A Crispr Conundrum: How Cells Fend Off Gene Editing

CRISPR is a great tool for learning about how cells operate, testing hypothesis, learning. Based on these results, the likelihood that edited cells would become cancerous will limit its usefullness in treating inherited conditions - UNLESS there is a way to temporarily disable P53 while the editing is taking place, and then re-enable it after the DNA has been edited (if the P53 doesn't retroactively fix the correction...)

I have always felt that Crispr was hyped too much and I am glad that it has become evident that tinkering with genes could have adverse consequences somewhere in the genome. Cancer due to unknown root causes is becoming very common at an alarming rate. Deactivating a cancer-fighting gene could have disastrous consequences and if that is what is needed for gene editing to work then substantial more basic research is needed to gain better understanding before companies tout Crispr as the best thing since crispy chips, a multi-million dollar business. Any biotech company that expects quick returns without sound backing of basic research needs to take a step back and find the gaps in knowledge and scale down dreams of taking sloppy work to the patient's bedside. Why have 100s of HIV vaccine candidates at the cost of billions of dollars failed to give us an HIV vaccine? Same reason. Insufficient stringent basic research. That is why this research high lighted by Carl Zimmer is such an eye opener and truly significant. FDA should take note.

Sounds like universe 1 scientists 0.

It is the ultimate arrogance for scientists to always assume a new technology will ""solve our genetic problems. Although they understand Crispr at some level, the idea that this amount knowledge would be enough to start biotech companies and cure cancers with it has always been a ludicrous pipe dream.

As an English and film major I can't help but compare real-life events to books and movies, and I have to say that this gives me a "Jurassic Park" shiver. Ever since I found out about Crispr a few years ago, the parallels between this JP have been unnervingly close. The bottom line is that we are playing with science balanced precariously between advantageous and dangerous. While I do agree that Crispr has the capability to benefit society in regards to curing genetic disorders, I don't get the feeling we have the self control to stop there. Hopefully the results won't be as disastrous as it was with dinosaurs, but I get the sinking feeling that this will come back to bite us in the butt. To finish with an appropriate quote: "Your scientists were so preoccupied with whether they could, they didn't stop to think if they should."

However well meaning this research is, and in truth it is fascinating to read about, it sets me in mind of scientists as little children playing at the margins of a vast, complicated, LEGO structure. One that is in a constant flux, whirling and morphing continually. A whirligig, the web, of life. They think in moving around a couple of little blocks at the edges, effecting some change, that they understand the vast thing before which they sit. They consider themselves wise and cautious students. They don't seem to comprehend this thing called the Butterfly Effect which this structure, call it what it is - Mother Nature, uses to maximal effect in all her variety. And they certainly don't seem to realize, while engaged in tampering with their curious hands, that they're playing with a sleeping Godzilla. They, and we, should be careful how we poke, prod and try to rearrange. We may not like it much should we wake the monster. John~ American Net'Zen

The body is holistic... Transplanted organs require medicines to suppress rejection for pretty much the rest of one's life. As the saying goes, the hip bones are joint to the leg bones. Any bionics require a lot of reworking and relearning of the nervous system. So Crispr is more a norm than an exception. Not a conundrum but an infancy of truly understand how the estimated 20K genes of a human body interact. What could be turned on when they were once dormant when a relevant event is triggered

“…it was easy to cut genes from the cancer cells [probably with a disabled p53 gene]…” "The scientists found signs that Crispr had caused p53 to switch on..." are not these findings interesting by themselves? what if you already have cancer cells, probably with a disabled p53 gene, or get cancer cells from environmental or other genetic factors?

I'm not too concerned about this; if anything the p53 defense that kicks in on a Crispr edit attempt is not unlike a disk's write-protect switch. It seems a matter of switching off p53, doing the edits, then bringing p53 back up ASAP. I can imagine this becoming a vaccine-like preventive measure in childhood, preferably for the narrow purpose of preventing cancer and other gene foes and (of course) single-payer'd for all. What does concern me is that patents appear to be granted not just to this but to the genes themselves. Those ought to be immediately void, as should patents for the editing technology (and other inventions) if the danger proves too great. Nature and mere ideas must never be claimed by individuals, let alone corporations, or we dignify "thoughtcrime".

This is another example of the hype cycle. https://en.wikipedia.org/wiki/Hype_cycle First, a new discovery is unknown outside of the specialist literature. But its use starts growing and the number of papers on it starts to increase exponentially. Then a couple of articles appear in e.g. Science News and Scientific American. Quietly, investors are already funding companies trying to exploit it. Then it hits the mainstream media. People's expectations rocket to the stratosphere, and companies investing in the new technology see their stock prices skyrocket. There is frenzied speculation about how the new technology is going to transform everything within the next few years. Techno-utopians have a field day. Eventually we hit the Peak of Inflated Expectations. Then the downturn begins. Some problems begin to become publicly known. Investors get leery and pull back. It becomes obvious that this new tool isn't a silver bullet, and it is going to take a while to learn to use for practical applications, outside the lab. Techno-utopians become disillusioned and move on to the Next Big Thing nearing its own Peak. But, quietly, the real work goes on. Five or so years later, the advance really is in production as we climb up the slow "Slope of Enlightenment". The tech is not a panacea, but it's clearly useful. Work continues, and some products hit the market/clinical trials. By the 10-15 year mark, the advance has slipped into the mainstream, used for all sorts of applications.

The difference of CRISP intolerance among p53-containing normal cells may point to potential new cellular ways that stop mutational activity, perhaps more ways for cells to allay cancer.

Another example of why life science and the study of nature is so much harder than computer science and the control of man made systems.

"They set out to develop new versions of Crispr to edit the DNA in stem cells. They planned to turn the stem cells into neurons, enabling them to study brain diseases in Petri dishes." This is where the money and the effort should be concentrated if we are serious about suicide in particular and diseases like severe depression, bipolar disorder, scizophrenia, etc. The research money going into cancer dwarfs by orders of magnitude the money going into brain diseases. We need these researchers to speak up about the stigmatization of "mental Illnesses" and to educate society that the brain is a physical organ subject to the laws of physics, chemistry and biology like the heart and the liver. All brain diseases are physical illnesses.

A natural mutagen actually limits the extent to which gene editing can be compelled by external forces? Whoa.

As pure scientific pursuit, this is well and good. To me, p53 sounds like a strong signal Mother Nature tell us, don't mess with it.

While scientists are always looking for a cure for cancer and CRISPR seems to be a new tool. However, you have to wonder why scientists are not trying to halt the creation of cancer through prevention and getting rid of the environmental and human factors that cause cancer in the first place. Solar power would eliminate pollution that causes cancer. Electric cars charged by the sun would be welcome. Cutting out coal powered electric plants would help stop pollution. Prevention is another avenue in dealing with cancer.

As has been claimed prematurely with so much in science, much remains to be learned about CRISPR and gene editing. The exuberance notwithstanding, the underlying premise that somatic mutations cause cancer remains unproven as previously published by us in "Somatic Mutation Theory - Why it's Wrong for Most Cancers" https://www.ncbi.nlm.nih.gov/pubmed/27160408

p53 may reduce the effectiveness of CRISPR, but there are abundant examples of p53 positive cells being edited using CRISPR, including embryos and stem cells. It's an interesting academic finding, and not especially surprising, but probably won't significantly slow CRISPR use.

So this is why our planet is dying? Because the humans on it in trying to play God are trying to make it look like the way they want it to look? Seems only natural then that the cells would react the same way too. They’re just little planets anyway.

Human beings never fail to amaze in their capacity for wishful thinking and their inability to properly anticipate consequences. Oh, this awesome new technology may cause cancer or ruin your eyes (see Lasik article), but don't worry about it! Technology is always good! Corporations care about you...which is why the article ended with talk of stock prices and not reassurance about the actual Crispr technology. They are assuring us that future non-Crispr molecules will be way better and that stock prices won't change their plans to destroy humanity. Good luck, guys!

Crispr "breaks DNA" and we are now surprised that other cells respond to this breaking in ways that were apparently not anticipated? Again, we are reminded that the natural world is far more complex than even the worlds leading scientists understand.