I had originally written this story in March 2018 on my Wordpress blog. Cross posting it here for better reach. It talks about a future where gene editing has become common, and the strange consequences the technology can bring with it. It is technical, because I wanted to explore the possibilities of where gene editing can take us.
At the time of writing the story, I did not understand the difference between Somatic and Germline Gene Editing, so people with more knowledge of the topic than me might find my story far fetched.
Note: All the technology mentioned in this article already exists as of 2018. Human gene-editing has already started happening.
Vaibhav sat in the coffee shop astounded by what he had just seen. His partner Rashmi came and sat beside him, holding two cups of coffee.
Dr. Vaibhav Damle and Dr. Rashmi Agarwal were owners of BrightFuture Clinic (BFC) in Mumbai. BFC specialised in human gene-editing using CRISPR, and was the leader in this field in India. The clinic had gotten licenses, technology, and commercial patent rights before other clinics had realised what was going on. They had built upon the technology and invented their own procedures that gave them a lead of a few years over anyone else in the country.
Here’s a short explanation of how this technology works. Bacteria have a defence mechanism against virus, where they store snapshots of virus genes in their own DNA after they’ve successfully killed that virus. The next time they encounter that virus, they are able to recognise the enemy by matching the DNA, and then go and destroy that exact gene. Scientists saw this happening, and succeeded in using this to perform DNA modification in other organisms, including plants, and animals including humans. Let’s say a person has a gene X which they want to replace with a gene Y. Scientists took the bacteria, and replaced the virus’s gene with X. Then they injected this bacteria into that organism. The next time the bacteria encountered the gene X, they destroyed it, and left everything else intact. Thus, the scientists were able to cut out unwanted genes from organisms with precision. To achieve the second part of the procedure, when they injected the bacteria into the organism, they also injected the gene Y. Once gene X was cut, and the body saw gene Y floating around, it check if Y was homologous (meaning it belonged to that position in the DNA where the cut had occurred). Once that is verified, the natural repair mechanism would assume that Y is the gene that was originally there, and somehow got loose. The repair mechanism would then put Y in place of X to complete the repair.
With CRISPR, scientists and doctors were able to perform gene editing reliably. It was also relatively cost effective.
Over the last three decades Vaibhav and Rashmi had used this technology to help thousands of people get fitter, stronger, taller, and lighter skinned.
On this day, they were sitting in a coffee shop outside a pre-school. They had just seen something that they’d never seen before.
The class teacher had noticed it the day that year’s kids joined. Out of the 42 kids in the class, 18 looked like siblings. Their looks were so similar that it was difficult to tell them apart. The class teacher knew that it was related to gene-editing, but was not sure how, and had asked Vaibhav and Rashmi to visit. She had noticed this trend in the last few years too, but not at this scale.
“I know gene-editing is involved, but I don’t know how”, said Vaibhav. “The numbers don’t add up. There are over 3 crore people in Mumbai. Only thousands have gotten their genes edited. The number is probably less than 1 lac, leading to a ratio of 0.03%. I understand that the demands of the rich are the same — taller, skinnier, lighter-skinned, with a different nose and better skin. And these children come from that crop of rich people. But the numbers don’t add up! It is not possible for kids of different parents to end up looking so similar to each other.”
“Don’t forget”, replied Rashmi, “that this is a rich Parsi neighbourhood. Parsi marriage with other communities is relatively infrequent, because anyone marrying a non-Parsi is no longer in the religion. So they have a small pool to choose from, esp for arranged marriages. Plus the Parsis in this neighbourhood are rich, so they have the money to get modifications done.”
“Even then, you would only see marginal increase,” said Vaibhav, with a tone of frustration in his voice. “ All parents don’t get the same gene enhancements done. Some get their eyes modified, some get their nose modified, and others focus on intelligence, temper, compassion, eyesight, fitness, height. They all have different areas of focus, even though the demands are similar. How did all these kids inherit all these characteristics, and end up so similar to each other? Even if there was extra-marital sex involved, or sperm donors involved, these ratios don’t make sense.”
And suddenly it struck Rashmi. It was something she knew was possible, and could happen, but she could not imagine it happening while she was alive. “I know,” she said.
“There are three things going on at once. First, the generation that started getting themselves enhanced are now starting to become grandparents — they originally got themselves modified 30 years ago. The generation following them got some more modifications, got a little closer to the ‘perfect image’. Thus it is expected that these kids will look more similar to each other, since they have genes with 2 generations of modifications.”
“Second, there is some sperm sharing going on. It could be because of a man who slept around with a lot of women, or it could be a sperm donor, or both.”
“The third, and the worst,” she continued, “ is that gene drives are playing a role here.”
Rashmi was referring to a powerful feature in gene-editing technology. There was a small flaw in the original gene editing technology. While the organism whose genes were edited had a 100% probability of getting that enhancement, the offspring had only a 50% chance, since the other parent might have a different gene. Thus even if you replaced the malaria carrying gene of a mosquito, there was very little chance it would cause an eradication of the malaria carrying gene, because the chances of the future generations getting the replacement gene would reduce every generation.
A technology called gene-drives overcame this. Gene-drive is a gene that has more than 50% probability of replicating in the child. Some gene-drives are naturally occurring. Naturally occurring gene drives were first documented in the 1940s, but CRISPR enabled scientists to construct them artificially.
Let’s call the original gene X, which is supposed to be removed. Let’s call the replacement gene Y. The bacteria used a protein called Cas9 to cut the gene, and RNA to identify the gene X to be cut. Thus RNA + Cas9 are effectively gene-scissors. Scientists found out a way to tightly bind a copy of the gene-scissors to the gene Y and called the combo a gene-cassette. So after the scissors cut X, the DNA repair not only put Y in its place, it put Y + gene-scissors. When the organism reproduced, the copy of scissors embedded with Y would cut the neighbouring gene X that came from the other parent, and replace it with the Y + gene-scissors cassette. Thus every gene would be eventually replaced by this combo. This could be used to change an entire species.
The gene-drive technology had taken off after Bill Gates had put $75 million USD into its research. This technology had been used successfully to alter entire populations of species, and had helped eradicate malaria from the planet. Vaibhav and Rashmi had decided never to use gene drives on humans, but apparently someone else had been doing it.
“The Gene Drive Technology is causing this”, said Rashmi again.
Vaibhav had a nauseated look on his face. “This makes me sick,” he said. “We all knew the power of gene drives. But it was a common decision amongst all of us that we’ll not use gene drives in humans. It’s like forcing your genetic choices upon someone else, and not letting it be a choice between this gene or the other parent’s gene. It is unethical. It almost seems criminal to me. What will people do now? What if they end up having babies with a person with a gene-drive?”
Rashmi thought for a few moments, and then spoke philosophically, “Do you remember a song called ‘Little Boxes’? It was a satire on the mentality and life of the upper middle class. It had this paragraph — “
“ And the people in the houses
All went to the university,
Where they were put in boxes
And they came out all the same. “
“The words of the song are now actually coming true.”
Originally published at http://aspoonfulofgyan.wordpress.com on March 30, 2018.
