Healthcare in the New Era

1. Can you share your insights on how advancements in genomic and sequencing technology have revolutionized healthcare in the past decade, particularly in terms of diagnosis, treatment, and patient outcomes?

The completion of the human genome project (HGP) sparked the new era of Genomic Medicine[1]. The identification of single-nucletoide polymorpshims (SNP) and the discoveries of genome-wide association stusies (GWAS) have since revolutionized diagnosis and prediction by providing information of many genes that are linked to the development of diseases, predispositions, and even predictive scores, the polygenic risk scores (PRS). So, today, we use genetic testing for diagnosis, for treatment decisions in cancer and elsewhere, and for prediction of health and disease. Many therapies are targeted, such as for example in cancer chemotherapy. And gene therapy is everywhere from metabolic disease to cancer. Hippocrates had foreseen individualized medicine, but I certainly hope he was alive today to see it happening!

2. As someone deeply involved in precision medicine, what do you see as the key benefits and challenges of integrating genetics into personalized healthcare? How do you address ethical considerations and privacy concerns in utilizing individualized genomic data?

The incorporation of genetics into personalized healthcare offers for the first time really in the history of medicine the opportunity to titrate everything to the specifics of the individual, from prevention efforts, to diagnostic markers, to therapy interventions. However, as said above, one of the main challenges for the incorporation of genetics into personalized healthcare is  protection of personal data and overall use of genomic information. The benefits of genetics informing the electronic medical or health record (EHR) of the individual  are beyond any doubt for interpretation and implementation but societies and communities in general, as well as professional bodies and organizations should establish procedures, guidelines, and frameworks that will ensure ethical use of the information and protect the privacy of the individual.

3. Could you elaborate on the role of artificial intelligence and machine learning in analyzing and utilizing individualized genomic data for improving patient outcomes? How do collaborations between academia, research institutions, and pharmaceutical companies contribute to advancing precision medicine and molecular research?

The power of artificial intelligence (AI) and machine learning in analyzing data to improve health outcomes have been presented extensivey. I will use the example of  hypertension (HTN) and one recent study that used machine learning (ML) to overcome a major hurdle in its diagnosis. A study by Chen et al. used ML to link genetic data with hormonal measurements in patients with adrenal adenomas. The study solved an old problem: how do you identify which tumor to operate on when you have more than one? ML helped identify the right tumor. So, AI and ML are already helping out and one can’t really imagine what the future holds. In pharmaceutical development, AI will be instrumental in identifying small molecules that will target genes and pathways that are affected in diseases. For the efficient use of such discoveries by the pharmaceutical industry, the tight collaboration between research institutions and industry is essential.

4. With the increasing focus on disease prevention, what strategies do you think are most effective in promoting healthy living and preventing future health issues? How can personalized genetics and precision medicine play a role in preventive care?

There is no question that where genetics will have a major impact is prevention: a healthy subject will remain healthy after the successful incorporation of genetic information into preventive diagnostic testing and health-promoting interventions in a way that are titrated to the individual’s needs. Health systems around the world will see the benefits of shifting focus from battling disease to preventing disease, in terms of total costs but also satisfaction of the population from their services. However, for that to happen there are three important steps that are summarized into one word: communication, communication, communication! First, communicating to the public the need for prevention; second, communicating to the leadership of health systems the benefits of a strategy that prioritizes prevention; and, third, communicating to the health care personnel efficient and user-friedly protocols that can be applied at the general practitioner’s level and beyond, at home, schools, etc.

5. You have a vast experience in clinical genetics and precision medicine. How do you envision the future of healthcare, particularly in terms of personalized medicine, preventive care, and addressing societal challenges such as rare diseases?

I envision a situation where every one of us has our own genetic information in our wallet or our phone or any other small device. This information will then be readily available whenever it is needed by our healthcare provider. Our check ups will be informed by it. Any suggestions for physical activity, diet, or environmental exposures, and any medications we need to take will be informed by it. This is vastly different from the current situation for the average person and promises a real improvement in healthspan! As for rare diseases, precision medicine promises a revolution in therapy: for most patiens with rare diseases there have been no treatments for centuries. Already, there are hundreds of gene therapy trials for many rare diseases. I do hope that the cost of such treatments will also decline as technology improves.

6. As the Chief Scientific Officer of ELPEN Pharmaceuticals and a director of human genetics and precision medicine at IMBB, FORTH, what initiatives are you leading or involved in to advance precision medicine and molecular research? Can you share any success stories or examples where personalized genetics and precision medicine have significantly impacted patient care and treatment outcomes?

Perhaps one of our best projects is the successful establishment of the Hellenic network for precision medicine in molecular oncology (www.edimo.gr) coordinated by our IMBB, FORTH-located laboratory DIGENIA (www.digenia.gr). It envisions a comprehensive oncological care for the Greek population all the way from prevention to diagnosis and treatment based on personalized molecular information.

These initiatives will undoubtedly lead to improvement of healthspan by averting neoplastic disease, as well improve lifespan by providing personalized and targeted therapies.

My personal experience is in the field of rare diseases. The discovery of genetic defects such as the PRKAR1A mutations in patients with Carney complex allowed for the early diagnosis, surveillance and treatment of these patients. Carney complex is a disease that among other problems predisposes to the development of heart tumors. Up to the discovery of the gene by my laboratory and the establishment of genetic testing and surveillance protocols, there were no families with Carney complex that had not lost a member, usually a child, due to sudden death caused by a heart tumor. I am proud to say, that in the last 20 years, of the hundreds of patients I know with Carney complex, I know of no sudden deaths due to a previously unknown heart tumor. This is clearly due to genetic diagnosis and implementation of preventive testing and care. There is more that needs to be done of course, such as for example gene therapy to treat recurrent heart tumors and the other manifestations of Carney complex. But precision medicine has already shown the miracles that it can accomplish by increasing lifespan of Carney complex patients to almost normal.

7. How important is it to educate both the public and healthcare professionals about personalized genetics, precision medicine, and preventive care? What steps are being taken in this regard, and how can we improve public understanding and acceptance of these technologies?

I mentioned before that communicating to health care providers the beneftis of implementing personalized genetics, precision medicine, and preventive care is essential. A number of healh systems are now educating their staff about personalized medicine protocols. This is essential in fields such as oncology, for example, where genetics plays a critical role for the choice of diagnostic testing, surveillance and even therapies. Slowly, but steadily, this is expanding in other fields of medicine but it has yet to be implemented widely in preventive care. For that to happen, we do have to have the public understanding and acceptance of new technologies. The use of social media to educate the public is essential and many communities are now doing that. Most clinics have enegaged in outreach efforts and information is widely available. But there is more that needs to be done. Perhaps, the best place to start is schools, primary education for example. Fortunately, many school systems are now educating young kids on the needs of prevention and what genetics means for them and their families

8. Considering your extensive background in academia and research, what advice would you give to young professionals aspiring to make a difference in the field of healthcare and precision medicine? How can they contribute to shaping the future of medical research and patient care?

I used before what Cicero said “O tempora, o mores!” which roughly translates to “What an age we live in!”.

It is a great time to be a professional today entering the field of healthcare and precision medicine. Technology advances allow for applications that were unimaginable just a few years ago. Thus, delivering care today can be very rewarding in ways that it could not be in the past. Yet, the new era has challenges, too: can we deliver these new therapies to all? Is technology accessible to all and by all? And can the complexity of the new knowledge be mastered by all staff? It is now estimated that medical knowledge doubles every 2 months or so, whereas this doubling time was counted in centuries until recently.

So, here is my advice: embrace new technology, master it, and make all you can do for all to benefit from it, regardless of costs, difficulties in access, and other challenges. And remember to protect society and the individual from the possible abuses of technology or its unethical applications.

9. Lastly, could you discuss the role of large data and predictive healthcare in shaping the future of medical research and patient care, as highlighted in the new NICHD Strategic Plan? How do you see these advancements influencing clinical practice and healthcare delivery?

While at the United States National Institutes of Helath, I co-led the strategic planning process of the National Institute of Child Health & Human Development (NICHD) (NICHD Strategic Plan 2020. Healthy pregnancies. Healthy children. Healthy and optimal lives. (nih.gov)). The plan emphasized the use of large data for predicitive care, biomedical research, and clinical practice.  The creation of user-friendy, accessible databases for clinical trials, molecules, genetic information is essential for the practice of medicine in the new era, and will lead to faster implementation of machine learning and artificial intelligence technology in daily care.

The most important way these large data affect daily practice is by providing easy access to accurate information for both patients and healthcare providers, but also to any individual that needs it. I will give you an example of my daily clinical practice in genetics. The other day, I saw a patient with frequent fractures and a family history of brittle bones. I made the provisional diagnosis of a form of osteogenesis imperfecta (OI). I ordered the enetic test and a mutations was found in the COL1A1 gene which infact causes OI. Then, we searched the databases and found out that the mutation had been described previsously. We provided the patient all the information and even showed him how to access the databases himself. Within days from when I saw the patient, he and his family have been diagnosed, they now have the tools for preimplantation genetic testing for future pregnancies, and can take control of their lifes having access to all the up-to-date information. This is the power of databases: large datasets, access to all, continuously updated. Not only useful for the clinicians but also for the patients and their families!

10. In conclusion, what do you believe are the most critical areas of focus for the future of precision medicine and healthcare, and how can stakeholders across the industry collaborate to achieve these goals effectively?

In conclusion, we live at fascinating times, yet times that are transitional and with huge opportunities opening up but also great challenges. In the preceding questions, and through our answers we presented the huge opportunities and mentioned some of the challenges. The most critical areas, as is obvious from what we have said so far, are those of access, cost, and ethics. Everybody should have access to precision medicine and modern healthcare with its preventive tools, large databases, and molecular therapies, both providers and the society as a whole (non-providers, every healthy citizen and patients). This means education, familiarity with new technologies, and bringing costs down. Affordability and costs are very important issues that are intertwined with access. And last but not least, ethics: how do the new tehcnologies get mastered without breaking privacy, how we use machine learning and artificial intelligence to society’s advantage without at the end being enslaved by non-human processes, how to make gene modification affordable and a therapeutical opportunity for many diseases and all patients, and how to prevent it from being used for eugenics or other practices that we all seem to find unacceptable. Stakeholders individually and through their professional societies should engage actively towards addressing these issues, bringing them to the forum and coordinate their actions, informing communities of their activism and making these issues important for the everyday political discussion. At the end, it is state policies that make healthcare accessible and create the proper legislation for the protection of citizens, dissemination of new technologies and their use for the benefit of many, as well as fostering further innovation.

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