CRISPR Part 1

see what we can make today

Tonight is Part 1 of a 4 part story unless you take the offramp. I decided to group these in a blitz on successive weekends SAT/SUN for two successive weeks so I would not just be doing a biology bonanza and not mixing in other kinds of stories in between. I am trying to do a mix of things and the "normal" schedule is TUE/THU/SAT with multi-part stories on the weekends. This whole sequence is inspired by the graphic below. When I heard this on my treadmill back in January it sounded like SciFi to me!

This turned out to be the last post I was able to finish. I hope you enjoy it.

We’ve been doing transplants since 1967.

The inspiration for today’s post was a remarkable story for humanity. A man in Maryland was ineligible for a human transplant and his heart was failing. Physicians at the University of Maryland Medical School performed a transplant from a genetically modified pig into the patient in early January 2022. The patient is now recovering and being monitored. The patient subsequently died in March of 2022.

In my newsfeed this morning (January 7th) (when I was inspired to consider writing this) there was a report of a heart transplant from a pig to human in Maryland. That is what inspired this search for knowledge. In a previous post, I noted that we share 98% of our DNA with pigs. What your heart (or a pig’s) will be like is destined from the beginning. The recipe is in the genes that tell our story. The part of the story that intrigued me was the pig DNA was edited, focusing on the expressive genes involved when stem cells construct the heart. The pig was then raised from birth with specific edits to the genome. The pig would be born and would have a heart that would be CRISPR-edited COMPATIBLE with a human. OMG. It is estimated that we diverged from pigs about 80 million years ago. Pigs are mammals but not even primates! Biological-based evolution is slow and steady (80 million years slow in this case). How slow is evolution? Well, it is estimated we have 20,000 to 25,000 genes that define us as humans across our 23 pairs of chromosomes. The difference between a human and pig heart for compatibility was only ten genes of which three were removed, one turned off and the other six edited.

Despite such facts, I am always amazed. I have little direct knowledge of organ transplants. What I always associate with transplants is the need to dose the body with anti-rejection drugs. How is it possible, only 54 years since the first heart transplant in 1967 (Dr. Christiaan Barnard in South Africa) that we have figured out how to transplant organs as essential as a heart directly from animals to humans, no fuss, no muss? The need for organs is always dire. Often the same is true for blood. Chalk those two facts on the board of things I do not understand.

Why do people in greater numbers not donate blood? Why do people refuse to be organ donors? I took a look at the statistics nationwide. Alaska, Montana, Washington, Oregon, and Iowa lead the nation in people opting to donate their organs among the fifty states. Try to guess who is 49th & 50th before looking at the link. The top five range from 73% to 82% opt-in. The lowest rates come in at 5% and 17% (yikes). I don’t think I could have chosen more dissimilar states as the bottom dwellers.

The number of people who die waiting for donor organs is still quite high. Hard to understand. I guess I am glad that science might try to save us from our peculiarly selfish tendencies by attempting to genetically modify and raise donor organs. While I don’t know when my end will come, I hope they can repurpose lots of me.

While a bit of a rabbit hole this is a fun and challenging story to tell. I love to read and often have to interpret complex stuff in a way I can understand. This is especially true for stuff I don’t know much about. I remember dissecting animals in high school biology but my biology education largely ended there.

Tonight’s story MIGHT NOT BE INTERESTING for everyone. I can understand if you skip it. My goal is to deconstruct a complex but inspiring story and make it accessible, interesting, and easy to follow. That sounds like creative writing to me. My plan is to do this in four parts.

This is our CRISPR Part 1. I only want to go far enough to give each of you an off-ramp if you are not interested since there are three more parts to go. In Part 2 I will continue with DNA and what scientists observed in simple bacteria. What they found helps define what the term CRISPR actually means. In Part 3, I will talk about CRISPR and how it seems to be the key insight into how our immune systems work. I always wondered how once we get sick, our body can remember how to fight something the next time we encounter it. Finally, in Part 4, I will wrap it all up and describe once we figured out what CRISPR is, we applied its methods to do cool and amazing stuff well beyond just fighting off a cold (like putting whole pig hearts into people).

The Norman Conquest

CRISPR is the dawn of a new age for humans. Direct intervention into the expression of life. Correction of mutation, customized disease mitigation. One of my favorite posts was “The Norman Conquest” profiled above. It was about the most famous graduate of the University of Minnesota. The star of that post labored for decades in a quest to feed the starving and is widely credited with saving one billion lives. The hero of the post likely accomplished his goal with thousands of steps. CRISPR allows the brilliance of what he accomplished to be reduced to perhaps a handful of steps.

Nature's Cookbook

For about two weeks after I heard this news story all I had was a file in my draft folder named CRISPR with a couple of links and videos in it. It sat dormant for a while and I nearly deleted it a couple of times. A while back I wrote a post titled “Nature’s Cookbook” which is profiled above. That was a fun post and explained how our body makes stuff from a simple cookbook and only twenty ingredients. I learned in that post that our bodies (my analogy) have a small pantry in the kitchen and only know how to make stuff from twenty basic ingredients. Imagine that despite our AMAZING diversity, it can all be reduced to just twenty amino acids we string together in different ways. It seems absurd that everything we need comes from only twenty ingredients but that seems to be how it works. That post was about how DNA codes a recipe. Same base-pairs, a cool way to put the recipes in order not so different than baking, so that amazing stuff can be made from a handful of ingredients. For those that like to bake, it is a bit like fats + sugars + wet ingredients + dry ingredients, and the next thing you know you got cookies.

I recommend, that if you made it this far without giving up, you should read Nature’s Cookbook at the previous link if you did not see it previously. I think it is a pretty accessible way to understand how our bodies sustain us and how all of its recipes are part of our DNA recipe book. If that bores you silly, abandon this series of posts. If you like that one, this one series just might be right up your alley. I think it does a decent job at explaining the kinds of things written down in our DNA. I was amazed when I read it the first time.

Special Request

If you decide this set of posts is not for you that is cool. My request is if you could leave a comment about when you gave up and why. Building out a story block by block is what I hope to someday do in a book. I’d love to know when my car leaves the road and falls in the ditch. Thanks for any feedback you might share.

Here’s another chance to look at Nature’s Cookbook. It is a pretty good story.

If you visit for the music, here is what I have. I like short stories because I don’t feel bad if I abandon them if they don’t hook me. Think of a four-part post as a road trip. You can always turn back, change your destination, or just take the scenic route. Here are two of my road music favorites in no particular order song1 and song2. While taste is subjective, this band is likely the best of all as it will get you a long way down the road with many songs to offer. I am confident my loyal musicologist friend “M” will agree that this band is synonymous with the road trip. The next song on this last link also fills the bill so you can just let it play on if you have the time and inclination.

WHAT’S NEXT

CRISPR Part 2 continues tomorrow. This link is dead until it is posted but will work for folks who read in the future.