The CRISPR Apple On the Tree of Knowledge
The title of this sermon is identical to the title of a conference I just attended on Star Island, a little bit of heaven out in the ocean 10 miles off the coast of Portsmouth, NH. We gather there each year under the auspices of the Institute on Religion in an Age of Science of IRAS, the oldest organization in the world dedicated to the dialogue between religion and science. We come back each year for most of us find that being surrounded by 360 degrees of horizon gives us a perspective on large problems of humanity and the natural world.
This year we caught up with one of the most radical developments in the world today: the power of precise editing of genomes of plants, animals, humans all life forms using a new technology called CRISPR.
To most of us, the first association of the word crisper in our minds is the name refrigerator makers have given to the plastic drawers in the bottom of the fridge which are supposed to keep vegetables fresh longer. If you’ve ever cleaned out limp carrots, soft green peppers and wilted celery from this drawer, you know that it often doesn’t live up to its name.
But that drawer is not what I’m here to talk about this morning. The CRISPR I’m talking about this morning does not have an E in it, and the word itself is an acronym, a word where each letter stands for another word, like NATO stands for the North Atlantic Treaty Organization. One of the first speakers on the subject of CRISPR at the conference I attended last week on Star Island started out by trying to get us to remember the words in the acronym, and I found it pretty helpful, so I’ll do the same now. The acronym is C-R-I-S-P-R and that stands for Clustered Regularly Interspaced Short Palindromic Repeats.
Let’s start with that word palindromic. It’s the adjective form of palindrome, which is a word or phrase that reads the same backwards as forwards. We’ll be talking later about the Garden of Eden story, but in some versions of that story, the very first words the first man spoke in introducing himself to his new mate were a palindrome: “Madam, I’m Adam” You see how it reads the same backwards and forwards. Other favorite palindromes include
“A man, a plan, a canal – Pamana!”
“Red rum, sir, is murder!”
“Was it a cat I saw?”
At the Star Island Conference, our own Frank Toppa illustrated a musical palindrome by playing a Bach piece called the Crab Canon first forward, then backward, then backwards and forward at the same time. He’s done the same here at the Meeting House too.
The CRISPR technology was first discovered in the way bacteria defend themselves from invasion, but now it has become a powerful tool of gene editing. What does it have to do with palindromes?
Well the two strands of the DNA molecule coil around each other like twisted ladders. And each connection of a rung of the ladder to the rail of the ladder is one of four nitrogen bases labeled A, G, T or C. The sequence of these four on the two strands may look random, but there is order to it.
As I understand it, you might have on a particular gene strand a sequence of the four bases such as this A T G T A C A T G T A C C T G T and there would be of interest because there are two palindromes in that sequence.
As I understand it, CRISPR did not get invented in order to edit genes, it was a natural process in the biology of bacteria. To understand this, I suggest you look at the diagram printed on the trifold insert in your order of service. When we are discussing Adam and Eve and the creation of the human race in a religious context, we often talk about the tree of life, and there are many ways people have drawn such a tree. But this is what the scientist sees as the tree of life. The first division of all life is into two domains: the eukaryotes and the prokaryotes. Most of the plants and animals and life-forms with which we are familiar are eukaryotes. Eukaryotes have cells in which the genetic material, the DNA, is contained in its own little sac called the nucleus. The prokaryotes cells don’t have a nucleus, the DNA strands are free-floating.
The prokaryotes also are two domains: the bacteria and a mysterious group called the archaea, which as the name suggests, may be the oldest life forms on earth. They used to think that the archaea were only in extreme environments like the plasma vents at the bottom of the ocean, but in the last decades, they have found new families of archaea in more common environment, including your gut.
Now that’s a lot of basic science, but it’s summarized in the first verse of a cute little song recently written by an entomology graduate student in Rhode Island:
Of three domains of all life, eukaryotes are we,
Inside each cell among us, a nucleus there be;
Bacteria, archaea, unfortunate are they,
They have no membrane wound around
Their strands of DNA.
Why am I telling you this? Because CRISPR was discovered, not invented. It was a process observed in bacteria to police its DNA. Once hostile DNA code had been eliminated from a bacterium’s DNA, the DNA somehow remembered this and when a new invader is detected, the DNA can recognize it and edit it out of the gene.
This process had been identified in bacteria and it was impressive in its precision. You see the double helix structure of DNA makes it hard to cut precisely, but somehow CRISPR could cut just where it needed to be cut.
Bacteria are interesting and important, but a lot of our concern is with the other domain, eukaryotes, and so the question arose, could the CRISPR process be adapted to edit genes in Eukaryotes, which meant in plants, animals and humans and the rest of life. That was the breakthrough which led us to the present.
It has become a surprisingly cheap and simple technology. If you go on Amazon right now and do a search for CRISPR, you will find that you can get a do-it-yourself CRISPR editing kit for $139. Hey, kids, let’s edit some genes!
Now let me name the horror that this raises: the fear is that we will soon have an unregulated population out there playing God with the genome of all living things, including the human. Franken foods, Franken flowers, Franken pets, Franken people.
But even if we didn’t have do-it-yourself kits sold on Amazon, there is plenty of CRISPR work going on at labs all over the world right now. It is big business and it will become bigger, and the lure of big money may weigh against ethical standards. The decisions may stay in university labs, where they can be overseen by ethical boards, but given the money to be made, there is an equal chance that they will locate in start-up companies in the developed world or offshore.
There are so many ramifications of CRISPR technology that we’d be here a week just cataloguing them all. What I want to concentrate on in the time remaining this morning is a religious dimension to all this.
Let’s start with the Garden of Eden story, which is the second creation story in the book of Genesis in the Bible. There is a garden created by God, and before he creates anything else, God gathers some dust together and breathes life into the dust, creating the first male human. He then makes the other animals as companions for the first man, but Adam still feels lonely, so God pulls a rib out of his side while he’s sleeping and fashions it in to a woman. Man and woman are naked as jaybirds but don’t know it, because after all, all the animals are naked.
Now the story says there are two trees growing in the garden, the tree of life and the tree of the knowledge of good and evil. God doesn’t give any instruction about the tree of life, leaving the tantalizing possibility that if Adam and Eve had just had a piece of fruit from that tree, we would all be immortal today. But God did give instructions on the other tree, and told them that if they ate that, they would die. This apparently roused some curiosity in Eve. Why that tree? What’s so bad about knowing Good from Evil?
Enter the serpent. He said, God’s lying, you’re not going to die if you eat that fruit, you’ll just become like one of the gods. So she and Adam eat it, and then they realize they are naked, and their attempt to cover their nakedness is a dead giveaway of their guilt when God comes walking in the garden later. The punishment God imposes is that they have to move out of the garden, Adam has to work by the sweat of his brow for a living, Eve will bear children in pain, and both will eventually die, as will their descendants.
Now this is a Jewish story, but the Jews have not agonized over it. But Christians have moved it to center stage. St. Paul had the idea of using this story to promote the idea that Jesus’s death was to atone for the sins of the world – “as in Adam all die, so in Christ shall all be made alive.” Four centuries later, St. Augustine got hold of Paul’s spin and worked it into his idea of Original Sin, that Adam’s disobedience tainted the entire human race, even innocent newborn babies, with a pall of sin which would condemn them to eternal torment unless they were lucky enough to receive God’s grace through Christ.
So the lesson that orthodox Christianity wants us to take from this story is that humans should know their place. God is God, infinitely wise, infinitely good and infinitely powerful and we should not attempt to know what God knows, we should not attempt to become as gods.
This reading mirrors an older myth: the Greek pagan legend of Prometheus. Prometheus was one of the Titans, the first generation of divine beings and while Zeus and the other Titans were occupied, Prometheus created humans. Zeus was mad about this, but then Prometheus made things worse by giving the power of fire to the humans he had created. Zeus punished Prometheus by having him chained to a rock, where an eagle flew upon him every day and devoured his liver. The Greeks were apparently aware of the medical fact that a human liver with a portion removed will regenerate itself, for the legend is that Prometheus’s liver regenerated every night.
Adam and Eve disobey God, and God’s punishment is carried out on their descendents, which includes you and me. Prometheus disobeys Zeus and gives fire to humankind, and Zeus’s punishment is meted out on Prometheus’s body. A third myth which ought to be compared with these two is the story of the tower of Babel in Genesis, where God is concerned that the humans are erecting a tower which will allow the humans race to visit heaven anytime they choose. This will allow humans a God-like power, and so to thwart this project, God creates languages and makes it impossible for the humans to understand one another.
The moral of all these stories is that humans need to know their place and must not aspire to be as Gods. Thus do the great monotheistic religions – Judaism, Christianity and Islam – teach us an ethic of humility. Eastern religions, by contrast – Hinduism, Jainism, Sikhism, Buddhism, Taoism – extol human progress as steps towards enlightenment. Humans should want to overcome delusion and understand the true nature of things. Salvation in these religions is variously defined, but it all involves a deeper understanding of the world and the place of humans in it.
This Eastern approach is also consonant with Universalism. Our Universalist forebears rejected Hell and rejected the punitive God of Calvinism. Rather than being condemned as the source of human sin, Eve should be praised as the first scientist. She dared to put a divine command to the test, and in fact what she showed was that God had instructed them wrongly, for neither she nor Adam died as a direct result of eating that fruit. She should have been awarded a Nobel prize.
More importantly, our Universalist forebears took pains to point out how destructive it was for the West to labor under the myth of primeval perfection. We could never get back to the Garden. Albert Ziegler, in the reading I did a moment earlier, makes clear that this is because we never were there. There may have been a state in which humans ran around with no clothes and did not know they were naked, but this was not a state of any moral perfection. It just was a state of clotheslessness. All the geologists, paleontologists, geneticists paint the same picture. Humans were not placed in nature first or specially created. Humans evolved out of nature, more complex forms out of simpler forms through the staggeringly beautiful process we call evolution.
Why do I go to such lengths to disown the creation myth common to three world religions? Because I agree with the Universalist critique that it is time to emerge from its shadow.
The idea that there was no primeval state of perfection, and thus no fall from that state, is not restricted to Universalists of half-century ago. It was preached in the fellowship which became this church by Peter Fleck; one of his best sermons, which gives its title to one of his books of essays, is called “The Blessings of Imperfection.” In the language of today’s computer programmers, imperfection in humans is not a bug, it’s a feature.
This myth of primeval perfection persists today in the assumption that anything which is “natural” is good for you. We had a speaker who had spent his career in the US Dept. of Agriculture, and he was asked whether we should be consuming organic foods. He said the law was set up so that anything a farmer put on her crops by way of pesticide or herbicide which was synthetic, human made, had to meet some rigorous tests to ensure it was safe, but if the farm production was labeled “organic,” it did not. Natural substances got a pass and did not have to meet the rigorous safety standards of the human-made products. But of course there are plenty of things in nature which can harm humans.
With that background, let’s look squarely at the claim that genetic manipulation of plants, animals or humans should be off-limits because it is “playing God.” This claim invokes the whole notion of hubris. But I have a counter myth: humans were put here to use the brains that evolution has given us to solve problems facing us. In the next two decades we will see the earth’s population increased by two billion people. The planet cannot possibly feed that many without significant advances in agricultural technology, some of which will involve CRISPR modification to crops. We have the technology to do this without making a complete hash of the biological genome.
Speaker after speaker at the conference advocated being cautious and thoughtful, but advocated going ahead with gene editing of plants and animals. As to humans, there is a world of difference between editing genes affecting the current conditions of the body, the soma, which affect only a single individual in one generation, and editing the germ-line or reproductive cells, which would impact future generations. The Chinese doctor who had performed gene editing on the twin children to remove a threat of HIV/AIDS found no defenders at the conference.
It is a scary time, and I think we all need to pay attention to the work that is going on around us. I think a bright line can be drawn between germ-line editing in humans and all other uses of CRISPR. I am not a person who shuns GMO foods, for I can’t see how genetic modification of what I eat can make any difference once the food is in my digestive tract, and genetically modifying plants to make them more pest-resistant diminishes the use of pesticides which can harm the consumer.
We talk about GMO foods as Frankenfoods, but that recalls Mary Shelley’s nineteenth century novel Frankenstein, which was a sensationalist warning about trying to create life. By the way, the title Frankenstein was the name of the doctor who created the monster, not the monster itself. Mary Shelley selected as the subtitle of her novel “The New Prometheus,” adopting squarely the mythical tradition I have been describing.
I think we need to sweep away the categorical commands of that Promethean mythic tradition. One quote I heard during the week from Carl Sagan, I think, said “we don’t have a choice about playing God, so we’d better get good at it.”
And to circle back around to Prometheus and his liver, the most moving moment of the week was one of the evening chapel services, conducted by Katharine Houk, who has been one of my best friends in the organization since I arrived there in 1997. In the last decade, Katharine developed a rare autoimmune disorder which produced a kind of hepatitis that did not respond to medical protocols.
As she advanced into her sixties, the prospect for a liver transplant donor waned. Many of us in IRAS volunteered, but we were not medically matched. She had to transfer her medical care out of New York State, for that state restricted organ donors to those related by blood or with a close personal relationship with the recipient. In her chapel talk, she told the improbable story of how she matched with a donor: a man in his late 20's had parents with big hearts who ran a foster home for children with rare diseases. This young man had been willing to give a portion of his liver to one such foster child with a rare disorder, but the child died before the operation could be performed. The medical team, knowing of Katharine’s need, asked him if he would be willing to donate to her. He agreed, the operation was a success, Katharine a year later met the young man and they have become friends. She has now become what is known in the gene editing business as a chimera, a person with two sets of genes. She has Y chromosomes, so she is genetically partly male.
I listened to her story and wept. I realized that we are all interconnected one to another, and without that interconnection and a lot of luck, my friend would have been resting in her grave instead of standing before me telling her story.
That’s why I came back from Star feeling some trepidation about the brave new world we are entering, but also excited for its prospects. Amen.
Reading Ziegler, Albert, Foundations of Faith (Boston: Universalist Publishing House 1959) p. 41
If free will means anything significant, it must mean that somehow, to some degree, man has the
ability to act without regard for influences on him, without regard to laws of the universe to which other parts are subject. As such, freedom is an evil too awful to contemplate. If, out of the freedom of his will, man has chosen to do wrong (and reason tells us that he has done and does do wrong) there is no force on heaven and earth that can move him from it. His case is hopeless. Even the religion which weeps over his plight is powerless to help him, as it has decleared him beyond influence.
“What awful ailment seemed to us to call for such a noxious remedy? The problem of evil, the fact that man does not do as he ‘ought’ to do; in short, the dilemma of man’s imperfection. The whole structure fails when we realize that it provides a solution for a dilemma which does not exist. Imperfection exists, but it is not a dilemma. Orthodoxy supposed a completed universe, a perfect, finished creation, and so finds a problem in the existence of imperfection in it. Reason, and any healthy faith which illumines it, must know that the universe is moving on, not running down; that the universe is in process; that life did not begin in perfection but, in the working out of a perfect purpose, is still moving from chaos into order. What is more natural, then, than that there is imperfection, in the universe and in man?”