Here to stay — inside the complex and fascinating world of biotech-crafted medicines
Part one: stories beyond molecules
Cell cultures, bioreactors, peptides, macromolecules. You can visualize the dance of the bio-molecules, how they bond, and how they form intricate interactions in our bodies. You can see the protein forming. You start envisioning its engineering, until it becomes the targeted therapy that can be delivered to a patient suffering from a life-threatening disease. You are not new to biotechnology.
But if peptides, macromolecules, and proteins sound like words coming straight out of a chemistry lab, buzzing in your ear and triggering your curiosity — then you have come to the right place. You are about to learn amazing facts about biopharmaceuticals. Just like I did, a few months ago when I started working at GE Healthcare Life Sciences.
For someone who lacks a first-hand account of the industry, biotechnology is the enabler of biopharmaceuticals. Also known as “biologics”, biopharmaceuticals are sophisticated therapies developed in living systems that enable new therapies with less side effects. Over the past three decades, their popularity as efficient treatments for many diseases including certain cancers, diabetes, and rheumatoid arthritis has grown so much that they now represent almost 30% of the pharmaceutical market. According to current predictions, in the next decade, 50% of all medicines in development will be biopharmaceuticals.
A Wednesday to Remember
I meet Dr. Henrik Ihre during a training for new employees. He is the Director of Custom Consumables at GE Healthcare Life Sciences, and one of the most knowledgeable scientists I’ve met. “We have to look at molecule sources to better understand our role in the overwhelmingly complex ecosystem of biopharma,” he tells me, as he prepares me for a back-to-school trivia.
“What is a medicine?” Henrik asks.
I am surprised at the apparent banality of the question which comes with a raised eyebrow, and a quirky smile. I am slightly hesitant at answering. A medicine is something that cures diseases and relieves pain, I reply.
“The truth is that most diseases cannot be cured. Medicines can treat diseases and alleviate symptoms. A medicine can also administered to prevent diseases and their spreading. With the continuous development of biopharmaceuticals, there is also potential for medicines to cure diseases that could not be cured in the past,” says Henrik.
“Is a medicine a molecule?”
No hesitation here. Yes! Is there anything that isn’t a molecule? I wonder.
“All living things around us are actually built from different molecules but not all matter is built from molecules,” he says. “So where do molecules come from?”
Understanding the source of molecules casts light on the complexity of medicines. And so it begins…
Rasputin and pig pancreas — a molecular connection
Most molecules come from nature. Since the dawn of time, people have been using natural remedies, like the salicylic acid, extracted from the bark of the willow tree, or snake venom, used to develop antidotes. Modern medicine was born in the 19th century when scientists learned to first synthesize molecules. This is often cited as the era of small-molecule or synthetic drugs — making synthetic processes to another source of molecules.
What exactly does a small molecule entail? I ask.
“Aspirin was among the first synthetic drugs on the market. Since it became commercially available in 1899, it’s been widely used as a wonder medicine to this day,” explains Henrik. I learn that small-molecule drugs remain the most common type of medicines, that most over-the-counter and even prescription drugs are predominantly synthetic. “Modern antibiotics, anti-depressives, and statins are among the drugs based on synthetic molecules.”
Despite their wide use, synthetic drugs have limitations in the treatment of life-threatening diseases, like hemophilia or diabetes.
“A famous account of the limitations of small molecule drugs goes back to Russia’s last tsar. His only son had hemophilia, and when doctors started treating him with aspirin, his condition aggravated. Rasputin advised the family to take him off the medication. The boy started feeling better and Rasputin rose to fame. Now it’s widely known that aspirin is a blood-thinning agent, which cannot be administered to patients with hemophilia,” says Henrik.
The 20th century is the time of revolutionary breakthroughs in biological medicines. “With the discovery of insulin in 1922, scientists started exploring the potential of protein-based therapies,” says Henrik. “In its early days, insulin was extracted from the pancreas of slaughtered pigs and cows. More than two tons of pig tissue and fluids were needed to obtain 200 grams of purified insulin.”
Decades later, in the 1970’s, the pioneering work on recombinant DNA technology ignites a strenuous journey to develop biopharmaceuticals. A new source of molecules — humans — or hybrids of human bio-molecules, are being used to develop insulin, a biopharmaceutical drug. Predominantly protein-based, biopharmaceuticals include monoclonal antibodies, and vaccines.
“Now let’s look at the composition of aspirin, next to a monoclonal antibody,” says Henrik.
“While a molecule of acetylsalicylic acid is made of only 16 atoms, that of a monoclonal antibody can be 1000 times larger in terms of number of atoms,” says Henrik. Biopharmaceuticals have complex structures, and they are more difficult to produce than small molecule drugs. The manufacturing process is as important as the product, as any process changes can have a profound impact on the therapy.
Small molecules revolutionized medicine, and large molecules are transforming the entire global healthcare, I reflect.
Join me next time for thought-provoking insights on small and large molecules — Of small and large-molecule drugs: decoding the whats and the whys for pharma rookies.
Interesting reads on some of the topics in this article:
Scientific American Mother Nature’s Medicine Cabinet
American Diabetes Association The History of a Wonderful Thing We Call Insulin
