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- CRISPR-Cas9
On December 31, 2024, I published “Innovations in Medical Technology for 2024 and Beyond.” In this newsletter, I presented significant innovations in medical science that received the Nobel Prize in recognition of their importance. It's important to recognize that such groundbreaking discoveries require time, usually 10 or 20 years, to become fully developed into practical procedures that can be incorporated into our healthcare system. In this edition, I discuss the discovery and use of CRISPR-Cas9 technology on a microscopic level. I usually do not delve into these complex technological innovations because they require the use of terminology that most people are unfamiliar with.
For me, the required nomenclature and its meaning are second nature because of my education. Instead, my greatest difficulty lies in presenting an accurate scientific description of the details and significance that this discovery embodies in the most understandable way for as many people as possible. To accomplish this daunting task, I use multiple video presentations, some of which include animations that provide graphic examples, allowing you to visualize components of the process rather than relying solely on text explanations. This approach reminds me of the saying, "A picture is worth a thousand words."
Keep in mind that if this discussion inspires you to explore further, you can revisit this document anytime to continue your learning journey. Take note of the related YouTube presentations that are displayed alongside the linked videos. Additionally, I’ve streamlined the companion podcast to cover the fundamental concepts and direct listeners to specific videos for a deeper dive into the content.
Where CRISPR Began
For some, discussions about advanced technologies like CRISPR might evoke apprehension, as the rapid evolution of these technologies can seem confusing and unnatural. Generally, the older you are, the more this applies, as you have witnessed many of the remarkable developments of the past 100 years. However, this exponential development is only going to accelerate from here on. So, as I’ve mentioned before, "get ready for a wild ride"—and I’m not referring to something you would find at an amusement park.…
These developments will be incorporated into everyday life, most especially into healthcare and scientific discovery. In my view, it is better to learn before an emergency arises that suggests the use of one of these new technologies to avoid making a rushed decision. In addition to simply telling you what these technologies are, I will attempt to explain how they were discovered. In doing so, I hope to demonstrate that these things are not the product of harebrained ideas that some mad scientist cooked up by accident.
Rather, their development was the result of logical, well-thought-out methods, with each step undergoing significant scrutiny and peer review. In this case, CRISPR likely evolved billions of years ago, long before the emergence of humans.
What I want to make clear is the enormous difference between this and developments brought forth at the urging of governmental elements, motivated by crisis or politics such as those implemented after WWII to address fatal diseases resulting from our diet. Ironically many of those actions had just the opposite effect, because we were not scientifically advanced enough to recognize the damage caused by these attempts…many of which persist today.
CRISPR was first discovered in 1987 by a Japanese researcher, Yoshizumi Ishino, who accidentally identified a pattern of repeating DNA sequences while studying the E. coli bacteria, although the function of these repeats was not understood at the time. This discovery was later recognized as a CRISPR sequence, which stands for "Clustered Regularly Interspaced Short Palindromic Repeats" and was found to be part of a bacterial immune system against viruses. The initial discovery of CRISPR was accidental while studying a gene related to phosphate metabolism in E. coli.
The researchers noticed unusual repeating DNA sequences interspersed with spacer sequences, which later became understood as the key component of CRISPR. Perhaps what I’m telling you has not quite registered yet… What I’m saying is humans did NOT invent CRISPR… They merely discovered it in one of the most common bacteria on earth, Escherichia coli. In essence, these bacteria had discovered a way to prevent viral infection by this process, referred to as Adaptive Immunity. Please watch the following short video that will explain each step and the scientists responsible for these developments.
How CRISPR-Cas9 Works
I believe the best, most easily understood way I can present this information is by the use of animated videos, which progress step-by-step in a logical fashion from inherent function to resulting changes that move from abstract to desired specific actions… Or what you might call “cures.”
I recognize that even this simplified explanation may be beyond the comprehension of some readers. That’s okay, because I will attempt a degree of redundancy by providing different approaches to the same subject. In addition, when a YouTube video loads, it is usually accompanied by other videos on similar subjects. Beyond this, I hope to produce an audio podcast capable of elucidating some of these more difficult-to-understand features, by virtue of its conversational structure—a sort of Q&A approach. The first presentation I offer is a 10-minute animated introduction to gene editing.
Next is a video that will surprise you. I believe it is ideal because it explains the technical complexity of CRISPR-Cas9 and demonstrates how it can be understood at different levels. The video also explores how its eventual application achieves results in treating genetic diseases that would otherwise be untreatable. Curated by a biologist, the video aims to make CRISPR-Cas9 comprehensible, starting with a grade school student and progressively moving to individuals with increasing levels of expertise, culminating with an expert in the field. I think you’ll be impressed by how well each group is able to grasp the concepts.
Surprisingly, as the video progresses to more and more sophisticated individuals, you will see that the level of caution and uncertainty rises even more than the excitement of using CRISPR-Cas9 to solve existing genetic illnesses. I am certain that many of you share the same concerns. In that regard, I hope you picked up on the issue specific to making changes to the “Germ Line”, which could carry edited changes forward several generations. This is as opposed to using this technology on “somatic cells” where inherited traits cannot result.
The thing I want to stress is that usually, when left to their own devices, scientists, particularly those at the top of their fields, are very cautious, because they are surrounded with realities that exist in scientific discoveries, that most of the public are unaware of. The exception to this occurs when political or economic pressure is put upon researchers because of critical need. The best example I can provide for you, is the way in which vaccines were developed for COVID-19, which for most of us, was the first and most serious pandemic of our lives.
I am certain that without the overreaching pressure present at the time, that the development of vaccines by Pfizer, Moderna, and Johnson & Johnson would have, and perhaps should have, taken longer. However, despite the skepticism that existed at the time, the results were far better than if nothing had been done at all…
Let me Briefly Take You Down the Rabbit Hole
The discussion of the previous topics triggered something in my mind that compelled me to include the following video. You might not see an immediate connection at first, but after watching this 16-minute exploration of LUCA, I hope it will all start to make sense. When I say "all," I’m referring to genetics—the fundamental building blocks of life as we know them. If you’ve been following my newsletters, you may have noticed that I view our place in history as a product of evolution, tracing back from the earliest living organisms to the present.
You may also have noticed my belief that we are connected to virtually everything that surrounds us. After watching the following video presentation, you will begin to understand why. We are indeed connected by the fundamental building blocks of life embodied in DNA. If you follow this belief, you will recognize that it is the very understanding of biological processes that will be responsible for the changes in healthcare we are about to witness in the next 100 years.
After watching this video, you will see how work done by Google’s DeepMind has now made possible the ability to predict “protein folding” which leads to a deeper understanding of how biological processes work. Importantly, this allows us to CREATE new proteins that solve specific problems, that “cure” disease by natural mechanisms, as opposed to using synthetic drugs produced by big Pharma.
The First FDA Approved use of CRISPR-Cas9
The FDA has approved two groundbreaking treatments, Casgevy and Lyfgenia, for sickle cell disease (SCD) in patients 12 and older. These are the first cell-based gene therapies for SCD, with Casgevy also introducing a new gene-editing technology.
Sickle cell disease, which affects about 100,000 people in the U.S. (mostly African Americans), is caused by a mutation in hemoglobin, the protein that carries oxygen in red blood cells. This mutation makes the cells take on a crescent or "sickle" shape, blocking blood flow and reducing oxygen delivery. This leads to intense pain, organ damage, and can result in severe complications or early death.
As a side note, I want to highlight another factor you might not have considered, which demonstrates how our environment affects our evolution. In this case, the gene responsible for sickle cell disease emerged as a defensive adaptation directly related to malaria—a life-threatening disease transmitted to humans by certain types of mosquitoes, still prevalent in Africa. Interestingly, one copy of this gene provides resistance to malaria, while two copies (one from each parent) result in sickle cell disease. This explains its prevalence among African Americans…
Sickle cell disease is a rare, debilitating, and life-threatening blood disorder with a significant unmet need. The approval of two cell-based gene therapies marks a major step forward in addressing this challenge, particularly for those whose lives have been profoundly impacted by the disease," said Nicole Verdun, M.D., director of the FDA’s Office of Therapeutic Products. "Gene therapy offers the potential for more precise and effective treatments, especially for individuals with rare diseases who have limited treatment options."
The safety and effectiveness of Casgevy were assessed in an ongoing multi-center trial involving adults and adolescents with SCD. Participants experienced at least two severe VOC (Vaso-Occlusive Crisis) episodes annually in the two years before screening. The primary goal was to achieve at least 12 consecutive months without severe VOC episodes during a 24-month follow-up. Among the 44 patients treated, 31 had sufficient follow-up for evaluation, and 29 (93.5%) met this goal. All treated patients successfully received therapy without any instances of graft failure or rejection.
Significantly, there are two major challenges surrounding treatment with Casgevy. First, the fact is that in order to be successfully treated, the patient must undergo a therapy to destroy their current blood manufacturing mechanism in the bone marrow. This enables the “transplanted” bone marrow to produce fetal hemoglobin which eliminates SCD. Regrettably, at this time that can only be accomplished using chemotherapy, which as you can imagine, is difficult and prolonged, but given the fact that the disease could be fatal, this becomes a reasonable option.
Secondly, the procedure currently costs around $2.2 million for a single course of treatment, which can take up to a year that involves multiple steps including stem cell collection, modification, and infusion. Going forward, the cost is likely to be reduced, by improvements or new procedures and methodology…this is only a first step.
What does this Mean for the Future?
Look ahead in time…Imagine what this means for the future of healthcare. With luck, we can treat the leading causes of death and disability to prolong our “Health Span” indefinitely. Listen to this 15-minute video narrated by Dr. Benjamin Oakes to learn what is possible.
Until next time, take care and stay POSITIVE…Dr. G
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