A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution

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CRISPR is the basis of a genome editing technology—the latest breakthrough in the grand tradition that began over 400 generations ago when we started to grow wheat and rice instead of just picking its wild cousins. We bred cattle for milk and meat, horses and oxen for labor, and dogs because they were useful, and anyway we liked them. We graduated from the banks of the Euphrates to Luther Burbank’s 800+ strains and varieties of plants. We didn’t understand the process but we did know enough to make a good thing better by selective breeding.

In the past couple of centuries our understanding of how our planet works has increased exponentially. We now face a vast jungle of detailed knowledge, more than any individual can understand in its entirety. We have specialists who can understand portions of it, and people who can relate those parts to the whole, and a lot of other people who don’t understand nearly as much as they need to. Meanwhile there are many experts in well-funded labs addressing parts of big and complex problems.

One benefit from all this recent growth is that science has been able to probe the inner workings of many mysteries that had eluded individual geniuses in earlier times. We’ve graduated again, this time from Luther Burbank to molecular physics and the nature of life itself.

In this new environment, discovery has many parents. Jennifer Doudna, a professor of chemistry and of molecular and cell biology at UC Berkeley, came up through a rigorously selective process to work first in someone else’s lab, then in one where she was the boss. She didn’t discover CRISPR, nor does she say she did; she was just one of the people who led the charge.

The first half of her new book, written with Samuel Sternberg and titled, A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution, describes the nature of that charge. It is too technical for the lay reader, at least this one. Just take the word CRISPR, an acronym, and spell it out: Clustered Regularly Interspaced Short Palindromic Repeats. See what I mean?

The book does try to explain why this isn’t just gobbledygook, but Doudna’s explanations require further explanations which you don’t find until you look for them, and then those explanations often require further explanation. I gave up at one point and rattled off my own stream-of-consciousness translation, which I offer here as a substitute for those too lazy to opt for a more authentic explanation of why CRISPR is important. Here goes:

Think double helix, and DNA. Think a typewriter that lets you erase or replace or insert DNA’s “letters” one at a time almost, or at least  in small groups. The genome has many letters, so each one is small. The best we’ve been able to do so far, when we want to get rid of bad DNA, is delete chunks of the letters—ponds not droplets. That’s okay if we don’t care about the stuff in the rest of the pond that came out with what we wanted to delete, but some of that may also be for something, and are there unforeseen consequences? And what if we’re inserting a chunk, not deleting, do we care what else in that chunk we are adding? Same thing. Yes, being accurate and specific and limited in what we change is important. And that, dear reader, is the point, the main point, about CRISPR. It’s not only easy to use, it’s about as precise as a typewriter, or will be once it’s been perfected. We have a tool that is an automobile compared to the horse and buggy we used to have.

If that explanation doesn’t satisfy you, tackle the first part of the book. You’ll not only have the full monty by way of explanation, you’ll also have a front row seat for what it means to be a class-A researcher with your own lab and all the personnel and other problems that entails. The rest of us can proceed to the second and final section, which also gets into some pretty complicated details but is focused more on the implications of this new tool, especially how we may decide to use it.

Doudna sets the stage for the “What Is It For” section with this:

CRISPR gives us the power to radically and irreversibly alter the biosphere that we inhabit by providing a way to rewrite the very molecules of life any way we wish… At the moment, I don’t think there is nearly enough discussion of the possibilities it presents—for good, but also for ill.

The key issue here is whether CRISPR should be used to alter the germline of human beings in ways that make the changes heritable. Are we going to alter the genetic code for our own species and create a population that will, for all time, be resistant to diseases that are otherwise incurable? Do we go on from there to “cure” features that we now consider undesirable? Make less intelligent people smarter?

We can use CRISPR to treat difficult diseases without making the immunity hereditary, of course, and a lot of that is already happening. To make the changes hereditary one has to make them in the embryo, before it completes the process of defining the code that will govern the formation of the new individual. If only one parent has a cell for Tay-Sachs, for example, and you knock it out, you eliminate the 50-percent possibility that the child will carry the disease. That would have been a sure thing in the unlikely event both parents have the same defective “letter” in their codes. And you can be pretty certain that that child, if it undergoes CRISPR, will never either have the disease, or carry it as a latent gene. As far as your bloodline is concerned, your action has eliminated the errant gene and rendered Tay-Sachs extinct.

No issue, you say, do it. But what if that recessive gene is valuable and you hope someday to produce a Wolfgang Amadeus Mozart or an Albert Einstein? Or, more likely, what if the world is arranged into two camps, with opposing views on this kind of issue? Who decides?

This question of who decides is going to surface from time to time over CRISPR-related issues. For the time being humanity may squeak by, by referring key decisions to some expert body, and that is probably the most we can accomplish until the world gets better at self-governance.

Another ethical issue might arise when some CRISPR-related action is proposed that either renders an existing species extinct or introduces a new one. There may be arguments based on specific gains or losses to human groups, but a larger issue might arise that could potentially affect all humanity. If we eliminate all mosquitoes wouldn’t we all benefit? Or would we, by eliminating an important food source for other species, set up a chain reaction that could prove costly? Again, this problem shouldn’t be resolved on a narrowly construed, cost-benefit basis but by a consensus including people with a broad understanding of the possible environmental consequences.

Doudna and Sternberg describe the use of animals in their laboratory and others. Mice are preferred to monkeys because they are more readily available, cheaper, and breed faster. Doudna wasn’t concerned with possible animal rights, and whether they attached more to monkeys, but others could be. This is a possible issue for humanists in the broader CRISPR context.

The least sensitive issues are already in the hands of patent lawyers and merchandisers. Doudna gives some amusing examples, like the Chinese firm that developed a dwarf pig that proved so amusing it was sold not for sausages but as a pet. It follows that there are different kinds of CRISPR issues, and a one-size-fits-all solution for settling them won’t suffice. A Crack in Creation gives plenty of examples.

Judging from Doudna and Sternberg’s book (brand new as it was only released earlier this year), the question of “Who controls CRISPR?” is very much up for grabs. In 2015 Doudna and some colleagues met in the San Francisco Bay Area and produced a paper that was published in Science on March 19, 2015, titled “A Prudent Path Forward for Genomic Engineering and Germline Gene Modification.” She lists four recommendations in the article, which strike me as a useful summation of where we stand at this moment on the whole CRISPR issue:

First, create forums to advise the public on both the scientific and the ethical issues involved;

Second, continue testing and developing the CRISPR model;

Third, convoke an international meeting to discuss relevant safety and ethical implications; and

Fourth, all scientists should refrain, for the time being, from “attempting to make heritable changes in the human genome.”

The last was the key. Let’s all hit the pause button on human germline changes until further notice. But will such a prohibition stick?

That’s where we stand right now. Is this an issue that concerns humanists? Of course, we are centrally concerned about the future of humanity and this germline issue goes right to the heart thereof.

Doudna expresses concern about the gap in understanding between the scientific community and the public. I agree. Can we do more to close that gap? On this issue, perhaps. Let’s try.

Predictably, the question of who controls CRISPR will soon be seen as a critical issue important to all humanity, comparable to climate change and the threat of nuclear war. Like the other two, it cannot, or at least will not, be settled by the United Nations as long as the UN remains subject to the vetoes of the more powerful states. Could this issue eventually provide the straw that breaks the camel’s back and persuades the big countries to surrender some of their precious sovereignty on the really big issues? Probably not, but it’s too early to be certain.