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 is sugar processed in the body?”. The gravity of drug discovery makes tinkering with sugar sound childish, but it is only because of the latter that we now have Remdesivir, the first drug to receive the United States Food and Drug Administration’s emergency authorization for use on COVID-19.

Remdesivir was adapted from a nucleotide (the building block of DNA) through subtle changes in its structure. This drug is similar enough to a nucleotide to fake its way into a virus’s own genetic code. Yet it is different enough such that once inside, it disables the virus from making more copies of itself. Thus, the answer to “How is sugar processed in the body?” enabled scientists to transform a simple sugar into a potential Trojan horse against COVID-19.

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 research is no exception; its contributions to regenerative medicine took flight riding the wind 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, a condition caused by a known genetic mutation, 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.

Thanks to the intellectual curiosity of past minds to answer these basic biological questions, Hassan’s stem cells were isolated and corrected in just four months. His now-healthy stem cells were then expanded to become large sheets of skin that were grafted back to his body. By November 2015, almost all of Hassan’s open lesions had been covered by the lab-grown skin, 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 is now a reality thanks to basic researchers and their sense of wonder about how the world and our bodies work. So be curious. No question is meaningless under the expanse of science’s sky. Because later in the scientific voyage, many lives – including yours – might be saved simply because the right question was already answered.

___________________________________________________________

Blog by guest contributor Kevin Gonzales, PhD, postdoctoral fellow in the lab of Elaine Fuchs at The Rockefeller University, NY, USA.