How Can Gene Editing Eliminate Lyme Disease?

Group Reading Project

As a group, read the following article and annotate important topic sentences and vocabulary words. After each section, you will pause to discuss your annotations and complete a task as a group. Your group can choose to read silently or read together.

Rewriting the Code of Life

(http://www.newyorker.com/magazine/20...e-code-of-life ) - abridged

Early on an unusually blustery day in June, Kevin Esvelt climbed aboard a ferry at Woods Hole, bound for Nantucket Island. Esvelt, an assistant professor of biological engineering at the Massachusetts Institute of Technology, was on his way to present to local health officials a plan for ridding the island of one of its most persistent problems: Lyme disease. He had been up for much of the night working on his slides, and the fatigue showed. He had misaligned the buttons on his gray pin-striped shirt, and the rings around his deep-blue eyes made him look like a sandy-haired raccoon.

Esvelt, who is thirty-four, directs the “sculpting evolution” group at M.I.T., where he and his colleagues are attempting to design molecular tools capable of fundamentally altering the natural world. If the residents of Nantucket agree, Esvelt intends to use those tools to rewrite the DNA of white-footed mice to make them immune to the bacteria that cause Lyme and other tick-borne diseases. He and his team would breed the mice in the laboratory and then, as an initial experiment, release them on an uninhabited island. If the number of infected ticks begins to plummet, he would seek permission to repeat the process on Nantucket and on nearby Martha’s Vineyard.

More than a quarter of Nantucket’s residents have been infected with Lyme, which has become one of the most rapidly spreading diseases in the United States. The illness is often accompanied by a red bull’s-eye rash, along with fever and chills. When the disease is caught early enough, it can be cured in most cases with a single course of antibiotics. For many people, though, pain and neurological symptoms can persist for years. In communities throughout the Northeast, the fear of ticks has changed the nature of summer itself—few parents these days would permit a child to run barefoot through the grass or wander blithely into the woods.

“What if we could wave our hands and make this problem go away?” Esvelt asked the two dozen officials and members of the public who had assembled at the island’s police station for his presentation. He explained that white-footed mice are the principal reservoir of Lyme disease, which they pass, through ticks, to humans. “This is an ecological problem,” Esvelt said. “And we want to enact an ecological solution so that we break the transmission cycle that keeps ticks in the environment infected with these pathogens.”

There is currently no approved Lyme vaccine for humans, but there is one for dogs, which also works on mice. Esvelt and his team would begin by vaccinating their mice and sequencing the DNA of the most protective antibodies. They would then implant the genes required to make those antibodies into the cells of mouse eggs. Those mice would be born immune to Lyme. Ultimately, if enough of them are released to mate with wild mice, the entire population would become resistant. Just as critically, the antibodies in the mice would kill the Lyme bacterium in any ticks that bite them. Without infected ticks, there would be no infected people. “Take out the mice,” Esvelt told me, “and the entire transmission cycle collapses.”

1. Compare annotations with your group. Write a list of 5-10 keywords​ that you identified as being important to this passage of reading. Define or describe each within the context of the article.

2. Identify 1-3 main topic sentences of this section. These are sentences that lead a paragraph and are often followed by specific details.

3. In this section, the author describes the method that will be used to eliminate lyme disease. Convert the description into a basic image showing how lyme is transferred and how Dr. Esvalt plans to stop the cycle.

Esvelt and his colleagues were the first to describe, in 2014, how the revolutionary gene-editing tool crispr could combine with a natural phenomenon known as a gene drive to alter the genetic destiny of a species. Gene drives work by overriding the traditional rules of Mendelian inheritance. Normally, the progeny of any sexually reproductive organism receives half its genome from each parent. But since the nineteen-forties biologists have been aware that some genetic elements are “selfish”: evolution has bestowed on them a better than fifty-per-cent chance of being inherited. That peculiarity makes it possible for certain characteristics to spread with unusual speed.

Until crispr came along, biologists lacked the tools to force specific genetic changes across an entire population. But the system, which is essentially a molecular scalpel, makes it possible to alter or delete any sequence in a genome of billions of nucleotides. By placing it in an organism’s DNA, scientists can insure that the new gene will copy itself in every successive generation. A mutation that blocked the parasite responsible for malaria, for instance, could be engineered into a mosquito and passed down every time the mosquito reproduced. Each future generation would have more offspring with the trait until, at some point, the entire species would have it.

There has never been a more powerful biological tool, or one with more potential to both improve the world and endanger it. Esvelt hopes to use the technology as a lever to pry open what he sees as the often secretive and needlessly duplicative process of scientific research. “The only way to conduct an experiment that could wipe an entire species from the Earth is with complete transparency,” he told me. “For both moral and practical reasons, gene drive is most likely to succeed if all the research is done openly. And if we can do it for gene drive we can do it for the rest of science.”

At the meeting on Nantucket, Esvelt assured residents that he and his team fully understood the implications of manipulating the basic elements of life. He said that he regards himself not just as a biologist but as the residents’ agent; if they stop showing interest in the research, he will stop the experiments. He also insists that he will work with absolute openness: every e-mail, grant application, data set, and meeting record will be available for anyone to see. Intellectual property is often the most coveted aspect of scientific research, and Esvelt’s would be posted on a Web site. And no experiment would be conducted unless it was approved in advance—not just by scientists but by the people it is most likely to affect. “By open, I mean all of it,” Esvelt said, to murmurs of approval. “If Monsanto”—which, fairly or not, has become a symbol of excessive corporate control of agricultural biotechnology—“did something one way,” he said, “we will do it the opposite way.”

There are fewer than a million white-footed mice on Nantucket, so a gene drive won’t even be necessary to insure the spread of Lyme-resistant genes. Esvelt plans to release enough genetically modified mice, tens of thousands of them, to overwhelm the wild population. (Since he could never house that many mice in his lab at M.I.T., he recently mentioned the idea of breeding them on a container ship.) That approach, however, would never work for Lyme on the mainland, where there are more than a billion white-footed mice scattered up and down the Eastern seaboard.

The battle against Lyme disease is just an early stage in an unprecedented effort to conquer some of mankind’s most pervasive afflictions, such as malaria and dengue fever. Despite a significant decline in deaths from these diseases over the past decade, they still threaten more than half the world’s population and, together, kill nearly three-quarters of a million people each year. Malaria alone kills a thousand children every day.

4. Annotate the text in the passage and underline any topic sentences you can locate. List 5-10 key words from this passage with a short definition.

5. Summarize this section with regard to the key statement made in the first paragraph: “ Esvalt was the first to describe how the gene-editing tool crispr could combine with a natural phenomenon known as a gene drive to alter the genetic destiny of a species.”

6. Esvalt is considered an advocate of science and not just a researcher. How does he plan to change the way science is conducted.

7. As a group, discuss his final goal of releasing thousands of genetically modified mice. Create a list of pros and cons for this plan.

It may be years before animals or plants with crispr gene drives are released into natural environments. There will be many regulatory, political, and social hurdles to negotiate along the way. Esvelt predicts that it will be nearly a decade, if all goes well, before Lyme-resistant mice appear on Nantucket or Martha’s Vineyard. But the scientific obstacles are disappearing rapidly. That makes it at least possible to envisage a day when gene-drive technology will be deployed to vanquish diseases that have killed billions of people, deter devastating pests, and protect endangered species like the black-footed ferret. (Plague has brought the ferrets to the edge of extinction, but it should now be possible to edit their genes to make them immune.) To consider implementing such fundamental scientific changes, though, will require a tectonic shift in public attitudes about the natural world.

One of Esvelt’s goals at M.I.T. is to facilitate that shift. Part of his job, as he sees it, is to challenge what he describes as “the ridiculous notion that natural and good are the same thing.” Instead, he told me, we ought to think about intelligent design as an instrument of genetics. He smiled because the phrase “intelligent design” usually refers to the anti-Darwinian theory that the universe, with all its intricacies and variations, is too complex to have arisen by chance—that there had to be a guiding hand. The truth is more prosaic, and also more remarkable: for four billion years, evolution, driven by natural selection and random mutation, has insured that the most efficient genes would survive and the weakest would disappear. But, propelled by crispr and other tools of synthetic biology, intelligent design has taken on an entirely new meaning, one that threatens to transcend Darwin—because evolution may soon be guided by us.

For Esvelt, that moment can’t come soon enough. “Natural selection is heinously immoral,” he said, invoking Tennyson’s view that nature is “red in tooth and claw.” Unlike Rousseau, Esvelt sees nothing “blessed” about man in his natural state. In fact, romantic notions of a natural world defined by innocence and harmony repel him. “The idea that nature is the essence of goodness, is purity and truth, is so foreign to my perception of the world that I can’t even conceive of how people can think that way,” he said. “There is such a fantastic degree of suffering out there.”

He went on to say that humans no longer need to be governed by nature, or rely on brutal and ruinous methods to control it. “When nature does something that hurts us, we respond with chemistry and physics,” he said. “We spread toxic pesticides that kill problematic pests, and often kill most of the other insects in the area as well. To get rid of mosquitoes, we use bulldozers to drain swamps. It works. But it also destroys wetlands and many other species. Imagine that an insect is eating your crops. If you have a gene drive and you understand how olfaction works in that pest, you could just reprogram it to go on its merry way. The pest would still be in the ecosystem, but it would just dislike the taste of your crop. That is a much more elegant way of interacting with nature than anything we do now.”

8. What is meant by this statement: Esvalt wants to challenge “the ridiculous notion that natural and good are the same thing.” Provide specific examples from your own experiences where people you know have this same perception that natural = good.

9. Final Task: On the back of this page, create an infographic or concept map that ties the main idea​s and keywords​ together.