Scientists Seek Ban on Method of Editing the Human Genome

Jennifer A. Doudna, an inventor of a new genome-editing technique, in her office at the University of California, Berkeley. Dr. Doudna is the lead author of an article calling for a worldwide moratorium on the use of the new method, to give scientists, ethicists and the public time to fully understand the issues surrounding the breakthrough. Credit Elizabeth D. Herman for The New York Times

A group of leading biologists on Thursday called for a worldwide moratorium on use of a new genome-editing technique that would alter human DNA in a way that can be inherited.
The biologists fear that the new technique is so effective and easy to use that some physicians may push ahead before its safety can be assessed. They also want the public to understand the ethical issues surrounding the technique, which could be used to cure genetic diseases, but also to enhance qualities like beauty or intelligence. The latter is a path that many ethicists believe should never be taken.

“You could exert control over human heredity with this technique, and that is why we are raising the issue,” said David Baltimore, a former president of the California Institute of Technology and a member of the group whose paper on the topic was published in the journal Science.
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Ethicists, for decades, have been concerned about the dangers of altering the human germline — meaning to make changes to human sperm, eggs or embryos that will last through the life of the individual and be passed on to future generations. Until now, these worries have been theoretical. But a technique invented in 2012 makes it possible to edit the genome precisely and with much greater ease. The technique has already been used to edit the genomes of mice, rats and monkeys, and few doubt that it would work the same way in people.

The technique holds the power to repair or enhance any human gene. “It raises the most fundamental of issues about how we are going to view our humanity in the future and whether we are going to take the dramatic step of modifying our own germline and in a sense take control of our genetic destiny, which raises enormous peril for humanity,” said George Q. Daley, a stem cell expert at Boston Children’s Hospital and a member of the group.

The biologists writing in Science support continuing laboratory research with the technique, and few if any scientists believe it is ready for clinical use. Any such use is tightly regulated in the United States and Europe. American scientists, for instance, would have to present a plan to treat genetic diseases in the human germline to the Food and Drug Administration.

The paper’s authors, however, are concerned about countries that have less regulation in science. They urge that “scientists should avoid even attempting, in lax jurisdictions, germline genome modification for clinical application in humans” until the full implications “are discussed among scientific and governmental organizations.”

Though such a moratorium would not be legally enforceable and might seem unlikely to exert global influence, there is a precedent. In 1975, scientists worldwide were asked to refrain from using a method for manipulating genes, the recombinant DNA technique, until rules had been established.

“We asked at that time that nobody do certain experiments, and in fact nobody did, to my knowledge,” said Dr. Baltimore, who was a member of the 1975 group. “So there is a moral authority you can assert from the U.S., and that is what we hope to do.”

Recombinant DNA was the first in a series of ever-improving steps for manipulating genetic material. The chief problem has always been one of accuracy, of editing the DNA at precisely the intended site, since any off-target change could be lethal. Two recent methods, known as

• zinc fingers and 
• TAL effectors, 

came close to the goal of accurate genome editing, but both are hard to use. The new genome-editing approach was invented by Jennifer A. Doudna of the University of California, Berkeley, and Emmanuelle Charpentier of Umea University in Sweden.

Their method, known by the acronym Crispr-Cas9, co-opts the natural immune system with which bacteria remember the DNA of the viruses that attack them so they are ready the next time those same invaders appear. Researchers can simply prime the defense system with a guide sequence of their choice and it will then destroy the matching DNA sequence in any genome presented to it. Dr. Doudna is the lead author of the Science article calling for control of the technique and organized the meeting at which the statement was developed.

Though highly efficient, the technique occasionally cuts the genome at unintended sites. The issue of how much mistargeting could be tolerated in a clinical setting is one that Dr. Doudna’s group wants to see thoroughly explored before any human genome is edited.

Scientists also say that replacing a defective gene with a normal one may seem entirely harmless but perhaps would not be.

“We worry about people making changes without the knowledge of what those changes mean in terms of the overall genome,” Dr. Baltimore said. “I personally think we are just not smart enough — and won’t be for a very long time — to feel comfortable about the consequences of changing heredity, even in a single individual.”

Many ethicists have accepted the idea of gene therapy, changes that die with the patient, but draw a clear line at altering the germline, since these will extend to future generations. The British Parliament in February approved the transfer of mitochondria, small DNA-containing organelles, to human eggs whose own mitochondria are defective. But that technique is less far-reaching because no genes are edited.

There are two broad schools of thought on modifying the human germline, said R. Alta Charo, a bioethicist at the University of Wisconsin and a member of the Doudna group.
One is pragmatic and seeks to balance benefit and risk.
The other “sets up inherent limits on how much humankind should alter nature,” she said.
Some Christian doctrines oppose the idea of playing God, whereas in Judaism and Islam there is the notion “that humankind is supposed to improve the world.” She described herself as more of a pragmatist, saying, “I would try to regulate such things rather than shut a new technology down at its beginning.”

Other scientists agree with the Doudna group’s message. “It is very clear that people will try to do gene editing in humans,” said Rudolf Jaenisch, a stem cell biologist at the Whitehead Institute in Cambridge, Mass., who was not a member of the Doudna group. “This paper calls for a moratorium on any clinical application, which I believe is the right thing to do.”

Writing in Nature last week, Edward Lanphier and other scientists involved in developing the rival zinc finger technique for genome editing also called for a moratorium on human germline modification, saying that use of current technologies would be “dangerous and ethically unacceptable.”

The International Society for Stem Cell Research said Thursday that it supported the proposed moratorium.

The Doudna group calls for public discussion, but is also working to develop some more formal process, such as an international meeting convened by the National Academy of Sciences, to establish guidelines for human use of the genome-editing technique.

“We need some principled agreement that we want to enhance humans in this way or we don’t,” Dr. Jaenisch said. “You have to have this discussion because people are gearing up to do this.”


ORIGINAL: NYTimes

By NICHOLAS WADE 

MARCH 19, 2015

Colombia: Minsalud ya firmó el decreto sobre medicamentos biotecnológicos

Si el Presidente lo suscribe, contenido de la controvertida norma se daría a conocer este miércoles.

Foto: Archivo / el tiempo

Biotecnológicos son aquellos que resultan de la manipulación de organismos vivos (células, bacterias y tejidos).

El ministro de Salud, Alejandro Gaviria, le aseguró a EL TIEMPO que el decreto de regulación de medicamentos biotecnológicos ya tiene su firma y está a la espera de la del presidente Juan Manuel Santos para ser expedido. Si supera este requisito, el contenido de la controvertida norma se daría a conocer este miércoles. (Lea también: Estados Unidos, preocupado por biotecnológicos, camiones y etanol)

El texto es fruto de varios años de debate y cinco borradores que han sido debatidos ampliamente por las partes interesadas; pese a eso, las multinacionales farmacéuticas siguen inconformes con algunos puntos, fundamentalmente con la llamada ‘ruta abreviada’.

Para entenderlo hay que decir que los biotecnológicos son aquellos que resultan de la manipulación de organismos vivos (células, bacterias y tejidos), mediante tecnologías muy avanzadas, y que se usan para tratar enfermedades como cáncer, artritis y otros males degenerativos. (Lea también: Proponen que bloqueo a genéricos sea delito de lesa humanidad).

Se trata de fármacos innovadores y costosos, cuyo mercado durante el primer semestre del 2014 representó el 20 por ciento del gasto farmacéutico nacional, aun cuando solo representan el 1 por ciento de todos los registros de fármacos vigentes en Colombia.

Quienes los crean aseguran que por sus características (derivados de organismos vivos) es imposible obtener medicamentos exactamente iguales, razón por la cual no podrían copiarse, sino obtener, a lo sumo, biosimilares.

Al no ser idénticos a los de la referencia, los biosimilares deben demostrar, con estudios clínicos comparativos, que tienen perfiles parecidos –en eficacia, potencia y seguridad– a los innovadores. Y esos no son procedimientos sencillos.

Para todos los biotecnológicos, el Ministerio de Salud propone en el decreto tres vías de registro: 

• la del innovador, que debe presentar evidencia clínica completa sobre sus beneficios, eficacia y seguridad; 
• la de los medicamentos altamente parecidos al fármaco de la referencia, cuyos fabricantes deben probar su biosimilitud, y 
• la ‘ruta abreviada’.

Esta ruta permite caracterizar moléculas al punto que se puede decir si una es similar a la otra mediante un proceso técnico, sin tener que hacer estudios clínicos en humanos. Se parte del hecho de que la molécula ya está estudiada.

Las multinacionales son contrarias a esta vía, porque consideran que por ella pueden colarse fármacos que no ofrecen la misma eficacia y seguridad. En el extremo opuesto están quienes aseguran que este argumento solo busca mantener el monopolio sobre los biotecnológicos y los precios altos.

Las dudas sobre la ‘ruta abreviada’ o ‘tercera vía’, y otros aspectos del decreto, fueron resaltadas por la Administración de Medicamentos y Alimentos de Estados Unidos (FDA), en una carta al Ministerio de Salud a la cual respondió Alejandro Gaviria, con otra misiva, dirigida a Margaret A. Hamburg, comisionada de la FDA.

En ella, el Ministro aclara las dudas de la agencia reguladora de ese país y acepta hacer algunos ajustes. No obstante, hace énfasis en que la ‘ruta abreviada’ responde a procesos que se ajustan al rigor técnico científico –de manera que evitan cualquier riesgo para la población– y en que, en términos generales, el decreto coincide con las perspectivas que sobre el tema tiene la propia FDA.

ORIGINAL: El Tiempo

Por: SALUD

14 de septiembre de 2014

Updated: FDA Orders 23andMe to Stop Genetic Tests

The U.S. government is concerned that some of 23andMe’s health assessments could mislead customers.

On Friday, the U.S. Food and Drug Administration told 23andMe CEO Anne Wojcicki that her company “must immediately discontinue marketing the [Personal Genome Service].”

Saliva Collection Kit Single

For $99, 23andMe will analyze the DNA in a saliva sample for genetic traits related to ancestry information, physical characteristics, disease risk, and drug response.
The health-related information is what concerns the FDA. The agency says that customers may make health decisions such as prophylactic breast removal surgery as a result of 23andMe’s report on their genetic risk for breast cancer. The problem, writes the FDA, is that the company has not provided the data to prove that the tests work, so consumers may make major health decisions based on faulty results.

Over a year ago, 23andMe announced that it was working with the FDA to get approval on at least some of the health traits in its service (see “Personal Genetics Company Seeks Regulatory Approval”). At the time, the company said it was looking forward to a collaborative process with the agency in the new territory of consumer genetics. So it was a bit surprising to read in the FDA’s letter that the company has not provided the agency with the data the regulatory agency requested in January to support marketing the health portions of the personal genomics test.

So what has 23andMe been doing instead? For one, they kicked off a large marketing campaign, which seems to have stirred up some ire in the FDA. From the agency’s letter to Wojcicki:


“[The] FDA has not received any communication from 23andMe since May. Instead, we have become aware that you have initiated new marketing campaigns, including television commercials that, together with an increasing list of indications, show that you plan to expand the [Personal Genome Service’s] uses and consumer base without obtaining marketing authorization from FDA.”

23andMe acknowledges that it has been remiss in responding to the FDA, but doesn’t say much else:

“We recognize that we have not met the FDA’s expectations regarding timeline and communication regarding our submission. Our relationship with the FDA is extremely important to us and we are committed to fully engaging with them to address their concerns.”


This post was updated 1:30 pm EST with comment from 23andMe.

ORIGINAL: Tech Review
Susan Young
November 25, 2013

Why Antibacterial Soap Is Dangerous

ORIGINAL: Google+ / Discovery

Jessica Meyer

Antibacterial equals safe, right? Think again. New research suggests that a particular ingredient common in antibacterial products is actually quite dangerous. Trace has all the details on Triclosan and what the FDA is aiming to do about it.

Decades-Old Question: Is Antibacterial Soap Safe?
http://hosted.ap.org/dynamic/stories/U/US_LIQUID_SOAP_SAFETY

"It's a chemical that's been in U.S. households for more than 40 years, from the body wash in your bathroom shower to the knives on your kitchen counter to the bedding in your baby's basinet."

Triclosan Facts

http://www.epa.gov/oppsrrd1/REDs/factsheets/triclosan_fs.htm

"Triclosan (2,4,4' --trichloro-2'-hydroxydiphenyl ether) is a chlorinated aromatic compound. Its functional groups include both phenols and ethers. It is used as a synthetic broad-spectrum antimicrobial agent."

Triclosan: What Consumers Should Know

http://www.fda.gov/forconsumers/consumerupdates/ucm205999.htm

"Triclosan is an ingredient added to many consumer products to reduce or prevent bacterial contamination."

Are Anti-Bacterial Soaps Poisoning Our Water?
http://news.discovery.com/earth/anti-bacterial-soaps-dioxins.htm

"A common chemical found in antibacterial soaps is turning up in lakes and streams and could potentially harm wildlife and human health."

Should I Avoid Products That Contain Triclosan?
http://www.mayoclinic.com/health/triclosan/AN02141 "There currently isn't enough evidence to recommend avoiding use of products that contain triclosan — an ingredient added to certain soaps, cosmetics, clothing, cookware, furniture and toys to reduce or prevent bacterial contamination."

---

Antibiotics and the Meat We Eat

ORIGINAL: NYTimes

By DAVID A. KESSLER 

March 27, 2013 

San Francisco 

Connect With Us on Twitter 

For Op-Ed, follow @nytopinion and to hear from the editorial page editor, Andrew Rosenthal, follow @andyrNYT. 

SCIENTISTS at the Food and Drug Administration systematically monitor the meat and poultry sold in supermarkets around the country for the presence of disease-causing bacteria that are resistant to antibiotics. These food products are bellwethers that tell us how bad the crisis of antibiotic resistance is getting. And they’re telling us it’s getting worse. 

But this is only part of the story. While the F.D.A. can see what kinds of antibiotic-resistant bacteria are coming out of livestock facilities, the agency doesn’t know enough about the antibiotics that are being fed to these animals. This is a major public health problem, because giving healthy livestock these drugs breeds superbugs that can infect people. We need to know more about the use of antibiotics in the production of our meat and poultry. The results could be a matter of life and death. 

In 2011, drugmakers sold nearly 30 million pounds of antibiotics for livestock — the largest amount yet recorded and about 80 percent of all reported antibiotic sales that year. The rest was for human health care. We don’t know much more except that, rather than healing sick animals, these drugs are often fed to animals at low levels to make them grow faster and to suppress diseases that arise because they live in dangerously close quarters on top of one another’s waste. 

It may sound counterintuitive, but feeding antibiotics to livestock at low levels may do the most harm. When he accepted the Nobel Prize in 1945 for his discovery of penicillin, Alexander Fleming warned that “there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to nonlethal quantities of the drug make them resistant.” He probably could not have imagined that, one day, we would be doing this to billions of animals in factorylike facilities. 

The F.D.A. started testing retail meat and poultry for antibiotic-resistant bacteria in 1996, shortly before my term as commissioner ended. The agency’s most recent report on superbugs in our meat, released in February and covering retail purchases in 2011, was 82 pages long and broke down its results by four different kinds of meat and poultry products and dozens of species and strains of bacteria. 

It was not until 2008, however, that Congress required companies to tell the F.D.A. the quantity of antibiotics they sold for use in agriculture. The agency’s latest report, on 2011 sales and also released in February, was just four pages long — including the cover and two pages of boilerplate. There was no information on how these drugs were administered or to which animals and why. 

We have more than enough scientific evidence to justify curbing the rampant use of antibiotics for livestock, yet the food and drug industries are not only fighting proposed legislation to reduce these practices, they also oppose collecting the data. Unfortunately, the Senate Committee on Health, Education, Labor and Pensions, as well as the F.D.A., is aiding and abetting them. 

The Senate committee recently approved the Animal Drug User Fee Act, a bill that would authorize the F.D.A. to collect fees from veterinary-drug makers to finance the agency’s review of their products. Public health experts had urged the committee to require drug companies to provide more detailed antibiotic sales data to the agency. Yet the F.D.A. stood by silently as the committee declined to act, rejecting a modest proposal from Senators Kirsten E. Gillibrand of New York and Dianne Feinstein of California, both Democrats, that required the agency to report data it already collects but does not disclose. 

In the House, Representatives Henry A. Waxman of California and Louise M. Slaughter of New York, also Democrats, have introduced a more comprehensive measure. It would not only authorize the F.D.A. to collect more detailed data from drug companies, but would also require food producers to disclose how often they fed antibiotics to animals at low levels to make them grow faster and to offset poor conditions. 

This information would be particularly valuable to the F.D.A., which asked drug makers last April to voluntarily stop selling antibiotics for these purposes. The agency has said it would mandate such action if those practices persisted, but it has no data to determine whether the voluntary policy is working. The House bill would remedy this situation, though there are no Republican sponsors. 

Combating resistance requires monitoring both the prevalence of antibiotic-resistant bacteria in our food, as well as the use of antibiotics on livestock. In human medicine, hospitals increasingly track resistance rates and antibiotic prescription rates to understand how the use of these drugs affects resistance. We need to cover both sides of this equation in agriculture, too. 

I appreciate that not every lawmaker is as convinced as I am that feeding low-dose antibiotics to animals is a recipe for disaster. But most, if not all of them, recognize that we are facing an antibiotic resistance crisis, as evidenced by last year’s bipartisan passage of a measure aimed at fighting superbugs by stimulating the development of new antibiotics that treat serious infections. Why are lawmakers so reluctant to find out how 80 percent of our antibiotics are used? 

We cannot avoid tough questions because we’re afraid of the answers. Lawmakers must let the public know how the drugs they need to stay well are being used to produce cheaper meat. 

David A. Kessler was commissioner of the Food and Drug Administration from 1990 to 1997. 

Harvard's Wyss Institute and Sony DADC Announce Collaboration on Organs-on-Chips

ORIGINAL: Wyss Institute

Date: Mar 18, 2013

Boston, MA -- Today the Wyss Institute for Biologically Inspired Engineering at Harvard University and Sony DADC announced a collaboration that will harness Sony DADC's global manufacturing expertise to further advance the Institute's Organs-on-Chips technologies. 

Human Organs-on-Chips are composed of a clear, flexible polymer about the size of a computer memory stick, and contain hollow microfluidic channels lined by living human cells -- allowing researchers to recapitulate the physiological and mechanical functions of the organs, and to observe what happens in real time. The goal is to provide more predictive and useful measures of the efficacy and safety of new drugs in humans -- and at a fraction of the time and costs associated with traditional animal testing.

"We are excited to apply Sony DADC's deep manufacturing expertise to confront one of the major challenges in the life sciences by helping to accelerate the translation of the Wyss Institute's Organ-on-Chips from the benchtop to the marketplace," said Christoph Mauracher, Senior Vice President of the BioSciences division of Sony DADC. "The Organs-on-Chips have the potential to revolutionize testing of drugs, chemicals, toxins and cosmetics."

Organs on a Chip from Wyss Institute on Vimeo.

This collaboration builds on the momentum the Wyss Institute team has gained recently on its Organs-on-Chips research program. With support from Defense Advanced Research Projects Agency (DARPA)*, National Institutes of Health (NIH), Food and Drug Administration (FDA), and pharmaceutical partners, more than ten Organs-on-Chips are currently under development at the Wyss Institute, including a lung, heart, liver, kidney, bone marrow, and gut-on-a-chip; there is also a major effort to integrate these organ chips into "human body on-chips" that mimic whole body physiology.

In February, Wyss Founding Director Don Ingber, M.D., Ph.D., who leads the Organs-on-Chips research program, received the prestigious 3Rs Prize from the UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research for the lung-on-a-chip. This month, the Society of Toxicology awarded him the Leading Edge in Basic Science Award for his "seminal scientific contributions and advances to understanding fundamental mechanisms of toxicity."

"Our work with Sony is a wonderful example of the Wyss Institute model in action," said Ingber. "We collaborate with industry to help de-risk the technologies we develop, both technically and commercially, and therefore expedite their translation into real world applications."

###

*Part of this research was sponsored by the U.S. Army Research Office (ARO) and DARPA; the views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of ARO, DARPA or the U.S. Government.

Contacts

Wyss Institute for Biologically Inspired Engineering 

Kristen M. Kusek

+1 617-432-8266

Kristen.kusek@wyss.harvard.edu 

Sony DADC

Manfred Koranda

+43 6246 880 8143

manfred.koranda@sonydadc.com

Approval for gene-modified salmon spawns controversy

ORIGINAL: New Scientist

by Sara Reardon

28 December 2012 

Fast-growing salmon have cleared another hurdle in an upstream battle to be the first genetically modified animal approved for human consumption. After a long and possibly politically motivated delay, federal regulators have released preliminary documents declaring the fish safe to eat and environmentally harmless.

Since 1995, a company called AquaBounty, based in Maynard, Massachusetts, has been seeking approval from the US government to sell its AquAdvantage fish. These Pacific salmon have been modified with a growth hormone gene from Chinook salmon, which causes them to grow twice as fast as normal fish.

Rather than releasing the fish into the wild, the company plans to engineer its eggs in highly secure tanks in Canada, then ship them to Panama to mature. As a precaution, the fish are all female and contain three copies of each chromosome rather than two, rendering them sterile.

Controversy has engulfed the fish since their creation, but the concern is more about their potential ecological impacts than dangers to human health. Organisations such as the Marine Fish Conservation Network, which promotes sustainable fishing practices, worry that the transgenic salmon could outcompete wild salmon if they escape. "The risk of escapes and damage to wild ocean fisheries is simply too great to be left to chance," director Matt Tinning said in a statement.

The organisation says it has not yet had time to review the newly released assessment, published on 27 December by the US Food and Drug Administration (FDA). In two preliminary documents, it declares that AquaBounty's safety measures are sufficient, that the fish would have no significant environmental impact and that they are safe for human consumption.

Delayed release

The timing of the release has sparked suspicion of political interference, as it came hours after a non-profit organisation called the Genetic Literacy Project published FDA documents showing that the assessment had been complete since April and should have been released immediately. The organisation's investigation suggests that the White House's Office of Science and Technology Policy (OSTP), concerned over the issue's sensitivity, had blocked the documents' release until after the presidential election.

Asked about the allegations, the OSTP referred New Scientist to the FDA, whose spokesperson Shelly Burgess declined to comment. But she says that the agency is being particularly cautious as the salmon are the first transgenic animal to reach this point in the approval process.

Final approval of the salmon could still be some way off, however. The public now has 60 days to comment on the documents before the FDA will review them again. Burgess says it is impossible to predict how long the next review might take.

In the Flesh: The Embedded Dangers of Untested Stem Cell Cosmetics

ORIGINAL: Scientific American

By Ferris Jabr

Unapproved procedures and skin care products endanger consumers and clinical research

Image: Credit: Nissim Benvenisty, via Wikimedia Commons

When cosmetic surgeon Allan Wu first heard the woman's complaint, he wondered if she was imagining things or making it up. A resident of Los Angeles in her late sixties, she explained that she could not open her right eye without considerable pain and that every time she forced it open, she heard a strange click—a sharp sound, like a tiny castanet snapping shut. After examining her in person at The Morrow Institute in Rancho Mirage, Calif., Wu could see that something was wrong: Her eyelid drooped stubbornly, and the area around her eye was somewhat swollen. Six and a half hours of surgery later, he and his colleagues had dug out small chunks of bone from the woman's eyelid and tissue surrounding her eye, which was scratched but largely intact. The clicks she heard were the bone fragments grinding against one another.

About three months earlier the woman had opted for a relatively new kind of cosmetic procedure at a different clinic in Beverly Hills—a face-lift that made use of her own adult stem cells. First, cosmetic surgeons had removed some the woman's abdominal fat with liposuction and isolated the adult stem cells within—a family of cells that can make many copies of themselves in an immature state and can develop into several different kinds of mature tissue. In this case the doctors extracted mesenchymal stem cells—which can turn into bone, cartilage or fat, among other tissues—and injected those cells back into her face, especially around her eyes. The procedure cost her more than $20,000, Wu recollects. Such face-lifts supposedly rejuvenate the skin because stem cells turn into brand-new tissue and release chemicals that help heal aging cells and stimulate nearby cells to proliferate.

During the face-lift her clinicians had also injected some dermal filler, which plastic surgeons have safely used for more than 20 years to reduce the appearance of wrinkles. The principal component of such fillers is calcium hydroxylapatite, a mineral with which cell biologists encourage mesenchymal stem cells to turn into bone—a fact that escaped the woman's clinicians. Wu thinks this unanticipated interaction explains her predicament. He successfully removed the pieces of bone from her eyelid in 2009 and says she is doing well today, but some living stem cells may linger in her face. These cells could turn into bone or other out-of-place tissues once again.

Dozens, perhaps hundreds, of clinics across the country offer a variety of similar, untested stem cell treatments for both cosmetic and medical purposes. Costing between $3,000 and $30,000, the treatments promise to alleviate everything from wrinkles to joint pain to autism. The U.S. Food and Drug Administration (FDA) has not approved any of these treatments and, with a limited budget, is struggling to keep track of all the unapproved therapies on the market. At the same time, pills, oils, creams and moisturizers that allegedly contain the right combination of ingredients to mobilize the body's resident stem cells, or contain chemicals extracted from the stem cells in plants and animals, are popping up in pharmacies and online. There's Stem Cell 100, for example, MEGA STEM and Apple Stem Cell Cloud Cream. Few of these cosmetics have been properly tested in published experiments, yet the companies that manufacture them say they may heal damaged organs, slow or reverse natural aging, restore youthful energy and revitalize the skin. Whether such cosmetics may also produce unintended and potentially harmful effects remains largely unexamined. The increasing number of untested and unauthorized stem cell treatments threaten both people who buy them and researchers hoping to conduct clinical trials for promising stem cell medicine.

When is a skin cream a drug?

So far, the FDA has only approved one stem cell treatment: a transplant of bone marrow stem cells for people with the blood cancer leukemia. Among the increasing number of unapproved stem cell treatments, some clearly violate the FDA's regulations whereas others may technically be legal without its approval. In July 2012, for example, the U.S. District Court upheld an injunction brought by the FDA against Colorado-based Regenerative Sciences to regulate just one of the company's several stem cell treatments for various joint injuries as an "unapproved biological drug product." The decision hinged on what constitutes "minimal manipulation" of cells in the lab before they are injected into patients. In the treatment that the FDA won the right to regulate, stem cells are grown and modified in the lab for several weeks before they are returned to patients; in Regenerative Sciences's other treatments, patients' stem cells are extracted and injected within a day or two. Regenerative Sciences now offers the legally problematic treatment at a Cayman Island facility.

Many stem cell cosmetics reside in a legal gray area. Unlike drugs and "biologics" made from living cells and tissues, cosmetics do not require premarket approval from the FDA. But stem cell cosmetics often satisfy the FDA's definitions for both cosmetics and drugs. In September 2012 the FDA posted a letter on its Web site warning Lancôme, a division of L'Oréal, that the way it describes its Genifique skin care products qualify the creams and serums as unapproved drugs: they are supposed to "boost the activity of genes," for example, and "improve the condition of stem cells." Other times the difference between needing or not needing FDA approval comes down to linguistic nuance—the difference between claiming that a product does something or appears to do something.

Personal Cell Sciences, in Eatontown, N.J., sells some of the more sophisticated stem cell–based cosmetics: an eye cream, moisturizer and serum infused with chemicals derived from a consumer's own stem cells. According to its website and marketing materials, these products help "make skin more supple and radiant," "reduce the appearance of fine lines and wrinkles around the eyes and lips," "improve cellular renewal" and "stimulate cell turnover for renewed texture and tone." In exchange for $3,000, Personal Cell Sciences will arrange for a participating physician to vacuum about 60 cubic centimeters (one quarter cup) of a customer's fat from beneath his or her skin and ship it on ice to American CryoStem Corp. in Red Bank, N.J., where laboratory technicians isolate and grow the customer's mesenchymal stem cells to around 30 million strong. Half these cells are frozen for storage; from the other half, technicians harvest hundreds of different kinds of exuded growth factors and cytokines—molecules that help heal damaged cells and encourage cells to divide, among other functions. These molecules are mixed with many other ingredients—including green tea extract, caffeine and vitamins—to create the company's various "U Autologous" skin care products, which are then sold back to the consumer for between $400 and $800. When the customer wants a refill, technicians thaw some of the frozen cells, collect more cytokines and produce new bottles of cream.

In an unpublished safety trial sponsored by Personal Cell Sciences, Frederic Stern of the Stern Center for Aesthetic Surgery in Bellevue, Wash., and his colleagues monitored 19 patients for eight weeks as they used the U Autologous products on the left sides of their faces. A computer program meant to objectively analyze photos of the volunteers' faces measured an average of 25.6 percent reduction in the volume of wrinkles on the treated side of the face. Analysis of tissue biopsies revealed increased levels of the protein elastin, which helps keep skin taut, and no signs of unusual or cancerous cell growth.

Only skin deep?

Supposedly, the primary active ingredients in the U Autologous skin care products are the hundreds of different kinds of cytokines they contain. Cytokines are a large and diverse family of proteins that cells release to communicate with and influence one another. Cytokines can stimulate cell division or halt it; they can suppress the immune system or provoke it; they can also change a cell's shape, modulate its metabolism and force it to migrate from one location to another like a cowboy corralling cattle. Researchers have only named and characterized some of the many cytokines that stem cells secrete. Some of these molecules certainly help repair damaged cells and promote cell survival. Others seem to be involved in the development of tumors. In fact, some recent evidence suggests that the cytokines released by mesenchymal stem cells can trigger tumors by accelerating the growth of dormant cancer cells. Personal Cell Sciences does not pick and choose among the cytokines exuded by its customers' stem cells—instead, it dumps them all into its skin care products.

Based on the available evidence so far, topical creams containing cytokines from stem cells pose far less risk of cancer than living stem cells injected beneath the skin. But scientists do not yet know enough about stem cell cytokines to reliably predict everything they will do when rubbed into the skin; they could interact with healthy skin cells in a completely unexpected way, just as the unintended interplay between calcium hydroxylapatite and stem cells produced bones in the Los Angeles woman's eye. Stern acknowledges that unusual tissue growth is a concern for any treatment based on stem cells and the chemicals they release. "Down the line, we want to continue watching that," he says. Unlike many other clinics, he and his colleagues have been keeping tabs on their patients through regular follow-ups. John Arnone, CEO of American CryoStem and founder of Personal Cell Sciences, says the fact that U Autologous skin care products contain such a diversity of cytokines does not bother him: "I've seen worse things out there. I've been putting this formulation for almost a year on myself prior to the study. I'm the best guinea pig here."

Beyond the considerable risks to consumers, unapproved stem cell treatments also threaten the progress of basic research and clinical trials needed to establish safe stem cell therapies for serious illnesses. By harvesting stem cells, subsequently nourishing them in the lab and transplanting them back inside the human body, scientists hope to improve treatment for a variety of medical conditions, including heart failure, neurodegenerative disorders like Parkinson's, and spinal cord injuries—essentially any condition in which the body needs new cells and tissues. Researchers are investigating many stem cell therapies in ongoing, carefully controlled clinical trials. Some of the principal questions entail which of the many kinds of stem cells to use; how to safely deliver stem cells to patients without stimulating tumors or the growth of unwanted tissues; and how to prevent the immune system from attacking stem cells provided by a donor. Securing funding for such research becomes all the more difficult if shortcuts taken by private clinics and cosmetic manufacturers—and the subsequent botched procedures and unanticipated consequences—imprint a stigma on stem cells.

"Many of us are super excited about stem cells, but at same time we have to be really careful," says Paul Knoepfler, a cell biologist at the University of California, Davis, who regularly blogs about the regulation of stem cell treatments. "These aren't your typical drugs. You can stop taking a pill and the chemicals go away. But if you get stem cells, most likely you will have some of those cells or their effects for the rest of your life. And we simply don't know everything they are going to do."

Yuck: Our Seafood Is Loaded with Unspeakably Gross Pollutants

ORIGINAL: AlterNet

November 30, 2012

Some of our most popular seafood treats come to us from filthy operations in other countries.

Photo Credit: © AJP/Shutterstock.com

This article was published in partnership with GlobalPossibilities.org.

When you tuck into a delicious seafood dish, is it possible that the fish you are eating once ate human poop? Surprisingly, that might be the case. A look at the U.S. seafood supply reveals that some of our most popular seafood treats might come to us from unsanitary and disgusting operations in other countries. And the federal government does not necessarily stop it from making its way to your dinner plate, either.

These days, 91 percent of U.S. seafood is imported, and half of that is farmed (the other half is wild-caught). Our top suppliers include China, Thailand, Canada, Chile, Indonesia, Ecuador, and Vietnam. And the production systems some of these countries use would make your stomach turn.

Michael Doyle, regents professor and director at the Center for Food Safety at the University of Georgia, described tilapia production in China, saying, “The farmers there grow the fish in ponds that are maybe one to two acres in size. That's their livelihood. And they use excessive antibiotics.” China is a leading supplier of tilapia to the U.S.

“It's not just antibiotic residues on the seafood. It's also antibiotic-resistant microbes that come with the fish or the shrimp,” he continued. “A primary source of salmonella is the raw manure that is used to feed the shrimp and fish. Many of these farmers have poultry -- maybe chickens, maybe geese, maybe ducks. The fecal waste of these animals is fed directly into these ponds, which is the source of nutrients for these fish and shrimp… Poultry can harbor salmonella... that's shed in the feces. And many of these little farms have the family outhouse just feed directly into the ponds."

If that makes you less interested in ordering the tilapia, then you surely don’t want any Vietnamese “catfish” either. U.S. aquaculture produces channel catfish, but these days, American producers compete with a flood of cheap Vietnamese fish that are marketed as catfish. Dr. Carole Engle, chair and director of aquaculture and fisheries at the University of Arkansas at Pine Bluff, says these Vietnamese catfish are “not only a different species, it's a different genus and a different family. We call it pangasius.”

To understand pangasius farming in Vietnam, one must first know a little bit about life in the Mekong Delta. Engle explains, “What's striking when you first get there is that there's more water than there is land in the Mekong Delta region. There are these large rivers coming through the Mekong Delta… These waters are everything. A lot of the transportation is on the water, and a lot of people live on the water, on houseboats. It's also a disposal system. People live on these rivers and their restrooms are right on these boats and they are discharging right on the rivers. And all the human waste, and all of the waste from cities… it's all going into the river and the river is the source of the water.”

That water is where the fish are raised. “A lot of the fish are raised in cages directly in rivers,” says Engle, but “more and more the pangasius are raised in what the Vietnamese call ponds.” But the ponds are nothing like U.S. aquaculture ponds that are closed systems using clean water. The Vietnamese ponds are regularly flushed with polluted river water. "Upstream a factory or a houseboat might have discharged something into it, and all that human waste is flowing through these ponds because they are flushing it through a few times a day," Engle explains.

Another concern with imported farm-raised seafood is the use of drugs and pesticides that are banned in the United States. A few that show up frequently include the drugs chloramphenicol and nitrofurans, and the fungicide malachite green. Each of these is banned in the United States for a good reason. Chloramphenicol can cause aplastic anemia, a condition in which the bone marrow does not produce enough new blood cells, in humans. Doctors use it as a drug of last resort to treat typhoid fever and meningitis. Nitrofurans and malachite green are potentially carcinogenic in humans.

What happens when a shipment of filthy or toxic seafood shows up in a U.S. port? Most likely, nothing. It enters the U.S. and unwitting Americans eat it. The Food and Drug Administration has an inspection program that is notoriously limited, underfunded and not at all transparent – particularly when compared to its counterparts in Japan, Canada and the EU.

In a study published last year, David Love, science director of the Public Health and Sustainable Aquaculture Project at the Johns Hopkins Center for a Livable Future, found that Japan physically inspected 12 to 21 percent of its seafood imports between 2004 and 2009. The European Union goes even further, physically inspecting either 20 percent or 50 percent of all imported seafood shipments, depending on the risk of each individual product. But the U.S. inspects less than 2 percent of seafood imports.

Since 1997, the U.S. has relied on the Hazard Analysis and Critical Control Points (HACCP) system (which some deride as Have a Cup of Coffee and Pray). The system essentially turns control over to industry, requiring it to identify and control for points in the production chain when food might become contaminated. When done properly, it’s an excellent system. But it’s fair to say that setting your family’s outhouse to flow into your aquaculture pond does not constitute a good HACCP system.

Most of the time, the FDA relies on inspecting documentation to verify that adequate HACCP programs are in place and that they are being followed. (Because, you know, no one would ever falsify paperwork…) For just over 1 percent of imported seafood shipments, the FDA performs sensory examinations, checking for things like color, texture and odor. These exams can easily discover whether the seafood is filthy or rotting, but might not catch residues of veterinary drugs or microscopic pathogens.

Less than 1 percent of U.S. seafood import shipments actually go to a lab for testing. Last year, a GAO report titled “FDA Needs to Improve Oversight of Imported Seafood and Better Leverage Limited Resources” chided the FDA for inadequate oversight and even failing to meet its own inspection goals. According to the report, “FDA”s sampling program is limited in scope, is not effectively implemented, and does not fully use the capabilities of FDA’s laboratories.”

For example, in 2009, the FDA tested only 0.1 percent of seafood imports for drug residues. When they do test, they only test for 16 drugs, whereas Canada tests for 40, some European countries test for 50, and Japan tests for 57. In recent years, the U.S. lagged behind other nations in starting to test for drugs. The EU began testing for chloramphenicol and nitrofuran in 2001, but the U.S. did not do so until 2002 and 2004, respectively. In 2003, the EU began testing for malachite green, but the U.S. waited until 2005 to do so.

Once the FDA rejects a shipment of seafood, “they don't destroy the product,” explains Engle. “So it can go out on the ship and come in on another port. And because there is such a small percentage being tested, then when they go to another port like that, it's equally unlikely to be caught. So that's what happens. They call it port swapping.” She concludes, “FDA is just simply not catching things, and the system is not set up to catch it.”

The U.S. catfish industry was so fed up with the FDA’s lack of oversight that it lobbied to have catfish inspected by the U.S. Department of Agriculture instead. The USDA requires equivalency, says Engle, meaning that imported catfish (including pangasius) are held to the same standards as domestically raised catfish. “Why should we have different standards for our US growers and... an imported product?” Engle asks.

But even though catfish oversight was transferred to the USDA in the 2008 farm bill, the change was never implemented. Engle calls it a "political battle” between states with many seafood importers and those with a domestic catfish industry. Vietnam joined in the fight too, threatening to boycott U.S. beef. “Why would they be worried about it unless they realized they couldn't meet the US safety standards right now?" Engle points out. “The battle was not about safety for US consumers or even safety for Vietnamese consumers. It's really a shame.”

Engle worries most about the veterinary drug residues and the antibiotic-resistant bacteria that have evolved alongside them in foreign aquaculture operations. "It's a long-term kind of a thing -- there aren't bodies for people to look at like an immediate acute kind of disease like salmonella and so people don't worry so much about it,” she says.

Even worse, because other importing nations have stricter regulations than the U.S., “the best quality fish goes to Europe and Japan and Canada, and we get lower quality products here." Engle is outraged by this. “I find it appalling as a U.S. consumer. I just don't think we should have lower standards than other countries in the world for our food safety,” she says. “I still believe this is the greatest nation on this planet, and yet we don't act like it sometimes.”

With the FDA asleep at the wheel, what can U.S. consumers do to avoid eating imported farmed fish produced in unsafe conditions? If you are buying unprocessed seafood at a grocery store, the product will be labeled with its country of origin.

Veterinary drug violations are disproportionately from China, Vietnam and Indonesia, and they are disproportionately found in shrimp. (Shrimp is also the cause of a large percent of shipments rejected for filth and salmonella.) Farmed salmon (particularly from Chile) is another product that has been caught with banned veterinary drug residues.

However, 70 percent of seafood consumption takes place in restaurants, which are exempt from country-of-origin labeling. That means that most of the time, U.S. consumers have no idea where their seafood comes from – unless they ask their waiter and receive an answer. Processed seafood is also exempt from country of origin labeling, so you might want to skip on the pre-cooked cocktail shrimp, too.

To truly ensure you are eating safe and sustainable seafood, check out the Monterey Bay Aquarium’s Seafood Watch program, which provides updated guides to buying and eating seafood. Of course, the real solution is improving federal oversight of imported seafood, and that does not seem forthcoming.

Jill Richardson is the founder of the blog La Vida Locavore and a member of the Organic Consumers Association policy advisory board. She is the author of Recipe for America: Why Our Food System Is Broken and What We Can Do to Fix It..

Genetically Modified: The 2 Words the Food Industry Spent $45 Million to Avoid Using

ORIGINAL: Daily Finance

By M. Joy Hayes, Ph.D., The Motley Fool

11/15/12

Getty Images

Despite significant popular support for the labeling of genetically modified foods in recent polls, when it came time to vote on election day, Californians rejected Proposition 37, which would have required businesses to label products containing genetically modified organisms, or GMOs.

Proponents of Proposition 37 argued that the labeling requirements would provide consumers with valuable information that would allow them to make better purchasing decisions. Opponents countered that labels would mislead consumers by creating the impression that GMOs are harmful to human health.

Many attribute the loss to a multimillion-dollar advertising campaign against the proposition funded largely by agriculture and food companies like Monsanto (MON), PepsiCo (PEP), Coca-Cola (KO), Kraft (KRFT), and Kellogg (K). Opponents of Proposition 37 raised at least $45 million to affect voter sentiment, while supporters of the proposed law -- mostly consumer advocacy groups -- raised only about $8 million.

Was it a fair fight?

Prop 37 advocates complain that their defeat wasn't merely due to being outspent, but also due to opponents using deceptive marketing practices to shift public opinion. One example called out was a mailing to state residents which used the FDA logo and a quote saying, "The US Food and Drug Administration says a labeling policy like Prop 37 would be 'inherently misleading.'" FDA spokesperson Morgan Liscinsky later pointed out that the FDA did not make this statement or express any opinion on the proposed legislation.

Valuable Tool or Unnecessary Information?

If Prop 37 had passed, the law would have forbidden food companies from labeling foods with GMO ingredients as "natural", "naturally made", "naturally grown", or "all natural." Businesses would have had to label raw GMO produce as "genetically engineered," and to label all processed foods containing GMOs as "partially produced with genetic engineering," or "may be partially produced with genetic engineering."

The law also would have empowered consumers to stand up to companies that label their products inaccurately by making it possible for them to win lawsuits against food companies without having to prove specific damages resulting from the labeling violation.

While Big Ag argued that studies haven't shown GMOs are harmful to human health, Prop 37 advocates point out that most industry-funded studies last only 90 days. And although the Food and Drug Administration has deemed GMOs safe for human consumption, proponents worry that the FDA doesn't actually test these foods before they go to market, and so they don't have sufficient evidence to declare these goods safe.

Other advocates argue that even if GMOs are safe to eat, mandatory labeling would provide valuable information for consumers who worry about the sustainability of GMO farming, and its potential to breed "superbugs."

The fight over Prop 37 isn't just a California issue: Opponents were worried the law would set a precedent for the rest of the country to pick up the anti-GMO torch. In fact, about 93% of the money raised to turn voters against the law came from outside the state.

Advocates in Washington state, Connecticut, and Vermont are pushing to require labeling in their own states. Others are trying to utilize the national awareness arising from California's campaign to gain signatures on a petition asking the FDA to require labeling of GMO foods nationally.

Do you think Prop 37's requirements would have been good for consumers? Would you like your home state to push for similar legislation? Chime in below!

Motley Fool contributor M. Joy Hayes, Ph.D., is the Principal at ethics consulting firmCourageous Ethics. She doesn't own shares of any of the companies mentioned. Follow @JoyofEthics on Twitter.

Nanoparticles deliver cargo inside mitochondria

ORIGINAL: Foresight Institute

Shanta Dhar, right, an assistant professor of chemistry in the UGA Franklin College of Arts and Sciences, and doctoral student Sean Marrache have fabricated nanoparticles that boost the effectiveness of drugs by delivering them to the mitochondria of cells (credit: University of Georgia).

Targeted drug delivery is one of the most important contributions of current and near-term nanotechnology to medicine. New research shows that specifically targeting one component of the cell makes nanoparticle-mediated drug delivery much more effective for a variety of applications. A hat tip to KurzweilAI.net for reprinting this University of Georgia news release “UGA researchers boost efficacy of drugs by using nanoparticles to target ‘powerhouse of cells’“:

Nanoparticles have shown great promise in the targeted delivery of drugs to cells, but researchers at the University of Georgia have refined the drug delivery process further by using nanoparticles to deliver drugs to a specific organelle within cells.

By targeting mitochondria, often called “the powerhouse of cells,” the researchers increased the effectiveness of mitochondria-acting therapeutics used to treat cancer, Alzheimer’s disease and obesity in studies conducted with cultured cells.

“The mitochondrion is a complex organelle that is very difficult to reach, but these nanoparticles are engineered so that they do the right job in the right place,” said senior author Shanta Dhar, an assistant professor of chemistry in the UGA Franklin College of Arts and Sciences.

Dhar and her co-author, doctoral student Sean Marrache, used a biodegradable, FDA-approved polymer to fabricate their nanoparticles and then used the particles to encapsulate and test drugs that treat a variety of conditions. Their results were published this week in early edition of the journal Proceedings of the National Academy of Sciences [abstract].

To test the effectiveness of their drug targeting system against cancer, they encapsulated the drug lonidamine, which works by inhibiting energy production in the mitochondria, and, separately, a form of the antioxidant vitamin E. They then treated cultured cancer cells and found that mitochondrial targeting increased the effectiveness of the drugs by more than 100 times when compared to the drugs alone and by five times when compared to the delivery of drugs with nanoparticles that target the outside of cells.

Similarly, the compound curcumin has shown promise in inhibiting formation of the amyloid plaques that are a hallmark of Alzheimer’s disease, but it quickly degrades in the presence of light and is broken down rapidly by the body. By encapsulating curcumin in the mitochondria-targeting nanoparticles, however, the researchers were able to restore the ability of brain cells in culture to survive despite the presence of a compound that encourages plaque formation. Nearly 100 percent of the cells treated with the mitochondria-targeting nanoparticles survived in the presence of the plaque-inducing compound, compared to 67 percent of cells treated with free curcumin and 70 percent of cells treated with nanoparticles that target the outside of cells.

Finally, the researchers encapsulated the obesity drug 2,4-DNP—which works by making energy production in the mitochondria less efficient—in their nanoparticles and found that it reduced the production of fat by cultured cells known as preadipocytes by 67 percent compared to cells treated with the drug alone and by 61 percent of cells treated with nanoparticles that target the outside of cells.

“A lot of diseases are associated with dysfunctional mitochondria, but many of the drugs that act on the mitochondria can’t get there,” Marrache said. “Rather than try to alter the drugs, which can reduce their effectiveness, we encapsulate them in these nanoparticles and precisely deliver them to the mitochondria.”

Dhar said that getting drugs to the mitochondria is no simple feat. Upon entering cells, nanoparticles enter a sorting center known as the endosome. The first thing Dhar and Marrache had to demonstrate was that the nanoparticles escape from the endosome and don’t end up in the cells’ disposal center, the lysosome.

The mitochondria itself is protected by two membranes separated by an interstitial space. The outer membrane only permits molecules of a certain size to pass through, while the inner membrane only permits molecules of a given range of charges to pass. The researchers constructed a library of nanoparticles and tested them until they identified the optimum size range—64 to 80 nanometers, or approximately 1,000 times finer than the width of a human hair—and an optimum surface charge, plus 34 millivolts.

Dhar notes the components they used to create the nanoparticles are FDA approved and that their methods are highly reproducible and therefore have the potential to be translated into clinical settings. The researchers are currently testing their targeted delivery system in rodents and say that preliminary results are promising.

“Mitochondrial dysfunctions cause many disorders in humans,” Dhar said, ” so there are several potential applications for this delivery system.”

Subject to the usual caveat that these nanoparticles are still in an early stage of testing, having been tested only in cell culture, it is remarkable that such effective targeting to reach the matrix of the mitochondria was achieved by the relatively crude strategy of optimizing only particle size and surface charge through engineering polymer composition. So success was achieved through clever application of biological knowledge more than through sophisticated atomically precise construction. It will be fascinating to watch the evolution of this technology as ever more sophisticated construction leads to increasing effectiveness. While we are waiting, this targeting of drug delivery to mitochondria is likely to be especially helpful because so many pathologies seem rooted in imperfections and consequences of the symbiosis that led to eukaryotic cells, and all complex life on Earth, nearly two billion years ago.

—James Lewis, PhD