Dear Mark: Gene Editing

Dear Mark CRISPR in lineFor today’s edition of Dear Mark, I’ll be addressing the concerns raised in the comment section of last week’s CRISPR post. Many of you were rather alarmed at my apparent whole-hearted endorsement and enthusiastic embrace of the latest gene-editing technology CRISPR. Actually, I am more cautious than I may have let on. You brought up some great points. And I’ll try to address some of them down below.

Let’s go:

Will there be 2 Olympics? One for sustainable grown people and one for genetically modified people? 2 types of baseball fields – one for organically grown humans and one for people designed to hit a baseball further so that homeruns are still an accomplishment? Will there be 2 university systems – one for naturally human people and one for intelligently designed people? Will natural humans be eligible for all jobs or will they be discriminated against? Will natural humans still have access to medical care? If a condition can be cured or improved by CRISPR, will medical authorities be allowed for force the procedure on people whether they want it or not? Will a natural person be denied insurance, medicare, medicaid, or welfare if they decline to be “adjusted?” Will CRISPR ignore the fact of environmental affects on epigenetic expression and presume all genetic disease markers must be revised according to some lobbyist’s ideas of how the human condition should proceed? Can CRISPR adjusted genes be down-regulated by too many Twinkies? Most importantly, will Dick Cheney live forever?


I get it. The way-down-the-line implications seem jarring. So let’s touch on a couple of these hypotheticals (remembering, of course, that they’re hypotheticals).

First, these divisions already exist. People aren’t born equally. Some folks are just smarter than others. Some are more athletic. Some are more attractive. Some are friendlier, or more open to new experiences, or better at tracking wildlife through dense foliage. Some have better spatial intelligence. Others are great wordsmiths. Some people can rewire your home’s electricity or fix the plumbing; others are really good at marketing the electrician’s and plumber’s businesses.

There are already multiple strata of athletic ability. You’ve got the Olympics, the professional sports leagues, the minor leagues, NCAAD1, NCAAD2. You’ve got the NBA and the WNBA. You’ve got the Men’s Pro Tour and the Women’s Pro Tour. You’ve got Masters divisions for every sport.

There are even natural bodybuilding competitions and “enhanced” bodybuilding competitions whose participants openly use PEDs.

If we introduce a “superhuman” tier of competition, that’ll just become the new normal. Our expectations will adjust. Dunks from behind the three point line will draw yawns. Maybe we will have different playing fields.

Maybe athletes won’t break down as often. Maybe an athlete’s prime will last thirty years instead of eight. Remember, a significant portion of doping is done to protect athletes against injury and improve recovery, not just give them enormous muscles.

Science won’t ignore gene expression or epigenetics. Scientists are the folks who discovered epigenetics. And as you’ll see down below, they’re already using CRISPR to further their knowledge of how environmental triggers affect gene expression.

As for the jobs stuff, if I had to place a bet, I think the rise of superintelligent machines will displace far more human workers than anything else.

And no, Dick Cheney probably won’t live forever.

But those hypotheticals aside, here’s the more important thing…

In the original post I left out that perhaps the biggest gain we’ll get from CRISPR (because all the other supergenius, superman stuff is speculative and far off) are the insights into how our genome actually works: how genes are turned on and off, what happens when they are, and where causality truly lies. Already, scientists are:

  • Using CRISPR to seek out, attach to, and block the activity of specific genes. Instead of slicing and editing, they’re watching what happens when they prevent the gene from turning on. 
  • Using CRISPR to deliver proteins that activate specific genes. This allows them to “flip a switch” and see what lights up.

This is huge. Sure, we know the basics for staying healthy via gene expression.

Everything we talk about on this blog will still hold true.

But CRISPR will give us insight into the specifics of how this all works. Why does walking through nature reduce stress, improve blood sugar regulation, and boost natural killer cell activity? It probably doesn’t matter to most people.

Knowing that doing the thing helps is enough. That’s where I am.

But we all have that loved one who simply won’t (or can’t) give the Primal Blueprint an honest shot. And for them, that can provide extra motivation (or ability) to hop on board.

CRISPR may help scientists come up with ways to deliver epigenetic-based therapies to people who are unwilling or unable to adopt the wholesale lifestyle changes necessary to trigger beneficial gene expression—therapies that don’t involve gene editing.

Beyond that, there are other applications that have nothing to do with editing human genes. Scientists have used CRISPR to study the conditions necessary for the development of colon cancer.  Altering a single gene to cut diabetes risk in half or nearly eliminate one’s chance of getting colon cancer should be congratulated.

Yes, nothing is wholesale guaranteed. Yes, there can be unforeseen consequences. And I don’t blame anyone for having healthy skepticism against new technologies when they haven’t performed yet (especially since all of us here have been bucking against the Conventional Wisdom of so-called authorities for years). But certain advances are also a grounds for some (albeit measured) optimism. Maybe “hope” is the right word, since it implies what I really mean: I’m hoping for the best case scenario, given what we know so far, not stating that it will happen.

Someone mentioned my identification as a Luddite. How do I square the two?

So far in this life, erring on the side of “nature” has worked and led to the biggest gains in health, happiness, and productivity. Trying to counter nature never works well. Thinking we can make a smoothie out of pills and powders that’s more nutritious than anything found in nature is folly. Thinking we can improve the egg while missing what makes it so nutritious just doesn’t work. Assuming we can boil down a person’s health status to a machine’s analysis of a single drop of blood is nonsense (and the market has spoken). But Soylent, the vegan faux-egg guys, Theranos, and most other examples of food technology and medicine trying to “fix” what’s wrong all approach health and wellness assuming that humans know better than the natural world. They tried to contradict it and ran into gene-environment mismatches. They thought they could ignore the epigenetic environment under which humans evolved.

On the other hand, CRISPR acknowledges, works with, and targets the foundation itself: the genome. That’s why there are risks. You’re altering the stuff of life. But it’s also why there are great opportunities. We can’t ignore the reality of genes.

What about GMO?

Current GMO technology inserts foreign genes into organisms. This would never happen absent human intervention, and it’s why it sketches people out. It circumvents natural selection entirely, taking a top-down approach to what is normally a bottoms-up phenomenon. CRISPR is actually much closer to standard breeding practices, only sped up and with more precision. Instead of getting the two friendliest dogs to mate and hoping they have friendly puppies, you directly alter the “friendly” genes. You go right to the genetic foundation—to the bottom.

As for the DIY scene, I’m a big fan of letting people alter their own bodies, their own consciousness, and—once it’s available—their own genetic code (with qualifications, as you’ll see below). I may not do it. You may not do it. But if it’s not hurting anyone but the person hacking their genome, what’s the issue? No one will be able to program telekinesis, the ability to fire energy beams from their eyes, mind-reading, or other capacities that threaten people around them. Gene-hacking has hard limits.

Well, here’s the issue. DIY hackers (and anyone editing human germ lines) may affect others: future generations. If the changes are hereditary, if they edit the germ line, those changes will persist through to the offspring. Future humans can’t consent.

That’s the real issue here. And that’s a concern I definitely understand.

Then again, of course, no one consents to being conceived and born in general. Your children never consented to being the product of yours and your partner’s genetic material. But the big question is: is there a moral difference? I honestly don’t know the final answer. I’d love to hear your thoughts on the subject. Because that’s definitely a conversation that needs to happen as this technology moves forward.

But the fact remains that other people/countries/entities will pursue gene-editing with CRISPR. It’s too alluring an opportunity to pass up, and the risk of being dominated by those who take the plunge will force everyone else’s hand. There’s no escaping it. It is coming.

All that said, I wouldn’t be surprised if the complexity barriers to using CRISPR or other gene editing technologies in living adults are just too high to overcome.

Editing an egg or a sperm cell or an embryo is relatively simple compared to editing genes in a liver or eyeball, which involves editing millions of cells. Nor would I be surprised if we never figure out how to edit the thousands of genes that help determine complex traits like intelligence or personality or height without also triggering unwanted effects. Some of those “intelligence genes” may have multiple effects, like an increasing risk of autism. We’ll have to walk a fine line there, or perhaps only target a few of the ones we know to be monogenic.

Where I remain hopeful and optimistic is when it comes to prevention of major health issues. Many of these conditions are monogenic, or close to it.

Huntington’s disease? Single gene. Scientists have already used CRISPR to target the Huntington’s gene and treat the disease.

Muscular dystrophy? CRISPR already cured it in (adult, humanized) mice without any off-target effects.

Obesity? Many genes contribute, but editing them one at a time shows promise. Consider common polymorphisms of the FTO gene which add about 3 kg body fat, increase energy intake without increasing expenditure, and increase the risk of Alzheimer’s and metabolic syndrome. CRISPR-editing the FTO gene in mice abolished obesity and made them totally resistant to an obesogenic lab diet.

Any recent parent has probably subjected their babies to the “newborn screening,” which uses blood draws to test for various diseases and disorders. Wouldn’t it be great to just eliminate those?

Or what about the fact that some people are more susceptible to tissue damage? I’ve got a genetic propensity towards damaging my tendons, ligaments, and other connective tissues that has been realized throughout my life; I’d love to have had that one altered from the start and can’t think of any real downsides, provided it doesn’t have any polygenic effects.

So we probably can make some edits and be reasonably secure in the outcome. But, as I said, having reasonable skepticism and asking the hard questions is healthy, necessary, and vital to the unrolling of this technology.

Those are my thoughts on the subject. I’m sure we’ll have to revisit this topic in the future, but I’d love to hear if today’s post assuaged any of your concerns about my perspective. Let me know in the comment section!

Thanks for reading and—as always—asking the hard questions.


About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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20 thoughts on “Dear Mark: Gene Editing”

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  1. will Dick Cheney live forever?

    I think he’s already lived too long, but that’s me. If it wasn’t for the LVAD keeping him alive long enough for the heart transplant, he’d already be a memory. Even though he now has a new heart, he’s still just as heartless as ever!

  2. I think the rise of superintelligent machines will displace far more human workers than anything else.

    Mark, you’re right in that one–robots don’t need lunch breaks, bathroom breaks, sleep, benefits, light, or social contact. They can be kept on-sight, powered up to work 24-7-365, and when the need arises, be stored in a basement (powered down) until needed again (such as holiday rush time).

    That will be the one thing that makes us humans (of any gene variety) obsolete.

    However, there is a bright spot: if they make us obsolete, just who is it that will be consuming the products made by these robots? PEOPLE WITH JOBS. If people don’t have jobs, then people cannot afford to consume. The whole employer-using-robots thing shoots itself in the foot. Employers are finding that out now, and raising wages to ensure some customers of their products–gotta keep the demand flowing, right?

    1. This is not a new problem, there are a lot books written about (utopia societies) and pretty much governments of the world will be forced to solve it soon. It is just question of How you get money and do you actually need money, search Internet for “universal income” and try to think outside the box (which is capitalism economy here). It would be just another big jump like from medieval kingdoms to industrial age, it was a huge shift in how life changed, for what it is worth right now people have quite incorrect understanding of history, because we project our way of living back and that is not going to work.

  3. I like your comment that “trying to counter nature never works well.” I think this also applies taking supplements in place of real, whole foods. Anyhow, when I think about the long term implications of gene silencing/manipulation, I can’t help but wonder if there are some severe detrimental effects that will be overlooked early and discovered later on. As far as single-gene suppression goes for curing disease, I’m all for it.

    1. Yes! This is my concern, also – that in experimenting on the DNA of the human race, something could go terribly wrong, which will then be passed to future generations.
      Our history of getting things right the first time is pretty lousy…just look at our SAD diet!
      In my view, CRISPR literally could be the way human beings finally manage to destroy themselves.

      1. Or who knows … some horrible biological weapon released by apocalyptic madmen that could wipe out the world’s population unless genetic modifications are made … CRISPR could literally save the human race. You know organizations are going to be experimenting with the technology and could potentially inoculate select populations then release some agent. Best to stay on top of this technology.

        1. I think I have to agree with Hombre that we best stay on top and understand it. When I think of all the human suffering that has been prevented with vaccines and antibiotics, and even hand washing before operations, it would seem cruel to go back in time and not do it.

          1. Amy – I believe the advent of clean water and safe sewer systems have saved more people than all the vaccines and antibiotic use combined.

          2. All of the above are good. When I did my ancestry research and saw so many infants and toddlers who died of issues which are non-issues now, I became very thankful for antibiotics. It was commonplace to lose several children then.

  4. There’s an aspect of CRISPR I haven’t seen addressed: population control.
    If we rid ourselves of disease, how will we feed ourselves?
    Primal food would get scarce fast.
    Or, do we edit genes to reduce frequency of pregnancy? Getting into rocky territory, there…

  5. Mark provides excellent advice and research each and every day and is one of the leading health improvement leaders out there. Regarding the previous forum, some folks were in an attack mode that started to get personal IMO. You can posit your take on a subject, even if you disagree, without resorting to name calling. As I opined the other day, we can’t bury our head in the sand on this technology, the potential to cure disease is too precious not to explore. Yes, ethical questions abound and must be grappled with.

    1. Completely agree, Healthy Hombre! I was (and still am) a little freaked out by some of the possibilities of gene manipulation, but I totally appreciate Mark tackling the subject, and revisiting it to explain further.

      1. Yes, Elizabeth. I share your perspective. I’m uncomfortable with some of this, but I like that CRISPR seems to work more with nature. Honestly, I haven’t taken the time to explore the subject. So, I feel that this post increased my understanding. I’ve been seeing references to articles about CRISPR on Twitter and have been ignoring them. There’s only so much information a person can take in at a time.

        Mark did an excellent job exploring all aspects of this technology – from the science to the natural psychological response. Now, I feel more prepared to tackle understanding and writing about it. There’s no point in hiding under a rock. For those of us from the “Brady Bunch” era, it’s tempting to opt out of the rhythm of life, which sometimes moves us uncomfortably forward. Although I may walk to the beat of a different drum, I don’t want to feel completely cut off from the culture in which I live.

  6. All interesting points, though trusting the science only to paid scientists as an ethically reliable source of human intervention is a shaky foundation considering revelations over the past 2/3 years about the level of scientific misconduct and outright fraud in the research/publishing markets and the mad scramble to limit access to raw data.
    One thing not mentioned yet regarding supply and demand is that, considering all your points, CRISPR seems destined to succeed as an intermediate protector of the food commodities / stock market system (corn, wheat, soy, etc) in which our government can continue to justify subsidizing the mega grain and big dairy markets and all their inflammatory results, including use of chemicals that cause long term epigenetic damage and create dependence on any medical system of one’s choice. With CRISPR, demand for items and services such as avocado oil and health coaching and intermittent high intensity training groups could stagnate and may indeed reach it’s peak within a couple years, as becoming healthy really will be placed squarely in the hands of the MDs, as opposed to the current increasing demands for non-chemical, regeneratively grown nutritionally packed food sources which the market was starting to respond to and which carry the potential to reign in the burgeoning costs of health care.

    1. Scientific fraud is nothing new. Consider Ancel Keys and his famous 7 country study about diets & cholesterol that turned out to be really a 22 country study, but the other 15 didn’t fit his theory so he eliminated them. Hence, 50 years of low-fat mess that is just now turning around.

  7. Hi Mark, there’s one thing about this whole genetic & epigenetic thing that I still quite don’t understand. When can the gene be turned on/off and when can’t it? For example (from what I understand anyway) things like down syndrome can’t be turned on/off, while things like MTHFR can (and that’s why people recommend to treat by actual health markers and not genetic alone). Which leads me to the next question, what type of gene is the CRISPR actually targeting? Thanks!

  8. In the approaching dystopian future where all the perfect cookie-cutter CRISPR people basically become the robots destined to take over society and attempt to eradicate all us “naturals”, can we all just agree on one thing??? We call in Will Smith to help lead our little tribe in triumphing over the threat to humanity that scientists unitentionally created when they began rewiring DNA and were overtaken by nefarious entities that used the well-intentioned discoveries for much more sinister purposes? Because, seriously, Will Smith is THE face of saving the human race from itself against all odds when bad guys stage a hostile takeover of civilization or when scientists accidentally cause mass destruction where opposite was intended, or a combination of the two (or even the off-chance hostile extraterrestrials somehow wind up in the mix:-)!!!

    Reading all of this seriously creates images in my head of Will Smith in some blockbuster movie similar to “I Am Legend” where CRISPR derailed is the central theme. The more I read, the more vividly my imagination conjures up scripting, scenery, dramatic background music, etc. And I see Will Smith as the main character! I can’t be the ONLY one picturing this while reading about CRISPR, right?!?!