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  • AI is the invisible hand of 21st-century capitalism
  • AI transforms economies by automating tasks, optimising resource allocation, and boosting productivity across industries
  • It drives innovation and growth in healthcare, finance, manufacturing, and transportation, while raising ethical and community related concerns
  • Addressing AI's ethical implications, investing in technical education and retraining are essential for equitable benefits and the wellbeing of society
 
AI: The New Wealth of Nations

In 1776, Adam Smith, a Scottish economist known as the father of Capitalism, published An Inquiry into the Nature and Causes of the Wealth of Nations, which laid the foundation for modern economics and introduced the concept of the invisible hand of capitalism, which describes how individual self-interest can benefit society through the efficient allocation of resources. This work became the cornerstone of the Industrial Revolution and modern capitalist society, transforming economies by emphasising the division of labour and market-driven growth. In the 21st century, artificial intelligence (AI) emerges as the invisible hand, poised to herald a new era of capitalism.

AI distinguishes itself from previous technologies through its ability to process vast amounts of information, make decisions, and implement outcomes with speed and accuracy far beyond human capability. Just as the division of labour allowed for increased productivity in Adam Smith's time, AI automates and optimises tasks, enhancing efficiency across industries. AI systems analyse datasets with unprecedented speed, uncovering insights and innovations that humans might miss. This capability mirrors the invisible hand Adam Smith described, where individual pursuits benefit society.

Moreover, just as Adam Smith argued that free markets lead to wealth generation, the adoption and integration of AI can democratise opportunities, creating new markets for economic development. Nations and corporations that embrace AI technology are positioned to gain competitive advantages, akin to how industrialised nations and leading companies surged ahead during the Industrial Revolution. AI stands as the new cornerstone of wealth creation, transforming economies, driving innovation, and reshaping the global economic landscape, echoing the impact of Adam Smith's principles in a contemporary context.

This being the case, we stand on the cusp of another economic revolution, driven not by the incremental advancements of traditional technologies but by the transformative power of AI, which ensures optimal resource allocation, minimises inefficiencies, and impacts individuals, organisations, communities, industries, and society. AI is not just enhancing human labour but redefining it, ensuring a future where economic growth and societal benefits are more aligned than ever before.

 
In this Commentary

This Commentary explores how AI emerges as the new invisible hand of capitalism, transforming our global economy. Drawing an analogy to Adam Smith’s principles, we highlight AI's ability to process vast amounts of data, optimise resource allocation, and enhance efficiency across various sectors. The Commentary delves into AI’s impact on individuals, organisations, communities, and industries, demonstrating its potential to drive innovation and economic growth. Additionally, it addresses AI’s ethical and societal implications, emphasising the need for inclusive policies to ensure benefits from the technology are equitably distributed and contribute to a more prosperous and sustainable future.
 
The Rise of AI and Its Economic Significance

AI, the ability of a machine to imitate intelligent human behaviour, has evolved from theoretical concepts to practical applications, embedding itself into the fabric of modern society. Unlike previous technological advancements, AI's capacity to learn from data, adapt to new information, and perform tasks traditionally requiring human intelligence, represents a significant shift in how industries operate and innovate.

In healthcare, AI enhances diagnostic accuracy and personalises treatment plans by analysing vast amounts of medical information and identifying patterns that might be missed by health professionals. Algorithms can detect diseases like cancer at early stages, substantially improving patient outcomes.
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In finance, AI optimises trading strategies by processing real-time market data and executing trades at speeds unattainable by humans, while also enhancing risk management through predictive analytics. Fraud detection systems powered by AI can analyse transaction patterns to identify suspicious activities, safeguarding financial institutions and their customers.

The manufacturing sector benefits from AI through automation and predictive maintenance, which boosts efficiency and reduces costs. Smart manufacturing uses AI to monitor equipment in real-time, predicting failures before they occur and minimising downtime.

Transportation systems leverage AI for route optimisation and the development of autonomous vehicles, transforming logistics and urban planning. AI-driven traffic management systems can reduce congestion and improve safety on the roads.

AI's impact extends to agriculture with precision farming techniques, where drones and sensors monitor crop health and soil conditions, leading to higher yields and sustainable farming practices. In customer service, AI-driven chatbots and recommendation systems provide personalised experiences and improve customer satisfaction.

Such widespread adoption across various sectors not only drives economic growth but also enhances productivity and innovation. As a force in shaping the global economy, AI continues to redefine the boundaries of what machines can achieve, promising a future where intelligent systems are integral to everyday life.
Optimal Resource Allocation

One of the principles of Adam Smith's economic theory is the efficient allocation of resources. In economies, this is achieved through the interplay of supply and demand, where the invisible hand guides resources to their most productive uses. AI elevates this concept to a new level. By analysing datasets in real-time, it can identify inefficiencies and develop processes with a precision unattainable by human efforts alone.

In supply chain management, for instance, algorithms can predict demand fluctuations, manage inventory levels, and streamline logistics. This reduces waste, lowers costs, and ensures that products are available where and when they are needed. Companies like Amazon and Walmart have harnessed AI to transform their supply chains, resulting in faster deliveries and higher customer satisfaction. Similarly, in agriculture, AI-powered systems can monitor crop health, predict yields, and regulate irrigation, leading to more sustainable and efficient farming practices. In healthcare, AI is transforming diagnostics by employing machine learning to detect early signs of diseases, enhancing patient care.

 
Minimising Inefficiencies

Flaws in any system represent lost opportunities and wasted resources. Traditional methods of identifying and addressing these are often reactive and limited in scope. AI, on the other hand, offers a proactive approach, continuously monitoring and optimising operations to minimise inefficiencies.
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The Shifting Landscape of ESG Reporting in the MedTech Industry

In the energy sector, AI can enhance grid management by predicting demand, optimising energy distribution, and integrating renewable energy sources more effectively. This leads to reduced waste and lower costs for consumers. In healthcare, AI can streamline administrative processes, improve patient care through personalised treatment plans, and predict disease outbreaks, thereby reducing the burden on healthcare systems and promoting overall public health.
Moreover, AI's ability to process and analyse unstructured data, such as text, images, and videos, allows it to uncover hidden patterns and insights that would otherwise go unnoticed. This capability is valuable in areas like fraud detection, where AI can analyse transaction data to identify suspicious activities in real-time, preventing financial losses and enhancing security.
 
AI's Impact on Individuals and Organisations

At the individual level, AI is transforming the way we live and work. From tailored recommendations on streaming platforms to virtual assistants that manage our daily schedules. In education AI-powered tutoring systems cater for individual learning styles and paces, offering support and improving educational outcomes.

For organisations, AI provides a competitive advantage by enabling data-driven decision-making and enhancing operational efficiency. Businesses can leverage AI to gain insights into customer behaviour, refine marketing strategies, and improve product development, driving growth and fostering innovation through rapid iteration based on real-time feedback.

AI also has the potential to transform the workforce. Although concerns about job displacement exist, AI can augment human capabilities and create new opportunities. In manufacturing, AI-powered robots can handle repetitive tasks, allowing human beings to focus on more complex and creative aspects of production. In healthcare, AI assists doctors in diagnosing diseases, freeing up time for patient care and reducing burnout. Additionally, robotic-assisted surgeries have improved surgical precision, enabling more complex and minimally invasive procedures.

 
Community Development

Beyond individuals and organisations, AI has the power to transform communities. Smart cities, which leverage AI to optimise urban infrastructure and services, are examples of this potential. By analysing data from sensors and cameras, AI can improve traffic management, reduce energy consumption, and enhance public safety. This leads to more liveable and sustainable cities, improving the quality of life for residents. In NEOM, the futuristic city being developed in Saudi Arabia, AI is being integrated into every aspect of urban planning and governance. From automated transportation systems to AI-driven energy grids and smart housing. NEOM aspires to become a paradigm of a sustainable and technologically advanced urban environment, showcasing the transformative capabilities of AI on a grand scale.

AI can also play a role in addressing social challenges. For instance, predictive analytics can help identify at-risk students in schools, enabling timely interventions and reducing dropout rates. In disaster management, AI can analyse data from various sources to predict natural disasters and coordinate emergency response efforts, potentially saving lives and reducing damage. Moreover, AI-driven platforms can facilitate greater civic engagement by providing citizens with real-time information and opportunities to participate in decision-making processes. This can lead to more transparent and accountable governance, as well as more inclusive and resilient communities.

 
Influence on Industries

AI's power extends across industries, reshaping their landscapes. In finance, algorithms are transforming trading strategies, risk management, and customer service. High-frequency trading, driven by AI facilitates faster and more accurate trading decisions, while AI-powered chatbots provide personalised financial advice and support.

In healthcare, AI is changing diagnostics, treatment, and drug discovery. Machine learning models analyse medical images to detect diseases early, improving patient outcomes. AI also accelerates drug development by identifying potential candidates and predicting their effectiveness, thereby reducing the time and cost associated with clinical trials.

In manufacturing, AI-powered robots and automation systems enhance production efficiency and quality control. Predictive maintenance, enabled by AI, reduces downtime and extends the lifespan of machinery, leading to cost savings.

 
Societal Implications

As AI continues to evolve, it raises ethical and societal questions. The concentration of AI capabilities in the hands of a few tech giants poses challenges related to data privacy, security, and inequality. Ensuring that the benefits of AI are distributed equitably requires thoughtful regulation and policies that promote transparency, accountability, and inclusivity.

Education and workforce development are critical to preparing society for the AI-driven future. Investing in science, technology, engineering, and mathematics (STEM) education and retraining programmes can equip individuals with the skills needed to thrive in an AI-dominated economy. Additionally, promoting a culture of lifelong learning and adaptability is essential, as the pace of technological change accelerates.

 
Takeaways

AI emerges not just as a technological advancement but as the new cornerstone of global economic evolution, akin to Adam Smith's invisible hand that shaped the Industrial Revolution. Its ability to process vast amounts of data and optimise resource allocation transcends traditional methods, promising unprecedented efficiency, and innovation across industries. Just as Adam Smith's principles drove economies forward by harnessing individual self-interest, AI enhances productivity and decision-making, driving societies towards new heights of prosperity. However, the transformative power of AI also necessitates consideration of its ethical and societal implications. The concentration of AI capabilities among a few entities raises concerns about privacy, security, and equitable access to benefits. Effective regulation and inclusive policies are important to ensure AI benefits society, promoting transparency and mitigating potential inequalities. As we navigate this era of AI-driven progress, investing in education and workforce readiness becomes important. Equipping individuals with the skills to thrive in a technology-dominated landscape is essential for encouraging innovation and maintaining societal wellbeing. In this rapidly evolving era, AI is not just a tool for economic growth but a catalyst for a more intelligent and connected world, heralding a new chapter in the wealth of nations.
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  • Healthcare is shifting from uniform treatments to personalised care, driven by genetics, lifestyle, and technology
  • Patients benefit from targeted therapies that deliver early disease detection, enhanced therapies and proactive prevention
  • Traditional MedTechs, accustomed to one-size-fits-all devices, face challenges but also can find opportunities from individualised care for growth and innovation
  • To capitalise on these opportunities, conventional corporations must recalibrate their strategies and collaborate with start-ups and healthcare institutions
 
The Impact of Personalised Healthcare on Traditional MedTechs

Personalised medicine, also known as precision medicine, marks a departure from traditional medical practices by acknowledging the interplay of genetics, lifestyle, and environment in shaping an individual's health. Rather than adhering to one-size-fits-all treatments, individualised care prioritises early detection and proactive prevention, tailoring interventions based on each patient's unique genetic makeup. Digitalisation, together with advances in medical technology, enables the combination and analysis of genomic information with other diagnostic data to identify patterns that help to determine an individual’s risk of developing a disease, detect illness earlier, and determine the most effective interventions. For example, in cancer treatment, personalised therapies target specific proteins driving cancer growth, offering more effective alternatives to conventional methods like customary chemotherapy. Findings of a 2012 study published in Trends in Molecular Medicine found that the response rate to a targeted therapy for acute myeloid leukaemia to be at 90% compared with 35% for standard chemotherapy. Another notable development in customised care is the DNA medication pass, which enables clinicians to identify the most suitable drugs for individual patients, reducing adverse reactions and hospital admissions due to drug-related complications. Such personalised approaches empower patients with treatments aligned to their genetic predispositions and foster greater autonomy and engagement in healthcare decisions.

In today's data-driven environment, the emphasis on precision care is growing, and creating a shift in healthcare delivery. A recent research paper published in the Journal of Translational Medicine suggests that personalised medicine will lead to the next generation of healthcare by 2030. While many traditional medical technology companies are content with supplying standardised medical devices to hospitals, an increasing number wish to pivot and capitalise on the rapidly growing targeted healthcare segment. However, they face the challenge of adapting their established frameworks, which are not designed to create bespoke solutions and services. This emphasises the significance of adaptability across diverse healthcare settings. Forward-thinking corporations, however, recognise the need to evolve. By investing in novel R&D initiatives and fostering collaboration throughout the healthcare spectrum, they position themselves favourably. Conversely, companies resistant to change risk stagnation and eventual obsolescence in an era where personalised care is rapidly gaining traction.

 
In this Commentary

This Commentary delves into the impact of personalised healthcare on traditional MedTech companies, highlighting the imperative for alignment with customised care to remain competitive. It explores how targeted medicine, driven by advancements in genetics, digitalisation, and medical technology, is reshaping healthcare delivery by prioritising individualised treatments tailored to patients' unique genetic makeup. The Commentary emphasises the need to adapt conventional strategies amidst industry trends, addressing challenges such as regulatory complexities and technology adoption barriers. Through initiatives like partnerships, novel R&D, diversification, and strategic M&A, traditional MedTechs can position themselves to lead in the era of precision care. The Commentary offers examples of start-ups and established firms addressing this segment, insights into the opportunities and challenges traditional companies face in adapting to the growing emphasis on personalised healthcare, and emphasises the importance of innovation, collaboration, and proactive responses to industry shifts.
 
Brief History

The roots of personalised healthcare can be traced back to ancient civilisations where healers recognised individual differences in response to treatments. However, formalised concepts began to emerge in the late 19th and early 20th centuries with the advent of modern medicine. The discovery of the structure of DNA by James Watson and Francis Crick in 1953 laid the foundation for understanding the role of genetics in health and disease. Advances in DNA sequencing technologies in the late 20th century, particularly the completion of the Human Genome Project in 2003, enabled scientists to decipher the entire human genetic code, ushering in the genomic era.
 
In the late 20th century, researchers began to explore how genetic variations influence an individual's response to drugs. Pharmacogenomics emerged as a field focused on tailoring drug treatments to a person's genetic makeup, aiming to maximise efficacy and minimise adverse effects. Rapid advancements in technology, such as next-generation sequencing and high-throughput screening, have made it more feasible and cost-effective to analyse large amounts of genetic data. This has accelerated research in tailored therapies and expanded their application beyond pharmacogenomics to include risk assessment, disease diagnosis, and treatment selection.
As we suggested, one of the earliest and most successful applications of customised healthcare has been in oncology. Precision oncology uses genomic profiling to identify genetic mutations driving cancer growth and matches patients with targeted therapies designed to address their specific mutations. The success stories in treating certain cancers, such as leukaemia and melanoma have fuelled further interest and investment in personalised approaches.
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Healthcare 2040


 
The rise of big data analytics and artificial intelligence (AI) has been instrumental in advancing targeted care. By integrating genetic, clinical, lifestyle, and environmental data, AI algorithms can identify patterns, predict disease risks, and recommend precise interventions targeted to an individual’s unique profile. Governments have recognised the potential of these approaches to improve patient outcomes and reduce healthcare costs. Endeavours such as the Precision Medicine Initiative in the US, the NHS Long Term Plan in the UK, and similar efforts in other countries aim to accelerate the adoption of customised medicine. As technology continues to evolve and our understanding of genetics and biology deepens, personalised healthcare is poised to become increasingly integral to mainstream medical practice, ultimately leading to better health outcomes.
 
Challenges and Barriers to Personalised Care

Customised medicine, while promising, faces challenges. One hurdle lies in the complexity and sheer volume of data required to tailor treatments to individual patients. Integrating diverse datasets from genomics, medical history, lifestyle factors, and environmental influences demands sophisticated analytics and robust privacy safeguards. Additionally, interoperability issues between different healthcare systems impede data exchange and collaboration among healthcare providers. Economic constraints further obstruct widespread adoption, as customised therapies often come with hefty price tags, limiting access for many patients. Regulatory frameworks must also evolve to accommodate the dynamic nature of tailored medicine, ensuring rigorous oversight without stifling innovation. Moreover, educating healthcare professionals and patients about the benefits and limitations of personalised approaches is essential for fostering trust and acceptance. Overcoming these challenges demands interdisciplinary collaboration, technological advancements, and a commitment to equitable access to focussed healthcare.
 
The Changing Landscape of Traditional MedTechs

Despite these challenges, the growing emphasis on personalised care represents a shift in traditional MedTech markets. Although the precise timeline for tailored therapies to substantially influence conventional corporations remains uncertain, the trend signals a clear direction for the industry. The International Consortium for Personalised Medicine (ICPerMed) envisions a healthcare landscape firmly rooted in customised medicine principles by 2030. This vision entails an ecosystem where individual characteristics inform diagnostics, treatments, and preventive measures, resulting in heightened effectiveness and economic value, all while ensuring equitable access for all individuals.
 
Historically, MedTech markets have exhibited a degree of reluctance in adopting new technologies, offering some comfort to conventional leaders in the field. However, the insights provided by the ICPerMed research should serve as a catalyst for traditional enterprises to re-evaluate their strategies and product offerings if they intend to capitalise on the growing trend of customised care. Notably, investments in innovative technologies that facilitate precision diagnostics, targeted therapies, and patient-centric interventions have already proven effective and are on the rise.
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Unleashing MedTech's Competitive Edge through Transformational Technologies
Furthermore, the integration of data analytics and remote monitoring capabilities is reshaping the dynamics among medical devices, patients, and healthcare providers. This integration fosters enhanced connectivity and delivers real-time insights, thereby helping to transform the healthcare ecosystem. As tailored care gains momentum, traditional corporations must embrace agility, collaboration, and an understanding of patient preferences to thrive. This necessitates a proactive re-evaluation of their strategies.
Healthcare Firms Leading the Shift Towards Personalised Care

Many early-stage MedTech companies and established healthcare firms are leveraging evolving technologies and data to meet the growing demand for personalised healthcare. Omada Health, for instance, offers a platform combining connected devices and data analytics to help manage chronic conditions through tailored lifestyle interventions. iRhythm Technologies' Zio patch, a wearable cardiac monitor, uses advanced algorithms to detect heart conditions more accurately. Butterfly Network's Butterfly iQ is the first smartphone-connected whole-body ultrasound system, enhancing imaging quality and diagnostic capabilities through AI. Mature enterprises like AliveCor and Fitbit, now part of Google, have also pivoted to tailored healthcare. AliveCor’s  KardiaMobile provides at-home ECGs and shares data for customised treatment plans, while Fitbit offers devices with advanced health monitoring features and personalised wellness programmes. Dexcom's G6 CGM System provides real-time glucose tracking integrated with health data platforms. Roche has shifted towards customised healthcare with digital health solutions like the Roche Diabetes Care platform and the NAVIFY Tumor Board for personalised cancer treatments. 23andMe, initially known for genetic testing, now partners with pharmaceutical companies for drug discovery and develops tailored treatment plans based on genetic data.
 
Transforming MedTech in the Era of Personalised Care

The healthcare industry is undergoing a transformation marked by a shift towards patient-centric care and the adoption of value-based healthcare models. This shift is driving increased collaboration among traditional MedTech firms, healthcare providers, and emerging players, all united in their goal to innovate and tackle the complex challenges facing healthcare today. Regulatory changes and technological advancements also are playing roles in reshaping the competitive landscape, guiding the industry towards more patient-centred, value-driven, and collaborative approaches. In response to these evolving dynamics, MedTech companies are transforming their product development strategies by embracing agile and interdisciplinary approaches. Leveraging digital technologies, they are adapting to changing demands through virtual testing, data-driven design optimisation, and rapid prototyping.
 
The move towards personalised care is not only transforming product development strategies but also reshaping business models within the MedTech industry. There is a growing emphasis on outcome-based pricing and service-oriented solutions, reflecting the industry's focus on delivering measurable results and comprehensive care experiences. Digital health platforms and software-as-a-service (SaaS) offerings are emerging as key drivers of revenue, highlighting the importance of innovation and customer engagement in staying competitive and relevant.
 
Amid these transformations, regulatory and compliance considerations are crucial. Regulatory frameworks are becoming more stringent, emphasising product safety, efficacy, and data privacy. Compliance with varying standards across geographies is essential for market access, requiring companies to navigate these landscapes skilfully to sustain growth. Regulatory bodies are also evolving to tackle emerging challenges like cybersecurity and interoperability, highlighting the need for effective regulatory management in today's MedTech ecosystem. Addressing these challenges demands collaboration among stakeholders to build trust, promote standards, and ease the adoption of innovative technologies. Only through concerted efforts can the industry overcome these obstacles and fully realise the potential of customised care in transforming healthcare delivery.
 
Adaptation Strategies for Traditional MedTech Companies

To strengthen their alignment with personalised healthcare, traditional MedTechs can adopt several strategies. One effective approach, which, in a previous Commentary, we referred to as the Third Way, involves forming partnerships and collaborations with start-ups, research institutions, or other industry players. Through these partnerships, corporations can gain access to novel technologies, broaden their market reach, and expedite the pace of innovation. Additionally, diversification emerges as another adaptation strategy, enabling companies to venture into adjacent markets or therapeutic areas. This not only helps in mitigating risks but also enables them to capitalise on emerging opportunities within the healthcare landscape. Furthermore, many traditional corporations opt for M&A to bolster their market position, acquire specialised capabilities, or tap into new customer segments. Collectively, these strategies empower traditional corporations to navigate industry transitions towards customised care, foster sustained growth, and uphold their competitive edge.
 
Takeaways
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This Commentary highlights the need for companies to re-evaluate their strategies in response to the industry's shift toward personalised care, a force shaping the future of healthcare delivery. It suggests traditional enterprises should proactively address challenges such as regulatory compliance, data security, and technological adoption barriers. Yet, within these challenges lie significant opportunities for growth and innovation. By pursuing strategic partnerships, investing in R&D, diversifying, and engaging in M&A, corporations can lead in the era of customised care, influencing healthcare's trajectory. Despite obstacles, the outlook for traditional enterprises is promising, driven by technological advancements and global healthcare demands. Success, however, depends on their agility, resilience, and proactive adaptation to the evolving landscape. By leveraging innovation and fostering collaboration, traditional MedTechs can navigate complexity and continue to drive positive transformation within the industry.
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Dame Deborah James, who died aged 40 of bowel cancer, spent the last 5 years of her life raising awareness about her type of cancer, but also fighting to make personalised medicine more widely available for cancer patients.

Personalized medicine is therapy customized for an individual and has become more readily available as the cost of gene sequencing has been significantly reduced. An example is when treatment is targeted to a specific type of cancer cells.

HealthPad had partnered with a consortium of leading cancer specialists to explain what personalised medicine means and what it can do for cancer patients.

The HealthPad Team would like to join the many people who have admired Dame Deborah for her courage and determination.

Thank you and farewell, BowelBabe.

#bowelbabe #damedeborahjames #personalisedmedicine

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  • Many people still view China as a ‘copycat’ economy, but this is rapidly changing
  • China is:
    • Pursuing a multi-billion dollar-15 year strategy to become a world leader in genomic engineering and personalized medicine
    • Systematically upgrading and incentivizing its large and growing pool of scientists who are making important breakthroughs in the life sciences
    • Empowering and encouraging state owned and private life science companies to own and control the capacity to transform genomic, clinical and personal data into personalized medicines
  • The difference in national approaches to individualism and privacy confers an added competitive advantage to China and its life science ambitions
  • China’s approach to individualism and privacy issues could have implications for society


The global competition to translate genomic data into personal medical therapies

 

PART 2
 
China is no longer a low cost ‘copycat’ economy. Indeed, it has bold plans to become a preeminent global force in genomic engineering to prevent and manage devastating and costly diseases. Here we briefly describe aspects of China’s multibillion-dollar, government-backed initiative, to own and control significant capacity to transform genomic data into precision medicines. This is not only a ‘numbers’ game. China’s drive to achieve its life science ambitions is also advantaged by a different approach to ‘individualism’ and privacy compared to that of the US; and this could have far-reaching implications for future civilizations.

Uneven playing field
Genomic engineering and precision medicine have the potential to revolutionize how we prevent and treat intractable diseases. Who owns the intellectual property associated with genomic engineering, and who first exploits it, will reap significant commercial benefits in the future. However, genomic technologies are not like any other. This is because genetically modifying human genomes could trigger genetic changes across future generations. Misuse of such technologies therefore could result in serious harm for individuals and their families. On the other hand, over regulation of genomic engineering could slow or even derail the prevention and treatment of devastating and costly diseases. Establishing a balance, which supports measures to mitigate misuse of genomic technologies while allowing the advancement of precision medicine is critical. However, this has proven difficult to establish internationally.

Chinese scientists have crossed an ethical line
Chinese culture interprets individualism and privacy differently to American culture, and therefore China responds differently to certain ethical standards compared to the US and some other Western nations. Indeed, national differences were ignited in 2012 when Chinese researchers published their findings of the world’s first endeavors to modify the genomes of human embryos to confer genetic resistance to certain diseases. Because such modifications are heritable critics argued that the Chinese scientists crossed a significant ethical line, and this was the start of a “slippery slope”, which could eventually lead to the creation of a two-tiered society, with elite citizens genetically engineered to be smarter, healthier and to live longer, and an underclass of biologically run-of-the-mill human beings.

International code of conduct called for but not adhered to
2 prominent scientific journals, Nature and Science, rejected the Chinese research papers reporting world-first scientific breakthroughs on ethical grounds. Subsequently, Nature published a note calling for a global moratorium on the genetic modification of human embryos, suggesting that there are “grave concerns” about the ethics and safety of the technology. 40 countries have banned genetically modifying human embryos. In 2016, a report from the UK’s Nuffield Council on Bioethics stressed the importance of an internationally agreed ethical code of conduct before genomic engineering develops further.
 
In 2017 an influential US science advisory group formed by the National Academy of Sciences and the National Academy of Medicine gave ‘lukewarm’ support to the modification of human embryos to prevent, “serious diseases and disabilities” in cases only where there are no other “reasonable alternatives”. The French oppose genomic modification, the Dutch and the Swedes support it, and a recent Nature editorial suggested that the EU is, “habitually paralyzed whenever genetic modification is discussed”. In the meantime, clinical studies, which involve genomic engineering, are advancing at a pace in China.

With regard to genome testing, western human rights activists have warned that China is targeting vulnerable groups and minorities to help build vast genomic databases without appropriate protection for individuals. Those include migrant workers, political dissidents and ethnic or religious minorities such as the Muslim Uighurs in China's far western Xinjiang region. Xinjiang authorities are reported to have invested some US$10bn in advanced sequencing equipment to enhance the collection and indexing of these data.


Different national interpretations of ‘individualism’
Individualism’, which is at the core of ethical considerations of genomic engineering, is challenging to define because of its different cultural, political and social interpretations. For example, following the French Revolution, individualisme was used pejoratively in France to signify the sources of social dissolution and anarchy, and the elevation of individual interests above those of the collective. The contemporary Chinese interpretation of individualism is similar to the early 19th century French interpretation. It does not stress a person’s uniqueness and separation from the State, but emphasizes an individual’s social; contract and harmony with the State. By contrast, American individualism is perceived as an inalienable natural right of all citizens, and independent of the State.

Further, American individuals are actively encouraged to challenge and influence the government and its regulatory bodies, whereas in China citizens are expected to unquestionably support the State. China is a one party state, where individuals generally accept that their government and its leaders represent their higher interests, and most citizens therefore accept the fact that they are not expected to challenge and influence policies determined by the State and its leaders. This difference provides China with a significant competitive advantage in its endeavors to become a world leader in the life sciences,

 
Human capital

By 2025, some 2bn human genomes could be sequenced. This not only presents ethical challenges, but also significant human capital challenges. The development of personalized medicines is predicated upon the ability to aggregate and process vast amounts of individual genomic, physiological, health, environmental and lifestyle data. This requires next generation sequencing technologies, smart AI systems, and advanced data managers of which there is a global shortage. Thus, the cultivation and recruitment of appropriate human capital is central to competing within the rapidly evolving international genomic engineering marketplace. The fact that China has a more efficacious strategy to achieve this than the US and other Western democracies provides it with another significant competitive advantage.

STEM graduates
Since the turn of the century, China has been engaged in a silent revolution to substantially increase its pool of graduates in science, technology, engineering and mathematics (STEM), while the pool of such graduates in the US and other Western democracies has been shrinking. In 2016, China was building the equivalent of almost one university a week, which has resulted in a significant shift in the world's population of STEM graduates. According to the World Economic Forumin 2016, the number of people graduating in China and India were respectively 4.7m and 2.6m, while in the US only 568,000 graduated. In 2013, 40% of all Chinese graduates finished a degree in STEM, over twice the share of that in US universities. In 2016, India had the most graduates of any country worldwide with 78m, China followed closely with 77.7m, and the US came third with 67m graduates.

University education thriving in China and struggling in the West
In addition to China being ahead of both the US and Europe in producing STEM graduates; the gap behind the top 2 countries and the US is widening. Projections suggest that by 2030 the number of 25 to 34-year-old graduates in China will increase by a further 300%, compared with an expected rise of around 30% in the US and Europe. In the US students have been struggling to afford university fees, and most European countries have put a brake on expanding their universities by either not making public investments or restricting universities to raise money themselves.
 

The increasing impact of Chinese life sciences
China's rapid expansion in STEM graduates suggests that the future might be different to the past. Today, China has more graduate researchers than any other country, and it is rapidly catching up with the US in the number of scientific papers published. The first published papers to describe genetic modifications of human embryos came from Chinese scientists

Further, according to the World Intellectual Property Organization, domestic patent applications inside China have soared from zero at the start of the 21st century to some 928,000 in 2014: 40% more than the US’s 579,000, and almost 3 times that of Japan’s 326,000.
 

China’s strategy to reverse the brain drain
Complementing China’s prioritization of domestic STEM education is its “Qianren Jihua” (Thousand Talents) strategy. This, established in the wake of the 2008 global financial crisis to reverse China’s brain drain, trawls the world to seek and attract highly skilled human capital to China by offering them incentives. Qianren Jihua’s objective is to encourage STEM qualified Chinese ex patriots to return to China, and encourage those who already reside in China to stay, and together help create an internationally competitive university sector by increasing the production of world-class research to support China’s plans to dominate precision medicine and life sciences.
 
Government commitment

In 2016, China announced plans for a multi-billion dollar project to enhance its competitiveness by becoming a global leader in molecular science and genomics. China is committed to supporting at least three principal institutions, including the Beijing Genomics Institute (BGI), to sequence the genomes of many millions.
 
In addition to investments at home, China also is investing in centers similar to that of BGI abroad. Over the past 2 years China has invested more than US$110bn on technology M&A deals, which it justifies by suggesting that emerging technologies are, “the main battlefields of the economy”. Early in 2017 BGI announced the launch of a US Innovation Center, co-located in Seattle and San Jose. The Seattle organization is focused on precision medicine and includes collaborations with the University of Washington, the Allen Institute for Brain Science, and the Bill and Melinda Gates Foundation. The San Jose facility, where BGI already has a laboratory employing over 100, supports its ambitions to develop next-generation sequencing technologies, which until now have been dominated by the US sequencing company Illumina.


Changing structure of China’s economy
Some suggest that China’s rise on the world life sciences stage will be short lived because the nation is in the midst of a challenging transition to a slower-growing, consumption-driven economy, and therefore will not be able to sustain such levels of investment; and this will dent its ambition to become a global player in genomic science. An alternative argument suggests slower growth forces China to act smarter, and this is what drives its precision medicine ambitions.

Between 1985 and 2015, China’s annual GDP rose, on average, by 9.4%. Fuelling this growth was a steady supply of workers entering the labour force and massive government led infrastructure investments. Now, because of China’s ageing population, its labour capacity has peaked and started to decline. Without labour force expansion, and investment constrained by debt, China is obliged to rely more heavily on innovation to improve its productivity. And this drives, rather than slows, China’s strategy to become a world leader in genomic technologies and personalized medicine.
 

China’s economic growth is slowing, but its production of scientific research is growing
Although China’s economy is slowing, it is still comparatively large. In 2000, China spent as much on R&D as France; now it invests more in genomics than the EU, when adjusted for the purchasing power of its currency. Today, China produces more research articles than any other nation, apart from the US, and its authors’ feature on around 20% of the world’s most-cited peer reviewed papers. Top Chinese scientific institutions are breaking into lists of the world’s best, and the nation has created some unparalleled research facilities. Even now, every 16 weeks China produces a Greece-size economy, and doubles the entire size of its economy every 7 years. Today, China has an economy similar in size to that of the US, and most projections suggest that, over the next 2 decades, China’s economy will dwarf that of the US.
 
Takeaways

China is cloning its successful strategy to own and control significant mineral and mining rights to the life sciences. Over the past 20 years China has actively pursued mining deals in different global geographies, and now controls significant mining rights and mineral assets in Africa and a few other countries. This allows China to affect the aggregate supply and world market prices of certain natural resources. Now, China is cloning this commercially successful strategy to the life sciences, and has empowered and encouraged a number of state owned and private companies to own and control genomic engineering and precision medicine. China’s single-minded determination to become a world leader in life sciences, and its interpretation of individualism and privacy issues could have far reaching implications for the future of humanity.
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  • In 2003 the US first discovered the genome and became the preeminent nation in genomics
  • This could change
  • World power and influence have moved East
  • China has invested heavily in genomic technologies and established itself as a significant competitive force in precision medicine
  • Ownership of intellectual property and knowhow is key to driving national wealth 
 

The global competition to translate genomic data into personal medical therapies

 

PART 1

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

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

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

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

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

What is DNA sequencing?


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

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

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

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

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

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

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

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

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

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

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

 
Ethical challenges

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

Despite the endeavours of the UK and US to remain at the forefront of the international competition to transform genomic data into personalized medical therapies for some of the worlds most common and intractable diseases, it seems reasonable to assume that China is on the cusp of becoming the most dominant nation in novel personalized treatments. Notwithstanding, China’s determination to assume the global frontrunner position in genomic science might have blunted its concerns for some of the ethical issues, which surround the life sciences. To the extent that this might be the case the future of humanity might well differ significantly from the generally accepted western vision. 
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  • A number of new studies on ovarian cancer show “promising” results for patients who develop chemo-resistance
  • A Dutch study uses conventional chemotherapeutics more intensively
  • Another study uses a new class of drug discovered by the UK’s Institute of Cancer Research
  • Genetic testing is playing an increasing role in the reduction of chemo-resistance
  • Since 2014 the Royal Marsden NHS Trust Hospital in London has employed genetic profiling of ovarian cancer patients
  • The UK’s Chief Medical Officer suggests that whole genome sequencing should become standard practice on the NHS across cancer care
  • A new class of chemotherapeutic agent is directed at targeting cancers with defective DNA-damage repair
  • Improvements in cancer care have been both scientific and organizational
  • Utilizing and sequencing the treatment options for ovarian cancer may have a significant impact on the overall survival rates of patients
  • Multidisciplinary teams are transforming ovarian cancer care 
 
Improving ovarian cancer treatment 

Part II

Part-1 described ovarian cancer, the difficulties of diagnosing the disease early, and the challenges of developing effective screening mechanisms for it in pre-symptomatic women. Here, in part-2, we report new studies, which hold out the prospect of improved treatment options for women living with ovarian cancer. Both Commentaries draw on some of the world’s most eminent ovarian cancer clinicians and scientists.
 
1

Established chemotherapy agents combined and used intensively

The first study we describe is Dutch, published in 2017 in the British Journal of Cancer. It reports findings of a pioneering type of intensive chemotherapy, which was effective in 80% of patients with advanced ovarian cancer and whose first line of chemotherapy had failed. Currently, such patients have few options because more than 50% do not respond to follow-up chemotherapy.
 
Intensive combinations
The study, led by Dr. Ronald de Wit, of the Rotterdam Cancer Institute, involved 98 patients who first responded to chemotherapy only later to relapse. Patients in the study were divided into three groups according to the severity of their condition, and treated with a combination of two well established chemotherapy agents:  cisplatin and etopside, but the new treatment used the drugs much more intensively than usual.
 
Usually, chemotherapy is delivered as a course of a number of 21-day sessions (cycles) over several months. Between cycles patients are given time to recover from the toxic side effects, including neurotoxicity, nephrotoxicity, ototoxicity, and chemotherapy-induced nausea and vomiting (CINV). In de Wit’s study the combined chemotherapy drugs were given intensively, on a weekly basis, along with drugs to prevent adverse side effects.
 
Findings
Among the group of women in de Wit’s study who were most seriously ill, 46% responded to the new treatment, compared with less than 15% for current therapies. The response rates of the two groups of women who were least ill to the new treatment were 92% and 91%. This compares to responses of 50% and 20 to 30% with standard therapies. Overall, 80% of the women's tumours shrank, and 43% showed a complete response, with all signs of their cancers disappearing.
 
Immediate benefit
"We were delighted by the success of the study. The new drug combination was highly effective at keeping women alive for longer, giving real hope to those who would otherwise have had very little . . . . We were worried the women would be too ill to cope with the treatment, but in fact, they suffered relatively few side effects. And since these drugs are readily available, there's no reason why women shouldn't start to benefit from them right away," says de Wit.
 
2
 
ONX-0801 study

The second study we report was presented at the 2017 American Society of Clinical Oncology (ASCO) meeting in Chicago. It describes findings of an experimental new treatment that was found to dramatically shrink advanced ovarian cancer tumors, which researchers suggest is, “much more than anything that has been achieved in the last 10 years”.
 
“Very promising” findings
Dr. Udai Banerji, the leader of the study, is the Deputy Director of Drug Development at the UK’s Institute of Cancer Research (ICR). Banerji and his team were testing a drug, known as ONX-0801, for safety, but found that tumors, in half of the 15 women studied, shrank during the trial. A response Banerji called, “highly unusual”, and “very promising”. The drug, which is, “a completely new mechanism of action,” could add, “upward of six months to the lives of patients with minimal side effects”. If further clinical studies prove the drug’s effectiveness, it could potentially be used in early-stage ovarian cancer where, “the impact on survival may be better,” says Banerji.
 
New class of drug
ONX-0801 is the first in a new class of drug discovered by the ICR, and tested with the Royal Marsden NHS Foundation Trust. It attacks ovarian cancer by mimicking folic acid in order to enter the cancer cells. The drug then kills these cells by blocking a molecule called thymidylate synthase. ONX-0801 could be effective in treating the large group of chemo-resistant sufferers for whom there are currently limited options. Additionally, because the new therapy targets cancer cells and does not affect surrounding healthy cells, there are fewer side effects. Further, experts have developed tests to detect the cells that respond positively to this new treatment, which means oncologists can identify those women who are likely to benefit from the therapy the most.
 
Cautious note
Although the study is said to be “very promising”, Michel Coleman, Professor of Epidemiology at the London School of Hygiene & Tropical Medicine, suggests caution in interpreting its findings as it is such a small study and while, “shrinkage of tumors is important . . . it is not the same as producing the hoped-for extension of survival for women with ovarian cancer.”
 
3
 
Genetic testing

Resistance to chemotherapy can be reduced by DNA testing to obtain an increased knowledge of the molecular mechanisms of ovarian cancer pathogenesis, which facilitate personalized therapies that target certain subtypes of the disease. “Some people choose to have DNA testing because either they have developed cancer or family members have,” says David Bowtell, Professor and Head of the Cancer Genomics and Genetics Program at Peter MacCallum Cancer Centre, Melbourne, Australia. “In the context of cancer, personalized medicine is the concept that we look into the cancer cell and understand for that person what specific genetic changes have occurred in their cancer. Based on those specific changes, for that person we then decide on a type of therapy, which is most appropriate for the genetic changes that have occurred in that cancer . . . . . Typically this involves taking a sample of the cancer, running it through DNA sequencing machines, and using bioinformatics to interpret the information. Then, the results, which include gene mutations need to be interpreted by a multidisciplinary team, in order to decide the best possible treatment options for that particular patient,” says Bowtell: see videos below.
.
 
How do genetic mutations translate into personalised medicine?


How is personalised medicine implemented?
 
Mainstreaming cancer genetics
Since 2014 the Royal Marsden NHS Trust Hospital in London has employed genetic profiling of ovarian cancer patients, and have used laboratories with enhanced genetic testing capabilities to streamline and speed up processing time, lower costs, and help meet the large and growing demand for rapid, accurate and affordable genetic testing. The program called, Mainstreaming Cancer Genetics, helps women cancer patients make critical decisions about their treatment options. Currently, fewer than 33% of patients are tested, but this study spearheaded the beginning of a significant change. In her 2017 Annual Report, Professor Dame Sally Davies, England’s Chief Medical Office suggested that within the next 5 years all cancer patients should be routinely offered DNA tests on the NHS to help them select the best personalized treatments.
 

Bringing genetic testing to patients
According to Nazneen Rahman, Professor and Head of the Division of Genetics and Epidemiology at the ICR, and Head of the Cancer Genetics Unit at the Royal Marsden Hospital, London, “There were two main problems with the traditional system for gene testing. Firstly, gene testing was slow and expensive, and secondly the process for accessing gene testing was slow and complex . . . . We used new DNA sequencing technology to make a fast, accurate, affordable cancer gene test, which is now used across the UK. We then simplified test eligibility and brought testing to patients in the cancer clinic, rather than making them have another appointment, often in another hospital.” 
 

More people benefiting from affordable rapid advanced genetic testing
Treatment strategies that improve the selectivity of current chemotherapy have the potential to make a dramatic impact on ovarian cancer patient outcomes. The Marsden is now offering genetic tests to three times more cancer patients a year than before the program started. The new pathway is faster, with results arriving within 4 weeks, as opposed to the previous 20-week waiting period. According to Rahman, “Many other centres across the country and internationally are adopting our mainstream gene testing approach. This will help many women with cancer and will prevent cancers in their relatives.” If the UK government acts on the recommendations of Davies, there could be a national center for genetic testing within the next 5 years.
 
4

PARP Inhibitors and personalized therapy
 
Since 2 seminal 2005 publications in Nature,  (Bryant et al, 2005; and Farmer et al, 2005) which reported the extremely high sensitivity of BRCA mutant cell lines to the enzyme poly (ADP-ribose) polymerase (PARP) inhibition, there has been a scientific race to exploit a new class of cancer drug called PARP inhibitors. The family of PARP inhibitors represents a widely researched and promising alternative for the targeted therapy of ovarian malignancies. Over the past few years, PARP inhibitors have successfully moved into clinical practice, and are now used to help improve progression-free survival in women with recurrent platinum-sensitive ovarian cancer.

 
Recent (PARP) approvals
In 2014, olaparib was the first PARP inhibitor to obtain EU approval as a treatment for ovarian cancer patients who had become resistant to platinum-based chemotherapy. In 2017, the FDA granted the drug ‘priority review’ as a maintenance therapy in relapsed patients with platinum-sensitive ovarian cancer while confirmatory studies are completed. In December 2016, the FDA granted ‘accelerated approval’ for rucaparib, another (PARP) inhibitor for the treatment of women with advanced ovarian cancers who have been treated with two or more chemotherapies, and whose tumors have specific BRCA gene mutations. 
 
Early in 2017, the drug niraparib was the first PARP inhibitor to be approved by the FDA for the maintenance treatment of adult patients with recurrent gynaecological cancers who are resistant to platinum-based chemotherapy.  The approval was based upon data from an international randomized, prospectively designed phase III clinical study, which enrolled 553 patients, and showed a clinically meaningful increase in progression-free survival (PFS) in women with recurrent ovarian cancer, regardless of BRCA mutation or biomarker status. In conjunction with the accelerated 2017 FDA approval for rucaparib, the FDA also approved a BRCA diagnostic test, which identifies patients with advanced ovarian cancer eligible for treatment with rucaparib.
 

New class of chemotherapies
PARP inhibitors may represent a potentially significant new class of chemotherapeutic agents directed at targeting cancers with defective DNA-damage repair. Currently, these drugs have a palliative indication for a relatively small cohort of patients. In order to widen the prospective patient population that would benefit from PARP inhibitors, predictive biomarkers based on a clearer understanding of the mechanism of action, and a better understanding of their toxicity profile will be required. Once this is achieved PARP inhibitors could to be employed in the curative, rather than the palliative setting.
 
5
 
The future of cancer care and multidisciplinary teams
 
According to Hani Gabra, Professor of Medical Oncology at Imperial College, London; and Head of AstraZeneca’s Oncology Discovery Unit, we now have “many options” for treating ovarian cancer. However, “how we utilize and sequence these options may have a significant impact on the overall survival of a patient. Better understanding of the disease through science is constantly turning up new options. For the first time in the last 5 years we are developing options in real time for patients. Patients almost are able to benefit from these options as they are relapsing from their disease. Keeping patients alive for longer allows them to access new treatments . . . It’s truly remarkable to see this in real time as a doctor,” says Gabra: see video.
 

A significant number of mostly private patients diagnosed with ovarian cancer draw comfort from the belief that they, “have the best oncologist”.  This view fails to grasp the challenges facing individual clinicians acting on their own to treat a devilishly complex disease such as ovarian cancer. “The main improvements in cancer care have been organizational and scientific.” says Gabra. “It is not enough to create new science and new treatments. It is also important to rigorously implement these. The most effective way to do this is via a ‘tumor board’ or a ‘multidisciplinary clinic or team’, where various specialists such as surgeons, radiotherapists, medical oncologists, pathologists, clinical nurse specialists, etc come together and discuss each individual patient. Such multidisciplinary discussion results in the best utilizations of currently available treatment options in the right sequence. It’s difficult to do this for a doctor acting on his or her own and making isolated decisions . . . Multidisciplinary decision-making has transformed cancer care,” says Gabra: see video.
 
 
Takeaways

This Commentary provides a flavor of some of the recent advances in ovarian cancer research and care, and suggests that treatment options have improved in the 4 years since Maurice Saatchi described ovarian cancer care as, “degrading, medieval and ineffective” leading “only to death”. However, it is worth stressing that care is both organizational and scientific, and multidisciplinary teams can transform care and prolong life.
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joined 7 years, 8 months ago

Laura Coates

NIHR Clinician Scientist and Senior Clinical Research Fellow

Dr Laura Coates joined the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), Oxford in 2017 as an National Institute of Health Research (NIHR) Clinician Scientist to research optimal therapeutic strategies for patients with psoriatic arthritis (PsA).

Laura is establishing a new psoriatic arthritis service in Oxford to see if a more practical version of ‘treat to target’, an approach where a patient’s treatment is increased regularly until a target was achieved can be run successfully in a routine NHS Clinic. Laura developed this approach to the condition when conducting the Tight Control of Psoriatic Arthritis (TICOPA) clinical study, which found that the ‘treat to target’ improves patients’ outcomes.

Laura is also testing different treatment options in an attempt to personalise care. She expects to discover whether patients with mild (PsA) can be treated successfully without more powerful arthritis drugs, and thereby avoid side effects. And also to discover whether patients with a severe form of the condition, do better if they start on stronger arthritis drugs.

Laura completed her rheumatology training and her PhD at the University of Leeds in the Leeds Institute of Rheumatology and Musculoskeletal Medicine. Her PhD focused on the development and validation of the minimal disease activity criteria for PsA, which she established in the TICOPA study.

Laura’s research is clinical and focuses on psoriatic arthritis and the spondyloarthritides including early diagnosis of PsA, development of PsA, specific and validated outcome measures, optimal treatment pathways and strategies in PsA. Laura has developed and validated screening questionnaires to identify PsA. She has experience in outcome measurement, and has been involved in the development and validation of novel clinical and imaging outcome measures.

Laura is the first author of the TICOPA study. This is the first study to address treating to target in PsA, and improved clinical and patient reported outcomes. In 2011 Laura’s publications and their impact was recognized and she was awarded one of eight UK Scopus Young Investigator Awards. In 2012 she obtained the University of Leeds Women of Achievement Award.

Laura is a member of the Steering Committee of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the British Psoriatic Arthritis Consortium (Brit-PACT). She is the first author on the 2015 GRAPPA treatment recommendations for psoriasis and PsA, and is also involved in the GRAPPA/OMERACT (Outcome Measures in Rheumatology) initiative to refine the core set of outcome measures for PsA.


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In July 2014 the European Translational Research Network in Ovarian Cancer (EUTROC), held its annual conference in London. High on its agenda was cancer's resistance to established drugs.

Cancer is a complex disease. It arises from random "errors" in our genes, which regulate the growth of cells that make-up our bodies. Error-laden cells either die or survive, and multiply as a result of complex changes that scientists don't fully understood.
 
Translational medicine
Translational medicine is a rapidly growing discipline in biomedical research, which benefits from a recent technological revolution that allows scientists to monitor the behaviour of everyone of our 25,000 genes, identify almost every protein in an individual cell, and work to improve cancer therapies.
 
Ovarian cancer is the forth most common form of cancer in women, after breast, lung and bowel cancer. Each year, in the UK some 7,000 people are diagnosed with ovarian cancer, in the US it's 240,000. Most women are diagnosed once the cancer has spread beyond the ovaries, which makes treatment challenging, and mortality rates high. Only 10% of women diagnosed with ovarian cancer at the latest stage survive more that five years. 
 
 
Molecular profiling
EUTROC employs a multi-disciplinary, collaborative, "bench-to-bedside" approach in order to expeditiously discover new therapies, which tailor medical treatment to the specific characteristics of specific cancers: personalised medicine.
 
Cancers are like people: not all are alike, and when examined at a molecular level they show that their genetic makeup is very different. Clinicians use molecular profiling to examine the genetic characteristics of a person's cancer as well as any unique biomarkers, which enables them to identify and create targeted therapies designed to work better for a specific cancer profile.
 
Combatting cancer resistance
Personalising treatment to target errors in specific cancers at the point of diagnosis fails to address the fact that cancers mutate in response to treatment. Even drugs that are initially effective may become ineffective as the cancer returns and re-establishes its ability to grow and spread. Cancer often behaves like a taxi navigating a way round a localised traffic jam

 

An approach to combat this is to treat a cancer with one target drug, and if the cancer returns with newly developed resistance, identify how that resistance occurred and target that with another drug, and so on, until the cancer and its resistances are beaten.  This is similar to accepting that a local traffic jam may be bypassed, and finding and blocking all the ways around the jam.
 
Another approach is to target and block something critical for the survival of a specific cancer. This is similar to blocking a strategic point that controls all the traffic coming in and leaving a city. For example, taxi drivers clogging up Trafalgar Square and bringing London to a standstill. But scientists are a long way from achieving this because researchers don't know whether such targets in relations to cancers exists, and even if they did, they don't know whether they can be blocked effectively. And, even if such targets were discovered and were blocked, scientists still don't know what would be the side effects of doing so. 
 
Takeaways
For personalised medicine to be successful, clinicians and scientists need to track the evolutionary trajectories of cancers in patients through sequential episodes of treatment and relapse. Besides being a major clinical and scientific challenge, this is also a significant informational and communication challenge, which networks such as EUTROC are addressing.
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