FDA

Viewpoint: Desperately seeking a new FDA commissioner, a critical presidential appointment

This article originally appeared at Forbes and has been republished here with the author’s permission.

In the Trump administration, we can expect a new head of the FDA, one of the 4,000 or so political appointees. The post of FDA Commissioner is one of the most important in the government because the FDA regulates products worth more than $1 trillion, 25 cents of every consumer dollar. Those products, which encompass food, drugs, vaccines, medical devices and your dog’s flea medicine, affect every American in innumerable ways every day.

Moreover, the FDA is a “gatekeeper,” which means that it must issue affirmative approvals of many classes of products before they can be marketed.

And yet, appointments to this critical job have often seemed to be treated by the White House as something of an afterthought.

The current FDA commissioner, Dr. Robert Califf, assumed the position only in February 2016, so he has not really had time to make his mark. His predecessor, Dr. Margaret Hamburg, was there for seven years, however, and provides an exemplar of what we don’t want in a Trump administration incumbent.

Dr. Hamburg was intelligent and experienced in public health before her appointment to head the FDA, but she chose to be primarily a figurehead, traveling extensively and gushing constantly about her agency’s commitment to sound science and its superior performance, although often the record told a very different story.

Hamburg hewed to the wishes of her political masters even when they conflicted with science, federal law and common sense, and she made inexplicable errors of judgment, neglected to crack the whip when her minions dragged their feet on approving important medicines and other products, and failed to exercise appropriate scrutiny over “compounded drugs.” Examples of injurious delays include vaccines for Meningitis B, and pirfenidone, a drug to treat a fatal disease called idiopathic pulmonary fibrosis. The delays in approving these products, which had been widely approved abroad before FDA sanctioned them, resulted in a palpable and preventable body count in this country.

The FDA needs renewal. It is dysfunctional, suffering from cultural, organizational and management problems that have been exacerbated by White House micromanagement and congressional mandates and meddling. Too often, FDA officials have gotten away with performing like Herman Melville’s fictional character Bartleby, who responds repeatedly to requests from his employers with, “I would prefer not to.”

A particularly egregious example of nonfeasance on Hamburg’s watch was the agency’s unwillingness to confirm as GRAS (Generally Recognized As Safe) the proteins lysozyme and lactoferrin obtained from genetically engineered rice, a process called “biopharming.” Clinical research had shown that when the proteins, which occur naturally in human tears and breast milk, are added to oral rehydration solution to treat children with diarrhea, they both lessen the duration of symptoms and reduce the rate of recurrence.

The availability of such a fortified oral rehydration solution for people in the developing world would be a near-miraculous advance. By having withheld GRAS affirmation for lysozyme and lactoferrin–again, presumably for political reasons–Hamburg is responsible for untold numbers of preventable deaths in Africa, Asia and Latin America. She deserves no “profiles in courage” awards.

As a result of FDA’s policies and performacne, drug development by major U.S.-based drug companies is less than robust, with R&D costs way up and regulatory approvals flat; and there are worrisome shortages of many essential drugs. Some entire FDA-regulated sectors, such as “biopharming” and R&D on genetically engineered food animals, have virtually disappeared because of regulatory excesses or uncertainty.

Rebooting the FDA will be one of the toughest jobs in Washington, and the incumbent will need the exceptional qualities discussed below:

Superior management skills and experience. The FDA commissioner should be able to direct, manage and make the tough policy decisions for a $5 billion, 15,000-employee organization that is constantly in the news and under pressure from various stakeholders. Because the agency’s scope is so sweeping–encompassing drugs, vaccines, cardiac pacemakers, x-ray machines, condoms, home pregnancy-testing kits, artificial sweeteners, fat substitutes and tobacco, among other products, a single person cannot be expected to master the body of science, medicine, pharmacology, toxicology, engineering and law involved.

Therefore, the commissioner must have the skills to organize the agency efficiently and possess sufficient technical understanding to discern whether FDA’s professional staff are properly framing the issues and options. The incumbent will also need to address what many observers of FDA consider to be excessive risk-aversion. That will require what Dr. Janet Woodcock, the long-serving director of the Agency’s Center for Drug Evaluation and Research, has called a “cultural and cognitive transformation.”

Unassailable integrity and honesty. The commissioner’s public health decision-making must meld law, science and regulatory precedents. The incumbent needs to earn the respect of those who have a stake in the FDA’s policies and decisions–consumers, political leaders, industries and public interest groups. But in the end, science–not public opinion, politics (see below), pressure from special interests, or congressional grandstanding–must dictate policy and decision-making.

I was struck by the dissonance between a statement by Dr. Hamburg several years ago and the FDA’s performance where it counts—getting new medicines to patients. She bragged that “[p]reliminary results of reviews completed during FY 2010 indicate that FDA has the potential to meet or exceed almost all (11 of 12) FY 2010 review performance goals.” But 2010 was the worst year for drug approvals in a quarter century. This kind of disconnect is typical of federal bureaucrats: They create easily-met performance milestones that may have little correlation with the agency’s actual mission. As the old medical cliché goes, the operation was a success but the patient died.

Distanced from politics. Politics should be banished from the agency head’s role insofar as that is possible, with the commissioner taking the heat for unpopular decisions and telling truth to power. Many commissioners, including notably Hamburg and David Kessler, who headed the agency during the 1990’s, have deferred to their political bosses, not only on matters of policy (which is often appropriate), but also on decisions about individual products.

Some of Hamburg’s political capitulations were inexcusable. They include allowing the Secretary of HHS to overrule the FDA’s decision to let the Plan B morning-after pill be sold over the counter to young teenagers; and permitting the White House to hijack what should have been a routine, scientifically uncontroversial approval of a faster-growing, genetically engineered farmed salmon (but which was under review for more than 20 years). The FDA has also unnecessarily and inexplicably delayed approval of a single small field trial of mosquitoes genetically engineered to control disease-causing mosquitoes. (The same product has been extensively tested in other countries and is approved for commercial use in Brazil.)

It should be noted that these failures are endemic, from entry-level medical officers up the food chain to policymakers and the agency head. Will the new commissioner show more spine and integrity, making reforms a high priority? Time will tell.

Committed to regulatory reform. At a time when drug development should have been spurred by huge increases in R&D expenditures–which doubled to more than $51 billion between 2000 and 2013–and by the availability of numerous new, powerful technologies, drug approvals have been essentially flat for the past 15 years. Bringing a new drug to market now requires on average 10-15 years, and costs have skyrocketed to more than $2.5 billion—largely because FDA requirements have increased the length and number of clinical trials per marketing application and the number of procedures per patient. Another ominous statistic is that drug manufacturers recoup their R&D costs for only one in five approved drugs.

Under Hamburg, the FDA extended its authority beyond statutory limits. The Federal Food, Drug and Cosmetic Act requires, for example, that for a drug to be marketed, it must be shown to be safe and effective. But the agency has invented new, arbitrarily-applied criteria, including a demonstration of superiority compared to other medicines. Proving that a drug is better than existing drugs often is much more difficult and vastly more expensive than just proving that it is safe and effective, because if two medicines’ efficacy differs only marginally, the clinical trials must be very large in order to attain statistical significance. Moreover, even if two drugs are both found to be effective in 40% of patients, they may not be effective in the same 40%. If this new criterion were widely implemented, many new (odrugs useful for some patients would founder, reducing competition in the drug market, limiting doctors’ choices, and causing prices to rise.

The FDA needs to streamline its existing regulatory procedures and requirements, and the agency’s senior and mid-level managers must be made more accountable for their decisions, especially when they delay the availability of important new drugs, vaccines and medical devices to patients in need of them. And as former FDA Commissioner Frank Young used to admonish his minions, rules and regulations need to be tempered with common sense.

Distanced from politics. Politics should be banished from the agency head’s role insofar as that is possible, with the commissioner taking the heat for unpopular decisions and telling truth to power. Many commissioners, including notably Hamburg and David Kessler, who headed the agency during the 1990’s, have deferred to their political bosses, not only on matters of policy (which is often appropriate), but also on decisions about individual products.

Some of Hamburg’s political capitulations were inexcusable. They include allowing the Secretary of HHS to overrule the FDA’s decision to let the Plan B morning-after pill be sold over the counter to young teenagers; and permitting the White House to hijack what should have been a routine, scientifically uncontroversial approval of a faster-growing, genetically engineered farmed salmon (but which was under review for more than 20 years). The FDA has also unnecessarily and inexplicably delayed approval of a single small field trial of mosquitoes genetically engineered to control disease-causing mosquitoes. (The same product has been extensively tested in other countries and is approved for commercial use in Brazil.)

It should be noted that these failures are endemic, from entry-level medical officers up the food chain to policymakers and the agency head. Will the new commissioner show more spine and integrity, making reforms a high priority? Time will tell.

Committed to regulatory reform. At a time when drug development should have been spurred by huge increases in R&D expenditures–which doubled to more than $51 billion between 2000 and 2013–and by the availability of numerous new, powerful technologies, drug approvals have been essentially flat for the past 15 years. Bringing a new drug to market now requires on average 10-15 years, and costs have skyrocketed to more than $2.5 billion—largely because FDA requirements have increased the length and number of clinical trials per marketing application and the number of procedures per patient. Another ominous statistic is that drug manufacturers recoup their R&D costs for only one in five approved drugs.

Under Hamburg, the FDA extended its authority beyond statutory limits. The Federal Food, Drug and Cosmetic Act requires, for example, that for a drug to be marketed, it must be shown to be safe and effective. But the agency has invented new, arbitrarily-applied criteria, including a demonstration of superiority compared to other medicines. Proving that a drug is better than existing drugs often is much more difficult and vastly more expensive than just proving that it is safe and effective, because if two medicines’ efficacy differs only marginally, the clinical trials must be very large in order to attain statistical significance. Moreover, even if two drugs are both found to be effective in 40% of patients, they may not be effective in the same 40%. If this new criterion were widely implemented, many new (odrugs useful for some patients would founder, reducing competition in the drug market, limiting doctors’ choices, and causing prices to rise.

The FDA needs to streamline its existing regulatory procedures and requirements, and the agency’s senior and mid-level managers must be made more accountable for their decisions, especially when they delay the availability of important new drugs, vaccines and medical devices to patients in need of them. And as former FDA Commissioner Frank Young used to admonish his minions, rules and regulations need to be tempered with common sense.

During confirmation hearings, senators should scrutinize the nominee’s resume carefully and broach a broad spectrum of policy issues and product delays that affect public health. Whoever the nominee is, I wish him (or her) well.

Henry I. Miller, a physician, is the Robert Wesson Fellow in Scientific Philosophy & Public Policy at Stanford University’s Hoover Institution.  He was the founding director of the FDA’s Office of Biotechnology. Follow him on Twitter @henryimiller.

control sano

Doctors turn to stem cell regeneration to treat heart defects in babies

The 4-month-old on the operating table has a shocking birth defect, nearly half his heart too small or even missing…In a bold experiment, doctors injected donated stem cells directly into the healthy side of [his] little heart, aiming to boost its pumping power as it compensates for what’s missing.

It’s one of the first attempts in the U.S. to test if stem cells that seem to help heart attack survivors repair cardiac muscle might help these tiniest heart patients, too.

[D]octors are conducting this early-stage study of whether stems cells might help that ventricle work better.

“This is very different than a surgical approach or giving a medicine just to treat the symptoms. This is trying to treat the underlying problem,” Dr. Kristin Burns, a pediatric cardiologist at the National Institutes of Health.

Even in adults, stem cell regeneration is highly experimental. But small studies involving heart attack survivors and older adults with heart failure have found what Dr. Denis Buxton, a stem cell specialist at NIH’s heart institute, calls a modest benefit in how well their hearts pump blood.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post: Testing Stem Cells in Tiniest Hearts to Fight Birth Defect

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Uganda promotes new drought tolerant, disease resistant maize varieties

Earlier this year, the Ministry of Agriculture , Animal Industry and Fisheries (Maaif) released four new maize varieties. It was part of the Water Efficient Maize for Africa (Wema) initiative, which aims at coming up with maize that withstand stresses of drought and insect pests.

The effort was a collaboration with scientists, farmers, national research organisations and other stakeholders in five countries. These are Uganda, Kenya, Tanzania, Mozambique and South Africa under a public-private partnership. Thus, the varieties are improved conventional white maize hybrids with the desirable qualities—drought tolerance, high yield and disease resistance.

. . . .

As the varieties are tolerant to conditions of drought, they have been tested to have a yield advantage of 20-30 per cent over the other commercial varieties.

[They give] an average yield of three tonnes in moderate drought and eight tonnes in good seasons and thus help farmers increase their productivity.

. . . .

It is expected that farmers will adopt the drought tolerant maize varieties because they can withstand the increasingly regular effects of climate change especially drought and greater disease pressure.

Against this backdrop, the new varieties would lead to increased production, improve food security, wealth creation and therefore improve farmer livelihoods.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion and analysis. Read full, original post: Growing maize when there is drought

human genome editing

“Cutting out” genes linked to muscle disorder may restore movement in patients

Scientists are using “gene scissors” to cut off the code of a defective gene that results in progressively weaker muscles and death in Duchenne muscular dystrophy and replace it with a synthetic code they hope will one day restore healthy life to these patients.

“We want to use genetically corrected stem cells to replace the stem cell pool and make new muscles that function normally,” said Dr. Yaoliang Tang, cardiovascular researcher in the Vascular Biology Center at the Medical College of Georgia at Augusta University.

 

So the scientists are using technology called CRISPR-Cas9 to cut the problematic piece of the dystrophin gene out of muscle cells, and replace it with a synthetic code that enables normal dystrophin.

The fact that the cells that will ultimately be returned, started with the individual – or the mouse in the case of this basic science study – also reduces concerns that giving the cells will result in a severe immune system response, Tang said. Gene editing also is more efficient in pluripotent stem cells than mature cells, he added.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post: Scientists replace piece of gene mutated in Duchenne muscular dystrophy in effort to make healthy

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Argentina’s soy farmers, seed sellers near agreement on GMO seed royalties

Argentine soy farmers and the companies that sell them genetically modified seeds could be close to a breakthrough in negotiations after a months-long deadlock that prompted Monsanto to stop selling new GMO technology in the country.

The negotiator representing seed companies in talks with farmers over a bill pending in Congress said … that both sides are ready to move toward a deal that would extend the period of time that growers would have to pay royalties on genetically modified seeds.

The government-backed bill says farmers will pay royalties for three seasons after the initial purchase of GMO seeds. But the companies want royalties to be paid for a longer period, according to Alfredo Paseyro, the negotiator for ASA, the group representing seed companies including Monsanto Co.

. . . .

Monsanto has said it is not selling new technology in Argentina until a royalties deal is reached. This threatens to put Argentine farmers at a disadvantage against their Brazilian and U.S. competitors.

. . . .

Almost all the soy grown in Argentina is genetically modified. Most of the seeds are bought on the black market or GMO beans used as seeds without paying royalties.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion and analysis. Read full, original post: Argentina soy farmers, seed sellers see progress in royalty talks

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What is the best strategy to market new GMO produce like pink pineapple?

Despite reservations many consumers and public health advocates have about genetically modified foods, researchers, farmers and ingredient suppliers continue to innovate to produce more numerous and more diversified GMO crops [most recently the deregulated genetically modified pink pineapple]. In recent years, GMO potatoes and apples have also received agency approval in the U.S.

However, it’s unclear how health-conscious consumers and manufacturers will accept these new GMO crops. Their perceptions may ultimately come down to how Del Monte and other GMO ingredient producers position the new products. If producers can scientifically prove the safety of the GM version of a crop, then promoting the product’s flavor or appearance benefits may resonate with consumers who haven’t entirely turned away from all GMOs.

Another key approach for GMO products has been sustainability…. GMO supporters claim that ingredients genetically engineered to produce higher yields or reduce crop death from disease are the best solution for feeding a growing population….

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion and analysis. Read full, original post: How will consumer and manufacturers respond to Del Monte’s GMO pink pineapple?

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“Getting Risk Right”: Geoffrey Kabat on health, risk and bad science

Why do things that are unlikely to harm us get the most attention?

Dr. Geoffrey Kabat, a cancer epidemiologist at the Albert Einstein College of Medicine in New York, makes his point quite clearly—that Americans, often through no fault of their own, are doing a poor job of assessing risk. We overreact to miniscule or theoretical risks, under react to real ones, and end up making poor decisions as a result.

[Dr. Kabat’s] second chapter…[examines] the different approaches elicited by comparing BPA, a ubiquitous component of plastic, with the 2014 Ebola outbreak…We overreacted to both, but for different reasons.

Neither [BPA nor Ebola] is likely to do us much harm in the US. But something else is—flu, which causes tens of thousands of deaths per year, many of which could be avoided by an annual flu vaccine. Flu represents a case of a known, serious threat, yet people routinely fail to get the vaccine, while worrying about the tiny amount of BPA in food can liners.

Kabat applies similar logic and reasoning to debunk other common, but unfounded fears, such as the cell phone-brain cancer link, the assault on our endocrine systems from everyday trace chemicals, and the pervasive, but entirely incorrect “natural equals safe” mindset

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post: Review: ‘Getting Risk Right,’ By Dr. Geoffrey Kabat

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GMO labeling law makes ‘Biggest Science Setbacks of 2016’ list

Scientific progress doesn’t always move in a straight line. In fact, as we’ve seen this year, sometimes things just turn around and move backwards. …

…These were the worst setbacks to science in 2016.

. . . .

In July, President Obama signed a GMO labeling law that much of the anti-GMO movement regarded as a sham. The law, which will require labeling on all food packages indicating whether they contains GMO ingredients, is indeed a watered-down version of legislation lawmakers sought to pass in Vermont. …

But even if the law is toothless, the fact that it exists is still a victory for the anti-GMO movement, and hence for yet another public backlash against science. After all, most scientists agree that GMOs, which are in upwards of 75 percent of our food, are safe to consume.

A recent Pew Research survey found that a fifth of those under 30 feel not only that non-modified foods are better, but that GM-varieties might lead to health problems, a claim which is not supported by science. Unfortunately, the anti-GMO frenzy has also blinded activists to the potential benefits of GMOs. Take the environmental group Greenpeace, which has worked vigorously to block GMOs designed to reduce vitamin A deficiency in economically impoverished nations.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion and analysis. Read full, original post: The Biggest Science Setbacks of 2016

cant sleep

Sleep disorders share genetic connection with obesity and schizophrenia

A team of American and British scientists have for the first time discovered genetic connections between sleep disturbance and a range of medical disorders including obesity.

The researchers identified for the first time areas of the genome that are associated with sleep disturbance – including insomnia and excessive daytime sleepiness – and also discovered novel genetic links with several medical conditions, including restless legs syndrome, schizophrenia and obesity. The strongest genetic association for insomnia symptoms fell within a gene previously linked to restless legs syndrome – a nervous system disorder…that leads to a strong urge to move one’s legs, which is often worse at night.

[Martin K Rutter, MD, FRCP, senior lecturer in Cardiometabolic Medicine from The University of Manchester] says, “This clinical science is an important step forwards in understanding the biological basis for these conditions…[T]his is the first time these biological links have been identified at a molecular level.”

 

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post: Genetics link sleep disturbance with restless legs syndrome, schizophrenia and obesity

WEB P Fertilisation SEM SPL

Studying coral could reveal evolutionary reason why humans develop sex cells as embryos

At the earliest stages of life, in the embryo, our germ cells begin to develop. These are the cells that will go on to form the sperm and the egg, with half the usual number of chromosomes…But corals, sponges and plants make no such cellular plans. They initially develop only body (somatic) cells, each with a full complement of chromosomes. When the time comes to mate, they produce their sex cells, or gametes, as needed by forming them out of stem cells from adult tissue.

maxresdefaultWhy the difference? According to biochemist Nick Lane of University College London, more complex animals create a devoted germline to preserve the quality of their mitochondria….

According to the team, the problem for humans and other complex animals is that if adult cells were allowed to divide repeatedly in a growing organism before some of them were turned into gametes, then their mitochondria would rapidly accumulate genetic mutations and errors,…leading to poor-quality tissues in the offspring.

There’s a delicate balance between the benefits and drawbacks of having a germline.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post: Why humans develop sex cells as embryos — but corals don’t

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Neonicotinoid pesticides ban proposed in Chicago

Poisonous chemicals that can “decimate the population” of bees, butterflies and other pollinators would essentially be banned in Chicago under a crackdown proposed by a rookie alderman.

Ald. Ray Lopez (15th) is taking aim at neonicotinoids.

Lopez introduced an ordinance last week that would prohibit “any person, organization and/or community garden operator” from using an insecticide classified as a neonicotinoid. The only exceptions would be veterinarians, farmers and certified pesticide applicators.

Neonicotinoids include imidacloprid, nithiazine, acetmiprid, clothianidin, dinotefuran, thiacloprid and thiamethoxam. These insecticides are water soluble, so they can be sprayed on plants or applied to the soil. They are more toxic to insects than to mammals and birds.

Pesticides containing neonicotinoids are not used on city property. But the products are widely used by landscapers, farmers and homeowners. Many flea powders for cats and dogs also contain a neonicotinoid.

. . . .

Lopez said the only people disputing scientific studies on the negative impact of neonicotinoids “are those making a profit off them.” Fifty years ago, the same forces were “dragging their feet over DDT,” he said.

. . . .

“There are plenty of other less harmful options for consumers who want to control pests. Chicago can be a national leader on this issue.”

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion and analysis. Read full, original post: Ban proposed on chemicals that ‘decimate’ bee population

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Séralini paper: Molecular analysis shows GMO corn differs from non-GMO–Is difference meaningful?

In the US, the Food and Drug Administration … GMO crops are deregulated once nutritional and compositional “substantial equivalence” is demonstrated. The set of parameters … necessary to declare a GMO as substantially equivalent  … focuses on a restricted set of compositional variables, such as the amounts of protein, carbohydrate, vitamins and minerals. …

. . . .

Recent technologies used to ascertain the molecular compositional profile of a system, … collectively referred to as “omics  technologies”, are used extensively in basic and applied science. … the majority of authors of [omics studies of crops] conclude that the statistically significant changes observed between the conventional and the GM varieties are not biologically significant because they fall into the range of variations … between different conventionally-bred varieties, and under different environmental conditions….

. . . .

url…[W]e have performed proteomics and metabolomics analyses of NK603 (sprayed or unsprayed with Roundup) and isogenic maize kernels.

. . . .

In this report we present the first multi-omics analysis of GM NK603 maize compared to a near isogenic non-GM counterpart. … Although NK603 had comparable nutritional and compositional profiles when originally accessed by the developer company upon registration of their product, our analysis … shows that NK603 grains, with or without Roundup spraying during cultivation, are not equivalent to isogenic non-transgenic control samples.

Several laboratory studies consisting of 90-day feeding trials in rodents have been conducted to evaluate the safety of GMO crop consumption. These investigations have frequently resulted in statistically significant differences in parameters reflective of disturbances in various organ systems and in particular liver and kidney biochemistry, but with interpretation of their biological significance, especially with respect to health implications, being controversial.

For more background on Seralini’s previous GMO studies and the funding for his research–this study was funded by an anti-GMO organic group, as listed in the paper–read the GLP’s Biotech Gallery profile.Screen Shot at AMEditor’s Note: The GLP has asked independent scientists to review this study. We will update this comments as they come in:

Seralini does not appear to understand the legal concept of “substantial equivalence”

1) There is no information as to whether he looked at compounds on the OECD list. These were chosen for their relevance to detect changes in key metabolic pathways. His list needs to be compared to the OECD one.

2) Once a difference has been found, the second step is missing altogether in this paper. Namely, all statistically significant, biologically relevant changes need to be compared to values in other varieties. If they are in the normal range, there is no issue. The actual differences observed are small, many much smaller than the differences found from one field to the next for the same crop. Statistically significant differences are not biologically significant differences.

3) At the end of the day, the OECD list covers about 60 metabolites that make up 95% of the grain. The remaining 5% contains many tens of thousand metabolites, where the “dose makes the poison” adage kicks in.

4)  Differences in proteomes are for the most part irrelevant to food safety assessment. The reason for this is both simple and complex. Stated simply, large differences in proteomes are often seen in specimens with essentially identical compositions. The underlying complexity is that the concentrations of metabolite(s) produced by a protein or a set of proteins in a pathway reflect the interaction of a panopoly of variables such as enzyme concentration, substrate concentrations, concentrations of regulators, metabolic fluxes within the organism, and environmental regulation. Maybe a simple way to put it is that under the conditions at which a cell operates a great deal more regulates the concentration of a particular metabolite than the concentration of the enzyme that catalyzes its synthesis. I can’t tell you how many papers there are that report that enzyme X was elevated 2-fold or 5-fold or 100-fold but no change was observed in the product of its metabolic product. The rate limiting step in the production of a metabolite is not necessarily dependent on how much of the enzyme that produces it is present. Changes of a few fold are often inconsequential, and changes of a few percent sometimes evoke larger changes than one might expect. At the end of the day the proteome doesn’t tell us anything about safety. Proteomics can be a valuable research tool in the hands of an investigator with an hypothesis, but as applied here its simply another data dredging tool looking for a statistically significant change that means nothing.

5) What really counts from and safety and nutrition perspective is the metabolome. That’s the part we eat isn’t it? All of the changes in minor metabolites that were reported are small compared to the magnitude of changes in minor metabolites that is often observed in the same crop plant or its seeds. They are also meaningless changes; a few-fold change in polyamine concentration has no biological significance and if this experiment was done 10 times with NK603 the polyamine concentration would probably be all over the place.

6) There are some more fundamental problems with omics as an assessment tool which are covered in my 2010 paper. In particular, Lay et al published a compendium of troubles that face -omics as a science tool. These include the more obvious data dredging and statistics arguments to some pretty interesting math that indicates in some cases omics is more likely to give a wrong answer than a correct one. Think of it this way, the science of analytical chemistry has spent the last few hundred years developing methods for measuring one compound with accuracy, precision, reproducibility, sensitivity, etc. Omics is the emerging science of measuring everything poorly. When used correctly and in competent hands, omic analysis can be a powerful research tool. What it can’t do is tell you if two varieties of corn are equally safe to eat. It can, however, tell you that they differ in some way, and to an investigator in lab that may (or may not) be important to know, however, since there will no doubt be 100s if not 1000s of differences observed, good luck figuring out what they all mean. Omic analysis may eventually provide high quality useful data that tells us something about safety, but we are not there yet. Which of course means that the paper in question should be disregarded as artifact. Ir was in fact surprising to see that they did not observe more and larger differences.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion and analysis. Read full, original post: An integrated multi-omics analysis of the NK603 Roundup-tolerant GM maize reveals metabolism disturbances caused by the transformation process

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Can water protect you from glyphosate ‘poisoning’? Gilles-Eric Séralini’s homeopathy “detox” hoax

Did you know that there are homeopathic products that can detox you from the malicious effects of glyphosate, the herbicide paired with many GMO crops? How do we know this? Anti-GMO French scientist Gilles-Eric Séralini says it’s so. For millions of science skeptics and deniers, that’s apparently a powerful endorsement.

Homeopathy is the bizarre idea that a concoction with ingredients diluted so much that they’re really not there anymore can cure illness. Because of quirks in the U.S. medical oversight system, quack homeopathic “remedies” to combat disease and toxins enjoy a unique status in the health marketplace: They are the only category of alternative medicine products legally marketable as drugs.

Complementing homeopathy, “detoxing” oneself is considered well outside the boundaries of modern science. It’s considered quackery by medical practitioners and scientists. But it is practiced by a sizable segment of the population, particularly those who embrace other fringe anti-science movements such as vaccine denialism and those who deny the safety of GM foods. And now homeopathy and detox supporters have a public champion in Séralini.

Gilles-Eric Seralini, consultant for Sevene Pharma
Gilles-Eric Seralini, consultant for Sevene Pharma

The French biologist, whose central work ‘documenting’ the dangers of glyphosate and GMO crops was retracted by the publishing journal (before being placed in a predatory pay-for-play open access journal without peer review) is back as a co-author of a study getting significant play in natural and alternative medicine websites.

Published earlier this year in BMC Complementary and Alternative Medicinea fringe open source org-7335-digeodren-homeopathie-digestionjournal—the article claims to document the protective effects of a homeopathic product called Digeodren, which is manufactured by the French natural products company Sevene Pharma. The study, which was funded by Sevene, concludes that Digeodren could reverse the locomotor problems and biochemical issues that arise from what he called long-term exposure to glyphosate, the active ingredient of the herbicide Roundup, which is paired with some herbicide-resistant GMO crops.

Sevene, based in Cevennes, France, has been a long-time funder of Séralini’s work. According to the Genetic Literacy Project’s Biotech Profile:

Séralini received significant funding from Sevene Pharma, a French company that promotes “cures” using homeopathy, which mainstream scientists consider pseudo-science. Sevene sells homeopathic remedies but is also paying Séralini to research atrazine and glyphosate risks.  Sevene markets “detoxification” homeopathy products to treat the alleged toxic effects of glyphosate and atrazine “contamination”, which is the focus of Séralini’s research, a clear conflict of interest the professor has apparently been forced by PLOS to now acknowledge.

Séralini is a consultant for the company, and conducts most of the company’s “research”, focusing on the alleged toxic effects or glyphosate and other pesticides. Two studies have been published in a low quality open-access journal. One focuses on how plant extracts presumably can protect the liver from toxic chemicals:

Worldwide used pesticides containing different adjuvants like Roundup formulations, which are glyphosate-based herbicides, can provoke some in vivo toxicity and in human cells. These pesticides are commonly found in the environment, surface waters and as food residues of Roundup tolerant genetically modified plants. In order to know their effects on cells from liver, a major detoxification organ, we have studied their mechanism of action and possible protection by precise medicinal plant extracts. The plants used were from Sevene pharma and the formula used is that of Digeodren.

The other study, almost promoted the company’s products:

We wanted to test the common pathways of intoxication and detoxification in human embryonic and liver cell lines. We used various pollutants such as Roundup residues, Bisphenol-A and Atrazine, and five precise medicinal plant extracts.

What about the new Séralini study?

The research team, which included two employees of Sevene, took 160 male rats and divided them into four groups of 40. One group was named the control (without precisely defining what that meant); a second group drank Roundup GT Plus at 0.5 percent dilution; a third received the Digeodren product at 2 percent dilution in water; and the last group received Digeodren at 2 percent for seven days and then a mixture of digeodren and Roundup for another eight days. The animals then were tested in actimeters to determine locomotor activity and their organs were analyzed for changes.

“Digeodren, without any side effect observable, presented strong preventive and therapeutic properties in vivo after a short-term intoxication by the widely used pesticide, Roundup,” the paper concluded.

Scientists have been sharply critical of the study’s methodology and conclusions. The first problem was the premise. Séralini and his colleagues stated that “we have previously demonstrated that very low levels of Roundup exert endocrine disrupting effects, such as sex hormone imbalance and hepatorenal toxicities.” However, that is based on Séralini’s retracted 2014 study.seraliniretracted

Other problems revolved around the dosages used. Steve Savage, a plant pathologist and genetics consultant, told the Genetic Literacy Project in an email:

The dose is absurd. They gave the animals the equivalent of what could be in the spray tank including the surfactants and the a.i. (active ingredients). If glyphosate or its AMPA metabolite ever end up in a food it is at extremely low concentrations and never with the surfactant. Unless you were a farmer or gardener who routinely drinks from the spray tank over 8 days, this study is meaningless.

Other scientists pointed to a lack of proper controls, stating that the study should have had controls for the other ingredients of Roundup (which are formulated along with glyphosate, and may affect its function and other effects, as discovered last year by the German Institute for Risk Assessment). There also was some confusion between when the researchers used glyphosate alone or Roundup as a mixture.

Another problem was the makeup of Digeodren. Its label includes Taraxacum officinalis/Dandelion D4, Berberis vulgaris/BarberryD5, and Lappa major/Burdock D4, but also shows it is diluted in 70 percent alcohol, which can have a number of effects on animal locomotion and other physiological processes.

It’s also not clear how the researchers selected the animals for study. It would be possible to select animals with superior (or, in the case of the Roundup animals, impaired) locomotion. The paper stated that the locomotor experiments were carried about according to a paper by J.J. Lynch and colleagues at Abbott Laboratories published in 2011, which addresses conducting locomotor analysis but does not address how experimental animals are selected.

Finally, the paper has no discussion on the natural variability in locomotion or physiological parameters, making it impossible to tell if anything was truly wrong with any of the animals.

Plant medicinal extracts and “detox” mythology

just-water-530x450Homeopathic treatments claim to use highly diluted chemicals—what amounts to almost pure water—to cure or prevent disease. “Detox” and homeopathic treatments that purport to cure a number of existing ailments and prevent other disorders by removing “toxins” from the body are becoming increasingly popular despite a complete lack of empirical evidence supporting such claims.

According to the Sevene website, Digeodren helps with “liver detoxification and digestion” and restores the health of those “feeling ‘sluggish & lethargic’ (by) stimulating the removal of environmental toxins from the liver.” These claims echo advertisements on fringe websites (like this one with detailed instructions and urging a detox once a year) and articles stating that the buildup of toxins from environmental exposures are sapping our strength and threatening our health.

According to Today Homeopathy, detox is supposed to work like this:

Detox, short for detoxification, is the removal of potentially toxic substances from the body.

The health of every single organ in the body depends on its ability to eliminate the waste products of the life process. Detoxification is a practice of resting, cleaning and nourishing the body from the inside out that is known for centuries by many cultures.

A detox program helps body`s own healing processes and everyone should do it at least once a year.

These faddish “detox” methods have been universally panned by the medical community as potentially dangerous for one’s health, or at least a drain on one’s wallet. The body already has a number of ways to rid itself of toxic substances, including the skin, respiratory system, immune system, intestines and the liver and kidneys. These “cures,” which are almost never available by prescription, can lead to dehydration, deplete necessary electrolytes and impair bowel function. They also can disrupt the microbiome balances in the intestine, and could even cause metabolic acidosis, which according to Harvard Medical School can be fatal.

Andrew Porterfield is a writer, editor and communications consultant for academic institutions, companies and non-profits in the life sciences. He is based in Camarillo, California. Follow @AMPorterfield on Twitter.

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Jon Entine breaks taboos on sports and ‘race’, and the future of human genetic research

In many sports in which the barriers to competition is level, athletes of African descent are over represented at the elite level. African descended athletes own every major running world record, and dominate in the elite sports of American football and basketball. But intriguingly, in the world’s strength-focused competitions, from weight lifting to the hammer throw, Eurasian whites dominate. Why is there these differences based on ancestry? And why are we so uncomfortable in discuss what appear to be ‘racial’ differences?

Genetic Literacy Project director Jon Entine, author of the best selling book Taboo: Why Black Athletes Dominate Sports and Why We’re Afraid To Talk About It, wrote about this phenomenon most recently in the wake of the Rio Olympics: “Kenyans sweep distance races, Jamaicans sprints: How evolution has shaped elite sports.”

Entine now addresses these and other questions on race, evolution, ethics and the implications for genetics research with Freedomain Radio host Stefen Molyneux.

Read full, original post and view interview: Why Black Athletes Dominate Sports

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Motherhood changes your brain to connect better with newborn

Elseline Hoekzema at Leiden University in the Netherlands and her team compared brain scans of 25 first-time mothers with those of first-time fathers, plus childless men and women.

After having a baby, the mums showed shrinking in some areas of the brain, changes not seen in any of the other groups. Most of the affected areas were in regions of the cerebral cortex that are particularly important for understanding others’ intentions and emotions.

“The changes could confer an advantage for the mother by strengthening her ability to read the needs of her relatively helpless infant,” says Hoekzema.

It may seem counter-intuitive that brain areas important for empathy shrunk in first-time mothers, but this is probably due to pruning processes that fine-tune and strengthen important neural connections, while getting rid of clutter.

Hoekzema says the changes may be triggered by the hormonal changes that accompany pregnancy. This could explain why similar changes are not seen in first-time fathers. And when women who had not had a second pregnancy returned for scans two years later, the changes were still there.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post: Becoming a mother may change the brain to read baby’s mind

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DIY genetic engineering kit to brew glow-in-the-dark booze runs into trouble with FDA

Josiah Zayner has made glow in the dark boo with a do-it-yourself DNA kit that his startup, the Odin, has just started selling online. The company conceived it as a gimmick to introduce homebrewers to genetic engineering. But in the short time the kit’s been for sale, it’s also become a test for the citizen scientists to see how far they can push the FDA.

With the kit, customers can genetically engineer yeast to make mead that gleams like a lantern …

. . . .

sub buzzBy initially marketing the kit as a food-making device, the startup may have exposed a loophole in laws that haven’t caught up to a generation of biohackers tinkering with the DNA of bacteria, plants, and animals in their kitchens and garages.

. . . .

…After BuzzFeed News asked Zayner about the product’s legal status, he contacted the FDA, and learned the agency had been waiting for his call.

. . . .

Three FDA staffers told Zayner that the green fluorescence protein was likely a color additive for food, and it hadn’t been recognized as safe to consume…. Zayner argued that the kits were being sold in part as an educational tool; the FDA disagreed.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion and analysis. Read full, original post: DNA Biohackers Are Giving The FDA A Headache With Glow-In-The-Dark Booze

Discovery of gene mutations for motor disorder leads to treatment in children

Doctors have discovered a new genetic disorder that robs children of the ability to walk normally and makes it hard for them to control their other limbs.

 

The analysis revealed that the patients had mutations in a single gene called KMT2B which is thought to play a central role in switching on other genes needed for the proper control of body movements. The corruption of the gene leads to what doctors call dystonia, when muscles contract involuntarily.

Doctors can already refer people with dystonia for what is called deep brain stimulation (DBS), but the treatment is a last resort, used only when drugs have failed.

When it is used to treat all forms of dystonia, DBS works well in some, but not in others…The younger ones seemed to fare best, to the point that some regained the ability to walk unaided. “So far all of the children we have seen seem to have a positive response,” said [Manju Kurian , a specialist in movement disorders who led the research].

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post: Discovery of genetic disorder allows breakthrough in treating children

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98% of U.S. farmers say GMOs help reduce environmental footprint of farming

survey of 282 U.S. farmers shows 98 percent of them think GMO seeds – typically bred to be resistant to things like certain crop protection chemicals – are the best way to lessen their environmental footprint, and 69 percent believe the technology leads to higher yields.

. . . .

[National Corn Growers Association] and [U.S. Farmers and Ranchers Alliance] – two groups that have publicly supported the use of biotechnology in the past – released the survey results.

Some other findings from the survey:

  • 87 percent of producers said GMO seeds allow them to reduce their pesticide and herbicide usage;
  • 64 percent said GMO seeds allow for efficient management of resources, specifically, fuel, time and less wear-and-tear on their equipment;
  • 78 percent foresee increased environmental impacts-including an increase in water usage and application of pesticides-if GMO seeds were not to be available to them as a choice in crop production;
  • 92 percent of those surveyed have been using GMO seeds for 10 or more years, and grow a variety of crops, including corn, soybeans, alfalfa, wheat and cotton.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion and analysis. Read full, original post: Survey shows producer support for GMO crops

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Vampire therapy: Can blood from the young fight aging?

Nobody wants to get old. Or no one wants to experience the slow decline of physical and mental capacities associated with aging. Billionaire venture capitalist Peter Thiel has expressed his reluctance to age quite vocally. He has also put his money where is mouth is by investing in startups that take anti-aging technologies from extreme basic research to potential therapies.

The most notorious of these ideas is parabiosis. In Thiel’s case, he means transfusing blood plasma from the young in order to fight aging. It sounds more vampiric than it is—no one is talking about drinking it. But early studies in mice have shown that there maybe some promise. There is some evidence that blood from young mice contain protein messengers that ramp up innate cellular repair and regeneration capacities in older mice.

New data presented at Society for Neuroscience meeting in November took the research to the next level. Researchers took blood from young human adults and transfused that into aging mice. Their memories improved. That was likely because some component of the transfused blood stimulated replication of neural stem cells in the hippocampus, the brains memory center. Neural stem cells decline significantly with age.

The idea of parabiosis has been around for more than 150 years. First experiments were done by surgically grafting the circulatory systems of a young mouse and an old mouse. The old mice would start doing better and the young mice would begin prematurely aging. Effects of parabiosis have been documented in many different organs. But scientists realized they could get the same results more simply by transfusing blood, specifically plasma. Megan Sculldelari at Nature explains the procedure:

By joining the circulatory system of an old mouse to that of a young mouse, scientists have produced some remarkable results. In the heart, brain, muscles and almost every other tissue examined, the blood of young mice seems to bring new life to ageing organs, making old mice stronger, smarter and healthier. It even makes their fur shinier. Now these labs have begun to identify the components of young blood that are responsible for these changes.

If this research holds up and plasma from young people becomes an anti-aging treatment, blood transfusions on a mass scale would be difficult to pull off. So the search for the active-ingredients in plasma is aggressively underway. It seemed early on that one protein, growth differentiation factor (GDF)11 and its cousin GDF 8, might be the important component. From Helen Thompson at New Scientist:

In both mice and humans, GDF11 falls with age. We don’t know why it declines, but we know it is involved in several mechanisms that control growth. It is also thought to mediate some age-related effects on the brain, in part by activation of another protein that is involved in neuronal growth and long-term memory. So the billion-dollar question is: would a GDF11 boost have the same effect in humans?

But researchers seem to agree that there are likely many active ingredients. Subsequent research has gone back and forth about whether GDF-11 declines naturally with age and whether it causes tissue regeneration and repair on its own.  And it’s unknown if the effect is transient, meaning you’d need continuous transfusions to have the same effect.

Some human studies are underway. One study is giving older adults with Alzheimers disease transfusions of blood from younger people. It’s run by a startup called Alkahest, founded by one of the scientists who published results in mice. The other, run by a startup called Ambrosia is more controversial, according to Science:

The firm’s co-founder and trial principal investigator is a 31-year-old physician named Jesse Karmazin. His company, Ambrosia in Monterey, California, plans to charge participants $8000 for lab tests and a one-time treatment with young plasma. The volunteers don’t have to be sick or even particularly aged—the trial is open to anyone 35 and older. Karmazin notes that the study passed ethical review and argues that it’s not that unusual to charge people to participate in clinical trials.

There is high potential for side effects, as well. When cells grow and divide unchecked they can create cancers:

There are also lingering concerns as to whether activating stem cells — which is what the young blood most often seems to do — over a long period of time would result in too much cell division. “My suspicion is that chronic treatments with anything — plasma, drugs — that rejuvenate cells in old animals is going to lead to an increase in cancer,” says [Thomas] Rando, a Stanford neurologist. “Even if we learn how to make cells young, it’s something we’ll want to do judiciously.”

Another side effect, seen in mouse studies, is ‘parabiosis disease’ a form of rejection that occurs despite blood type matching. In experiments, researchers use genetically engineered mice to get around this problem, but that would not be possible for humans.

And there are many ethical implications. Where do we get this surplus blood from? Steven Novella at Science Based Medicine paints a dim picture:

The article focuses on how billionaire Peter Thiel is interested in plasma transfusions from young donors as a life extension and rejuvenation treatment, based on the science of parabiosis. I can’t help but also see the supervillain angle to this story – an aging billionaire, desperate to live forever, is feeding off the blood of young healthy victims. Of course, to get the full effect, a simple transfusion will not do. He will have to connect their circulatory system to his own.

Even the way we talk about this line of research is telling. Although it’s largely framed as what young blood can do to help aging, let’s not forget all those young mice who prematurely aged during the experiments. Parabiosis research may have as more to tell us about aging than how to artificially stay young. We can already gentetically engineer mice to model human diseases of aging. Adding that to parabiosis research could provide a lot of information about how aging and genetic risk for disease interact. In terms of basic research, parabiosis might be on track for a revival, a group of parabiosis scientists wrote in a Swiss medical journal:

Parabiosis and heterochronic parabiosis in particular could help answering some of the fundamental questions in this regard: are circulatory factors or cells in a young organism protecting against age-related disease, and vice versa, are factors or cells in the old organism predisposing or promoting disease in a younger organism?

Meredith Knight is a frequent contributor to the Genetic Literacy Project and a freelance science and health writer based in Austin, Texas. Follow her @meremereknight

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