Tag: Genetic Engineering

The Medicine Is a Miracle, but Only if You Can Afford It

A wave of new treatments have cured devastating diseases. When the costs are too much, even for the insured, patients hunt for other ways to pay.

A Dilemma for Governments: How to Pay for Million-Dollar Therapies

A wave of transformative but hugely expensive treatments is challenging the budgets of health systems in wealthy nations. Now countries with far fewer resources are wrestling with how to cover the therapies.

CRISPR, 10 Years On: Learning to Rewrite the Code of Life

The gene-editing technology has led to innovations in medicine, evolution and agriculture — and raised profound ethical questions about altering human DNA.

Blind Man’s Sight Partially Restored with ‘Optogenetics’ Gene Therapy

Using a technique called optogenetics, researchers added light-sensitive proteins to the man’s retina, giving him a blurry view of objects.

A team of scientists announced Monday that they had partially restored the sight of a blind man by building light-catching proteins in one of his eyes. Their report, which appeared in the journal Nature Medicine, is the first published study to describe the successful use of this treatment.

“Seeing for the first time that it did work — even if only in one patient and in one eye — is exciting,” said Ehud Isacoff, a neuroscientist at the University of California, Berkeley, who was not involved in the study.

The procedure is a far cry from full vision. The volunteer, a 58-year-old man who lives in France, had to wear special goggles that gave him the ghostly perception of objects in a narrow field of view. But the authors of the report say that the trial — the result of 13 years of work — is a proof of concept for more effective treatments to come.

“It’s obviously not the end of the road, but it’s a major milestone,” said Dr. José-Alain Sahel, an ophthalmologist who splits his time between the University of Pittsburgh and the Sorbonne in Paris.

Dr. Sahel and other scientists have tried for decades to find a cure for inherited forms of blindness. These genetic disorders rob the eyes of essential proteins required for vision.

When light enters the eye, it is captured by so-called photoreceptor cells. The photoreceptors then send an electrical signal to their neighbors, called ganglion cells, which can identify important features like motion. They then send signals of their own to the optic nerve, which delivers the information to the brain.

In previous studies, researchers have been able to treat a genetic form of blindness called Leber congenital amaurosis, by fixing a faulty gene that would otherwise cause photoreceptors to gradually degenerate.

But other forms of blindness can’t be treated so simply, because their victims lose their photoreceptors completely. “Once the cells are dead, you cannot repair the gene defect,” Dr. Sahel said.

For these diseases, Dr. Sahel and other researchers have been experimenting with a more radical kind of repair. They are using gene therapy to turn ganglion cells into new photoreceptor cells, even though they don’t normally capture light.

The scientists are taking advantage of proteins derived from algae and other microbes that can make any nerve cell sensitive to light.

In the early 2000s, neuroscientists figured out how to install some of these proteins into the brain cells of mice and other lab animals by injecting viruses carrying their genes. The viruses infected certain types of brain cells, which then used the new gene to build light-sensitive channels.

Originally, researchers developed this technique, called optogenetics, as a way to probe the workings of the brain. By inserting a tiny light into the animal’s brain, they could switch a certain type of brain cell on or off with the flick of a switch. The method has enabled them to discover the circuitry underlying many kinds of behavior.

Dr. Sahel and other researchers wondered if they could use optogenetics to add light-sensitive proteins to cells in the retina. After all, they reasoned, retinal cells are nerves as well — an extension of the brain, in other words.

For Ed Boyden, a neuroscientist at M.I.T. who helped pioneer the field of optogenetics, the quest to use these proteins to cure blindness took him by surprise. “So far, I’ve thought of optogenetics as a tool for scientists primarily, since it’s being used by thousands of people to study the brain,” he said. “But if optogenetics proves itself in the clinic, that would be extremely exciting.”

Dr. Sahel and his colleagues recognized that the optogenetic proteins created by Dr. Boyden and others were not sensitive enough to produce an image from ordinary light entering the eye. But the scientists could not beam amplified light into the eye, because the glare would destroy the delicate tissue of the retina.

So the scientists chose an optogenetic protein that’s sensitive only to amber light, which is easier on the eye than other colors, and used viruses to deliver these amber proteins to the ganglion cells in the retina.

The experimental set-up, where the volunteer was asked to say whether or not the cup was on the white table. Behavioral responses and brain activity were recorded simultaneously during the test.
The experimental set-up, where the volunteer was asked to say whether or not the cup was on the white table. Behavioral responses and brain activity were recorded simultaneously during the test.Sahel, et al.; Nature Medicine

Next, the researchers invented a special device to transform visual information from the external world into amber light that could be recognized by the ganglion cells. They created goggles that scan their field of view thousands of times a second and register any pixels in which the light changes. The goggles then send a pulse of amber light from that pixel into the eye.

The researchers reasoned that this strategy might be able to create images in the brain. Our eyes naturally dart around in tiny movements many times a second. With each jump, many pixels would change light levels.

Still, it was an open question whether blind people could learn to use this information to recognize objects. “The brain has to learn a new language,” said Botond Roska, an ophthalmologist at the University of Basel and a co-author of the new study.

After testing their gene therapy and goggles on monkeys, Dr. Roska, Dr. Sahel and their colleagues were ready to try it out on people. Their plan was to inject gene-bearing viruses into one eye of each blind volunteer, then wait several months for the ganglion cells to grow optogenetic proteins. They would then train the volunteers to use the goggles.

Unfortunately, they only managed to train one volunteer before the coronavirus pandemic shut down the project. After years of preparation for the study, it was now stuck in limbo.

But then the one volunteer they had managed to train got in touch. For seven months, he had been wearing the goggles at home and on walks. One day he realized he could see the stripes of a crosswalk.

When the pandemic subsided in France over the summer, the scientists managed to bring him into their lab for more training and tests. They discovered that he could reach out and touch a notebook sitting on a table, but had less luck with a smaller box of staples. When the scientists set out either two or three tumblers in front of the volunteer, he managed to count them correctly 12 out of 19 times.

During some of the trials, the volunteer wore a cap with electrodes that could detect brain activity through his scalp. When the goggle sent signals to his retina, it activated parts of the brain involved in vision.

“It is a major achievement from a scientific point of view, and most importantly for blind people,” said Lucie Pellissier, a neuroscientist at the University of Tours in France who was not involved in the study.

Dr. Sahel and his colleagues founded a company called GenSight to move their technique through clinical trials with the hopes of getting it approved by regulators. They’re not alone. Dr. Isacoff and his colleagues have founded a similar company called Vedere Bio that was acquired last October by Novartis.

It will take many more positive results from clinical trials before optogenetics can become a standard treatment for some forms of blindness. For now, Dr. Sahel and his colleagues are bringing in the other volunteers for training, as well as testing higher doses of the virus and upgrading their goggles to thin spectacles that would be more comfortable while also delivering more information to the retina.

Dr. Isacoff and his colleagues have carried out experiments of their own that raise the possibility that other optogenetic proteins could make retinal cells sensitive enough to detect light without the help of goggles. “I think it’s going to perform quite well,” he said.

For all the time that Dr. Sahel has put into his own system, he hesitated to guess how far it could improve. “Until you have a patient tell you what they are seeing, you really can’t predict anything,” he said.

Is Your Food ‘Natural’? F.D.A. to Weigh In


Credit Tony Cenicola/The New York Times

Can you define the word “natural”?

The Food and Drug Administration is certainly trying. Since 2014, the agency has asked the public to weigh in on how the term should be defined and used on food labels — or whether it is even appropriate for the F.D.A. to regulate the use of the word at all. By the time the agency closed its public commenting period on May 10, about 7,600 comments had poured in from consumers, companies, food experts and health and legal authorities.

A spokeswoman for the F.D.A. said that the agency is now reviewing all of those comments. While the process could take months, experts say there is a great sense of urgency. Americans spend more than $40 billion a year on cereals, breads, yogurts, beverages, and other foods identified as “all natural.” Surveys show that consumers seek out the “all natural” label because they believe — wrongly — that it means the food was produced without genetically modified organisms, hormones, pesticides and artificial ingredients.

In fact, more than a hundred class action lawsuits have accused companies of misleading consumers by slapping the words “all natural” on products that contain synthetic, artificial and genetically engineered ingredients. A number of federal judges have urged the F.D.A. to weigh in, saying that they cannot rule on whether companies improperly used the term on their products until the F.D.A. defines what it actually means.

But can it?

Until now, the F.D.A. has “respectfully declined” judges’ requests. It has mostly referred the public to an informal advisory it published more than two decades ago, which stated that natural means that “nothing artificial or synthetic,” such as color additives, has been added to a food that would not normally be expected to contain it.

But that advisory is not legally enforceable, nor was it intended to address processing methods such as pasteurization and irradiation or, for that matter, genetic engineering.

The issue of whether genetically modified foods can be labeled natural has been raised in more than 50 legal cases, including a lawsuit against the makers of Mission tortilla chips. According to the suit, Mission’s tortilla chips were labeled “all natural” despite being made from genetically modified corn, which the suit called misleading.

Among those who have called on the F.D.A. to take a stronger stance on the meaning of the word is Eric T. Schneiderman, the New York State attorney general, who wrote a letter this month urging the agency to adopt a definition that excludes synthetic and artificial ingredients, as well as genetically modified organisms, or G.M.O.s.

Mr. Schneiderman asked the agency to restrict the definition to minimally processed foods like ground nuts and washed salads, or foods that were prepared using traditional techniques like roasting, drying, smoking and fermenting.

Forbidding genetically modified foods to be called natural would be similar to the standards for organic labeling, which are tightly regulated by the United States Department of Agriculture and which exclude G.M.O. foods from carrying the organic certification.

Under Mr. Schneiderman’s definition, “natural” would essentially mean not made by humans, and subjected to little or no processing.

But other experts say it’s not so simple. For decades, countless varieties of crops that ultimately became supermarket staples were created through breeding practices that involved subjecting the crops to radiation to attain favorable genetic mutations — including the ruby red grapefruit, said Michael Jacobson of the Center for Science in the Public Interest, a consumer advocacy group in Washington.

“I think if you ask the average person they would say that ruby red grapefruits are natural,” Dr. Jacobson said. “But ruby red grapefruits were derived decades ago from seeds that had been treated with irradiation. Some people would say that’s human intervention and so it’s not natural. There are plenty of reasons why the natural issue has gotten so messy and why the F.D.A. has run the other way from it.”

To avoid those issues, some argue that the definition should refer only to the post-harvesting period, so that foods that are plucked from the ground or produced by farms and brought to market as is are considered natural, while those that are subjected to extensive processing are not.

All would agree, for example, that an organic peach at a farmer’s market is natural. But what about a peach that is sliced, dried and preserved with citric acid, an organic compound that can be isolated from lemons or made in a factory? What if the peach is sliced and preserved with sugar, and then sold in a can? And what if that sugar is high-fructose corn syrup, or cane sugar from G.M.O. crops?

“Everyone is always going to have their own conception of what is natural,” said Marsha Cohen, a law professor and expert on food law at the University of California, Hastings College of the Law. “The most logical position is to say this word is never going to be meaningful enough to not be misleading to people.”

With so many nuances and thorny questions to address, the F.D.A. could choose to ban the use of the word natural from labels entirely. Food labels have become so crowded with information — nutrition facts, organic certifications, claims about hormones, gluten, whole grains and G.M.O.s — that for many people it is difficult to figure out what to focus on, said Margot Pollans, an expert on food law at the Elisabeth Haub School of Law at Pace University.

After a while, all the label claims can start to seem like white noise. But while “all natural” seems to confuse consumers even further, the F.D.A. is unlikely to forbid its use altogether.

“The problem that the F.D.A. would then encounter is the First Amendment – free speech,” said Ms. Cohen of U.C. Hastings. “The F.D.A. would have a very long road ahead of it to just ban the word completely.”

In the end, that may not be necessary. The fear of litigation has already caused food industry giants like PepsiCo, Frito-Lay, Campbell Soup and others to abandon their use of the word on products, said Jason J. Czarnezki, the executive director of environmental law programs at Pace University. Across the food industry, the number of products claiming to be “natural” fell to roughly 22 percent in 2013 from about 30 percent in 2010.

“I think companies are moving away from words that in some ways might be considered consumer fraud,” Mr. Czarnezki said.

The F.D.A. should nonetheless issue a strict definition of “natural,” he said — one that not only excludes artificial, synthetic and genetically engineered ingredients but that also restricts foods that have a large carbon footprint. Mr. Czarnezki said it is up to the agency to help consumers make sense of all the confusion.

“Even the most educated consumer can’t know what the word means,” he said.


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