CRISPR (not your tortilla chips mi hermano)
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)
A year ago, I stood up to the microphone for comments about a superb paper just given by the Chairman of Surgery at my Alma Mater Baylor College of Medicine..on a recent research paper he had done regarding improving blood flow in the human heart. At another institution, fifteen years earlier he treated a small group of patients who had angina pectoris (chest pain) from inadequate blood flow to the heart. Being a cardiac surgeon (like me) he had gone into the chest of these patients expecting to do a coronary artery bypass operation with vein grafts or left internal mammary artery bypass. As would have I. All cardiac surgeons are eventually faced with finding the recipient coronary arteries on the surface of the heart are so small it is impossible to suture a “bypass graft” on to them - We usually do three to five bypasses, so missing out on one is not the end of the road. But in a tiny percentage of patients there are no suitable recipient arteries. Dang what do you do then? Back before 2000 I had two options, but really only one. If I absolutely knew there were no targets, I would explain to the patient the conundrum, and then send them to Dr Bud Frazier at Texas Heart Institute for his determination of 1.) heart transplant ( I didn’t do those in the community) or 2.) Laser revascularization of the heart muscle… (I didn’t have a laser to do that). The laser could cut/blast a small hole all the way from the surface of the heart down into the inner chamber where the oxygenated blood was being pumped out. The laser hole was tiny all the way through, so the surface hole could be stitched over and the blood could run up the hole from inside the heart and seep out into the muscle tissue of the left ventricle. Being Texans, Dr Frazier and I both knew a little about the oil business and fracking. the Laser was sorta reverse fracking for the heart! I also heard Bud’s chosen number of laser holes was 47 because that was the jersey number of one of his favorite Texas football players…. But back to the story..Now if I got caught unaware in the operating room with a patient’s chest open and only determined then their were no bypass targets (dang!!!) then I had one last option. Crude but it had been described and so I did a handful of these…. I took the mobilized left internal mammary artery down from the chest wall and instead of clipping the intercostal branches, I left them open, squirting oxygenated blood.. I would “cram” (excuse the rudeness) a large blunt hemostat backward from the apex of the heart toward the base, of the left ventricle - lateral to the left anterior descending. Through the muscle, not into the chamber below. I would divide, then grab the bottom end of the internal mammary and pull it through the heart muscle, squirting nice oxygenated blood, into the muscle. That was the “bypass” - Several authors had written about this and proved patency with angiograms post operatively. I maybe did that on 5 or 6 out of 3000 to 4000 patients and honestly all of my patients did well and their chest pain resolved. This was before the days of fancy nuclear scans so I don’t have any proof other than a happy pain free patient.
But back to the Chairman’s paper…he had encountered that same conundrum— but he had available an research compound that would stimulate the EGFR gene. (endothelial growth factor). So he injected this gene into the ischemic heart muscle where no bypass was possible. He expected that the shot (an m-RNA shot) would upregulate the native EGFR thus improving the patient own ability to “grow new blood vessels” albeit small.. into the oxygen starved heart muscle. He figured it would work for about 14 days and then the injection would fade away. Indeed, pain free patients. But - the good part of this story is that his paper, given to the Texas Surgical Society was a followup 15 YEARS after that experiment. He had followup on a small number (less than ten) patients and ALL of them still were pain free. Superb paper, Superb results.
So - that gets me to standing in from of the microphone in 2021 and “discussing his paper” Basically I said that CRISPR and gene editing was going to change surgery forever as we learned more and more about genes and the genetic impact on cancers and vascular disease. I joked with the “elderly” crowd who were mostly all grey hairs like me - that they thought CRISPR had something to do with the tortilla chips we had for lunch at our San Antonio meeting. They didn’t know enough to even laugh… but there I was joking about CRISPR. Heck I hardly knew anything about it, except it was a tool to dissect out protein strands (for example in tumors or viruses etc) So really I didn’t know much more about it than my colleagues.. until now.
Actually I didn’t know then the inventor got the Nobel prize for the discovery just one year before my “joke” - I did know I was seeing incredibly good results with “genetic” treatments in some of my lung cancer patients as well as breast cancer… I posited that ten years from now most all of our fancy surgical “extirpations” or removal of cancers from organs will be in the dust bin of history. That is a good thing unless you really need that operation and you might want to find a grey hair to do that procedure. He may not know about CRISPR but he will know how to do a safe pneumonectomy.
I ran cross the following article about CRISPR. Yes I know there seems to be some oligarch impact and world wide conspiracy politics involved.. but I was fascinated with the actual brief history of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)… So that is what that means..?!!!!
You might want to read this article below. It is as usual well done- Hat tip to—-2nd Smartest guy in the world.
After reading it, you will be smarter about CRISPR - and maybe a little concerned about our future. Maybe VERY concerned…not only as a nation, but as a race or as an entire WORLD population.
Dr. Bob,
Sure wish we could have worked together more. I've read some of Doudna's writings but my wee brain is embarrassed lol. And people Dr. Feldtman did all those he mentioned for sure and he always had Olan B and C ready in the back of his mind.