Editing Genes Shouldn’t be too Scary – Unless They Are the Ones that Get Passed to Future Generations

Eleanor Feingold wrote . . . . . . . . .

Gene editing is one of the scarier things in the science news, but not all gene editing is the same. It matters whether researchers edit “somatic” cells or “germline” cells.

Germline cells are the ones that propogate into an entire organism – either cells that make sperm and eggs (known as germ cells), or the cells in an early embryo that will later differentiate into different functions. What’s critical about those particular cells is that a change or mutation in one will go on to affect every cell in the body of a baby that grows from them. That’s why scientists are calling for a moratorium on editing the genes of germ cells or germline cells.

Somatic cells are everything else – cells in particular organs or tissues that perform a specific function. Skin cells, liver cells, eye cells and heart cells are all somatic. Changes in somatic cells are much less significant than changes in germline cells. If you get a mutation in a liver cell, you may end up with more mutant liver cells as the mutated cell divides and grows, but it will never affect your kidney or your brain.

Our bodies accumulate mutations in somatic tissues throughout our lives. Most of the time humans never know it or suffer any harm. The exception is when one of those somatic mutations grows out of control leading to cancer.

I am a geneticist who studies the genetic and environmental causes of a number of different disorders, from birth defects – cleft lip and palate – to diseases of old age like Alzheimer’s. Studying the genome always entails thinking about how the knowledge you generate will be used, and whether those likely uses are ethical. So geneticists have been following the gene editing news with great interest and concern.

In gene editing, it matters enormously whether you are messing with a germline cell, and thus an entire future human being and all its future descendants, or just one particular organ. Gene therapy – fixing faulty genes in individual organs – has been one of the great hopes of medical science for decades. There have been a few successes, but more failures. Gene editing may make gene therapy more effective, potentially curing important diseases in adults. The National Institutes of Health runs a well-respected and highly ethical research program to develop tools for safe and effective gene editing to cure disease.

But editing germline cells and creating babies whose genes have been manipulated is a very different story, with multiple ethical issues. The first set of concerns is medical – at this point society doesn’t know anything about the safety. “Fixing” the cells in the liver of someone who might otherwise die of liver disease is one thing, but “fixing” all of the cells in a baby who is otherwise healthy is a much higher-risk proposition. This is why the recent announcement that a Chinese scientist had done just that created such an uproar.

But even if we knew the procedure was safe, gene editing of the germline would still catapult us straight into all of the “designer baby” controversies and the problems of creating a world where people try to micromanage their offspring’s genes. It does not take much imagination to fear that gene editing will could bring us a new era of eugenics and discrimination.

Does gene editing still sound scary? It should. But it makes a big difference whether you are manipulating individual organs or whole human beings.

Source: The Conversation

Genome-editing Tool Could Increase Cancer Risk

Therapeutic use of gene editing with the so-called CRISPR-Cas9 technique may inadvertently increase the risk of cancer, according to a new study from Karolinska Institutet, Sweden, and the University of Helsinki, Finland, published in Nature Medicine. Researchers say that more studies are required in order to guarantee the safety of these ‘molecular scissors’ for gene-editing therapies.

CRISPR-Cas9 is a molecular machine first discovered in bacteria that can be programmed to go to an exact place in the genome, where it cuts the DNA. These precise ‘molecular scissors’ can be used to correct faulty pieces of DNA and are currently being used in clinical trials for cancer immunotherapy in the US and China. New trials are expected to be launched soon so as to treat inherited blood disorders such as sickle cell anemia.

Two independent articles published in the journal Nature Medicine now report that therapeutic application of the genome-editing tool may, in fact, increase the risk of cancer. In one of the studies, scientists from Karolinska Institutet and the University of Helsinki report that use of CRISPR-Cas9 in human cells in a laboratory setting can activate a protein known as p53, which acts as a cell’s ‘first aid kit’ for DNA breaks. Once active, p53 reduces the efficiency of CRISPR-Cas9 gene editing. Thus, cells that do not have p53 or are unable to activate it show better gene editing. Unfortunately, however, lack of p53 is also known to contribute to making cells grow uncontrollably and become cancerous.

“By picking cells that have successfully repaired the damaged gene we intended to fix, we might inadvertently also pick cells without functional p53,” says Dr Emma Haapaniemi, researcher at the Department of Medicine at Karolinska Institutet in Huddinge and co-first author of the study. “If transplanted into a patient, as in gene therapy for inherited diseases, such cells could give rise to cancer, raising concerns for the safety of CRISPR-based gene therapies.”

“CRISPR-Cas9 is a powerful tool with staggering therapeutic potential,” adds Dr Bernhard Schmierer, researcher at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet, and Head of the High Throughput Genome Engineering Facility of Science for Life Laboratory (SciLifeLab), who co-supervised the study. “Like all medical treatments however, CRISPR-Cas9-based therapies might have side effects, which the patients and caregivers should be aware of. Our study suggests that future work on the mechanisms that trigger p53 in response to CRISPR-Cas9 will be critical in improving the safety of CRISPR-Cas9-based therapies.”

Source: Karolinska Institutet

Today’s Comic

More Gene-Edited Food Could Soon Be Coming to Store Shelves

Lydia Mulvany wrote . . . . . . . .

Agricultural startup Pairwise Plants, which recently attracted a $100 million investment from seed giant Monsanto Co., is looking to take its genetic-modification tools to the produce aisle.

The company will use a technology called gene-editing to come up with new traits for row crops, such as corn and soybeans. They’re also interested in other foods that haven’t typically been genetically modified, like fruits and vegetables.

Genetic engineering has mostly been reserved for large commodity crops because regulatory testing costs so much. But gene-editing, which modifies a plant’s DNA directly without injecting foreign genes, isn’t regulated. Editing methods promise to be faster and cheaper, opening up the technique to foods that haven’t usually been modified, say strawberries or spinach.

Traits could directly benefit consumers, like making a certain vegetable healthier, or saving fruits threatened by diseases, said Haven Baker, chief business officer for Pairwise. The tool could allow for developing better sliced apples, or making heirloom tomatoes more robust and abundant, he said.

By creating foods that are “really beneficial to people, they’re much more likely to have a positive view of the technology,” said Tom Adams, who will join Pairwise on April 1 as chief executive officer, leaving a vice president role at Monsanto. There’s an “an opportunity to expand in a broader way into crops that can directly affect people’s lives,” Adams said.

Source : Bloomberg

A Potato Made with Gene Editing

Plant scientists can swiftly modify crops in ways that would take years with conventional breeding.

Dan Voytas is a plant geneticist at the University of Minnesota. But two days a week he stops studying the fundamentals of DNA engineering and heads to a nearby company called Cellectis Plant Sciences, where he applies them.

His newest creation, described in a plant journal this month, is a Ranger Russet potato that doesn’t accumulate sweet sugars at typical cold storage temperatures. That will let it last longer, and when it’s fried it won’t produce as much acrylamide, a suspected carcinogen.

What’s different about the potato is that it was bred with the help of gene editing, a new kind of technique for altering DNA that plant scientists say is going to be revolutionary for its simplicity and power. The technology could also be a way to engineer plants that avoid the stigma, and the regulations, normally associated with genetically modified organisms (GMOs).

In the case of the Ranger Russet, Voytas’s gene-editing technique, known as TALENs, left behind no trace other than a few deleted letters of DNA. The edit disabled a single gene that turns sucrose into glucose and fructose. Without it, Voytas thinks, the potatoes can be stored far longer without loss of quality.

The potato is a prototype of what plant scientists say is a rapidly arriving new generation of genetically modified plants. With gene editing, small companies think they can very quickly develop new crops for a fraction of the typical cost—even in species so far mostly untouched by biotechnology, like avocados, sorghum, and decorative flowers.

Most genetically modified crops that have been grown commercially so far incorporate genes from bacteria to make them produce insecticides or resist weed killers. Public opposition and regulatory requirements make these transgenic plants expensive to develop. That is why nearly all biotech plants are lucrative, big-acreage crops like soy, corn, and cotton and are sold by just a few large companies, like Monsanto and DuPont.

In August, the U.S. Department of Agriculture told Cellectis that unlike transgenic plants, its potato wouldn’t be regulated. That means instead of being grown in fenced-in test plots and generating folder upon folder of safety data, the Ranger Russet may go quickly to the market. Two years ago the agency reached a similar conclusion when it considered a DNA-edited corn plant developed by Dow AgroSciences, although it isn’t being sold yet.

* * * * * * *

Scientists say products like the potato are just the start for gene-editing techniques in plants. The same technologies are going to allow far more sophisticated engineering, including manipulation of photosynthesis to make plants grow faster and yield more food. “It’s an enormous opportunity, an unfathomable opportunity,” says Martin Spalding, a plant researcher at Iowa State University.

For now, the techniques are being used to modify plants in more modest ways. “The first wave of this technology is just removing a few base pairs,” says Yinong Yang, a professor of plant pathology at Penn State University, referring to the combinations of DNA letters—A, G, C, and T—that make up a genome. By “knocking out” just the right gene, as researchers did with the potato, it’s possible to give a plant a few valuable properties.

The next step, Yang says, will be to change the DNA letters of plant genes, swapping one plant’s version of a gene for that of another known to offer, say, resistance to disease. Yang says there is a blight-resistant form of rice that differs from commercial species by only a few DNA letters. “I could just change that over to resistance,” he says. “It’s like gene therapy in humans.” He says he’s negotiating a contract to produce the gene-edited rice now.

As for Voytas, this isn’t the first time he has set out to gene-edit plants. A decade ago he started a company called Phytodyne based on an earlier technology, called zinc finger nucleases, but it folded after Dow AgroSciences paid more than $50 million for exclusive rights to use that type of gene editing in plants.

Voytas teamed up with the French biotechnology company Cellectis in 2010 after it offered to install him as science chief of a new plant engineering division. But initial efforts ran into difficulty when another gene-editing system, meganucleases, proved challenging to work with and also got tied up by patent disputes.

Eventually, Voytas returned to the lab and coinvented a new way to edit genes, using specially engineered proteins called TALENs. That technology was used to make Cellectis’s potato, as well as a soybean with improved oil. Since then, Voytas and Cellectis have also worked with a newer technique, called CRISPR (see “Genome Surgery”).

Voytas says the potato took only about a year to create. “If you did it via breeding it would take five to 10 years,” he says.

Altogether, says Luc Mathis, CEO of Cellectis Plant Sciences, developing the potato cost a tenth of what it does to create and bring to market a transgenic plant, like corn or soy. “We will still need to generate some data, but it will not be a huge process,” says Mathis, who continues to meet with regulators to determine what steps remain before the potato can be sold.

Cellectis will move ahead with preliminary planting as soon as warm weather arrives in Minnesota. The first crops will determine whether the potatoes have the commercial benefits seen in greenhouse tests. “We need to check that we can store the potato in the cold,” says Mathis. “Once we have the commercial proof of concept, we can discuss with farmers what the interest level is.”

Kevin Folta, a professor of horticultural sciences at the University of Florida, says about 50 experts, including scientists and lawyers, met in Arizona earlier this year to discuss gene editing and how to orchestrate the industry’s approach to regulators in the United States and abroad. “Anyone who works in any kind of plant engineering is vigorously pursuing these technologies, especially with crops that have complex genomes or that you can’t breed easily,” he says. “There are lots of plants that need solutions.” He says gene editing will allow citrus trees to be modified in ways that would take 150 years with conventional breeding.

Folta says opponents of GMOs were not included in the planning meeting. “To invite people who view things nonscientifically would clog the discussion,” says. “There is no technology they are happy with.”

Source: MIT Technology Review