In De Palma’s film there is a clear overtone that the mother’s central motivation is her fear of abandonment. She claims ‘the devil made your father leave us,’ and ‘God cursed us because I was weak and let him put it in me’. She undermines Carrie much more out of a lack of control within her own world view; that she fears will take her daughter, in whom she sees redemption, away from her.

Spacek – who has a reputation for Daniel Day Lewis style character acting – took the role very seriously. She plays three different women; the timid and terrified girl at the beginning, she is radiant with happiness at the Prom and finally a silent psychic banshee of vengeance and bulging eyes. With each change she moves differently, changes her posture, her way of speaking. It is subtle and brilliant.

Morretz and Moore are very capable actors as we have seen before but here, for whatever reason they fall flat. Sure, Morretz hunches her shoulders and puts on an ugly cardigan but she is clearly still a confident young woman. The way she moves, particularly entering rooms/scenes does not have the timidity or frailty the role demands. In the role of her fanatical mother Moore is left with nowhere to go but histrionics. Every argument and condemnation just gets louder. Piper Laurie in the original adopted a preacher’s tone, she sermonizes to Carrie as if addressing a room making her seem detached and all the more threatening. The scene where she visits another student’s mother seeking converts but is turned away with a dismissive donation is a perfect example of how she turns the mood of a scene.

Then finally there is the double catch within the denouement. The popular boy (Tommy) is taking her to the prom at his popular girlfriend’s (Sue) request. We know another couple, their friends, are planning to humiliate Carrie. At first we assume they are in on it. Especially when the girl goes to watch them at the prom. Yet we see in their reactions that they are not, they actually are trying to give Carrie something nice. The audience knows about the bucket but as the camera lingers on the couple we realize they do not. Carries eyes well up and Tommy smiles gallantly if not a bit patronsingly at her. She is transformed we are witnessing the brightest moment of her life. She knows it is an act of charity but accepts the bittersweet. They are chosen as prom king and queen and Sue wells up too.

If we were to leave the story there, to abandon the bucket, we may have seen a reborn Carrie. A moment of acceptance, a few minutes of fame. Her picture would be in the yearbook and she would have graduated with a new found confidence. She had stood up to her mother that night and would soon be leaving for college. Most likely a good student she would have had opportunities and ‘creepy Carrie’ would be a passing memory.

As Sue wipes away her tears she sees the rope. The camera runs in slow motion as she tracks the pulleys to the bucket. She tries to stop it and is thrown out by a teacher who believes she is here to cause a scene. She will be the only survivor. The bucket falls and everything burns. Ultimately, you are left without a doubt that she was the victim here and in her frightened final moments there is a sense that the audience is as responsible for this as the bullies. ‘Why couldn’t you all have just left her alone?’

In all of the remakes, and in film in general now, there is an obsession with surface. The effects are loud and polished. Furniture lifts and objects rush through the air. Every actor cast is beautiful, rich and usually pushing 30. There is no way that someone at 2013’s Bates High wouldn’t have said ‘that Carrie White is a bit weird but she has a really striking look’. Why not? No reason. It’s the same on TV too; no-one in Dawson’s Creek ever asked, ‘why are there no ethnic minorities in our town at all?’ No reason. We all agree to suspend our logic gland when we buy a cinema ticket. Why is it a galaxy far far away? No reason. However, everything is hyped to the point of saturation and gimmicks bolster takings.

It would be fabulous if the various online services could come together into one giant library like we had in piracy’s heyday but the market will dictate that and most likely many great IP’s will languish under supported and under exposed. Another option would be a curated version of YouTube allowing people to upload serious works and bring some semblance of culture to the noise of web 2.0.

As we increasingly hear about democratisation of media we increasingly see its fallacy. Yes you can get news online from innumerable sources but at least our mass media is governed by some semblance of law which allows us to trust it or at least to make informed decisions based on our view of it. The more people ‘broadcast yourself to the world’ the more we see that in the face of our entire world’s problems a grumpy cat or an adolescent idiot is higher on the agenda. So many images and messages fly past us everyday that there is a risk of the loss of authority and credibility of information, we need some way of wading through the lies and rubbish and thus far we have trusted common sense but the simple fact that more people have watched Gangdam Style than have read Wikileaks illustrates our misplaced confidence.