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Dr. Julie Losman, a physician-scientist at Dana-Farber Cancer Institute and Brigham and Women’s Hospital, told a memorable tale of sickle cell anemia and science at a Harvard rally before Boston's March for Science. It echoed a common theme, that support for basic science is crucial because it's not clear where the next great cure will come from. Her speech, lightly edited:
Sickle cell anemia has a very special place in the history of medicine: It was the first human disease that was understood on a molecular level.
Sickle cell anemia is caused by a single mutation in a gene, the hemoglobin gene, that produces a mutant protein with an abnormal structure. This abnormal hemoglobin disrupts the function of red blood cells.
The mutation was discovered in 1949 by a scientist named Linus Pauling. Pauling was not a medical doctor. He was a chemical engineer, a basic scientist. In fact, he won the Nobel Prize in 1954 for helping to invent the field of quantum chemistry, which is the study of how atoms and molecules interact. He was as fundamental and "basic" a scientist as you can be.
And yet it was Pauling's work on how small molecules bond together that led him to study how very big molecules, like proteins, bond together. This, in turn, led him to try and understand how a mutation in a gene could change the structure of a protein and alter the way that the protein bonds to other proteins.
That is how a chemical engineer who began his career studying protons and electrons made the first discovery of a human disease caused by a specific mutation.
The importance of this discovery to modern medicine cannot be overstated. Linus Pauling’s work laid the foundation for the entire field of medical genetics, which has absolutely revolutionized how we think about human disease.
For many, many, years, and even today, for many, many patients, the treatment for sickle cell anemia is palliative: Avoid things that trigger pain crises, treat pain crises when they happen, and try to protect organs from the damage that a crisis can cause. That is basically it.
A very few people with sickle cell anemia have successfully been cured with a transplant. Stem cell transplants are complicated, dangerous and very, very expensive. Undergoing a stem cell transplant requires absolute dedication from the patient, their families, their friends, their communities and their medical teams. Unfortunately, not everyone with sickle cell anemia has that kind of support or the access to exceptional medical care. A stem cell transplant for them is simply not an option.
But there is basic research going on right now -- here in Boston and in labs across the United States and around the world -- that has the potential to revolutionize how we treat sickle cell anemia. Right now, scientists are working on how to use an extraordinary new discovery called CRISPR to fix genetic mutations like the mutation that causes sickle cell anemia.
When this technique is perfected -- not if it is perfected, but when it is perfected -- it will be possible to take the stem cells of a patient, correct their mutation, and give them back their own stem cells. Because these reinfused stem cells would be perfectly at home in the patient’s body, there would be no need for months and months of post-transplant recovery.
Instead of being a leap of faith, a transplant would be a simple and safe procedure. It could even be done in young children with sickle cell anemia, before they ever have their first excruciating pain crisis.
The discovery of CRISPR and gene editing was not made by a geneticist or a stem cell biologist. CRISPR was discovered by a bunch of microbiologists, scientists who study bacteria and viruses.
In fact, much of the foundational work in CRISPR was done by nutritional microbiologists who wanted to understand how the bacteria we use to make cheese and yogurt are able to fight off viral infections. Imagine that! The future of gene therapy began in a yogurt vat.
The lesson we need to take away from Linus Pauling and these ‘yogurt scientists’ is that basic fundamental research -- the kind of research that is being done not just by the National Institutes of Health, but also by the National Science Foundation, the Department of Energy, NASA, the Environmental Protection Agency, the Department of Defense -- is all absolutely crucial to advancing human health.
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