A copyedited version of this article was originally posted in Stem Cells in Focus on August 2020
Biomedical research, the science of investigating the mechanisms and causes of disease, has been the driving force for many of the greatest medical advances in history: from drugs like penicillin to fight bacterial infections, to medications like insulin to control diabetes. Its importance feels even more pertinent nowadays amidst the COVID-19 pandemic. While the wait for treatments might feel long, vaccine development is moving forward at an exceptional pace. Such rapid progress can be achieved because scientists are armed with the knowledge from earlier discoveries that laid the groundwork for today’s progress.
Research falls under two broad categories: applied and basic. Applied research solves practical questions, for instance, “What is the cure for COVID-19?”. Basic research answers curiosity-driven questions about fundamental principles, like “How do you get RNA molecules into living cells?”. The gravity of drug discovery makes the question of RNA delivery sound impertinent, but it is only because of the latter that we now have vaccines against COVID-19, protecting individuals from COVID-19 contraction by at least 2X, and death by at least 6X.
When the body encounters a pathogen, the immune system is trained to attack the next time it sees the same pathogen. Vaccinations exploit this by injecting just a small chunk of protein from the pathogen that can provide protection without causing disease. While it sounds simple, making a protein vaccine is a long and grueling process. But for RNA, it is indeed simpler. Once the genetic sequence of COVID-19 was published in January 2020, RNA that can instruct cells to make the pathogenic protein chunk was designed within a couple days. The answer to “How do you get RNA molecules into living cells?” enabled scientists to turn this RNA into a vaccine – the fastest vaccine ever developed.
Solving basic scientific questions allows us to comprehend the elementary processes of the world around us, without which, the innovation of new tools, technologies or cures would not be possible. Stem cell biology is no exception; its contributions to regenerative medicine took flight riding the winds of basic research. For example, decades of basic research have recently led to a cure for the fatal skin disease known as junctional epidermolysis bullosa (JEB) through the development of stem cell therapy.
With JEB, the skin’s attachment to the body is severely weakened. Blisters and wounds appear from the slightest amount of friction: from wearing a shirt, laying on bed, or receiving what should be a warming hug. This disease is so devastating that patients rarely survive beyond childhood. They are dubbed “butterfly children,” with skin as fragile as butterfly wings.
In June 2015, this cruel genetic disease endangered a 7-year old boy named Hassan by leaving only 20% of his skin intact. Hassan was hospitalized at the brink of death, weighing a mere 17 kilograms (37 pounds) and suffering from multiple life-threatening bacterial infections. With no cure available, doctors turned to scientists, who came up with an idea: cultivate the boy’s skin stem cells in the laboratory, repair the mutation that causes the disease, grow skin with the corrected gene, and transplant this healthy skin onto his body.
This experimental treatment was not conceived by chance; rather, it was a completed puzzle, pieced together from knowledge obtained by asking questions about how biological systems operate.
Can stem cells survive outside the body? After numerous failed attempts and rigorous optimization, scientists in 1975 succeeded in growing the first human stem cells in a dish from skin tissue. Decades later, Hassan’s skin stem cells were grown from a small skin biopsy using the same technology.
What anchors the skin to our bodies? To appreciate why our skin remains attached to our bodies, molecular biologists in the early 1990s examined the proteins that sit under the skin’s bottommost layer. They identified a protein called laminin-332, which plays a critical role in adhesion. Scientists later determined that JEB patients have a mutation in the laminin-332 gene, identifying the error in Hassan’s stem cells that needed to be corrected.
How can a virus cause cancer in chickens? Basic research from a different field provided another critical step. Virologists from the 1960s hoped to understand cancer better by investigating what exactly a tumor-causing virus does inside chicken cells. While they did not unlock the secrets of cancer (we’re still trying to figure that out!), they instead observed that the virus can permanently write genetic information onto the chicken cells’ DNA. This unexpected discovery led geneticists to meticulously refashion those viruses to deliver nearly any gene without any inherent detrimental effects on humans. In Hassan’s case, a virus modified to contain a functional version of laminin-332 gene was sufficient to repair his stem cells.
All that was left was to grow these genetically-corected stem cells to the sufficient quantity (almost 1 square meter) and graft them back as sheets of skin. The process was rapid. By October 2015, doctors had already started transplantation, and within a month, almost all of Hassan’s open lesions have been covered by the lab-grown skin. Hassan was discharged only four months since the therapy started, and today, he is living not as a butterfly child but as a normal 12-year-old boy, attending school and playing soccer.
This transgenic stem cell therapy, COVID-19 vaccines, and many other clinical breakthroughs are now reality thanks to basic researchers and their sense of wonder about how the world and our bodies work. So stay curious. No question is meaningless in science. Because later down the road, many lives, including yours, might be saved simply because the right question had already been answered.
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