Senior Project: Gene Modification Rodell Biteng Note Cards #61-227

JACOBSEN, ROWAN 85

"As living matter becomes engineerable, some things actually should change," he stressed to me. "Having these capacities emerge changes our understanding and appreciation of who we are and how we interact with everything else that's alive."

JACOBSEN, ROWAN 87

"As potential parents, would you prefer to spend your savings on college tuition for a natural child or on realizing a genetically engineered offspring?" (this is a potential of question we may have to answer as a result of this technology)

ADLER, JERRY 142

. As a human being I don't want to be involved in the eradication of a species, even an insect." James has successfully engineered the antibody-producing genes and is working on the gene drive (what if this also has a similar effect as killing them)

ADLER, JERRY 129

2012, the UC Berkeley researcher Jennifer Doudna and her colleagues developed a revolutionary new technique for editing DNA Researchers,CRISPR. This development brought Crisanti's dream a giant step closer to reality. Now, he and his team could program Cas9's guide RNA to pinpoint any part of a gene and transfer over the material they wanted to copy

ADLER, JERRY 128

A "gene drive" involves copying a mutated gene from one chromosome onto the other member of the pair. The key is that when the pairs split to form the eggs and sperm, it won't matter which chromosome gets passed along--the engineered gene will be there either way. Thus a single mutation would, in theory, be "driven" into practically every mosquito in a breeding population

Satyajit Patra, Araromi Adewale Andrew 67

A frightening scenario to consider is the destructive use of genetic engineering. Terrorist groups or armies could develop more powerful biological weaponry.

ADLER, JERRY 125

A. gambiae has been called the world's most dangerous animal. Its bite is a minor nuisance, unless it happens to convey the malaria parasite, Plasmodium falciparum. Although a huge international effort has cut malaria mortality by about half since 2000, the World Health Organization still estimates that there were more than 400,000 fatal cases in 2015, primarily in Africa. Children are particularly susceptible. Gene editing may be able to contribute to the fight against this

Talbot, David 165

beijing genomics institute) BGI has been using high-throughput technology to systematically compare these strains. The goal is to identify the genes that might be important for traits such as yield, flavor, pest and herbicide resistance, and tolerance to drought, salt, and immersion. Combined with the gene-editing tools, this new wealth of knowledge means that an era of very rapid and precise GMO development is at hand

Satyajit Patra, Araromi Adewale Andrew 63

it is expected that there will be a reduction in genetic diversity and if human beings will have identical genomes, the population as a whole will be susceptible to virus or any form of diseases

Chamary, J and Hurst, Laurence 177

sickle cell anemia, a missense mutation exchanges a water-loving (hydrophilic) amino acid for a water-avoiding one (hydrophobic), causing the proteins to clump together and produce characteristic sickle-shaped blood cells

ADLER, JERRY 136

when the sterile insect technique was tried against mosquitoes, the results were mixed researchers have also been looking at variants of sterile insect technology that don't require radiation. A pilot project has begun in the city of Piracicaba, in southeastern Brazil, by the British biotech company Oxitec. The target insect is A. aegypti, the main culprit in spreading yellow fever, dengue and other viral diseases

Talbot, David 161

"Certainly we [the United States] aren't doing much--and the big multinationals aren't doing much right now in terms of spending on plant biotech research," Rozelle says. "And yet China continues to do it." So far China has been able to feed itself, so there is no impetus to deploy this new technology, he adds. "Yet they continue to pour money into it. Are they doing it for the love of science? They are putting away for a rainy day--or a non-rainy one. And when that day comes, I think they will have more GM technologies than anyone.

JACOBSEN, ROWAN 88

"Given that human genome synthesis is a technology that could be used to completely redefine the core of what now joins all of humanity together as a species, we argue that discussions of making such capacities real, like today's Harvard conference, should not take place without open and advance consideration of whether it is morally right to proceed."

WHEELWRIGHT, JEFF 117

"It's a future play," Laderman says cagily. "We're not just making the tool, [but also] making measurements that determine what the tool did." By measurement, he means the validation of experiments, the part that investigators sometimes neglect. It's one thing to buy a Crispr-Cas9 package, a cool new tool for your project, and another thing to ensure that it has worked

WHEELWRIGHT, JEFF 121

"Researchers have millions and so companies mark up the price," he grumbles as we move into the living room. "Why should I have to pay to access publicly funded research? I think science needs democratization. The public doesn't have the necessary DIY protocols for Crispr-Cas9. What is the best Cas9 sequence to use? Where do you get the chemicals?

JACOBSEN, ROWAN 76

"Sometimes I feel like we're not on a slippery slope—we're flying off a cliff," Marcy Darnovsky, executive director of the Center for Genetics and Society, which opposes the use of human germline modification for any purpose, told me recently. "People used to see this as a speculative science fiction future, and now it's an urgent social-justice challenge."

Hall, Stephen S. 204

"They basically want the public to calm down," he says. "That was their goal. And no matter what we said, that was going to be the goal. I don't want to stir [the public] up, and I don't want to calm them down, either. I want them to have an accurate view of where things are going." And the public needs to start thinking about gene-editing the human genome now, Church says, because science is already bumping up against the red line.

ADLER, JERRY 147

"We can remake the biospheretobe what we want, from woolly mammoths to non biting mosquitoes," Greely muses. "How should we feel about that? Do we want to live in nature, or in Disneyland?"

Regalado, Antonio 226

"What I learned about gene therapy is that the rabbit does not win the race. The tortoise wins the race," says Weiss, who leads the St. Jude effort to apply gene editing to sickle-cell disease. We must take our time and work with great detail to perfect our grip on this new technology in order to make the best out of it

WHEELWRIGHT, JEFF 122

"You have this potentially awesome therapy. What if, at hackerspaces, you had 1,000 people working on Cas9? People would come in and contribute stuff. You'd have to educate them, but then you would unleash them.

Regalado, Antonio 217

"editing" is a bit of a misnomer. Scientists have mastered cutting into DNA, which gives them something akin to a "delete" key for genes, in addition to the "add" function offered by traditional gene therapy

ADLER, JERRY 135

"sterile insect technique," involves breeding and hatching millions of flies, sterilizing the males with low-level gamma rays, then releasing them in numbers sufficient to swamp the wild population. Females that mated with the sterile males produce infertile offspring.

Hall, Stephen S. 197

(Kyle Orwig) he hopes to trigger a wider awareness that editing human genes is not an abstract, long-term technical challenge, as some have suggested, but a near-term possibility with practical medical consequences. Which is why Orwig recently told a colleague, "Let's just do this and piss some people off. Show them that it's possible, so nobody can say it's impossible. And get people talking about it

JACOBSEN, ROWAN 91

(noninvasive prenatal testing) A since the new test could allow parents to screen for individual genes, over time it could result in certain undesirable genes being eliminated from the gene pool, Endy noted. "That's shaping the future of the human lineage."

Hall, Stephen S. 211

A majority of Americans do not like the idea of editing genes in either embryos or germ cells, according to a recent analysis of 17 public opinion polls published in the New England Journal of Medicine. Yet paradoxically, most people support gene editing in adults "aimed at preventing one's children from inheriting certain diseases."

WHEELWRIGHT, JEFF 118

A mutation could be implanted in a critical mass of mosquitoes or rodents or some other pest, and the mutation would spread through the population for good or for ill. Would biologists do the right thing? And the thing they thought was right — would it work as planned? "I hope I'm a good wizard," says Martin. "I'm afraid of the magic, though.

JACOBSEN, ROWAN 75

A possible use for genetic engineering are edits to ones sperm The invention of CRISPR could even fix the code in your sperm or eggs before conception, ensuring an embryo that's free of any Genetic Disease

Chamary, J and Hurst, Laurence 188

A recent experiment at the International Institute of Molecular and Cell Biology in Warsaw illustrates how silent mutation sites could be manipulated for human benefit. Grzegorz Kudla and his colleagues took three genes and did nothing more than change the relative proportion of specific nucleotide bases at the silent sites, then transferred the altered genes to mammalian cells. Remarkably, the investigators found that increasing G and C content led to gene activity and protein manufacture that was up to 100-fold more efficient as compared with GC-poor versions of the same genes

Talbot, David 173

After the Famine China helped pioneer rice hybridization, and its government is now the world's top spender on GMO crop research. 1958: China's Great Leap Forward bans private food production and creates farming communes-resulting in mass starvation over the next four years. 1973: Agricultural scientist Yuan Longping creates and reproduces high-yield hybrid rice in China, dramatically increasing the nation's rice yields. 1985: China begins establishing 30 national biotech labs. Today nearly 400 academic or national labs work on plant biotech. 1992: China becomes the first country to grow a commercial GMO crop: a virus-resistant tobacco. 1997: Farmers plant transgenic insect-resistant cotton. 2008: China becomes a net importer of food. It is now the world's largest food importer. 2009: Government issues five-year safety certificates for insect-resistant rice and GM corn that's more digestible to pigs--but never allows planting. 2014: Using new gene-editing technologies, Chinese researchers develop a disease-resistant wheat.

Regalado, Antonio 220

Already, a Chinese drug company has opened a study to create supercharged immune cells to battle cancer, and scientists at the University of Pennsylvania have announced similar plans with the financial backing of the billionaire Internet entrepreneur Sean Parker.

Hall, Stephen S. 201

Although society applauded the scientific community's decision in 1974 to hit the pause button on the headlong rush of research, many scientists felt it was an overreaction to hypothetical safety concerns.

ADLER, JERRY 148

Another fear is that CRISPR puts a potential weapon in the hands of terrorists, who could use it to engineer epidemics. "Just as gene drives can make mosquitoes unfit for spreading the malaria parasite, they could conceivably be designed with gene drives carrying cargo for delivering lethal bacterial toxins to humans," warns David Gurwitz of Tel Aviv University.

Chamary, J and Hurst, Laurence 183

Another instance of a silent mutation affecting a protein is also among the most direct effects and involves a gene known as multidrug resistance 1. The gene is so named because its protein product is a cellular pump that in cancer cells helps to expel chemotherapy drugs, thus conferring drug resistance on those cells

Regalado, Antonio 215

At 24, Benjamin Dupree has outlived many people with Duchenne muscular dystrophy. It was diagnosed 15 years ago, after he struggled to get up the stairs without using the banister. Doctors say the disease is terminal, but they tell you little about living with it.

JACOBSEN, ROWAN 96

Because of how noticeable the effects of these edits, will the economic gap be much more visible? Will the economic gap determine ones social standing to an even greater extent then it does now?

Chamary, J and Hurst, Laurence 184

Because the translation process and protein folding can occur simultaneously, the researchers theorized that the rarer synonymous codon produced by the silent mutation caused a pause during translation, which in turn allowed the protein time to adopt an unusual structure. If this pause occurs, the precise cause is unclear and can be added to the list of as yet unsolved mysteries about the workings of genes and proteins

WHEELWRIGHT, JEFF 113

Before moving on to human trials, they will need to study all instances of "off-target" effects: Years before Crispr, the viruses employed to deliver DNA in gene therapy trials occasionally damaged the whole system, causing cancer. The problem was that researchers couldn't direct the packet to the proper place on the chromosomes

Talbot, David 171

But few doubt that at some point, when costs rise and supply gets tighter, the government will decide it's time to plant what it has been developing in its labs. And when that happens, given China's centrally managed economy, farms and families can be expected to adopt the technology quickly. "Once the official attitude is changed, everything will be changed very soon," says Huang

ADLER, JERRY 149

But many scientists think this is an overblown concern (along with the other horror-movie scenario, of a high-school student in his basement using CRISPR to make a dog that glows in the dark). "A gene drive in a mosquito would make a very poor bioweapon," says Kevin Esvelt, an ecologist at MIT, who has written extensively on the subject. "They are slow [compared with disseminating a deadly microbe], they are easy to detect, and it's straightforward to build a reversal mechanism."

ADLER, JERRY 126

Crisanti, a tousled, sad-eyed man with a gentle smile, was trained as a physician in Rome. Later, studying molecular biology in Heidelberg, he developed his lifelong interest in malaria. He set out on the trail of A. gambiae some 30 years ago, after he concluded that the best way to eradicate the disease was to attack the mosquito rather than the parasite.

Talbot, David 169

Crises will come. The Chinese government that wants to avoiding provoking the outrage of its GMO-wary citizens may at some point face a broader and even more distressed constituency: farmers watching crops dying, and citizens who can't afford--or even find--enough food

Regalado, Antonio 224

CRISPR has the potential to cause accidental, unwanted edits that could not be erased if they ended up written into a person's genome. Currently, researchers rely on academic computer programs to predict such effects. (One, maintained at Harvard, is called CHOPCHOP.) But a program can't predict everything. Two early tests of gene therapy, in the 2000s, accidentally caused leukemia in several children.

WHEELWRIGHT, JEFF 114

Caribou aims to bring Crispr-Cas9 to all domains of the life sciences, from agricultural and industrial biotech to medicine and molecular biology. The company's coolly boastful motto: "Engineering any genome, at any site, in any way."

Talbot, David 158

Cautious though they are of arousing public opposition, Chinese leaders are well aware that their country will need a lot more food. Growing it will require new agricultural tricks. The world's most populous nation, China has more than 1.3 billion inhabitants, a number expected to rise to almost 1.4 billion by 2030.

Satyajit Patra, Araromi Adewale Andrew 64

Certain changes in a plant or animal could cause unpredicted allergic reactions in some people which, in its original form, did not occur. Other changes could result into the toxicity of an organism to humans or other organisms.

Talbot, David 163

China became a net food importer in 2008 and the world's top food importer four years later; it now imports about 5 percent of its food. This makes China's stance on GMO food crops critical for the entire global market; if China green-lights GMOs, many other countries that export to China may accept them too

Talbot, David 172

China's Research Output Hundreds of state-funded research groups in China are working on GMOs, including these three examples. Disease-resistant wheat A wheat with three genes edited out, conferring resistance to the fungal disease called powdery mildew. Bt rice A transgenic rice that wards off major insect pests, the leaffolder and yellow stem borer, without reducing yield. Phytase corn A transgenic corn that releases phosphorus from phytate molecules, aiding digestion for chicken and pigs.

Talbot, David 154

China's ruling Communist Party faces rising popular opposition to GMOs. As in any other nation, there are a variety of views within China about whether it's safe to eat food made with genetically engineered ingredients. But Chinese citizens have lately witnessed a number of major food safety scandals, including a 2008 disaster in which melamine-tainted milk products killed six babies or toddlers, sending 54,000 more to the hospital, and a 2010 revelation that some cooking oil sold to consumers had been recovered from drains and probably contained carcinogens.

WHEELWRIGHT, JEFF 111

Crispr-Cas9 has leveled the playing field, Corn says. Investigators with big labs and deep pockets could afford earlier gene editing tools, but Crispr-Cas9 presents almost no barrier to entry. As Corn elaborated in a blog post: "This turns an exclusive practice, where people with questions had no way to get answers, into an inclusive one, where many questions lead to many answers. I often call this the 'democratization' of gene editing."

WHEELWRIGHT, JEFF 105

Crispr-Cas9) it's simple enough for high school kids to use Is this a good or bad thing? What are the implications for the use of the technologies if it were to go in the wrong hands?

Satyajit Patra, Araromi Adewale Andrew 70

Critics have questioned the safety of genetically engineered bovine somatotropin (BST) to increase the milk yield of dairy cows (BST) for both the cows that are injected with it and the humans who drink the resulting milk; owing to the fact that it increases a cow's likelihood of developing mastitis, or infection of the udder, and it also makes cows more susceptible to infertility or lameness

WHEELWRIGHT, JEFF 112

DeWitt's experiments are intended to be a proof-of-principle that Crispr-Cas9 can help the hundreds of thousands of people, most of them in Africa and India, who carry two flawed copies of the HBB gene. Theoretically, when the stem cells are returned to the patient, they will generate enough of the normal hemoglobin to counter the symptoms, if not eliminate the disease.

Hall, Stephen S. 207

Developing such a clinical treatment would face technical hurdles, of course. For one thing, scientists would have to find a way to maintain human spermatogonial stem cells long enough to select the right ones for transplantation—still not a trivial task.

JACOBSEN, ROWAN 97

Do not expect the powers that be to stop our slide down this slope. "No one's minding the store on this stuff," Darnovsky told me. Congress passed a law in 2015 forbidding the Food and Drug Administration from reviewing applications for germline editing of human embryos, meaning no clinical trials can move forward.

WHEELWRIGHT, JEFF 107

Doudna's team reprogrammed the natural operation by synthesizing their own version of the guide-RNA. Together, the synthetic guide-RNA and Cas9 form a complex capable of editing any gene.

JACOBSEN, ROWAN 83

Each of us has billions of letters of genetic code. We can't yet synthesize DNA strands nearly that long—it's complicated to print more than about 10,000 letters—but last year George Church and other scientists held a summit down the street that explored that possibility.

ADLER, JERRY 150

Esvelt has other ethical concerns about using CRISPR technology on animals: "We will have engineered the ecosystems of people elsewhere in the world without their knowledge or consent. as soon as you're thinking of a gene drive technology, you have to assume whatever you're making will spread once it gets outside the lab

Satyajit Patra, Araromi Adewale Andrew 71

Ethical/social issue Human genes are now being inserted into tomatoes and peppers to make them grow faster. This suggests that one can now be a vegetarian and a cannibal at the same time.

Talbot, David 170

Even if China can increase yields by improving existing agricultural practices, as it probably can, Rozelle and other China watchers expect the country to approve GM corn at some point; the demand for corn for animal feed will become too urgent, and using the crop for animal feed is far less controversial than growing it for human consumption

Chamary, J and Hurst, Laurence 176

Examples certainly abound of the first three types of point mutations having a major impact on human health. Three different point mutations in the genes encoding proteins that make up the hemoglobin molecules in red blood cells are responsible for three separate and grave diseases, for instance sickle cell anemia polycythemia disorder thalassemia

Satyajit Patra, Araromi Adewale Andrew 72

For meateaters, the same question could be posed about eating pork with human genes. Would humans be classified as Cannibals? Where do the line get drawn and who gets to draw the line?

Talbot, David 166

Gao and colleagues are doing similar systematic studies on the next-most-important crops: corn, wheat, and soybeans. They recently invented a wheat strain that resists the second-most-common wheat disease, powdery mildew. The GMOs included a soybean plant whose beans produce more oil and an acre or so of rice that can avoid leaf death.

Talbot, David 164

Gao's trays are part of a massive nationwide enterprise. In 2002, Chinese scientists were among the first to sequence a rice genome; this year they released the sequences of 3,000 varieties as part of a continuing effort with the International Rice Research Institute (IRRI) in the Philippines and the Beijing Genomics Institute to develop a crop known as "green super rice"

Satyajit Patra, Araromi Adewale Andrew 61

Genetic engineering can be explained as the alteration of an organism's genetic or hereditary material to eliminate undesirable characteristics or to produce new desirable characteristics. Methods in this techniques involve the selective breeding of animals and plants, hybridization (reproduction between different species), and recombinant deoxyribonucleic acid (rDNA)

WHEELWRIGHT, JEFF 116

Haurwitz has honed her sales pitch. "To really benefit mankind," she says, "you have to commercialize. There is investor excitement, but they understand that [the payout] could be a decade away. We've been building the plane as we've been flying it. If you win, it's a tremendous win."

JACOBSEN, ROWAN 86

He can't imagine that we'd invent one of the most potentially beneficial technologies of all time and not use it. (meaning it is useless to stop the progress and that we should be more attentive at those researching and developing it)

JACOBSEN, ROWAN 90

He pointed out that when he and his wife recently had their second child, they took advantage of a new technique called noninvasive prenatal testing that can sequence part of a fetus' genome from fragments of fetal DNA circulating in the mother's blood. "It has become the standard of care at Palo Alto's children's hospital. Everybody's doing it.

JACOBSEN, ROWAN 93

Here are a few examples of rare gene variants LRP5 gene results in ultradense, nearly unbreakable bones ANGPTL3 gene metabolize triglycerides in their blood so efficiently that they are virtually immune to heart disease. hDEC2 variant need less sleep than normal people variants of the CCR5 gene don't get AIDS

ADLER, JERRY 131

Homo sapiens have driven other species to extinction by eating them, shooting them, destroying their habitat or accidentally introducing more successful competitors to their environment. But never have scientists done so deliberately, under the auspices of public health. Possible? Ethical? Unforeseen consequences?

JACOBSEN, ROWAN 103

Humans first learned how to synthesize DNA decades ago, but until recently the technique was so expensive that it was fairly useless outside the lab. But thanks to breakthroughs, the cost of printing a base pair of genes has plunged from $600 in 1980 to a fraction of a cent and is continuing to drop. This is where new genes now originate

ADLER, JERRY 130

If Crisanti's approach works, you could, in theory, wipe out an entire species of mosquito. You could wipe out every species of mosquito, although you'd need to do them one at a time, and there are around 3,500 of them, of which only about 100 spread human disease.

Hall, Stephen S. 196

If shown to be safe, effective and ethically acceptable, germ-line modification would confer unprecedented power on scientists—the power to edit the susceptibility to disease out of our species' DNA, for example, but also the power to manipulate human inheritance and "improve" the species, an aim that darkly harkens back to the eugenics movement of the early 20th century that reached its nadir in Nazi Germany.

ADLER, JERRY 143

If society chooses to eliminate one or more species of mosquito, what are the downsides? Mosquitoes play a critical role in a few environments, such as the Arctic tundra, where they hatch out by the billions over a short period and are a significant food resource for birds. In most other places, biologists believe, the ecosystem could survive the loss.

ADLER, JERRY 140

Important Note - evaluation of content Could businesses such as this one abuse the power they have for economic gain? Who will regulate these businesses (will it be on national or global level)

ADLER, JERRY 138

Important Note - evaluation of content Could population control techniques such as these be applied to humans? If so should they be in the hands of any group?

ADLER, JERRY 132

Important Note - evaluation of content With a project at this scale (global) who is responsible for deciding whether or not they should go through with it? Is it possible to have the entire planets voice heard?

JACOBSEN, ROWAN 99

Important Note - self evaluation of content In terms of competing countries If country A adopts this tech to common use and country B does not then A will have an advantage over B Once B realizes this advantage they will then adopt the tech however they will not be as experienced with the teach as A is Knowing the outcome of a situation like this, countries would most likely try to be in the position of Country A

JACOBSEN, ROWAN 82

Important Note - self evaluation of content Simply banning the technology or deeming it as illegal will not solve the problem As we see with recreational drugs making it illegal does not completely solve the problem It caused black markets and illegal businesses (even more issues the law has to deal with) Making it legal while putting many restrictions will do much more than simply banning the use of the technology

WHEELWRIGHT, JEFF 109

Important Note - self evaluation of content Already widely accepted in other countries (being in the curriculum of high schools) By exposing and teaching how to use the tech to the younger generation, the tech will improve at an exponential rate

JACOBSEN, ROWAN 101

Important Note - self evaluation of content What will be the societal responses of individuals that are artificially created?? Will there be a social hierarchy created because of this? Who will be on top? And why ?

ADLER, JERRY 127

In 2003, Austin Burt, a colleague of Crisanti's at Imperial College, suggested a solution: coupling the desired mutation with a "gene drive" that would overwrite the ordinary processes of inheritance and evolution. Recall that genes are spelled out by DNA sequences woven into chromosomes, which come in pairs (23 pairs in a human, 3 in a mosquito).

WHEELWRIGHT, JEFF 124

In November, Zayner mounted an Indiegogo campaign to fund the production of Crispr-Cas9 kits. The online pitch was "DIY Crispr Kits, Learn Modern Science By Doing." The goal was to raise $10,000 via crowdsourcing within a month. He got $65,000. Buying the components, he negotiated with suppliers abroad and individual manufacturers. Not Addgene or Agilent? No way. "My kits are ridiculously cheaper," Zayner says Implications of tech being much more available to the public

ADLER, JERRY 137

In Oxitec's program, male larvae bred with a lethal mutation are raised in water dosed with the antibiotic tetracycline, which inactivates the lethal gene. When those males mate with wild mosquitoes, their offspring, deprived of tetracycline, die before they can reproduce.

Talbot, David 160

In anticipation, the nation is building a storehouse of genetically modified crop strains for future use. China sees this as a way of protecting its long-term security. In fact, the country is the world's top public spender on genomics and genetic modification of crop

Regalado, Antonio 221

In fact, Editas has been lying low. CRISPR could potentially treat so many different diseases that the company has been reluctant to announce what its do-or-die project will be. And proving that any CRISPR drug is effective could easily take a decade. That puts Glucksmann in a tough position

ADLER, JERRY 146

In the long term, the pathogens could evolve to be spread by the mosquitoes that are still around, but there's plenty of time for humans to worry about that.

JACOBSEN, ROWAN 84

In the meeting, some of the world's top biotechnologists discussed a new 10-year undertaking called Human Genome Project-write, or HGPwrite. While the original Human Genome Project (HGP-read), which was completed in 2003, sought to sequence (read) the full human genome, part of HGP-write's goal is to build a complete human genome. In theory, that DNA could be inserted into a cell nucleus and grown into a human being.

Hall, Stephen S. 205

Ina Dobrinski, an expert in reproductive biology at the University of Calgary who works on gene editing of large animals such as pigs, adds, "Theoretically, we can do it. Practically [speaking], nobody is even touching it because of the ethical issues."

Regalado, Antonio 222

Individual treatments One thing that's already apparent is that many inherited genetic diseases will require tailoring a CRISPR treatment to very specific mutations—those affecting small subsets of patients or even individual people.

Satyajit Patra, Araromi Adewale Andrew 74

Initially, human genetic engineering was developed to aid in the elimination of disease used in fighting problems such as cystic fibrosis, diabetes, and several other diseases However more recently we are starting to see more use of the tech (cosmetic, destructive, food production, etc)

Regalado, Antonio 216

Intellia is one of a trio of startups that have set up shop around Boston and raised about $300 million each to create CRISPR treatments; the others are Editas Medicine and CRISPR Therapeutics. Barnes says CRISPR vastly simplifies gene editing because of the way the cutting works. Just as bacteria spot and slice the viral genetic material, CRISPR can zero in on specific stretches of human DNA

Regalado, Antonio 227

It may take a lot longer than we think, but sooner or later gene editing will change what medicine looks like. The biotechnology industry began in the 1970s when someone grafted insulin into E. coli, showing that a human protein could be manufactured outside the body. Now there's a way to change DNA where it lies, inside your genes.

Hall, Stephen S. 210

It probably will not happen in the U.S. unless the public—and political—perception of germ-line modification becomes more accommodating, but Orwig is quietly preparing for that day. "We're going to work real hard behind the scenes," he says, "until the worldview changes."

Hall, Stephen S. 195

It sounds simple enough, and, according to Orwig, it would be relatively straightforward to try—indeed, he has been transplanting sperm-forming stem cells into mice for 20 years. The consequences, however, could be momentous. Has the potential to push society right up to the brightest red line in contemporary biology: altering the gen etic text of the human species in a way that is passed down to future generations.

JACOBSEN, ROWAN 77

It's easy to see how today's enhancements become tomorrow's standard of care. Sure, we all just want normal kids. But "normal" is a moving target. The idea of what makes an individual normal, will change.

ADLER, JERRY 144

It's possible, even likely, that another species would take the place of the mosquitoes we exterminated. For instance, A. aegypti could be replaced by a mosquito from the Culex pipiens species complex. Culex, which is a vector for the West Nile virus, "does very badly when Aedes is present," Juliano notes, but it might be expected to thrive in its absence

ADLER, JERRY 141

James realized that if he could endow the mosquito with genes that produce antibodies to P. falciparum, he could destroy the parasite without having to kill even one insect. He created the gene for the antibodies, but he needed a way to make it spread in the wild

Chamary, J and Hurst, Laurence 194

KEY CONCEPTS . Scientists long assumed that any DNA mutation that does not change the final protein encoded by a gene is effectively "silent." Mysterious exceptions to the rule, in which silent changes seemed to be exerting a powerful effect on proteins, have revealed that such mutations can affect health through a variety of mechanisms. Understanding the subtler dynamics of how genes work and evolve may reveal further insights into causes and cures for disease

JACOBSEN, ROWAN 100

Last year, a team of scientists in Japan took the skin cells of mice, transformed those cells into eggs, fertilized them, and implanted the resulting embryos, which resulted in the birth of 26 healthy pups. Some of the pups have now grown up and given birth to families of their own. It shouldn't be much more difficult to do the same thing with humans

Chamary, J and Hurst, Laurence 192

Manipulating the sites of synonymous mutations has allowed scientists to design genes that speed up protein manufacture, but the same technique can also be used to slow it down

Talbot, David 159

Meanwhile, accelerating climate change will pose great challenges for farmers, bringing deeper droughts, more flooding, and hotter heat waves (see "Why We Will Need Genetically Modified Foods," January/February 2014). Although crop yields in China tripled from the 1960s through the 1990s, thanks to hybrid varieties and generous spraying of pesticides, those gains slowed significantly 15 years ago

Regalado, Antonio 218

Medical researchers have given it relatively little attention in the past, but there's an obvious DNA cut that might solve it, meaning a potentially elegant cure. "The interest right now is incredible," he says. "Before, no one was interested. No one cared. But they need a proof of principle, and this is a good one."

Chamary, J and Hurst, Laurence 193

Mueller's group took advantage of microbes' preference for using certain codons to maximize the efficiency of protein production by designing a poliovirus that substituted rarer, less efficient codons in sequences encoding the viral shell This technique for taking advantage of codon bias to create a live but weakened vaccine could be applied to other pathogens as well to produce potent but safer vaccines

JACOBSEN, ROWAN 102

NOT LONG AGO, i STOOD in a Cambridge, Massachusetts, office building on the banks of the Charles River, minutes from Harvard and MIT, and watched a printer spit tiny drops of liquid onto a slide. Instead of ink, each of its nozzles shot one of the four nucleotides that create DNA—the As, Cs, Gs, and Ts. The nozzles flew over the glass, with each drop adding a nucleotide—a single letter—to one of thousands of infinitesimal stacks on the one-by-three-inch slide, where they bound in place. The machine was printing DNA

Hall, Stephen S.213

New gene-editing techniques may soon be used in treatments for male infertility that involve altering the genetic code of sperm cells. Such alterations would be passed down to future generations, constituting a permanent change in the human genome. Scientists seeking to quell the public's fears that such a step would cross an ethical red line have argued that the technology is not yet feasible, but others believe the line will be crossed soon. The demand for infertility treatments has for decades fueled the adoption of new biotechnology, for better and worse.

WHEELWRIGHT, JEFF 110

Next, she turns to the thrust of her summer project: editing stem cells from the heart to learn more about a congenital heart disorder. Researcher Casey Gifford, Arreola's mentor at Gladstone, asked me not to name the disorder or the gene that her lab is tinkering with — she doesn't want to alert any possible competitors. "With Crispr-Cas9, it's so easy," Gifford says. "I have a head start. But others could quickly do it."

Chamary, J and Hurst, Laurence 185

One lesson scientists can take from the recent discoveries about the effects of silent mutations is to be careful in our assumptions. Confidence that synonymous mutations must be "silent" was widespread when there was no mechanism to connect a silent change with an alteration in protein production

JACOBSEN, ROWAN 78

One of the most interesting judgment calls might be for the so-called warrior gene, MAOA, which seems to play an important role in aggression. People who have the MAOA-L variant are more likely to commit a violent crime than people who have the "normal" version.

WHEELWRIGHT, JEFF 119

Patel zeroes in on the Hox genes of a tiny crustacean, Parhyale hawaiensis, commonly known as a beach hopper. When Crispr-Cas9 knocks out a Hox gene in an embryonic beach hopper, strange things ensue, like a clawed foot forming where a swimming foot ought to be, or an antenna growing out of a mouth. The opposite tack, knocking-in, inserts foreign DNA into a Hox gene, resulting in, for instance, a claw that glows green under fluorescent light. Very possible that results like this may happen to humans as well

Regalado, Antonio 225

People's expectations are up here." Ryu warns that basic, unresolved biological problems remain. One is whether editing will work often enough in cells such as those in the bone marrow, the type that need to be changed to correct sickle-cell disease. If too few cells end up edited, the treatments won't be effective. "It's a numbers game," says Ryu

ADLER, JERRY 151

Public-health officials are already bracing for the possibility of a spate of babies with the devastating diagnosis of microcephaly and associated brain damage. It was human transportation technology that spread these diseases across the globe. Now technology is offering a way to contain them, or even defeat them altogether, at the risk of unleashing powerful forces whose effects we can only dimly predict.

WHEELWRIGHT, JEFF 115

Rachel Haurwitz, Caribou's 30-year-old CEO and co-founder, who earned her Ph.D. in molecular and cell biology under Doudna, joins us in the conference room "We make Cas9 proteins, and we have the tools, the bioinformatics, to analyze large numbers of experiments. We're driving to understand the details, to gain understanding and explain why it's safe.

Talbot, David 156

Recent informal opinion surveys in Chinese social media suggest that large majorities believe GMOs are harmful, and scientific surveys also indicate that opposition is significant. An academic survey this year found that roughly one-third of respondents opposed GMOs outright and another 39 percent worried about them--a stark difference from earlier government surveys

Chamary, J and Hurst, Laurence 186

Recognizing the power of not so silent mutations is beginning to help investigators improve methods for genetic engineering. Knowing which nucleotides in a gene need to be retained and which could potentially be replaced has an immediate application in biotechnology

Satyajit Patra, Araromi Adewale Andrew 62

Repercussion of the tech/ techniques are still unknown. May even replace the important genes, instead of mutated genes lead to another health condition or disease to human.

JACOBSEN, ROWAN 98

Research continues around the world, and the lack of regulation in some countries means that anyone who wants to escape the rules can do so. If the majority of the world is using the technology then the remaining minority of world will use it as well

ADLER, JERRY 133

Researchers are skeptical about whether it is even possible to wipe out mosquitoes. "Global elimination of an entire species, I think, is a little far fetched," says Steven Juliano, an ecologist at Illinois State University. But, he adds, "I think they have a good chance of reducing local populations, maybe even eradicating a species in a locality."

Talbot, David 167

Researchers sometimes wonder if their work will ever see the light of day. "We can do research--we have enough financial support--but I don't know if Chinese scientists can produce the product," Gao says.

Hall, Stephen S. 200

Scientists began to acquire the Promethean ability to rewrite the language of heredity in the early 1970s, when biologists discovered that they could crudely cut and paste DNA with the use of enzymes harvested from bacteria, a technique called recombinant DNA. That advance caused unease about dangerous, genetically engineered microbes escaping the lab, prompting a voluntary—and unprecedented—moratorium on recombinant DNA research in 1974 and a historic meeting in 1975 of scientists at the Asilomar conference in California.

JACOBSEN, ROWAN 92

Scientists have already identified a handful of rare gene variants that seem to be upgrades of the standard version most of us possess. Hundreds of other upgrades are likely waiting to be discovered.

JACOBSEN, ROWAN 94

Seeing how amazing these rare gene are, how will we (as a country or even as a planet) regulate its use? Are we entitled to certain variants? How will these variants be commercialized?

ADLER, JERRY 134

Something like that has been done with other creatures. Starting in the 1950s, the American entomologists Edward F. Knipling and Raymond C. Bushland eliminated the screwworm, an agricultural pest, from the United States and much of Central America. It took decades, but it worked--and the same technique now is used to contain outbreaks of the Mediterranean fruit fly.

Satyajit Patra, Araromi Adewale Andrew 65

The presence of antibiotic-resistance genes in foods could have lethal effects. Therefore, eating these foods could reduce the effectiveness of antibiotics to fight disease when these antibiotics are taken with meals

WHEELWRIGHT, JEFF 108

Soon after Crispr-Cas9 came out, Cachianes put a demonstration into his curriculum: His Lincoln High students transform E. coli bacteria, which are relatively easy to work with. Cachianes obtained bacteria genetically engineered to express a red fluorescent protein, RFP for short. The mission of the students' Crispr-Cas9 project is to shut off the RFP gene and return the bacteria to their normal color.

Hall, Stephen S. 209

That does not mean Orwig's mouse experiment would be against the law—just a gentle nudge down the slippery slope toward germline modification. The step across the red line could happen in private IVF clinics, which have a long (and blemished) history of pushing the envelope on new reproductive technologies

Hall, Stephen S. 208

That is what makes Orwig's potential mouse experiment so politically inconvenient. Because of prohibitions enacted by Congress in the 1990s, the National Institutes of Health cannot fund any research that involves the destruction of human embryos.

ADLER, JERRY 139

That is, of course, a temporary solution to a perennial problem. Mosquitoes don't usually travel more than a few hundred yards from where they hatch, but people do, and they can take yellow fever with them. And the mosquitoes themselves can travel the globe on airplanes and ships. Aedes albopictus, the "Asian tiger mosquito," arrived in the Western Hemisphere a few years ago, possibly in a shipment of tires, and spreads many of the same diseases as A. aegypti. So even if the Oxitec program succeeds, it will likely need to be repeated at intervals. "You begin to see why Oxitec is a business," one American entomologist said dryly.

ADLER, JERRY 152

That, in the eyes of most ethicists, is an insurmountable problem. An International Summit on Human Gene Editing in Washington, D.C. last December aired many of these issues, revealing a split between the medical community, which wants to help patients in the here and now, and some researchers, who worry about the implications of the tabloid headline announcing the birth of the first Frankenbaby.

Talbot, David 155

The Chinese press and social media lit up when, in 2012, Greenpeace released a scary-sounding report on a research project that involved feeding children "golden rice," which is engineered to produce beta-carotene and thus make up for vitamin A deficiencies. (It turned out that the parents were not told the rice was genetically modified; China fired three researchers involved.)

WHEELWRIGHT, JEFF 123

The bacteria are in. The template DNA is in. The Cas9 enzyme is in, and the guide-RNA. A plasmid, a simple kind of DNA-delivery vehicle, will move a gene for antibiotic resistance into the bacterial cells, jump-starting the Crispr-Cas9 system. The object of the experiment is to mutate a gene in the bacteria, giving it antibiotic resistance, then prove it by dosing the cultures with antibiotics. We won't know the outcome for about a day. (Spoiler alert: success.)

WHEELWRIGHT, JEFF 120

The biohacker movement is about non-scientists, quasi-scientists and a substantial number of moonlighting professional scientists who are taking molecular biology into their own hands with big and little "why not?" projects.

Chamary, J and Hurst, Laurence 174

The classic view assumed that what are termed "silent" mutations were inconsequential to health, because such changes in DNA would not alter the composition of the proteins encoded by genes. Proteins function in virtually every process carried out by cells, from catalyzing biochemical reactions to recognizing foreign invaders. Hence, the thinking went, if a protein's makeup ends up being correct, any small glitches in the process leading to its construction could not do a body harm

Hall, Stephen S. 198

The field of reproductive medicine has a well established track record for pushing headlong into the clinic with technological innovations. Infertility is also big business. If Orwig were to demonstrate in animals that a simple genetic fix is possible, it would be a tempting procedure for the tens of thousands of men who cannot make their own sperm, for whom options are currently limited, as well as for the in vitro fertilization (IVF) industry, which did an estimated $2 billion in business last year in the U.S. (and perhaps 10 times that amount worldwide).

Chamary, J and Hurst, Laurence 182

The investigators found that 25 percent of the silent mutations they induced in one exon of the cystic fibrosis transmembrane-conductance regulator (CFTR) gene disrupted splicing and presumably would thus contribute to cystic fibrosis or related disorders

Chamary, J and Hurst, Laurence 189

The new understanding should also inform efforts to understand the root causes of disease. Central to many hunts for the genes underlying diseases are ongoing genome mapping projects to catalogue genetic variation among humans. By identifying all the point mutations, or single-nucleotide polymorphisms (SNPs), in individuals with a given disease, scientists can now home in on regions of the genome containing gene variants that may cause the disease

Hall, Stephen S. 203

The organizers of the Washington meeting framed the issue as "when, if at all." But a different word often crops up in private conversations with biologists when you ask about the prospects for germline editing. That word is "inevitable."

Regalado, Antonio 223

The price of manufacturing a single dose also might not be an obstacle. Two existing gene therapies approved in Europe cost $1 million and $665,000. Even if it cost twice that, a one-time gene fix with CRISPR would be cheaper than a lifetime of costly drugs, wheelchairs, and dependency

Satyajit Patra, Araromi Adewale Andrew 73

The production of medicines through the use of genetically altered organisms has generally been welcomed. However, critics of rDNA fear that disease-producing, organisms used in some rDNA experiments might develop extremely infectious forms that could cause worldwide epidemics

Satyajit Patra, Araromi Adewale Andrew 66

The resistance genes could be transferred to human or animal pathogens, making them impervious to antibiotics. (antimicrobial drug used in the treatment and prevention of bacterial infections)

WHEELWRIGHT, JEFF 106

The system has two major parts. Crispr, the programmable part, is the mechanism by which bacteria identify and target foreign genes introduced by viruses. In bacteria, Crispr produces a type of RNA dubbed guide-RNA. The guide-RNA — think of it as the navigator — delivers the enzyme Cas9 to just the right place in the foreign genome, whereupon Cas9 performs a disruptive cut.

JACOBSEN, ROWAN 80

The warrior gene is a classic example of the risks of Gattaca-style genetic determinism. Most people with the MAOA-L variant are probably normal citizens—hell, it could even make them great football players or Wall Street traders—but if it's just a matter of which box to check on my child's trait list, I'm going with the non aggro version

JACOBSEN, ROWAN 95

They will certainly be able to buy looks. Features such as a dimpled chin or the way your earlobes attach are easily determined. The genes responsible for hair, eye, and skin color are fairly clear-cut. If you want a freckle-faced redhead, no problem

Regalado, Antonio 219

This August, at the annual CRISPR meeting in Cold Spring Harbor, New York, researchers from the company showed that with a single dose, they could alter the genomes of at least half the cells in a mouse's liver. If Intellia can successfully edit liver cells in a person, that may let the company treat a slew of previously unassailable metabolic conditions like a form of hereditary amyloidosis, in which painful plaques build up in the body.

Hall, Stephen S. 199

This isn't theoretical," Orwig says. "The mouse is here, and the human is not too far in the future. The pieces are already in place." Yet another example that there is no stopping this technology

Talbot, David 162

This makes China's stance on GMO food crops critical for the entire global market; if China green-lights GMOs, many other countries that export to China may accept them too. Meanwhile, the rising use of imports puts pressure on China to do more to feed its own people, and that helps drive internal research on GMOs.

Chamary, J and Hurst, Laurence 181

To date, some 50 genetic disorders have been linked to silent mutations, many of which also appear to interfere with intron removal. Splicing enhancers can overlap with a considerable length of a gene's protein-coding sequence, imposing significant limitations on where a silent mutation would be tolerated.

Satyajit Patra, Araromi Adewale Andrew 69

Transgenic plants also present controversial issues. Allergens can be transferred from one food crop to another through genetic engineering. Another concern is that pregnant women eating genetically modified products may endanger their offspring by harming normal fetal development and altering gene expression

Chamary, J and Hurst, Laurence 191

We estimate that between 5 and 10 percent of human genes contain at least one region where silent mutations could be harmful

Satyajit Patra, Araromi Adewale Andrew 68

Weapons engineered using this technology could be resistant to medicines, or even targeted at people who carry certain genes. Genetically engineered organisms used for biological weapons might also reproduce faster, which would create larger quantities in shorter periods of time, increasing the level of devastation

Hall, Stephen S. 206

What Orwig wants to do is take infertile mice, which have a dysfunctional version of one of these genes, remove the sperm-forming stem cells from their testes and correct the defect in those cells by using the new gene-editing techniques

JACOBSEN, ROWAN 89

When I asked the prominent Stanford bioengineer Drew Endy if he believed we'd soon be designing our heirs, he said, "We already are. It's happening and everybody's happy about it."

JACOBSEN, ROWAN 104

When a genetic engineer needs a human gene for cancer therapy, she no longer needs a Henrietta Lacks to source the gene; she just looks up the sequence for that gene and emails it to a DNA synthesis company. A few days later, the gene arrives in the mail. This could be a blessing but also a curse (if attaining sequences for certain genes are that easy could one potentially use it to harm others)

Hall, Stephen S. 202

When the National Academy of Sciences debated recombinant DNA in 1977, protesters opposed to genetic engineering unfurled a banner quoting Adolf Hitler: "We Will Create the Perfect Race.

JACOBSEN, ROWAN 81

Will a society that can pick its offspring converge on a sort of Ivy League blandness? Or will daring parents opt for the shar-peis in their prospective litters? What will become of the human race if variance is smoothed out? Perhaps most important, will everyone have access to this technology, or only the well-off?

Hall, Stephen S. 212

Will sex become obsolescent? No, but having sex to conceive babies is likely to become at least much less common. In 20 to 40 years we'll be able to derive eggs and sperm from stem cells, probably the parents' skin cells. This will allow easy preimplantation genetic diagnosis on a large number of embryos—or easy genome modification for those who want edited embryos instead of just selected ones."

ADLER, JERRY 153

Will we do it--we humans, the species with the relentless appetite for knowledge? The fruit of that particular tree has never been left uneaten for very long.

Hall, Stephen S. 214

With Gene Modification A corrective approach, being pursued in animal research, would be to remove defective SSCs from infertile males and, using gene-editing techniques, replace the dysfunctional gene with an intact version through gene editing. One advantage of this approach is that the gene-edited stem cells can be screened both for correct insertion of the new gene and for any unwanted "off-target" hits. Cells that pass this safety check could be transplanted back into the patient to restore fertility. The genetic correction would then be passed on to the next generation— the very definition of germ-line modification.

Talbot, David 157

Yet despite the uncertainties, research on GMO crops continues. By one count published in Nature Biotechnology, 378 Chinese groups employing thousands of scientists are engaged in this work. The government will have spent some $4 billion on GMOs by 2020. Researchers are using the latest modification technologies and drawing from high-throughput genomic analysis of thousands of crop strains, accelerating the pace of discovery.

Chamary, J and Hurst, Laurence 175

Yet detective work occasionally traced a disorder to a silent mutation, even though researchers presumed that it could not possibly be the culprit. Similar mysteries popped up in studies of genome evolution, where patterns of changes in the DNA of various species indicated that many silent mutations were preserved over time--a sign that they were useful to the organisms possessing them

Talbot, David 168

Yet even promising startups--ones encouraged by the government-are holding back on GMOs. A few years ago, Xing Wang Deng arrived in Beijing to start a lab at Peking University through China's 1,000 Talents Program, which attempts to bring Chinese-born experts back from abroad.

Chamary, J and Hurst, Laurence 187

n human genes, most introns seem to be dispensable (only one, usually the first intron, appears to be required for the gene to give rise to a protein). This observation means that trans-genes can be made compact by removing introns. It also implies that some silent mutation sites could be tweaked without detrimental effect, because leaving out introns does away with the need for splicing enhancers.

Chamary, J and Hurst, Laurence 180

nitially researchers had no idea how such mutations could disturb protein manufacture in mammals. Lately, however, studies of human disease have provided not just one mechanism but many. Silent disease-causing mutations interfere with several stages of the protein-making process, from DNA transcription all the way through to the translation of mRNA into proteins

JACOBSEN, ROWAN 79

ntelligence—the holy grail of germline editing—involves incredibly complex interactions between myriad genes and environmental factors. It can't be significantly enhanced by simply fiddling with a few genetic dials. Then again, in May researchers announced the identification of 52 genes that may correlate with intelligence, so parents of the future may be able to buy their child a few extra IQ points.

Chamary, J and Hurst, Laurence 178

polycythemia disorders, a nonsense mutation truncates one of the hemoglobin proteins, resulting in thickened blood.

Chamary, J and Hurst, Laurence 190

t is likely that the causes of some diseases have been wrongly attributed to mutations that change proteins, when in fact synonymous mutations are at fault. Investigators need to keep this possibility in mind as they look for a damaging mutational needle in the genomic haystack. And who knows what additional mechanisms of disease such surveys will turn up?

Chamary, J and Hurst, Laurence 179

thalassemia, a sense mutation changes a stop codon (TAA) to the codon for glutamine (CAA), creating a much longer and nonfunctional protein.

ADLER, JERRY 145

the newcomer might be a relatively harmless species; the ecological niche for mosquitoes doesn't require them to carry diseases fatal to human beings. (however this is all speculation and it is impossible to predict the future, should we take the risk?)