From DNA to smartphones, Macrogen is reshaping the future of healthcare through genomics

In developed markets, especially those of Japan, USA and EU, medical organizations and practitioners are reputed for being conservative, and changing suppliers or adopting new technologies for medical procedures is a difficult challenge to overcome for new products and companies. How are you working to overcome this barrier?

When I graduated from medical school, I majored in molecular biology and biochemistry. During my early years, I was deeply interested in molecular biology and greatly admired Jacques Lucien Monod, who won the Nobel Prize in Physiology or Medicine in 1965 for discovering the operon. His book, Chance and Necessity, made a profound impact on me. Inspired by Monod, I aimed to uncover fundamental truths about life and scientifically validate the enduring principles governing various species.

However, the field has evolved significantly since then. The focus has shifted from molecular biology to data science and big data. Our current understanding and technological advancements represent the culmination of 300 years of scientific progress. One crucial discovery, highlighted in Monod's work, is that living organisms, unlike inorganic substances, possess blueprints within themselves. This insight differentiates living beings from non-living matter. Charles Darwin's theory of evolution and Gregor Mendel's principles of inheritance laid the groundwork, which culminated in the Human Genome Project, revealing the genetic blueprints of life.

Today, our understanding has further expanded with Lynn Margulis's concept of the holobiont, which suggests that a significant fraction of the microbiome genome, along with the host genome, is transmitted across generations. Simply put, a holobiont encompasses both the human genome and the microbiome. This marks a shift towards individualization in modern science and medicine.

Medicine's primary goal is to cater to individual needs. While evolution emphasizes species over individuals, modern medicine prioritizes individual care. With access to genetic blueprints, today's medicine can tailor treatments to individual requirements. For the first time in history, humans can hold their genetic blueprints, a feat unique to our species in 4 billion years of life on Earth.

The magnitude of this change is immense, necessitating adaptation. Although medicine traditionally advances through experience, the rapid pace of technological and scientific evolution demands that we adapt quickly. Macrogen, now 27 years old, must also evolve to keep pace with these changes.

Comprehensively mapping the genetic basis of human disease across diverse individuals is a long-standing goal for the field of human and animal genetics. The acceleration of genome analyses has greatly boosted research and opportunities for understanding living organisms. For example, conserving nature's biodiversity is one of the great challenges of our time, and genomic data can be used to determine a species' ability to adapt to changing environmental conditions. Ten years from now, what applications and breakthroughs will genomics unlock?

Back in 2000, Francis Collins succeeded in the Human Genome Project and stated that it could contribute to the well-being of humanity in three ways: genome to biology, genome to medicine, and genome to society. First, genome to biology means that academically, we will learn many things from the human genome project, such as the underlying principles of life, which contribute to academic knowledge. The second field is medicine, where genomics is applied to diagnostics and treatments. This is the stage we are currently in. However, in the future, everything is moving towards digital transformation, with the ultimate goal being genome to society.

In ten years, I believe that the integration of genomics into society will be profound. Addressing societal issues, including healthcare, will extend beyond just treating diseases. Genomic data will be utilized much like a GPS for navigating vehicles, helping us to avoid health hurdles and improve overall well-being.

We are now living in an era of AI. With the release of GPT-4 in March 2023, offering enhanced performance and features, it became more widely available. By April 2024, the world had already experienced significant changes due to this technology. The next major revolution will be in medicine.

Digital transformation is affecting all sectors, including finance and society, but medicine has been slower to adapt due to the licensing requirements for medical practitioners, which act as a barrier to change. However, since 2018, we have seen gradual changes, especially starting in the United States.

As the number of senior citizens grows worldwide, this increases the burden on governments and raises medical costs. In 2019, 18% of the US GDP was spent on medical expenses. If we do not respond to this trend in a timely manner, medical expenses could reach 26% of GDP by 2040, which would paralyze the global economy. This is why, in 2015, the Obama Administration advocated for precision medicine and called for changes in the medical system.

The COVID-19 pandemic over the past three years has accelerated digital transformation. The most important keywords for the current era are individualization and democratization of healthcare. In 2018, Stanford released a healthcare report that predicted the democratization of healthcare. Reflecting on the present, the advance of AI is blurring the lines between different sectors, and medicine is no exception. AI-enabled healthcare will inevitably become mainstream, and we must not be complacent because this will rapidly change everything.

As Eric Topol has claimed, medicine must also undergo significant changes. He added that medical expenses need to be reduced to one-tenth of today's costs, or we will not be able to escape the burden of rising medical costs.

In the field of genetics and genomics research, there are several historical challenges. The first challenge involves samples, specifically the diversity, quantity, and quality of samples, which are crucial for creating generalizable findings. Then managing a large volume of data from diverse sources presents significant analytical challenges that require specialized skills and a multidisciplinary approach. Additionally, while genomics and genetic research have shown great potential, translating these advances into clinical applications and products has been difficult. How do you think AI and digital technologies will help address these four challenges?

One of the most important aspects of overcoming these challenges is transforming everything into big data. Fortunately, we now have the technology to achieve this. For example, we have advanced tools like MRI and CT scanners, as well as Electronic Medical Records (EMR) systems in hospitals. Since 2014, we have had the technological capability to handle vast amounts of genomic data, EMR data, and lifelog data. Now, with the advent of AI, we have a groundbreaking tool that enables us to process and analyze these massive datasets. This represents a revolutionary change in the field.

You mentioned four specific challenges in genomics research. Let me address each one in turn:

1. Ethnic Diversity in Samples: Historically, there is a wealth of data available for Caucasians, while data for other ethnic groups, such as Asians, is less abundant. For instance, there are about 1.1 billion Caucasians in the world, including Europeans and Americans, compared to 4.5 billion Asians. At Macrogen, one of our primary goals is to bridge this gap and generate extensive genomic data for Asian populations.
2. Low Clinical Utility: A significant challenge is the lack of practical applications for genomic research in clinical settings. Medical practitioners often lack the necessary knowledge and training to utilize genomic data effectively. Educating these practitioners is time-consuming, but AI can facilitate this process, not only for medical professionals but also for the general public. In the United States, there are only 5,000 genetic counselors, which is a problem in itself. AI has the potential to accelerate the education and training needed to address this gap.
3. Cost of Genomic Data: The cost of sequencing and analyzing genomic data has been a barrier. In 2022, Illumina introduced the NovaSeq X, which provides genomic data services at $2 per gigabyte. Ultima Genomics also developed a sequencer that offers similar services for $1 per gigabyte. Despite these advancements, sequencing services still cost around $300. At Macrogen, we offer these services at $180, and we are working to reduce costs even further. Sequencing will become as routine as PCR technology, which is widely used today.
4. Human vs. Machine in Patient Interaction: Finally, there is the issue of the human element in medicine. People generally prefer to receive diagnoses and treatment from human doctors rather than robots. As Eric Topol has pointed out, while AI and technology will play crucial roles, we will always need doctors to provide the compassionate and empathetic care that machines cannot fully replicate.

In summary, AI and digital technologies are set to address these challenges by making data processing more efficient, expanding educational opportunities, reducing costs, and ultimately complementing, rather than replacing, the essential human touch in healthcare.

While the majority of the world's population resides in Asia, they are underrepresented in genome mapping. Macrogen is working towards creating a more comprehensive Asian genome database and is participating in several related research projects by leveraging its genome center capabilities. What new discoveries or advancements can be expected from these studies?

Asia is home to a vast and diverse population, yet the Asian genome has often been compared to a "bio-semiconductor," thanks to cutting-edge AI integration. We lead the way in global genome research, boasting top-tier data quantity, quality, and interpretation skills. In Japan, we hold the number one spot in genome analysis, known for our unmatched analysis capacity and bioinformatics resources.

We have made big strides in this field, especially with Asian genome analysis. In February 2016, we worked with Bundang Seoul National University Hospital and launched the Genome Asia 100K Initiative, an international project focused on identifying disease-related genes specific to Asians. This effort significantly advanced precision medicine, even earning a cover story in Nature for releasing the largest Asian genome database.

When this consortium started, about 87% of available genome data was from Westerners, with Asians barely represented. This new database has the potential to revolutionize precision medicine for Asians. Take the anticoagulant 'Warfarin,' for instance. It’s commonly prescribed for cardiovascular issues, but it can cause adverse reactions in people with certain genes. Research suggested that North Asians, like Koreans, Chinese, Japanese, and Mongolians, might be more sensitive to it. This underscores the importance of personalized diagnosis and treatment for different regions and ethnicities.

We didn’t stop there. We are building a robust database of Asian genomes, including Koreans and Mongolians. In 2008, we made headlines by completing the whole-genome sequencing of a Korean—the fifth in the world to do so. We followed this up with major studies: a copy number variant analysis on Asians in 2010, and genome and transcriptome analyses on Koreans in 2011, both published in Nature Genetics. In 2016, we collaborated with the Genome Medicine Research Institute of Seoul National University College of Medicine, to publish the most complete Korean genome sequence to date in Nature.

Thanks to the genetic variation database from these large-scale studies, we are paving the way for precision medicine tailored to Asians. Custom treatments based on genetic profiles can enhance therapeutic effects and reduce side effects, leading to more accurate diagnosis and treatment of specific diseases.

Understanding genetic variations also opens the door to predicting and preventing diseases common in Asian populations. With a deeper grasp of disease mechanisms, there’s potential for developing new drugs that better suit Asian genetic traits, offering more effective treatment options. Personalized healthcare could soon mean tailored health plans—including diet, exercise, and medication—based on your genes.

Plus, with early diagnosis and prevention through personalized treatment, we could cut down on unnecessary medical expenses, leading to overall healthcare savings. This research isn’t just significant for Asia—it’s a big step forward for global healthcare, driving progress worldwide.

GenTok – Discover your personal Genome

Macrogen initially focused on providing B2B services, primarily catering to medical institutions and research projects. However, according to your past interviews, around 2018-2019, and significantly more in 2020, you began discussing making genomic analysis accessible to consumers. This has been a long-term goal for you to popularize genomics among the general population. This effort recently culminated in the launch of GenTok. Why do you believe it is so important to bring genomics to the general population rather than keeping it confined to medical institutions?

While medicine is undoubtedly crucial, and addressing disease-related issues is essential, I believe it is equally important to enable healthy individuals to experience genetic technologies. There is a concept called MBTI, a personality test that many Koreans take, which categorizes people into different personality types. When taking the MBTI, individuals respond to various questions, some of which can be ambiguous and challenging to answer definitively. In contrast, our genetic test provides answers based on one's original genes, which are constant and unchanging.

We refer to our genomics test as "Mom-BTI," where "mom" signifies "body" in Korean. This Mom-BTI is significantly more accurate than MBTI because it is grounded in one's genetic makeup. We promote GenTok as Mom-BTI, allowing people to categorize themselves based on their genes. Today's Gen Z and millennial generations often have less interest in diseases; they are more focused on understanding themselves and their identities. GenTok caters to this desire, providing them with an opportunity to experience genetic testing in a way that is engaging and educational.

However, it is important to note that while the initial aim is self-discovery and education, the ultimate goal remains the prevention and treatment of diseases. By making genomics accessible to the general population, we not only satisfy their curiosity but also lay the groundwork for a future where personalized medicine can thrive.

The Biome Kit

“GenTok” application offers DTC (Direct-to-Consumer) genetic testing services and microbiome (microbiota) testing services. GenTok is currently focused on Korea, where genetic testing and health monitoring are popular among Millennials and Generation Z.

• Could you explain in detail how users can maximize the benefits of this platform?
• Are there plans to further expand the digital healthcare platform in the future, such as adding more features or expanding services overseas?
• Could you share your vision on how digital healthcare platforms will innovate future health?

Our 'GenTok' platform offer personalized health management by analyzing your genes and microbiome. We recently added an AI chatbot for even more precise health consultations. The GenTok Genetic Testing All-Package covers 129 items across six categories, including skin/hair, exercise, nutrients, health management, eating habits, and personal traits. All you need is a saliva sample collected at home. Categories include things like obesity, exercise effects, hair loss, blood sugar, nutrients, and sleep habits. With GenTok’s testing, you can adopt healthier daily habits. The platform features cool result cards styled as character types and provides tailored health tips based on your results.

GenTok’s "The Biome" service digs into your microbiome, analyzing 11 wellness indicators such as constipation, bloating, happiness, obesity, sleep, aging, fatigue, and immunity. It also tracks 14 nutrient metabolism scores and 19 types of probiotics approved by the Ministry of Food and Drug Safety. You can easily apply for the service, send samples, and get results through the GenTok app, all from the comfort of your home. This lets you manage your health based on your gut environment, which changes with your lifestyle and habits.

The microbiome is gaining attention for its impact on diseases like obesity, diabetes, and metabolic syndrome, as well as overall health. Market research predicts the microbiome industry will grow from $6.18 billion in 2022 to $10.09 billion by 2026, with an annual growth rate of 13.1%. We plan to expand its microbiome services, including regular monitoring and exploring intestinal, oral, female, and infant microbiomes. It also acquired Ubiome’s intellectual property to boost its analytical edge.

We aim to help people live long and healthy lives by using genetic data for "navigation." While you can’t change your genes, analyzing them can help you tweak your eating and lifestyle habits to prevent diseases and improve your life. Sometimes, medication effectiveness varies with genotype. Clinical trials have shown that some people respond better or worse to certain drugs based on their genes. With our insight, you can know in advance if a medication might not work for you or if you need a dosage adjustment.

The Macrogen Medical Foundation offers customized genetic health check-ups at hospitals like the Health Check-up Center in Songdo, Incheon, Korea. These check-ups focus on preventive care rather than just cancer testing, providing everyone with a DNA blueprint to guide their health decisions. Understanding your potential disease risks can help you make healthier lifestyle choices.

As Korea faces a rapidly aging population and rising medical costs, early health understanding and improved habits can help prevent diseases and reduce healthcare expenses. Since national health insurance began in 1977, Korea's GDP has surged 116-fold, while medical expenses have jumped 511-fold. While South Korea's healthcare expenditure is not exceptionally high compared to the average of OECD countries, what's noteworthy is the speed at which it's increasing. This trend poses a significant financial burden on segments of the population with limited spending capacity, such as the elderly and young adults.

How does GenTok guide customers to derive the best benefits from their genome testing?

GenTok currently provides results for wellness categories in accordance with domestic regulations. However, including the disease prediction genetic tests that Macrogen currently offers through hospitals, understanding our genetic blueprint through genetic testing can ultimately be greatly beneficial. For example, approximately 5% of the population inherits two copies of the ApoE4 gene, one from each parent. Individuals with this genetic marker have a higher likelihood of developing Alzheimer's disease after the age of 60.

Knowing that one has the ApoE4 gene can be crucial. Although we don't yet have a definitive solution for preventing Alzheimer's, there are various ways to strengthen memory and maintain cognitive function. One effective method is regular exercise, which helps keep the brain active and healthy. In conclusion, having access to genetic information can help individuals take proactive steps to maintain their health.

GenTok provides actionable insights based on genetic data. For instance, if the test indicates a predisposition to weight gain, we offer personalized dietary and lifestyle recommendations. The goal is to empower individuals to make informed decisions about their health and well-being. By understanding their genetic predispositions, people can adopt preventive measures and healthier lifestyles, ultimately enhancing their quality of life.

Selling to consumers presents unique challenges. What challenges are you encountering as you transition from a B2B to a B2C model? Additionally, how will you ensure that GenTok becomes not only a compelling project but also a profitable one going forward?

Increasing profitability will indeed be a challenge. The smartphone revolution is comparable to the Gutenberg press, and GenTok has the potential to be similarly transformative. We have innovative ways to communicate with individuals, positioning GenTok as an educational platform. As people become accustomed to using GenTok, we can integrate medical functionalities, utilizing the data acquired through the platform for medical purposes.

If global IT/mobile device companies were to incorporate GenTok into their products, it would be an excellent trial and a significant milestone for us. This is one of our goals. Additionally, Macrogen operates its own hospital, accumulating data from 30,000 patients annually. Over three years, this will amount to nearly 100,000 data points. Leveraging this extensive dataset will enable us to develop and enhance our offerings further.

Our commercialization strategy involves making GenTok accessible and affordable to the general population while ensuring it remains scientifically robust and valuable. We are focusing on reducing costs through economies of scale and continuous technological advancements. Branding and marketing efforts are geared towards educating consumers about the benefits of genomic testing and its impact on their health and lifestyle.

By combining educational outreach with strategic partnerships and leveraging our substantial patient data, we aim to create a sustainable and profitable business model for GenTok.

I would like to ask you a more personal question. Considering everything you've achieved already, is there anything left that you want to accomplish? What would you like to tell us? What would you like to have achieved?

I have always been a scholar at heart. My background is in academia, and I used to be a professor. When I graduated from medical school, I was driven by the desire to discover something fundamental. There are still two or three questions I haven't been able to solve. One of them is understanding the genomic determinants of the youthful appearance, or "baby face," common among Asian people. I believe this is related to neoteny, which involves delayed physical development.

There are three types of neoteny. The first type is seen in amphibians, like tadpoles that retain their tails into adulthood, such as some Mexican salamanders. Typically, tadpoles lose their tails during metamorphosis, but these salamanders do not. The second type is seen in dogs, where some breeds retain features like flat noses. The third type is observed in humans, particularly Asians, who often have larger eyes and flatter faces compared to Europeans or Americans, resembling the early stages of Mickey Mouse’s design. I am interested in identifying the genetic markers responsible for these traits. They might be related to transcription factors or specific mutations.

Of course, our ultimate goal is to provide DNA blueprints to everyone worldwide, enabling them to lead healthier and happier lives. Additionally, I have a dream of using genomics to address unanswered questions.

For more details, explore their website at: https://www.macrogen.com/en/main