3339. Mike Davis: Capitalism Is the Disease

By Mike David and Andy Hsiao, March 31, 2020

2540. "Genetically Edited" Food Have No Regulations Whatsoever

By Kenneth Chang, The New York Times, January 9, 2017

These genetically edited mushrooms will have longer shelf-life before getting dark

In a few years, you could be eating the next generation of genetically altered foods — potatoes that do not turn brown or soybeans with a healthier mix of fatty acids.

And you may have no idea that something is different, because there may be no mention on the labeling even after a law passed by Congress last year to disclose genetically modified ingredients takes effect.

A new generation of crops known as gene-edited rather than genetically modified is coming to the market. Created through new tools that snip and tweak DNA at precise locations, they, at least for now, largely fall outside of current regulations.

Unlike older methods of engineering genes, these techniques, like Crispr, so far have generally not been used to add genes from other organisms into the plants.

The federal Agriculture Department has asked companies to advise it of their plans. But once the companies submit data to show the agency that the gene edits do not introduce foreign genes from plant pests into the crops, the agency is giving businesses the green light.

Hundreds of acres of gene-edited crops have already been grown in several states, unencumbered by oversight or regulations. And a few people have eaten them already. “This is not Frankenfood,” said André Choulika, chief executive of Cellectis, one of the companies developing gene-edited crops.

In October, Cellectis hosted a dinner at Benoit New York, the Alain Ducasse Manhattan restaurant, and served dishes made from its gene-edited soybeans and potatoes. Guests included professors, journalists and celebrities like Neil Patrick Harris, the actor.

“I don’t even know what gene editing is,” Mr. Harris said. “I thought we were supposed to wear jeans.”

Calyxt, a subsidiary of Cellectis doing the gene-edited food, is also developing new versions of wheat including one with greater resistance to fungal diseases, another lower in carbohydrates and higher in dietary fibers.

Other companies also developing gene-edited crops including DuPont Pioneer, which has used the technology for a new variety of waxy corn, used most commonly not for food but for starch in adhesives. Scientists at Pennsylvania State University have used Crispr to create mushrooms that do not turn brown as quickly.

The current regulations were written for the earlier generation of genetically modified organisms, where scientists used bacteria and viruses — typically from plant pests — to drop a payload of new genes into the nuclei of the plant cells where they merge with the plant’s DNA. That worked, but scientists could not control where the new genes would be inserted, and that led to worries of potentially dangerous genetic disruptions or crossbreeding with non-G.M.O. crops.

Companies like Calyxt have portrayed gene editing more like moving the cursor in a word processor to a particular location and making a small change to the text.

Federal agencies have not yet said how they intend to regulate gene-edited foods, and the incoming Trump administration, while criticizing overregulation in general, has not weighed in.

Other parts of the world are also considering whether to regulate gene-edited foods and how to do so. In Europe, where many countries have banned the cultivation of G.M.O.s, the European Commission has created a scientific panel to study the issue, with debate resuming this year.

Dr. Choulika said the inspiration for the October gathering was a dinner more than two centuries earlier, by Antoine-Augustin Parmentier, a French scientist who was enthralled with potatoes brought to Europe from South America. But many Europeans scorned the potato. France even outlawed the growing of potatoes in 1748. Largely because of Parmentier’s work, potatoes were declared to be safely edible in 1772, and the ban was lifted. Still, few wanted to eat them.

In 1778, Parmentier organized the first in a series of lavish dinners for the high society of Paris, serving dishes all made with potatoes. Potatoes became a fixture in French cuisine.

With farmers harvesting the first substantial plantings of the Cellectis gene-edited potatoes and soybeans last year, Dr. Choulika thought of throwing a modern version of Parmentier’s gathering.

“This is the first dinner on Earth with gene-edited foods,” Dr. Choulika said to the diners. “Things that you eat today, millions of people are going to eat during the 21st century, and this will not stop.”

After some collaborations with big companies like Monsanto and DuPont Pioneer, Cellectis started Calyxt, to explore opportunities for using gene editing for foods.

Dr. Choulika said he considered G.M.O.s safe, but that the gene-editing techniques like those used by Calyxt would be more acceptable to consumers. Often in G.M.O.s, the inserted genes came from unrelated species, like the bacterial genes that were added to cotton so that it would exude a toxin to repel bollworms, a mixing of species known as transgenesis.

“There’s not this blockage of transgenesis that freaks out people for no reason,” he said. “I think it is a question of perception.”

Instead of using bacteria and viruses to burrow into a cell, gene-editing techniques — Calyxt uses one called Talen — create molecules that act as a template to match a specific segment of DNA and then make a cut there.

For the Calyxt soybeans, for example, the only change was to turn off two genes. “There is nothing taken out or added to the plant,” Dr. Choulika said. “It’s what nature would have produced.”

Those edits change the mix of fatty acids and perhaps make for a better cooking oil. “Better than olive oil,” Dr. Choulika said.

At the dinner, the soybeans were transformed into a several dishes including soy blinis, mini tofu and soy burgers, and soybean hummus. Carole Pourchet, director of the Lab, the research and development arm of Mr. Ducasse’s food enterprise, said the gene-edited soy cooked like normal soy, but that the potatoes were a little drier, leading to the idea to confit them to retain moisture.

The potatoes showed up in mashed potatoes, potato pie and blinis.

“The dinner was maybe potatoes cooked 10 ways,” said Richard C. Mulligan, a professor of genetics at Harvard Medical School who was one of the guests. Dr. Choulika worked as a postdoctoral researcher in Dr. Mulligan’s laboratory two decades ago.

Federico Tripodi, chief executive of the Calyxt subsidiary, said the company hoped the soybeans would be used in cooking oil for commercial and industrial use by 2018.

The potatoes, edited to remain fresher longer and not produce carcinogens when fried, could be grown and sold in 2019. A second potato that is slower to turn brown just got word from the U.S.D.A. that it, too, is not subject to regulation.

Gene editing is not being used only with plants. A Minnesota company, Recombinetics, is editing the genes of farm animals — for example, creating cattle without horns.

Critics warned that the industry was repeating the same mistakes of G.M.O.s.

“We’ve never been against any of this technology,” said Michael K. Hansen, a senior staff scientist at Consumers Union. “We don’t say it’s inherently bad or these crops are inherently dangers. It’s just they raise safety issues, and there should be required safety assessments.”

While the gene-editing templates match a specific sequence, it is possible that the same sequence occurs elsewhere in the genome or they will match similar sequences, and the DNA will be sliced in those places, too, with unknown consequences. “They make it sound very exact,” Dr. Hansen said. “It will have off-target effects.”

Dr. Hansen said unregulated gene-edited crops could also create trade havoc if traces of them accidentally mixed into exports to countries that prohibited them.

Daniel Voytas, chief science officer of Calyxt who was one of the inventors of the Talen gene-editing technology, said the company had not checked the entire genomes of their plants, but did look for unintended changes within sections that were similar to the parts they were editing. “We didn’t find any,” he said.

Dr. Voytas said it would not be “a huge amount of work” to sequence the entire genome and that all of the data they presented was available on the U.S.D.A.’s website.

A U.S.D.A. advisory board in November unanimously recommended that standards for organic foods exclude gene-edited crops even if they were grown without chemical fertilizers and abided by the other strictures of organic farming.

Dr. Mulligan of Harvard said he was not sure that people would see much difference between gene-edited and genetically modified. “The objection that people have is a more visceral and vague objection to messing with DNA,” he said. “It’s hard to see that the public would see the difference.”

He admitted that he was more excited by the chef.

“The good thing with this is Ducasse is such a culinary artist,” Dr. Mulligan said. “He is really well known for being able to take anything and make it taste good.”

For Mr. Harris, the dinner provided a whirlwind introduction to biotechnology — “realities that I thought were theoreticals,” he said.

2539. Roundup Causes Non-Alcoholic Fatty Liver Disease at Very Low Doses

By Claire Robinson, GMWatch, January 9, 2017

Cutting-edge molecular profiling analyses reveal that the popular weedkiller Roundup causes liver damage at doses permitted by regulators.

The weedkiller Roundup causes non-alcoholic fatty liver disease at very low doses permitted by regulators worldwide, a new peer-reviewed study shows. The study is the first ever to show a causative link between consumption of Roundup at a real-world environmentally relevant dose and a serious disease.

The new peer-reviewed study, led by Dr Michael Antoniou at King's College London, used cutting-edge profiling methods to describe the molecular composition of the livers of female rats fed an extremely low dose of Roundup weedkiller, which is based on the chemical glyphosate, over a 2-year period. 

The dose of glyphosate from the Roundup administered was thousands of times below what is permitted by regulators worldwide. 

The study revealed that these animals suffered from non-alcoholic fatty liver disease (NAFLD). 

Dr Antoniou said: “The findings of our study are very worrying as they demonstrate for the first time a causative link between an environmentally relevant level of Roundup consumption over the long-term and a serious disease – namely non-alcoholic fatty liver disease. 

“Our results also suggest that regulators should reconsider the safety evaluation of glyphosate-based herbicides.”

Potentially serious implications for human health

The new results demonstrate that long-term consumption of an ultra-low dose of Roundup at a glyphosate daily intake level of only 4 nanograms per kilogram of bodyweight per day, which is 75,000 times below EU and 437,500 below US permitted levels, results in NAFLD. 

Regulators worldwide accept toxicity studies in rats as indicators of human health risks. So the results of this latest study have serious implications for human health.

NAFLD currently affects 25% of the US population and similar numbers of Europeans. Risk factors include being overweight or obese, having diabetes, or having high cholesterol or high triglycerides (a constituent of body fat) in the blood. However, some people develop NAFLD even if they do not have any of these known risk factors. The new study raises the question of whether exposure to Roundup is a hitherto unrecognized risk factor.

Symptoms of NAFLD include fatigue, weakness, weight loss, loss of appetite, nausea, abdominal pain, spider-like blood vessels, yellowing of the skin and eyes (jaundice), itching, fluid build-up and swelling of the legs and abdomen, and mental confusion. 

NAFLD can progress to the more serious condition, non-alcoholic steatohepatitis (NASH). NASH causes the liver to swell and become damaged. 

Most people with NASH are between the ages of 40 and 60 years. It is more common in women than in men. NASH is one of the leading causes of cirrhosis in adults in the United States. Up to 25% of adults with NASH may have cirrhosis.

Background to the study

The rat body tissues used in this analysis were obtained from a previous study led by Prof Gilles-Eric Séralini of the University of Caen, France. In this original investigation, rats were given an extremely low, environmentally relevant dose of a commercial Roundup formulation at 0.1ppb (parts per billion)/50ppt (parts per trillion) glyphosate via drinking water for 2 years. Daily intake of glyphosate from the Roundup was 4 nanograms per kilogram of body weight per day, which is thousands of times below what is permitted by regulators.

Analysis of the organs and blood/urine biochemical levels in the original study by Prof Séralini suggested a higher incidence of liver and kidney damage in the animals given Roundup compared to controls given plain drinking water. 

Dr Antoniou’s group has conducted distinct followup investigations on the rat body tissues from this ultra-low-dose Roundup treatment group, using in-depth molecular analytical procedures and statistical analytical methods that are appropriate for this type of research.

In the first followup investigation, a transcriptomics (gene function profile) analysis was performed on the livers and kidneys from the female animals. The results strongly supported the observations made at an anatomical (organ) and blood/urine biochemical level in the Séralini study – namely that the organs of the animals given Roundup suffered more structural and functional damage than the controls.

The transcriptomics results indicated an increased incidence of fibrosis (scarring), necrosis (areas of dead tissue), phospholipidosis (disturbed fat metabolism) and damage to mitochondria (the centres of respiration in cells) in the Roundup-fed animals.

However, although transcriptomics analysis is able to predict health or disease status of an organ, it does not provide definitive proof of harm. This is mainly because it does not give a direct measure of the actual biochemistry of the organ under study. Also, alterations in gene function resulting from a test do not always result in the types of changes in physical composition that could lead to disease.

Definitive confirmation of liver dysfunction from low dose of Roundup

In the new study the researchers undertook a followup protein composition profile (“proteomics”) and small molecule metabolite biochemical profile (“metabolomics”) investigation of the same liver samples to confirm the prediction of disease suggested by the transcriptomics gene expression profile analysis. As the proteomics and metabolomics directly measure the actual composition of the organ, these analytical methods provide a definitive assessment of its health or disease status.

Overall, metabolomics and proteomics disturbances showed a substantial overlap with biochemical hallmarks of NAFLD and its progression to steatohepatosis (serious fatty liver disease). Therefore they definitively confirm that serious liver disease has resulted from chronic ultra-low dose Roundup exposure.

The findings in detail

Proteins significantly disturbed (214 out of 1906 detected), as shown by the proteomics profiling, reflected a type of cell damage from reactive oxygen (peroxisomal proliferation), steatosis (serious fatty liver disease) and necrosis (areas of dead tissue).

The metabolomics analysis (55 metabolites altered out of 673 detected) confirmed lipotoxic (excess fatty tissue) conditions and oxidative stress. Metabolite alterations were also associated with hallmarks of serious liver toxicity.

The new study

Mesnage R, Renney G, Séralini GE, Ward M, Antoniou MN. Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide. Scientific Reports, 2016; 6:39328. http://www.nature.com/articles/srep39328

1606. Ebola Vaccine, Ready for Test, Sat on the Shelf Because Africans Could Not Pay

By Denise Grady, The New York Times, October 23, 2014

GALVESTON, Tex. — Almost a decade ago, scientists from Canada and the United States reported that they had created a vaccine that was 100 percent effective in protecting monkeys against the Ebola virus. The results were published in a respected journal, and health officials called them exciting. The researchers said tests in people might start within two years, and a product could potentially be ready for licensing by 2010 or 2011.

It never happened. The vaccine sat on a shelf. Only now is it undergoing the most basic safety tests in humans — with nearly 5,000 people dead from Ebola and an epidemic raging out of control in West Africa.

Its development stalled in part because Ebola is rare, and until now, outbreaks had infected only a few hundred people at a time. But experts also acknowledge that the absence of follow-up on such a promising candidate reflects a broader failure to produce medicines and vaccines for diseases that afflict poor countries. Most drug companies have resisted spending the enormous sums needed to develop products useful mostly to countries with little ability to pay.

Now, as the growing epidemic devastates West Africa and is seen as a potential threat to other regions as well, governments and aid groups have begun to open their wallets. A flurry of research to test drugs and vaccines is underway, with studies starting for several candidates, including the vaccine produced nearly a decade ago.

A federal official said in an interview on Thursday that two large studies involving thousands of patients were planned to begin soon in West Africa, and were expected to be described in detail on Friday by the World Health Organization.

With no vaccines or proven drugs available, the stepped-up efforts are a desperate measure to stop a disease that has defied traditional means of containing it.

“There’s never been a big market for Ebola vaccines,” said Thomas W. Geisbert, an Ebola expert here at the University of Texas Medical Branch in Galveston, and one of the developers of the vaccine that worked so well in monkeys. “So big pharma, who are they going to sell it to?” Dr. Geisbert added: “It takes a crisis sometimes to get people talking. ‘O.K. We’ve got to do something here.’ ”

Dr. James E. Crowe Jr., the director of a vaccine research center at Vanderbilt University, said that academic researchers who developed a prototype drug or vaccine that worked in animals often encountered a “biotech valley of death” in which no drug company would help them cross the finish line.
To that point, the research may have cost a few million dollars, but tests in humans and scaling up production can cost hundreds of millions, and bringing a new vaccine all the way to market typically costs $1 billion to $1.5 billion, Dr. Crowe said. “Who’s going to pay for that?” he asked. “People invest in order to get money back.”

The Ebola vaccine on which Dr. Geisbert collaborated is made from another virus, V.S.V., for vesicular stomatitis virus, which causes a mouth disease in cattle but rarely infects people. It had been used successfully in making other vaccines.
Continue reading the main story
The researchers altered V.S.V. by removing one of its genes — rendering the virus harmless — and inserting a gene from Ebola. The transplanted gene forces V.S.V. to sprout Ebola proteins on its surface. The proteins cannot cause illness, but they provoke an immune response that in monkeys, considered a good surrogate for humans, fought off the disease.

The vaccine was actually produced in Winnipeg, Manitoba, by the Public Health Agency of Canada. The Canadian government patented it, and 800 to 1,000 vials of the vaccine were produced. In 2010, it licensed the vaccine, known as VSV-EBOV, to NewLink Genetics in Ames, Iowa.

The Canadian government donated the existing vials to the World Health Organization, and safety tests of the vaccine in healthy volunteers have begun.

NewLink’s product is one of two leading vaccines being tested. The other, which uses a cold virus that infects chimpanzees, was developed by researchers at the National Institutes of Health and GlaxoSmithKline. The first tests of an earlier version of it, employing a different cold virus, began in 2003.

Several other vaccine candidates, not as far along, are also in the pipeline and may be ready for safety testing next year. Once any drugs or treatments pass the safety tests, they will be available for use in larger numbers of people, and health officials are grappling with whether they should be tested for efficacy in the traditional way, in which some people at risk are given placebos instead of the active drug.

Governments and the military became interested in making vaccines against Ebola and a related virus, Marburg, during the 1990s after a Soviet defector said the Russians had found a way to weaponize Marburg and load it into warheads. Concerns intensified in 2001 after the Sept. 11 terrorist attacks and anthrax mailings.

“The National Institutes of Health came up with a program called Partnerships in Biodefense that partnered researchers like me with companies, usually small companies,” Dr. Geisbert said.
The government money led to major advances in the laboratory, Dr. Geisbert said, but was insufficient to cover the huge costs of human trials. Nor could the small companies that were involved in the early studies in animals afford to pay for human trials. No finished product came to market.

Dr. Geisbert moved on, working on treatments for Ebola and another version of the V.S.V. vaccine. For the vaccine work, his main collaborator has been Dr. Heinz Feldmann, the chief of virology at the Rocky Mountain Laboratories in Hamilton, Mont., part of the National Institute of Allergy and Infectious Diseases.

The newer version of the vaccine uses a slightly different form of V.S.V., one that Dr. Geisbert said he thought might be less likely to cause side effects, and more likely to gain quick approval because it has been used as the basis for an H.I.V. vaccine and is known to the Food and Drug Administration. But the new version, VesiculoVax, made by Profectus Biosciences in Baltimore, has not yet been tested in humans.

The V.S.V. products are live vaccines, with replicating viruses that may cause a reaction. It is not clear what level of side effects will be considered acceptable.

Chills and nausea are possible, Dr. Geisbert said, but he added, “Who cares, if you survive Ebola?”

Most vaccines are given to prevent disease before people are exposed to it, and the plan is to use Ebola vaccines that way. But the V.S.V. vaccines have also been shown to protect monkeys even after the animals have been exposed to a heavy dose of Ebola — if given soon after exposure.

Researchers hope that they will work that way for people, too. If they do, health workers and family members who have been in contact with a patient might be protected, instead of having to spend 21 days of dread, waiting to see if they get sick.

Dr. Geisbert spends much of his time working with Ebola and other deadly viruses in a Biosafety Level 4 laboratory at the Galveston National Laboratory, where the researchers wear spacesuits that each come with an independent air supply, and visiting journalists are required not to report which floor the labs are on.

This month, one of his tasks is to test the Profectus vaccine and an experimental treatment against the Ebola strain that is causing the current epidemic. The virus is from a species called Ebola Zaire, against which the products have already been shown to work. But different strains within a species can vary genetically by 2 percent to 7 percent, Dr. Geisbert said.

Most of the time, those small variations do not matter, and a drug or treatment that works against one strain will work against all. But once in a while, the difference matters.

“We don’t know for 100 percent certainty until we prove it in animals,” Dr. Geisbert said. “The companies I work with are smart. They want that answer sooner rather than later, before they go investing millions of dollars to put this into humans.”