Buckle Up

is this scary, amazing, or both

Emmanuelle Charpentier and Jennifer Doudna shared the Nobel Prize for Chemistry. Their contribution to humankind was the discovery and commercialization of gene editing. The promise is to end disease, and remove the limitations of evolution by making changes to the genome without trial and error and mutation.

Serious Taste

I have a broad mix of what I read here on Substack. I toiled reading mostly history the last few years but have branched out. My last post, “Taste” was a mixture of serious and light-hearted. Here is a post that captures the coming collision with how we raise or create our food, how we must change, and how it is likely to happen. I am not sharing this because I am a spoilsport nor because I happen to be diabetic. The changes profiled are coming. Even when change is “good for us” there will always be forces aligned to fight every step. Carter Williams writes seriously and succinctly. I wish he would write more!

When Will Sugar become the New Tobacco

Regularly Scheduled Programming

My pattern of discovery as to what to learn about next can be reduced to what I read or hear when I am exercising. Today’s story comes from the article provided. I will undoubtedly watch for the new book discussed in the link. It has already been added to my To Be Read (TBR) list. A while back before taking a 3-month sabbatical from posting, I explored the wonders of CRISPR. In a tribute to the limitations of my taste, while a fascinating topic for me, readers gave it a solid meh. The angle I explored was the gene editing of a pig heart to make it suitable for use in a human transplant. When I researched the topic, I found Jennifer Doudna to be the rarest of experts. Jennifer shared the Nobel Prize for Chemistry with Emmanuelle Charpentier. Because of the remarkable breakthroughs that qualify for the Nobel, it is rare for a single person to win prizes anymore. Jennifer and Emmanuelle were the first pair of women EVER to share the Nobel.

It is not surprising that Jennifer is brilliant in the field of biochemistry. What is surprising is she couples her scientific prowess with perspective and seems to grasp the challenges CRISPR might present to our future. While this touches on ethics, it also foresees the possibilities of world-changing (and even world-ending) consequences. I am quite sure the same might also apply to Emmanuelle; I simply heard an interview with Jennifer.

CRISPR 101

Way back in January of 2022, I heard a scientific report about growing a purpose-built heart for a human candidate needing a transplant. A piglet birthed with a porcine heart. Genes were added, deleted, and modified to “build” a heart that would be accepted in a human being BEFORE the piglet was born! Surprisingly even though pigs and humans split more than 70 million years ago, only a handful of genes had managed to “evolve” in the intervening period. While a bit editorial, whenever I write a sentence like the last one, it FLABBERGASTS me to consider how many people still embrace less than 10,000-year-old earth. I am a respectful and patient person. As I’ve aged I’ve become an open-minded listener. Such ideas are difficult for me to entertain.

When a plain-as-day example is provided, (the patient), it is hard to construct an alternate explanation when a pig heart, with only 12 changes amongst tens of thousands of genes, can be made compatible with a human being, there are not a lot of off-ramps for alternate explanations of how we came to be.

The ability to edit genes is made possible by the breakthrough set of tools called CRISPR. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. If ever the meaning of an acronym was not particularly helpful, this is it. While for many the connections between all living things might give you pause and perhaps doubt, the CRISPR story is quite convincing. It turns out that the mechanism by which an E. coli bacteria operates WILL OPERATE similarly in us and all living things!

My CRISPR story was a longish, multi-part tale starting below. I have NO DOUBT that CRISPR will transform life as we know it. It has required 150+ years to ferret out evolution. Until that time our best explanations varied widely. For the next 75 years, doubt emerged for the likelihood of the evolutionary theory. The emergence of genetics and discovery of DNA brought us all closer. It has taken 75+ years so far to unlock an understanding of genetics. CRISPR now brings us to the edge of creation with the realization of gene editing becoming a tool in our hands. When I consider we’ve been wandering for 2M years, adhering to an alphabet for about 4000 years, almost all of human history and our breakneck progress is QUITE RECENT. I often believe we are getting close to a breakthrough in different fields when we develop a way to observe nature in great detail. I think most of our advancement on this planet has been to study and emulate nature. CRISPR leverages a great understanding of how bacteria operate a basic immune system. Once we FINALLY understood what we were looking at, we figured out how to make tools that emulate it. The link is the beginning of a longish story about CRISPR. Only go there if you have a bit of time.

CRISPR Part 1

What Could Go Wrong?

I am afraid what could go wrong is where our minds travel when we ponder new technology. I am an optimist. I believe that CRISPR will do more good than harm. Will harm occur? Sure. With that, let’s stir the pot and try to understand three capabilities we have with CRISPR and the challenges they bring.

1. Introducing heritable mutations — mutations are inherited from our parents or occur in the course of living. While I have not posted about it, the latter source, aka epigenetics is CRAZY and INTERESTING. The concept is heritability due to environment and nurture!

2. Gene Drives — We are combinations of our parents. We have an approximate 50-50 mix. A gene drive replicates a desired trait to near 100% certainty rather than 50%.

3. Gain of Function Studies — this is particularly pertinent to cancer and its treatment. Controlling the ability to gain or lose function is key to cancer understanding.

Heritable Mutations

We’ve all heard about nature versus nurture. The role of CRISPR can rapidly become the selection of favorable traits upfront. I think this makes us nervous when we apply it to humans. In reality, we’ve expressed no issue with trait selection when it comes to our rotisserie chickens, hogs, beef cattle, dairy cows, and all sorts of the GMO foods we consume every day.

The explosion of the human population since 1800 is either amazing or absurd (or perhaps something in-between). The current propensity of the famous purveyor of SpaceX, Tesla & Twitter to lecture humanity on its crisis pending of not enough people is a tribute to folks who embrace the talk as suspending belief! It required 2M years to get to the first billion of us around 1800. By the year I was born we had tripled the world population to around 3B. I spent my elementary school years raising pennies for the missions and was traumatized by black-and-white images of distended bellies around the world. If not for the Green Revolution and the burgeoning mastery of genetic cross-breeding, it seems we would have sat idly by while 1 in 3 of humanity died the harshest of deaths due to slow starvation. The Green Revolution, despite all of the folks today who are sure they don’t want to eat anything GMO is a case of cognitive dissonance. The Green Revolution, in my estimation, is one of the GREATEST ACHIEVEMENTS IN THE HISTORY of humankind. I wrote a post about one of the key actors involved. When people engage in their bar bets and want to make claims about “the greatest person who ever lived”, it is not hyperbole to say that the star of my old post may have saved up to one billion lives. While my writing has not reached a critical mass of persuasion, I think saving one billion lives when there were only about three billion of us is quite a parlor trick.

The Norman Conquest

Of course, hubris is never in short supply amongst humans. Our response to keeping starvation at bay for 1 of 3 humans is to up the ante and increase our population to a now staggering 8 billion as of a week or so ago. I am not proposing population controls or anything of the sort. However, one common sense rule when you find yourself in a hole is to stop digging.

After two billion years of cruising the land wearing animal hides, humans got down to business and reached a population of 1 billion in the last 200 years. Science has given us hair dye and we seem committed. It seems there are toxicity issues with hair dye so why sign up for chemical shocking when it might easily be addressed by turning on a gene? The hair coloring market was a $24B business and is growing fast. If we could select for hair color, should we? It seems we do it with horses and dogs, why not us?

Gene Drives

Gene drives are a fascinating conundrum. With the exception of war (humans killing humans), mosquito-borne illness is the number one killing creature on the planet.

Randomness, environment, poisons, and stress are all sources of spontaneous mutations — all the stuff that can go wrong in life. Managing the starting point for such traits as Down’s Syndrome, and cystic fibrosis does not seem controversial to me. I’m on the side of less human misery. The Cliff Notes version of a gene drive might be useful here. I am avidly interested in genealogy and the companion practice of DNA testing to find relatives. Depending upon how much biology you studied (my coursework ended my sophomore year in high school), we don’t teach that much biology. As far as genetics I got along most of my life believing that we get half of our genes from each of our parents. Well, not exactly. You see we all have a special type of DNA that is part of all of us called mitochondrial DNA (mtDNA) and we get it EXCLUSIVELY FROM OUR MOM! We have another class of DNA exclusively from our fathers. These narrow snippets of DNA provide the inspiration for a gene drive. Both of my parents had something wonderful to offer the world but I, like all of you, can single out some traits in one parent that would be wonderful to GUARANTEE we inherit.

So why this rabbit hole? There are certain genes we 100% get from our Moms or Dads. What if we could take all sorts of other genes that we intersperse from our parents and GUARANTEE we would get the preferred gene from one side? This is the concept of a gene drive. Imagine a genetic defect that one of your parents carries. By incorporating a gene drive, you could control from where the result would draw its inspiration. While there are additional complexities and scenarios in inheritance, suffice it to say particular genetic disorders could be driven from existence.

All technologies bring with them the risk of misuse or misunderstanding of consequences. The human misery wrought by the mosquito is finally being studied and perhaps tackled within the context of a gene drive. What if we could introduce a change in mosquitoes that would guarantee the study group would inherit the trait of sterility? Maybe the end of mosquito-borne illness? Each of these steps brings with it the fear of Doctor Frankenstein and unanticipated consequences. My sense is humanity lived with profoundly debilitating diseases like smallpox. Did you realize we have only been doing vaccinations since there were about one billion of us in the late 1790s?

The last four years have taught us that many of us would prefer the pre-1800 approach of no vaccines as long as our tribe is “owning” the other side. In fact, about three weeks ago I experienced my first bout of inane foolishness in my Newsletter. A person had stumbled upon my Newsletter and was encouraging me to repost it on his YouTube channel. I carefully opened a private internet session and checked on the link he provided. Oh boy, those vaccines have microchips in them and the end goal is the creation of a drone army of super-soldiers. Who knew? I was thankful Substack provides an easy way to block such foolishness. I am not intolerant. I simply accept that I only get so many cycles on this Earth and I don’t wish to spend too many contemplating drone armies of super-soldiers with mRNA vaccines and microchips floating inside them.

Gain of Function

The phrase gain of function sure sounds scary. It is probably an overbroad term as anytime a mutation occurs, a function of some sort is gained. Gain of function is a term that applies to one of the most insidious of conditions (or class of conditions) named cancer. Cancer cells have evolved in many cases to evade control by triggering continuous cell division. Cancer cells have gained a function we associate with life in its earliest stages. Triggering division in a mature person quickly overwhelms us. While cancer cells have gained a function, CRISPR provides a mechanism to perhaps target and insert mutation into a cancer cell to cause it to LOSE A FUNCTION. I believe CRISPR will be the mechanism by which the war on cancer can be won. It will be won at the molecular level rather than our current crude toolbox of general poisoning aka chemotherapy.

The Cup is Half-Full

I constantly state this is the very best time ever to be alive and hence this is “Why Living Today Rocks”. Every technology in the history of humankind has likely been discovered and then for some period of time we struggled with how to apply it. Certainly, there are moments when we directed technology toward less civilization rather than more. For this, we must organize and be vigilant. The technology itself, however, is neutral. In these amazing times of rapid change, it is increasingly important to “get it right” and steer toward more civilization. For me, optimism and vigilance in equal measure will keep us moving forward. I imagine in ten years, only the Luddites will be shouting in the fields to shutter activities like CRISPR. I expect it is the same crowd that would turn back the clock on such things as IVF. Having known people who struggled and desired to have a child, IVF was their only option. As I hear the rise of intolerance spout about the need for limiting such efforts, I struggle to find my voice. Here is a famous quote attributed to Edmund Burke that often swirls in my frontal cortex.

The only thing necessary for evil to triumph in the world is that good men do nothing.

I believe each time fear and ignorance take hold, we are mostly looking backward to the illusion of “the good old days”.

I am perfectly willing to patiently listen to reasoned arguments. My biggest fear is that progress only can be set back by shouting, intimidation, and ignorance. If you are not sure of something read a book with reasonable attribution and standing. I have no doubt there are SOME THINGS we studied and understand to be true that were expressed hundreds and perhaps even a thousand years ago. Modernity does not have the market cornered on knowledge. However, I think it is a simple and non-controversial statement I will end with:

I believe human beings are gifted with a rather unique brain to contemplate and refine their beliefs. Therefore, it seems, we should remain OPEN to ALWAYS consider what we may learn. In this context the older the knowledge or belief, the MORE LIKELY it may benefit from further refinement. Ideas that have survived a long time are likewise likely to provide highly refined knowledge. While there is much to learn from what Moses, Jesus, Mohammed, Buddha, Newton or Einstein had to say, we are fools if we do not apply our best efforts to refine what has come before to make what comes next even better. Nothing that came before should be discounted. Neither should what came before negate what is to come. Fearing either seems a fool’s errand.

The Poll & Music

What was today’s post about? For me, big ideas like CRISPR are about big changes and how they might disrupt our feelings and beliefs. I recently finished a long philosophy book titled “The Cave and the Light”. A wonderful cohort in my creative writing group was kind enough to share it. The book starts with the Italian fresco “School of Athens” painted in the Vatican by Raphael, a contemporary of Michaelangelo. The central figures at the center of the work are Aristotle and Plato. It is fun to compare the two. I looked at a few overviews. The fun is the bias in language that permeates how one describes their differences. I have a close relative who has shared his opinion. It is fun to have read this LONG book and get a better sense of myself.

While a bit of a segue, I strongly recommend the “Google Arts and Culture” application. It’s a great place to learn about things like the “School of Athens”. It is my go-to application to learn (and view) so much of the art of the world. It is quite an accumulation of the world’s masterpieces across many museums. I happen to be more prone to the Android side of the street. I am most thankful, however, that unlike Apple, which manages its applications in a walled garden, Google makes its applications accessible to all rather than a paywall for the few. I invite everyone if you have a few minutes to kill, to download the Arts and Culture application. I think what is made freely available to all will bring a smile to your face. I sincerely hope that Google never resorts to a walled garden even if it’s a better path to more revenue. The world is a better place when it’s available to all. For those on a journey to learn, the quizzes have helped me become more knowledgeable about art. Here’s a web link. It is also available for Android (and iPhone of course) for those that are interested. Enjoy the concept of broad sharing. It’s fun once you get used to it.

We recently finished a book in our book club about a historical person who made early observations about atoms. That book portrayed the singular importance of those early insights and their rediscovery centuries later. For me, it is great to honor those insights. It seems, depending on your worldview (bias), you can naturally align with Aristotle or Plato. I consider it a trap to be either or when such rigidity is simply unnecessary. To assume that what two great minds thought about thousands of years provides the only way to see current truth is limiting.

I imagine that how you feel about CRISPR might depend upon how you feel about Aristotle vs. Plato even if you haven’t considered the connection. Here is the best of the comparisons I found that didn’t seem to drip of bias.

So this was two longish paragraphs leading to my poll for the day. Click and vote as I am INTERESTED to hear what others think. As always, I provide something else as an option. It may be I see this stuff too narrowly also.

Here’s a pretty darn good philosophy song from Robert Allen Zimmerman. Minnesotans and music aficionados know who that is before they press the link.

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What’s Next

My next post is inspired by the classic movie “The Wizard of Oz” and is titled “Pay No Attention”. The link is dead until it formally publishes but is provided as a teaser to what is next and will come alive for people who poke around my archive in the future. I love the ending of the “The Wizard of Oz”. The question at hand is what is the message?