Chronic Excess Energy Intake Drives Cancer and Modern Degenerative Disorders”

lim ju boo, alias lin ru wu

(林 如 武)

 I published an article on: 

Unlocking the secrets of a longer life through nutrition here: 

https://scientificlogic.blogspot.com/2026/03/unlocking-secrets-of-longer-life.html

About a week ago, I read an article in Straits Times that more young adults and teens in Singapore being diagnosed with cancer here: 

https://www.straitstimes.com/singapore/health/more-young-adults-teens-in-singapore-being-diagnosed-with-cancer

So I thought I should continue on this subject the reasons why more young adults, teens in Singapore are being diagnosed with cancer.

 

We shall look at how the abundance of nourishment becomes toxic that drives cancer and modern degenerative disorders.

For most of human history, hunger was the greatest threat to survival. The human body evolved under conditions of scarcity, uncertainty, and intermittent food supply. Our physiology is therefore exquisitely designed to conserve energy, store excess calories efficiently, and protect us from starvation. Fat storage, insulin signalling, and powerful appetite mechanisms were all evolutionary advantages in a world where the next meal was never guaranteed.

In the modern world, however, this same biological machinery is exposed to a radically different environment. Food is continuously available, heavily processed, highly palatable, and calorically dense. What was once a survival system has become chronically overstimulated. The result is a profound mismatch between ancient biology and modern abundance, a mismatch that lies at the heart of the global epidemic of obesity, cancer, diabetes, cardiovascular disease, and other chronic degenerative disorders.

Over the past seventy years, epidemiological data from almost every region of the world reveal a remarkably consistent pattern. As societies move from traditional diets toward Western-style eating,  characterized by excessive calories, refined carbohydrates, animal fats, sugary beverages, and ultra-processed foods, rates of obesity and metabolic disease rise sharply. This transition has been observed in North America and Europe since the mid-twentieth century, and more recently across China, India, Southeast Asia, and the Middle East. Within one or two generations, populations that once had low rates of cancer and diabetes now exhibit disease profiles similar to those of industrialized nations.

Among all lifestyle-related risk factors, obesity has emerged as one of the most powerful predictors of cancer, second only to smoking. The World Health Organization and the International Agency for Research on Cancer now recognize excess body fat as a causal factor in at least thirteen different malignancies, including colorectal, postmenopausal breast, pancreatic, liver, kidney, esophageal, endometrial, ovarian, and thyroid cancers. The steady rise in these cancers across decades parallels almost perfectly the rise in average caloric intake and body mass index in modern populations.

At first glance, it may seem paradoxical that something as natural as eating,  the very act that sustains life,  could eventually promote cancer and degeneration. The explanation lies not in eating itself, but in chronic metabolic excess sustained over long periods of time. The human body is not designed for a permanent nutritional surplus. When energy intake continuously exceeds energy expenditure, the entire internal environment of the body is altered in subtle but profound ways.

Adipose tissue, once thought to be inert fat storage, is now known to function as a highly active endocrine and immune organ. In states of obesity, fat cells secrete a wide range of inflammatory cytokines, including tumor necrosis factor-alpha and interleukin-6, while attracting immune cells that further amplify inflammation. This produces a state of chronic low-grade systemic inflammation, a biological background noise that quietly damages tissues, alters immune surveillance, and creates a micro-environment favorable for malignant transformation. Cancer, in many respects, thrives in inflammatory soil.

At the same time, chronic overeating leads to persistently elevated blood glucose and insulin levels. Insulin is not merely a metabolic hormone; it is also a potent growth signal. Together with insulin-like growth factor 1 (IGF-1), it activates intracellular pathways that stimulate cell proliferation, inhibit programmed cell death, and promote angiogenesis. These same signals that help tissues grow and regenerate under normal conditions become dangerous when permanently activated. Cancer cells, in effect, hijack the body’s own growth machinery and use it to fuel uncontrolled expansion.

Hormonal changes add another layer of risk. In postmenopausal women, adipose tissue becomes the primary source of estrogen through the action of the enzyme aromatase. Higher levels of circulating oestrogen are strongly linked to increased risks of breast, endometrial, and ovarian cancers. Obesity thus transforms fat tissue into a chronic endocrine stimulator of hormone-sensitive tumors.

At a deeper biochemical level, chronic overnutrition drives excessive mitochondrial activity. The continuous breakdown of large quantities of glucose, fats, and proteins generates increased amounts of reactive oxygen species,  free radicals such as superoxide and hydrogen peroxide. These molecules are highly unstable and chemically aggressive. Over time, they damage DNA, proteins, and cell membranes through oxidative stress. The cumulative effect across decades is progressive molecular injury, genetic mutations, and increasing genomic instability,  the fundamental substrate from which cancer arises. In this sense, chronic overeating leads to a kind of slow internal “metabolic rusting” of the body.

Cancer cells themselves are particularly adept at exploiting this nutrient-rich environment. Unlike normal cells, they preferentially rely on glycolysis even in the presence of oxygen, a phenomenon known as the Warburg effect. They consume large amounts of glucose, amino acids such as glutamine, and lipids to support rapid division. Modern diets, rich in refined sugars and continuous caloric supply, create an ecological niche that actively feeds malignant cells. Cancer is therefore not only a genetic disease, but also a metabolic and ecological one, shaped by the internal environment in which cells exist.

Beyond total calorie load, the nature of modern food plays an important role. Processed meats are now classified by the IARC as Group 1 carcinogens, with strong evidence linking them to colorectal cancer through the formation of nitrosamines and oxidative damage. Ultra-processed foods, increasingly dominant in modern diets, have been associated with higher risks of overall cancer, cardiovascular disease, and metabolic disorders. These foods introduce preservatives, emulsifiers, endocrine-disrupting chemicals, advanced glycation end-products, and microbiome-altering compounds into the body,  all of which may subtly contribute to inflammation, insulin resistance, and carcinogenesis.

The consequences of chronic over nutrition extend far beyond cancer. Type 2 diabetes arises when pancreatic beta cells eventually fail under relentless insulin demand. Cardiovascular disease develops as excess lipids and glucose damage blood vessels, leading to atherosclerosis, heart attacks, and strokes. Fatty liver disease, now one of the most common liver disorders worldwide, progresses silently from simple fat accumulation to inflammation, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Even neurodegenerative conditions such as Alzheimer’s disease are increasingly linked to insulin resistance and metabolic dysfunction within the brain.

Seen from a systems perspective, chronic disease in modern society represents a state of continuous biological overstimulation without recovery. The body is forced into permanent digestion, permanent insulin signalling, permanent oxidative metabolism, and permanent cellular proliferation. Yet biological systems evolved around rhythms , feeding and fasting, activity and rest, growth and repair. When these rhythms are lost, regulation breaks down. Repair mechanisms cannot keep pace with damage, and degeneration becomes inevitable.

At a deeper philosophical level, the modern epidemic of chronic disease may be understood as a consequence of violating the metabolic design limits of the human organism. We were shaped by biological evolution - one of my areas of my interest -  for sufficiency, not excess; for periodic nourishment, not constant intake; for balance, not permanent abundance. What was once life-sustaining becomes, when sustained without restraint, slowly life-eroding.

In this sense, over nourishment through over eating - perhaps among young adults and youth in wealthy Singapore as reported in the Straits Times - is not merely a matter of calories and waistlines. It is a biological, ecological, and even civilizational problem. The same abundance that symbolizes human progress now quietly undermines human health. Too little food kills quickly. Too much food, over decades, kills silently. And between these two extremes lies the fragile metabolic harmony upon which long life and genuine health ultimately depend.

Briefly Summarized:

At a deeper level, cancer and chronic diseases  emerging  in rich modern society, such as in Singapore as reported in the Straits Time -  is not simply a medical problem,  it is a civilizational pathology. We have created an environment where:

Food is abundant but biologically alien

Eating is constant but fasting is forgotten

Growth is promoted but repair is neglected

Cancer, diabetes, and cardiovascular disease may therefore be understood not only as biological failures, but as signals that we have exceeded the metabolic design limits of the human organism.

In that sense, too much nourishment, sustained long enough, becomes a form of slow biological toxicity.

Not starvation kills us,  but so does excess without restraint.

Below are some strong, well-established references I like to cite for medical researchers, nutritionists, dieticians, physicians and clinicians for their further knowledge:

 

Key Epidemiological and Scientific

References (Foundational)

1. Obesity and Cancer IARC (2016) – Body Fatness and Cancer
International Agency for Research on Cancer Monograph.

2. WHO (2022) – Obesity and Overweight Fact Sheet

3. Renehan et al., Lancet (2008) – Body-mass index and incidence of cancer.

4.  Ultra-Processed Foods

5. Fiolet et al., BMJ (2018) – Consumption of ultra-processed foods and cancer risk.

6. Srour et al., BMJ (2019) – Ultra-processed food intake and cardiovascular disease.

7. Insulin / IGF-1

8. Pollak, Nature Reviews Cancer (2008) – Insulin and IGF signalling in neoplasia.

9. Oxidative Stress

10. Valko et al., International Journal of Biochemistry & Cell Biology (2007) – Free radicals and antioxidants in normal physiology and disease.

11. Metabolic Syndrome

12. Grundy et al., Circulation (2005) – Diagnosis and management of metabolic syndrome.

Integrative Medicine: Beyond the Silver Bullet. How Integrative Medicine Is Transforming Modern Healthcare.

 Integrative Medicine: Beyond the Silver Bullet. How Integrative Medicine Is Transforming Modern Healthcare.

 

https://medium.com/@medicaldiscovery1/integrative-medicine-beyond-the-silver-bullet-08532ab3e01f?postPublishedType=initial

 

Unlocking the Secrets of a Longer Life Through Nutrition

Caloric Restriction and Longevity: Unlocking the Secrets of a Longer Life

When I was studying for my postgraduate in nutrition in the mid 1960's  at the University of London, I first heard from one of my senior  professors there that caloric restriction extends the lifespan of rats as shown by Clive McCay. 

Let me now extend this knowledge I gained to share it with readers here. 

The quest to understand how we age, and whether we can slow it down, has intrigued scientists for generations. Among the many strategies studied, caloric restriction (CR), the practice of reducing daily caloric intake without malnutrition, stands out as one of the most consistently effective interventions for extending lifespan in various organisms. From its humble beginnings in laboratory rats to the frontiers of human aging research, CR has opened a promising window into the biology of aging.

The Pioneering Discovery

The roots of caloric restriction research trace back to 1935, when Dr. Clive McCay and colleagues at Cornell University made a groundbreaking observation. In their experiments with rats, they found that animals fed a reduced-calorie diet, introduced after weaning and sustained throughout life, lived significantly longer than those given unrestricted access to food. More than just living longer, these rats also showed delayed onset of diseases and signs of healthier aging.

At the time, McCay hypothesized that the longevity observed might be due to slower growth, which conserved energy and metabolic wear. This idea was later refined by researchers like Berg and Simms in the 1960s, who proposed that the life-extending effects of CR might be more closely related to lower body fat and metabolic efficiency rather than growth alone.

Expanding Horizons: CR Across the Tree of Life

The decades that followed saw a proliferation of research, expanding to many different organisms. The consistent pattern that emerged was striking: caloric restriction, when properly administered, could extend lifespan and delay aging in a wide range of species.

In rodents, the evidence was especially robust. Mice and rats on calorie-restricted diets lived up to 40–50% longer than their ad libitum-fed counterparts. These animals also showed reduced incidence of cancer, diabetes, cardiovascular disease, and age-related cognitive decline.

Research extended to simpler organisms such as yeast, worms, and fruit flies, where CR also conferred significant longevity benefits. These findings suggested that the biological response to caloric restriction might be evolutionary conserved—a shared survival mechanism hardwired into the fabric of life.

Studies in non-human primates, especially rhesus monkeys, brought CR research closer to human relevance. Two prominent long-term studies, one conducted by the National Institute on Aging (NIA) and the other by the University of Wisconsin-Madison, both demonstrated improved health outcomes in calorie-restricted monkeys, such as reduced risk of cancer, diabetes, and cardiovascular disease. However, results differed in terms of overall lifespan extension, suggesting that other variables like diet composition and feeding protocols also play key roles.

Delving Into the Biology: How CR Might Work

As researchers explored how CR works, several biological mechanisms were proposed. Though no single explanation can account for all effects, several interconnected processes seem to underlie the benefits of caloric restriction:

1. Reduced Metabolic Rate and Oxidative Stress
CR appears to lower the body’s metabolic rate, thereby reducing the production of harmful reactive oxygen species (ROS). These molecules, often byproducts of energy metabolism, can damage cells and tissues over time, accelerating the aging process. By decreasing oxidative stress, CR may slow the biological clock.

2. Improved Insulin Sensitivity
Caloric restriction improves how the body responds to insulin, lowering blood sugar levels and reducing the risk of type 2 diabetes. Enhanced insulin sensitivity is also linked to better cellular energy management and less systemic inflammation.

3. Activation of Autophagy
CR promotes autophagy, a cellular housekeeping process where damaged or unneeded components are broken down and recycled. This function is essential for cellular renewal and protection against age-related dysfunction.

4. Suppression of the mTOR Pathway
One of the most studied pathways influenced by CR is the mechanistic target of rapamycin (mTOR) pathway. mTOR plays a central role in regulating growth, metabolism, and aging. Caloric restriction inhibits mTOR activity, which is associated with increased lifespan and protection against age-related diseases.

5. Hormetic Response and Stress Resistance
CR may induce a mild biological stress, prompting the body to activate protective mechanisms, a concept known as hormesis. This “adaptive stress” can strengthen cells and improve resistance to disease.

6. Lowered Inflammation
Chronic inflammation is a major driver of aging and many age-related diseases. CR has been shown to reduce systemic inflammation and enhance immune function.

Caloric Restriction in Humans: Evidence and Challenges

While caloric restriction has clearly shown benefits in animals, translating these findings to humans is more complex. Long-term CR studies in humans are rare due to ethical and practical challenges. However, short-term trials and observational studies offer valuable insights.

The CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) study, one of the most important human trials, demonstrated that even moderate CR (about 12% over two years) led to improvements in several biomarkers of aging. Participants showed reduced fasting insulin levels, lower core body temperatures, decreased oxidative DNA damage, and improved cholesterol profiles.

Observational evidence also supports CR’s potential role in longevity. The Okinawan population of Japan, known for their exceptional longevity and low rates of chronic diseases, traditionally consumed a diet lower in calories than mainland Japanese or Americans. While cultural and genetic factors certainly contribute, their diet likely played a role.

Despite these promising signs, the impact of CR on human lifespan extension is thought to be modest, perhaps slowing the biological aging process by 2–3% and reducing the risk of early death by 10–15%. This effect is small compared to the gains achieved through modern medicine and public health interventions such as antibiotics, vaccines, and cardiovascular care.

Caution and Considerations

While CR shows potential, it is not without risks. Prolonged or extreme calorie reduction may lead to:

Nutritional deficiencies

Bone and muscle loss

Impaired immune response

Fertility issues

Psychological effects such as irritability, fatigue, and anxiety

Moreover, studies have shown that excessively low body mass index (BMI) in older adults can actually increase mortality risk. A balanced approach, ensuring adequate nutrient intake and avoiding undernutrition, is essential.

Emerging Alternatives: Beyond Traditional CR

Given the difficulties of adhering to strict CR, scientists are investigating alternative dietary strategies that might offer similar benefits:

Intermittent Fasting (IF): Patterns such as time-restricted feeding or alternate-day fasting can mimic the metabolic effects of CR and may improve longevity-related markers.

Protein and Amino Acid Restriction: Limiting certain amino acids, especially methionine, appears to activate some of the same longevity pathways affected by CR, including mTOR inhibition.

CR Mimetics: Compounds like resveratrol, metformin, and rapamycin are being explored for their ability to mimic the effects of CR without dietary changes. While promising, these approaches are still in early stages of research. 

A Window into the Aging Process

Caloric restriction remains one of the most compelling biological tools for understanding the aging process. It has consistently extended lifespan and delayed disease in a wide range of animals. In humans, it shows promise in improving health markers and reducing age-related risks, although its effects on lifespan are likely smaller.

As science continues to unravel the intricate mechanisms of aging, CR has helped pave the way for new therapeutic strategies, whether through diet, fasting, or pharmacological mimetics. Until then, the most practical advice remains: eat moderately, choose nutrient-rich foods, and maintain a lifestyle that supports both physical and mental well-being.

A longer, healthier life may not come from eating less alone, but it may begin there.

Further Reading and References

1. McCay, C. M., Crowell, M. F., & Maynard, L. A. (1935). The effect of retarded growth upon the length of life span and upon the ultimate body size. Journal of Nutrition, 10, 63–79.

2. Fontana, L., & Partridge, L. (2015). Promoting health and longevity through diet: from model organisms to humans. Cell, 161(1), 106–118.

3. Colman, R. J., et al. (2009). Caloric restriction delays disease onset and mortality in rhesus monkeys. Science, 325(5937), 201–204.

4. Mattison, J. A., et al. (2012). Impact of caloric restriction on health and survival in rhesus monkeys. Nature, 489, 318–321.

5. Redman, L. M., et al. (2018). Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of living and oxidative damage theories of aging. Cell Metabolism, 27(4), 805–815.

6. Most, J., Tosti, V., Redman, L. M., & Fontana, L. (2017). Calorie restriction in humans: An update. Ageing Research Reviews, 39, 36–45.

 

 

 

 

A Violin, a Teacher, and an Orchestra: Memories of Music in Calcutta

 A Violin, a Teacher, and an Orchestra: Memories of Music in Calcutta

 by blogger lim ju boo, alias  lim ru wu  (林 如 武)

When I look back on my student days in the early 1960s in Calcutta (now - Kolkata), I realize that some of the most precious memories of that period were not confined to my academic studies. Alongside the long hours devoted to medicine and science, there existed another world that nourished the spirit, a world filled with music.

During those years I had the privilege of learning the violin under the guidance of the distinguished violinist Stanley Gomes. At that time he served as the concertmaster - the leader and 1^st violinist of the Calcutta Symphony Orchestra, which performed under the baton of conductor Bernard "Bunny" Jacob.

Under Stanley Gomes’ kind and patient instruction I studied the violin until I reached Grade 6 of the examinations conducted by the Associated Board of the Royal Schools of Music.

My lessons took place once a week at his home. Each lesson lasted about an hour. I would travel there from my student hostel carrying my violin, usually after spending many evenings practising scales and études in my room.

Despite his reputation as a very famous violinist and the leader of the city’s orchestra, Stanley Gomes was an extraordinarily humble, jovial, and friendly man. There was not the slightest hint of pride in him. He spoke warmly, laughed easily, and taught with the patience of someone who truly loved music and enjoyed sharing it with younger students. I remember asking him to transcribe the song "Roses of Picady" a British ballad composed by Haydn Wood into musical notations for me to play on the violin, he immediately obliged into sheet music without difficulty. 

He even introduced me briefly to the piano. For a short period he showed me how to play it, but the violin had already captured my heart and remained the instrument on which I focused my efforts.

Those weekly lessons were not limited to technical instruction. Very often he would speak about orchestras—their structure, their discipline, and the remarkable cooperation required for so many musicians to perform together as one.

For readers who may wish to visualize how musicians are arranged on stage, a typical orchestral seating plan can be seen here:

 

https://en.wikipedia.org/wiki/Orchestra#Seating_arrangement

 

The arrangement of musicians in a symphony orchestra is the result of centuries of musical evolution. The string section—violins, violas, cellos, and double basses, sits closest to the audience and forms the foundation of the orchestra’s sound. Traditionally the first violins sit to the conductor’s left while the second violins sit on the opposite side. Violas occupy the centre area, with cellos and double basses usually placed to the right.

Behind the strings sit the woodwind instruments—flutes, oboes, clarinets, and bassoons, whose voices add colour and expressive nuance. Further back are the brass instruments - horns, trumpets, trombones, and tubas; capable of producing majestic power when required. At the rear of the orchestra are the percussionists, whose instruments provide rhythmic energy and dramatic emphasis.

At the centre front stands the conductor, guiding the orchestra with gestures of the baton. Yet among the musicians themselves the most important leader is the concertmaster— the principal first violinist.

In the Calcutta Symphony Orchestra, that leader was Stanley Gomes.

The concertmaster plays a crucial role in shaping the sound of the string section. One of the most fascinating aspects of orchestral performance is the synchronized movement of the violinists’ bows. To the audience it appears almost magical that dozens of bows move up and down together in perfect harmony.

This unity is not accidental. The bowing directions—up-bow and down-bow—are usually marked in the music (printed sheet music) but they are often modified during rehearsals. The concertmaster determines the bowings that will best shape the sound and phrasing of the section.

A down-bow generally produces a stronger tone because the bow begins near the frog where the player’s hand applies more weight. An up-bow often creates a lighter sound. By carefully choosing bow directions, the leader ensures that the entire violin section speaks with a single expressive voice.

During performance the violinists watch the concertmaster’s bow through peripheral vision. If the leader changes direction, the section follows immediately. The goal is not strict obedience to the printed page but unity of sound and movement.

There are exceptions, of course. In passages marked divisi, the violinists split into separate musical lines and their bowings may differ. Sometimes the first and second violins even bow in opposite directions because their musical phrases require different articulation. In rare situations a conductor may ask for “free bowing,” allowing players to change bow direction independently in order to produce an especially smooth, continuous tone.

Yet most of the time the bows rise and fall together with graceful precision. Watching the violinists can feel almost like observing a corps de ballet, their movements forming a silent choreography that mirrors the music.

During my student years I often had the pleasure of attending concerts by the Calcutta Symphony Orchestra at the historic Empire Theatre. Those evenings remain among the most vivid memories of my youth.

Sometimes the orchestra performed symphonies, and at other times the concerts featured visiting foreign soloists—perhaps a violinist performing a concerto, a brilliant pianist appearing as guest soloist, or occasionally a soprano whose voice soared above the orchestra.

For a young violin student these performances were deeply inspiring. I watched the musicians carefully, observing the unity of their playing and the effortless leadership of Stanley Gomes at the front of the violin section.

Years later I had the pleasure of corresponding with his son, Ian Gomes. I had known Ian when he was still a young boy in Calcutta. He later became a very accomplished pianist and eventually worked in London as a pianist at the famous The Ritz London.

Like many musicians, he had first been taught by his father. Writing to him after so many years brought back a flood of memories of those earlier days—of his father’s warm personality and the music that had filled those years of my youth.

But perhaps my most vivid memory remains one particular evening at the Empire Theatre.

The orchestra had gathered on stage, and the audience waited in quiet anticipation. Stanley Gomes stood at the front of the violin section, and the conductor raised his baton. The concerto began softly, almost like a whisper.

Then the solo violin entered.

Its sound rose gently above the orchestra—clear, singing, and luminous. The violin seemed to speak in a human voice, at times tender and reflective, at times soaring with passion. Beneath it the orchestra breathed like a living organism, supporting and answering the soloist’s phrases.

The bows of the violinists moved together like a field of wheat swaying in the wind.

For a young student like me sitting quietly in the audience, that moment felt almost magical. It was as if the entire orchestra had become a single instrument—many musicians united by discipline, listening, and shared purpose.

Even now, many years later, whenever I think of orchestral music, my mind returns to that stage in Calcutta, to the sound of that violin concerto, and to the gentle guidance of Stanley Gomes.

A few years later as a postgraduate student at the University of London Queen Elizabeth College, I had a good fortune with the help of British Council,  to listen to Yehudi Menuhin (1916 - 1999),  who was the world most famous violinist during his time,  performed   Beethoven's two Romances for Violin and Orchestra (No. 1 in G major and No. 2 in F) on April 26, 1966 for his 50th birthday with the London Symphony Orchestra at the Royal Festival Hall. It was so amazing to watch him play the violin. The violin was just like a toy to him. 

For alongside science and medicine, music too has the power to shape a life—and to leave behind memories that resonate long after the final note has faded.

Today it gives me much joy playing the violin - thanks to the dedication of Stanley Gomes. 

The Joy of Playing a Violin 

https://scientificlogic.blogspot.com/search?q=joy+of+playing+violin

A Quiet Reflection Before the Next Dawn: When Science Meets the Human Heart”

“A Quiet Reflection Before the Next Dawn: On Science and the Human Heart”

Dear Friends,

I could not sleep the entire night.

As I lay awake in the quiet stillness before dawn, I found myself wondering what subject I should write next in my blog. Many ideas came and went, but none seemed to settle comfortably in my mind.

Just before Chap Goh Meh ended at midnight, the final evening of the Chinese New Year celebrations — I took out my German violin, the one that cost me RM 65,000, and played ten different Chinese New Year songs.

To my ears, they sounded quite horrible.

I have not played my violin for at least eight months. When one loses daily practice, the fingers lose their memory. The delicate precision of fingering falters. Intonation suffers. The bow no longer glides with confidence. And with my poor eyesight, I struggled to read the musical notes on the sheet music, those little black symbols that look like “taugay” or bean sprouts to anyone without musical training.

In my younger days, I passed Grade 6 in violin performance and also in music theory under the Associated Board of the Royal Schools of Music (ABRSM) in England. That foundation has always remained precious to me.

But a violinist rarely plays alone. A violinist is usually accompanied by a pianist — or better still, surrounded by fellow violinists within an orchestra, blending with violas, cellos, double basses, woodwinds, brass, and percussion. Music, especially orchestral music, is a communal experience.

Years ago, I was a member of the Symphony Club of the Malaysian Philharmonic Orchestra. I played together with other violinists in symphonic settings. The collective sound, the harmony, the shared breathing of the orchestra — that was music in its full glory. I have since lost touch for many years.

That is why, perhaps, it sounded so harsh to me, playing alone after months of neglect, without accompaniment, without the warmth of an orchestra.

I own four violins. This German violin is the most expensive of them all, almost the cost of a small car. Yet the price of an instrument does not guarantee beauty of sound. Only disciplined practice, sensitive listening, and musical companionship can do that.

If you ask me honestly, I would say I prefer being a violinist rather than being a research scientist or a doctor. Medicine and research were my profession. Music is my love.

Just like astronomy — another passion of mine. Even after retirement, I studied astronomy at Oxford, simply for the joy of learning and looking up at the heavens.

Perhaps life is not only about achievement, titles, or productivity. Perhaps it is also about returning, again and again, to the things that make our hearts quietly happy, even if, at times, they sound imperfect.

If you would like to read more about my reflections on music and the violin, do visit my earlier write-up:

“The Joy of Being A Violinist”

https://scientificlogic.blogspot.com/search?q=joy+of+playing+violin

 

With warm regards in the stillness of this pre-dawn hour

From Molecule to Medicine: The Hidden Army of Scientists Behind Every New Drug

I have already written an article on the various scientists involved in the development of new drugs here in this link:

https://scientificlogic.blogspot.com/2025/04/the-immense-contributions-of-scientists.html

It was written and published in this blog of mine on Wednesday, April 9, 2025

Yesterday, on 2^nd March 2026 - towards the end of Chinese New Year of the Horse we get readers in WhatsApp chat group asking me almost the same issue on who are the scientists who develop drugs for medical doctors to prescribe for their patients?

Let me on this last day of CNY in Chinese Hokkein dialect  called “Chap Goh Mei” in  rewrite my article in a different language style and in greater technical depths  for  doctors, biomedical scientist, their patients and also for curious,  but highly knowledgeable and intelligent ordinary readers. Below is my rewritten version entitled:  

 

From Molecule to Medicine: The Hidden Army of Scientists Behind Every New Drug

Technical Abstract for Medical Doctors and Biomedical Scientists.

 

Technical Abstract

 

Modern drug discovery and development is a multidisciplinary, capital-intensive, and highly regulated enterprise requiring 10–15 years of coordinated scientific effort and investments frequently exceeding several billion US dollars per approved therapeutic agent. The process encompasses target identification and validation, hit discovery, lead optimization, preclinical pharmacology and toxicology, clinical development (Phases I–III), regulatory review, large-scale manufacturing, and post-marketing pharmacovigilance.

This article provides a comprehensive overview of the scientific ecosystem underlying pharmaceutical innovation, detailing the expertise, methodologies, regulatory frameworks, computational tools, and educational backgrounds of the diverse specialists involved — including molecular biologists, medicinal chemists, pharmacologists, toxicologists, pharmacokineticists, formulation scientists, analytical chemists, biostatisticians, clinical investigators, pharmaceutical engineers, quality assurance professionals, regulatory affairs experts, and emerging artificial intelligence scientists. Emphasis is placed on the translational continuum from molecular design to population-level therapeutic deployment, highlighting the scientific rigor, attrition rates, compliance standards (GLP, GMP, GCP), and technological platforms that collectively enable safe and effective drug approval.

 

Main text for All Readers:

 

When a new medicine appears in a pharmacy, it looks deceptively simple,  a tablet in a blister pack, a vial for injection, a capsule in a bottle. Yet behind that small object lies 10 to 15 years of work, thousands of experiments, regulatory scrutiny across continents, and investments that often exceed several billion US dollars. What the public rarely sees is the vast multidisciplinary team of scientists whose combined expertise makes modern drug development possible.

Drug discovery and development is not the work of a lone genius in a laboratory. It is a coordinated scientific orchestra in which chemists, biologists, pharmacologists, toxicologists, clinicians, engineers, statisticians, and regulatory experts each play indispensable roles.

The journey begins in discovery laboratories, often long before a compound has a name.

In the earliest phase, disease biologists and molecular biologists identify a therapeutic target, typically a protein, receptor, enzyme, gene product, or signalling pathway believed to drive a disease. Their work relies on genomics, proteomics, transcriptomics, CRISPR gene editing, and advanced microscopy. They use software tools such as bioinformatics platforms (BLAST, Gene Ontology tools), pathway analysis systems (Ingenuity Pathway Analysis), and molecular databases to understand disease mechanisms at the cellular and molecular levels.

Once a viable target is identified, medicinal chemists enter the scene. These are specialists in organic and pharmaceutical chemistry who design and synthesize new chemical entities. Their task is intellectually demanding: they must design molecules capable of binding precisely to the biological target while maintaining favourable physicochemical properties such as solubility, stability, and membrane permeability. They use computer-aided drug design software such as Schrödinger Suite, MOE (Molecular Operating Environment), AutoDock, and molecular dynamics simulation tools. High-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry are essential laboratory instruments in their daily work.

Parallel to medicinal chemists, computational chemists and structural biologists use X-ray crystallography, cryo-electron microscopy, and AI-driven protein modelling tools to visualize target structures at atomic resolution. Structure-based drug design allows refinement of molecules into optimized “lead compounds.”

After promising compounds are synthesized, pharmacologists test them in vitro and in vivo. Pharmacologists study how drugs interact with biological systems and determine their mechanisms of action. Using cell-based assays, receptor binding studies, and animal models, they measure potency, efficacy, selectivity, and functional outcomes. Laboratory techniques include ELISA, Western blotting, flow cytometry, and electrophysiology. Their software tools often include GraphPad Prism for dose-response curves and statistical analysis platforms.

Simultaneously, pharmacokineticists — experts in drug metabolism and pharmacokinetics (DMPK) — examine how the body handles the compound. They study absorption, distribution, metabolism, and excretion (ADME). Using in vitro liver microsomes, hepatocyte assays, and in vivo animal studies, they determine half-life, bioavailability, clearance rates, and metabolic pathways. They frequently use modeling software such as Phoenix WinNonlin and physiologically based pharmacokinetic (PBPK) modeling platforms like GastroPlus or Simcyp.

Toxicologists then perform rigorous safety assessments. No matter how effective a molecule may be, unacceptable toxicity ends its development. Toxicologists conduct acute, sub-chronic, and chronic toxicity studies, genotoxicity testing, reproductive toxicity studies, and carcinogenicity assessments in animal models under Good Laboratory Practice (GLP) standards. Histopathology, clinical chemistry analysis, and organ system monitoring are routine. Safety pharmacology also examines effects on the cardiovascular, respiratory, and central nervous systems. Specialized assays such as hERG channel testing evaluate cardiac arrhythmia risk.

Once a compound demonstrates acceptable efficacy and safety in preclinical studies, it enters the clinical phase. Here, clinical research physicians and clinical pharmacologists design and oversee human trials. Phase I trials test safety and dosing in healthy volunteers. Phase II trials explore efficacy and dose-ranging in patients. Phase III trials involve large patient populations to confirm effectiveness and monitor adverse events.

Clinical research scientists coordinate trial logistics across hospitals and countries. Biostatisticians design the study protocols, calculate sample sizes, define endpoints, and perform complex statistical analyses to determine whether observed benefits are significant and clinically meaningful. They rely heavily on statistical software such as SAS, R, and SPSS. Data managers ensure data integrity, while clinical operations teams ensure compliance with Good Clinical Practice (GCP).

Throughout clinical development, pharmacovigilance experts monitor safety signals. They analyse adverse event reports and conduct risk-benefit assessments. After regulatory approval, this monitoring continues in Phase IV post-marketing surveillance.

While clinical trials proceed, formulation scientists work on transforming the active molecule into a usable medicine. A compound must not only be effective — it must remain stable, bioavailable, manufacturable, and convenient for patients. Formulation scientists determine excipient compatibility, optimize dissolution rates, control-release mechanisms, and ensure shelf stability. Techniques include differential scanning calorimetry (DSC), powder X-ray diffraction, and stability chambers under ICH guidelines.

Analytical chemists develop and validate methods to measure drug purity, potency, degradation products, and impurities at every stage. They ensure compliance with pharmacopeial standards (USP, EP, JP). Their instruments include HPLC, GC-MS, LC-MS/MS, UV spectroscopy, and capillary electrophoresis. Method validation follows strict regulatory requirements for accuracy, precision, specificity, and robustness.

When a drug approaches commercialization, pharmaceutical engineers and chemical engineers design large-scale manufacturing processes. Scaling up from milligram laboratory batches to multi-ton industrial production is a highly complex endeavor. Process engineers optimize reaction conditions, ensure reproducibility, manage heat transfer and solvent recovery, and design reactors compliant with Good Manufacturing Practice (GMP). Increasingly, they use process analytical technology (PAT) and continuous manufacturing systems.

Quality control scientists test every batch produced. Quality assurance teams oversee documentation, audits, and regulatory inspections. Regulatory affairs specialists compile massive dossiers, sometimes exceeding hundreds of thousands of pages — for submission to agencies such as the U.S. FDA, EMA in Europe, and other global regulatory authorities. They ensure compliance with international standards, interpret regulatory guidelines, and manage communication between the company and authorities.

Educationally, these professionals are highly trained. Medicinal chemists typically hold PhDs in organic chemistry or pharmaceutical sciences. Pharmacologists and toxicologists often hold PhDs or MD / PhDs. A PhD in Medicine is far, far more advanced and sophisticated  than just an ordinary MD. 

Clinical investigators are medical doctors with research training. Biostatisticians possess advanced degrees in statistics or biostatistics. Pharmaceutical engineers are trained in chemical or biochemical engineering. Regulatory affairs professionals may come from pharmacy, law, or biomedical science backgrounds with specialized regulatory certification.

Increasingly, artificial intelligence and machine learning specialists are joining drug development teams. AI models assist in target identification, virtual screening, toxicity prediction, and clinical trial optimization. Software environments such as Python, TensorFlow, and machine learning frameworks are becoming integral tools.

Thus, the creation of a single medicine represents the coordinated labour of hundreds, sometimes thousands  of highly specialized professionals over more than a decade. Many promising compounds fail along the way. Only a small fraction of molecules entering preclinical testing ever reach approval. This high attrition rate contributes significantly to the enormous cost of drug development.

Yet despite the complexity and cost, this multidisciplinary enterprise has given humanity antibiotics, vaccines, targeted cancer therapies, immunotherapies, antivirals, and life-saving biologicals and biosimilars. Each pill carries within it not merely chemical ingredients, but the cumulative knowledge of molecular biology, organic chemistry, physiology, engineering, statistics, ethics, and regulatory science.

Happy and A Blessed  Chap Goh Mei to all my interested readers

The Lady of the Moon in Chinese mythology is called  Change's  (嫦娥, pronounced Cháng-é). 

Here are the key details about her name and story:

Original Name: She was originally called Heng'e (姮娥, Héng'é), but her name was changed to Chang'e due to a naming taboo during the reign of Emperor Wen of Han. She is said to live in the Guanghan Palace (廣寒宮, Vast-Cold Palace) on the moon. She is accompanied by the Jade Rabbit (玉兔, Yù Tù), who pounds the elixir of life, and sometimes a toad.

The Year of the Rabbit is also my year of Birth in Batu Pahat, Johore, Malaya, then called

Look up for her tonight on Chap Goh Mei, shinning in all her glory. 

Coincidentally, there is a lunar eclipse tonight, but the moon is below the horizon part of time over Kuala Lumpur and Malaysia. By the time the moon at maximum eclipse rises over the horizon in Malaysia, it is 7:33:46 pm. The full eclipse ends at 8:02:49 pm and the eclipse  penumbra phase ends at 10:23:06 pm. Only certain parts of the world  the full lunar eclipse is visible from beginning to finish.     

-   Lim ju boo

3^rd March, 2036