Will AI find better medicines than the miracle drugs we've been using since the Middle Ages?
Ari Massoudi
I do stuff enabling Mankind to live longer, stronger and smarter ?????????=>??
The Journey of Metformin from Diabetes to Cancer to Life Extension
Imagine a world where a single pill could revolutionize the way we think about health and aging. Welcome to the captivating story of metformin, a drug that has been quietly transforming lives for over a century.
In the roaring twenties, a misunderstanding captivated the medical world. Physicians believed that the plunge in blood sugar levels following thyroid removal was due to a surge in guanidine, a molecule derived from urea. This led to an intriguing hypothesis: could an infusion of guanidine lower blood sugar levels? Meanwhile, a French chemist, Charles Tanret, had just isolated galegine, a guanidine derivative, from a plant known as Galega officinalis.
Rewind to the Middle Ages, where Galega officinalis, or goat's rue, was a staple in medieval medicine cabinets. This humble plant was prescribed to alleviate the intense thirst and frequent urination that accompanied the symptoms of the affection known far later as diabetes. It was even used during the dreaded plague epidemics to induce sweating, believed to be a sign of healing.
The Birth of a Medical Marvel
Metformin’s journey began in 1922, when it was first synthesized. Originally, researchers were exploring its potential as a treatment for malaria. However, fate had other plans. As scientists delved deeper, they discovered that metformin had an unexpected side effect: it could lower blood sugar levels. This serendipitous finding set the stage for metformin’s future as a groundbreaking diabetes medication.
Fast forward to the early 20th century, where the structure of galegine was finally unveiled in 1923. It was a breakthrough - galegine was less toxic than guanidine, sparking hope for a new diabetes treatment. But the path to a viable drug was fraught with challenges. Early pharmacological experiments showed promise but also revealed variability in responses and a frustratingly short duration of action.
By the late 1950s, metformin had become a go-to drug for treating type 2 diabetes. It wasn't until the late 1950s that biguanides made a comeback. Two German diabetologists, Hellmuth Mehnert and Walter Seitz, championed a new biguanide for type II diabetes treatment. Then, in 1959, a French scientist named Jean Sterne presented a groundbreaking finding to the French Society of Therapeutic Chemistry. N,N-dimethyl-guanyl guanidine, or metformin, was a game-changer. It worked wonders for patients who weren't very responsive to insulin or had unstable diabetes.
But the story doesn’t end there. Researchers, driven by curiosity and the desire to uncover more, continued to explore metformin’s potential. They found that this little pill was far more than just a diabetes treatment; it was a multitasker with a plethora of hidden talents.
Unraveling the Mysteries of Metformin
Metformin doesn’t force the pancreas to produce more insulin. Instead, it targets insulin resistance, the underlying problem in type 2 diabetes. By helping the body use insulin more effectively, metformin allows cells to work smarter, not harder. This unique mechanism of action makes it a safer option, as it doesn’t cause dangerous low blood sugar levels, a common side effect of other diabetes medications.
But metformin’s magic doesn’t stop at diabetes. It affects the mitochondria, the powerhouses of our cells, by tweaking their machinery. This fine-tuning leads to a cascade of downstream effects, influencing how cells utilize glucose and fat, and how they respond to stress.
The Power of AMPK
One of the key players in metformin’s story is AMPK, or AMP Activated Protein Kinase. Think of AMPK as the cell’s energy sensor. When energy levels dip, AMPK gets activated, signaling the cell to conserve energy and ramp up efficiency. Metformin is a potent activator of AMPK, sending a signal to our cells to get their energy management in check.
The Gut Connection
Metformin’s reach extends beyond the cellular level. It can change the composition of our gut bacteria, promoting the growth of beneficial bacteria while reducing harmful ones. This is crucial, as a healthy gut microbiome is linked to overall well-being. Metformin also stimulates the release of GLP-1, a hormone that helps regulate insulin secretion and appetite.
Beyond Diabetes: The Future of Metformin
The potential benefits of metformin are staggering. Research suggests that it may protect the heart by improving endothelial function, the lining of our blood vessels. This keeps blood flowing smoothly and reduces the risk of heart attacks and strokes.
But perhaps the most intriguing aspect of metformin research is its potential role in fighting cancer. Epidemiological studies have shown that diabetic patients taking metformin have a lower risk of developing certain types of cancer. This is thought to be due to metformin’s impact on insulin and IGF-1 signaling, as well as its ability to interfere with the abnormal energy metabolism of cancer cells.
Protecting the Brain and Slowing Aging
Metformin’s potential extends to neuroprotection, with emerging research suggesting it may help protect against neurodegenerative diseases like Alzheimer’s. By reducing oxidative stress and inflammation, and affecting cellular energy pathways, metformin could offer protection against cognitive decline.
And if that wasn’t enough, metformin is also being studied for its potential to slow down the aging process. The TAIM study (Targeting Aging with Metformin) is directly assessing whether metformin can delay age-related diseases and extend lifespan in humans.
The Role of AI in Drug Discovery
While the discovery of metformin was largely based on serendipity and empirical practice, the future of drug discovery lies in artificial intelligence (AI). AI can analyze vast amounts of data, identify patterns, and predict outcomes with unprecedented accuracy. This could revolutionize the way we discover and develop new medications, making the process faster, more efficient, and more targeted.
If researchers had access to AI during the early days of metformin, the history of this drug might have been very different. AI could have accelerated the discovery of metformin’s multiple mechanisms of action, identified its potential benefits beyond diabetes, and even predicted its impact on the environment. The story of metformin would have been one of precision and foresight, rather than serendipity and incremental discovery.
If you're interested by AI-driven drug discovery ??????
ITW Dr. Ivan De Weber, PhD - Cofounder-CEO at Cortex Discovery
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?? From Academia to AI-Powered Drug Discovery
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