How human biology can prevent drug deaths

Thousands of people die from adverse effects of medicines that have been tested on animals. There is a better way, say geneticist Kathy Archibald and pharmacologist Robert Coleman

ADVERSE drug reactions are a major cause of death, killing 197,000 people annually in the European Union and upwards of 100,000 in the US. Little coverage is given to such grim statistics by governments or pharmaceutical companies, so patients and their doctors are not primed to be as vigilant as they should be, and adverse drug reactions (ADRs) remain seriously under-recognised and under-reported.

The €5.88-million EU-ADR project, which published its final report in October, showed that it is possible to spot these reactions earlier by applying data-mining techniques to electronic health records. These techniques could, for example, have detected the cardiovascular risk signals of arthritis drug Vioxx three years before the drug was withdrawn in 2004 - saving many tens of thousands of lives. But invaluable as such systems are, it would be even better to detect risk signals before a drug reaches humans, thus saving even more lives.

Currently, 92 per cent of new drugs fail clinical trials, even though they have successfully passed animal tests. This is mostly because of toxicity, which can be serious and even fatal for the people taking part in the trials. For example, in 2006, six people enrolled in a UK trial of the drug TGN1412 were hospitalised after developing multiple organ failure. Many clinical trials are now conducted in India, where, according to India's Tribune newspaper, at least 1725 people died in drug trials between 2007 and 2011. Clearly, there is an urgent need for better methods to predict the safety of medicines for patients as well as volunteers in clinical trials.

At the patient safety charity, Safer Medicines, we believe this goal is most likely to be achieved through a greatly increased focus on human, rather than animal, biology in preclinical drugs tests. New tests based on human biology can predict many adverse reactions that animal tests fail to do, and could, for example, have detected the risk signals produced by Vioxx, which in animal studies appeared to be safe, and even beneficial to the heart.

These techniques include: human tissue created by reprogramming cells from people with the relevant disease (dubbed "patient in a dish"); "body on a chip" devices, where human tissue samples on a silicon chip are linked by a circulating blood substitute; many computer modelling approaches, such as virtual organs, virtual patients and virtual clinical trials; and microdosing studies, where tiny doses of drugs given to volunteers allow scientists to study their metabolism in humans, safely and with unsurpassed accuracy. Then there are the more humble but no less valuable studies in ethically donated "waste" tissue.

These innovations promise precious insights into the functioning of the integrated human system. Many are already commercially available, but they are not being embraced with the enthusiasm they merit.

Pharmaceutical companies would make much greater use of them if governments encouraged it, but inflexible requirements for animal tests is a major deterrent. Ever since the thalidomide birth-defects tragedy, animal testing has been enshrined in law worldwide, despite the irony that more animal testing would not have prevented the release of thalidomide, because the drug harms very few species.

So how well have animal tests protected us? Many studies have calculated the ability of animal tests to predict adverse reactions to be at or below 50 per cent. In 2008, a study in Theriogenology (vol 69, p 2) concluded: "On average, the extrapolated results from studies using tens of millions of animals fail to accurately predict human responses." And a recent study in Regulatory Toxicology and Pharmacology (vol 64, p 345) shows that animal tests missed 81 per cent of the serious side effects of 43 drugs that went on to harm patients.

It is hard to understand why governments defend a system with such a poor record, or why they are dismissive of new technologies that promise increased patient safety while decreasing the time and cost of drug development, not to mention the savings to healthcare systems from fewer adverse drug reactions. Proposals to compare human-based tests with animal-based approaches have been strongly supported by members of the UK parliament. The Early Day Motions they signed were among the most-signed of all parliamentary motions between 2005 and 2006, 2008 and 2009, and 2010 and 2012.

Safer Medicines has put these concerns to the UK Department of Health and the prime minister - to be told that "human biology-based tests are not better able to predict adverse drug reactions in humans than animal tests".

It is a tragedy that so many suffer or die through the use of inadequately tested drugs when tests based on human biology are readily available. Yet governments continue to mandate animal tests, despite the lack of a formal demonstration of fitness for purpose, and a growing global realisation among scientists that animal toxicity tests are inadequate and must be replaced.

In its 2007 report, Toxicity Testing in the 21st Century: A Vision and a Strategy, the US National Research Council called for the replacement of animal tests: "The vision for toxicity testing in the 21st century articulated here represents a paradigm shift from the use of experimental animals... toward the use of more efficient in vitro tests and computational techniques." To its credit, the US government is at least working on initiatives to hasten this. The UK government, however, still denies there is a problem. How many must die before it listens?

Kathy Archibald is director of the Safer Medicines Trust. She is a geneticist who worked in the pharmaceutical industry.

Robert Coleman is a pharmacologist with pharmaceutical industry experience. He is now a drug discovery consultant and adviser to the trust

If you would like to reuse any content from New Scientist, either in print or online, please contact the syndication department first for permission. New Scientist does not own rights to photos, but there are a variety of licensing options available for use of articles and graphics we own the copyright to.

All comments should respect the New Scientist House Rules. If you think a particular comment breaks these rules then please use the "Report" link in that comment to report it to us.

If you are having a technical problem posting a comment, please contact technical support.

Read More..

Myanmar courts wary investors on port project

YANGON: Myanmar is seeking to drum up investment in a stalled multi-billion-dollar sea port project at the heart of the former junta-ruled country's efforts to revive its impoverished economy.

Thai Prime Minister Yingluck Shinawatra and a host of Thai business leaders flew to Dawei on Myanmar's southern Andaman coast for talks with President Thein Sein and other officials about the joint development.

In July the two countries signed a memorandum of understanding to create a special economic zone for Dawei, with Bangkok agreeing to provide assistance in areas including security, infrastructure and logistics.

The huge project -- led by Thai industrial giant Ital-Thai -- would bring foreign investment for Myanmar as it emerges from decades of military rule, and provide Thailand with a gateway to the Indian Ocean and Western markets.

But it has faced funding difficulties and resistance from local villagers.

"Thai investors are afraid and hesitating about Myanmar's political policies and the funding," Ital-Thai marketing manager Pravee Komolkanchana told AFP in Bangkok ahead of the visit.

"Thai banks are less likely to lend money if it is to invest in other countries, especially in Myanmar."

He said a number of Japanese investors were also due to join the trip, which the company hopes will put the project back on track.

Potential Myanmar investors are also wary, according to a businessman in Yangon who did not want to be named.

"We dare not invest there because of the costs," he said. "We would have to pay Thai salary rates."

"The project won't benefit Myanmar much but mainly Thailand," he added.

Work has yet to progress far beyond the construction of new homes for the thousands of villagers due to be resettled.

Next year the developers hope to begin work on infrastructure and factories in a planned industrial zone.

Opponents to the plan were emboldened by Thein Sein's decision last year to suspend construction of a $3.6 billion Chinese-backed hydropower project in the northern state of Kachin in a rare response to public outcry.

But local resistance to Dawei appears to have eased, although some villagers are still reluctant to move despite the offer of new homes.

"We understand that we cannot stop the whole project," said a local environmental activist who did not want to be named, adding that campaigners had instead vowed to oppose any coal-fired plant or chemical factory.

- AFP/ck

Read More..

Suspected security hole found in many Samsung devices

Samsung's Galaxy Note 2.

(Credit:
Josh Miller/CNET)

A suspected security hole affecting a handful of Samsung smartphones could give apps access to user data and leave the handset vulnerable to malicious apps and bricking, according to a developer.

The vulnerability, which was discovered and detailed by an XDA member with the handle "alephzain," lies in Exynos 4, the ARM-based system-on-chip typically found in Samsung smartphones and
tablets. Alephzain developed an exploit he said bypasses the system permissions, allowing any app to extract data from the device's RAM or inject malicious code into the kernel.

Alephzain said that he stumbled upon the vulnerability while trying to find a new way to root his Galaxy S3, but that the exploit affects the Galaxy S2,
Galaxy Note, and Meizu MX as well. However, the
Nexus 10 is unaffected as it uses the Exynos 5 chip.

"The good news is we can easily obtain root on these devices and the bad is there is no control over it," alephzain writes.

CNET has contacted Samsung for comment for comment and will update this report when we learn more.

Read More..

Space Pictures This Week: Frosty Mars, Mini Nile, More

Photograph by Mike Theiss, National Geographic

The aurora borealis, also known as the northern lights, illuminates the Arctic sky in a recent picture by National Geographic photographer Mike Theiss.

A storm chaser by trade, Theiss is in the Arctic Circle on an expedition to photograph auroras, which result from collisions between charged particles released from the sun's atmosphere and gaseous particles in Earth's atmosphere.

After one particularly amazing show, he wrote on YouTube, "The lights were dancing, rolling, and twisting, and at times looked like they were close enough to touch!" (Watch his time-lapse video of the northern lights.)

Published December 14, 2012

Read More..

Obama: Nation Faces 'Hard Questions' After Shooting

President Barack Obama said at an interfaith prayer service in this mourning community this evening that the country is "left with some hard questions" if it is to curb a rising trend in gun violence, such as the shooting spree Friday at Newtown's Sandy Hook Elementary School.

After consoling victims' families in classrooms at Newtown High School, the president said he would do everything in his power to "engage" a dialogue with Americans, including law enforcement and mental health professionals, because "we can't tolerate this anymore. These tragedies must end. And to end them we must change."

Mandel Ngan/AFP/Getty Images

President Obama: 'Newtown You Are Not Alone' Watch Video

Sandy Hook Elementary Shooting: Remembering the Victims Watch Video

The president was not specific about what he thought would be necessary and did not even use the word "gun" in his remarks, but his speech was widely perceived as prelude to a call for more regulations and restrictions on the availability of firearms.

The grieving small town hosted the memorial service this evening as the the nation pieces together the circumstances that led to a gunman taking 26 lives Friday at the community's Sandy Hook Elementary School, most first graders.

"Someone once described the joy and anxiety of parenthood as the equivalent of having your heart outside your body all of the time, walking around," he said, speaking of the joys and fears of raising children.

"So it comes as a shock at a certain point when you realize no matter how much you love these kids you can't do it by yourself," he continued. "That this job of protecting kids and teaching them well is something we can only do together, with the help of friends and neighbors, with the help of a community, and the help of a nation."

CLICK HERE for Full Coverage of the Tragedy at Sandy Hook

Read More..

Zebrafish made to grow pre-hands instead of fins

PERHAPS the little fish embryo shown here is dancing a jig because it has just discovered that it has legs instead of fins. Fossils show that limbs evolved from fins, but a new study shows how it may have happened, live in the lab.

Fernando Casares of the Spanish National Research Council and his colleagues injected zebrafish with the hoxd13 gene from a mouse. The protein that the gene codes for controls the development of autopods, a precursor to hands, feet and paws.

Zebrafish naturally carry hoxd13 but produce less of the protein than tetrapods - all four-limbed vertebrates and birds - do. Casares and his colleagues hoped that by injecting extra copies of the gene into the zebrafish embryos, some of their cells would make more of the protein.

One full day later, all of those fish whose cells had taken up the gene began to develop autopods instead of fins. They carried on growing for four days but then died (Cell, DOI: 10.1016/j.devcel.2012.10.015).

"Of course, we haven't been able to grow hands," says Casares. He speculates that hundreds of millions of years ago, the ancestors of tetrapods began expressing more hoxd13 for some reason and that this could have allowed them to evolve autopods.

If you would like to reuse any content from New Scientist, either in print or online, please contact the syndication department first for permission. New Scientist does not own rights to photos, but there are a variety of licensing options available for use of articles and graphics we own the copyright to.

All comments should respect the New Scientist House Rules. If you think a particular comment breaks these rules then please use the "Report" link in that comment to report it to us.

If you are having a technical problem posting a comment, please contact technical support.

Read More..

N Korea marks first anniversary of late ruler's death

SEOUL: North Korean leader Kim Jong-Un led thousands of officials on Sunday in a memorial ceremony for his late father and ex-ruler Kim Jong-Il, days after a successful long-range rocket launch.

The ceremony followed a mass rally two days earlier hailing the launch of the three-stage rocket, a move which was condemned by the UN Security Council and seen by many countries as a disguised ballistic missile test.

Kim Jong-Il, who ruled the communist state for 17 years, died of a heart attack on December 17 last year.

His youngest son Jong-Un immediately took over, the second dynastic succession by the Kim dynasty which has ruled the isolated country for more than six decades with an iron fist and a pervasive personality cult.

Officials in black suits and uniformed military leaders convened in a cavernous stadium in the capital Pyongyang Sunday morning for the hour-long memorial event, which was televised live on state TV.

Jong-Un, stone-faced and clad in a black suit, sat on stage with dozens of other top officials against the backdrop of a giant red flag featuring a large portrait of a smiling Kim Jong-Il.

"The heart of the great leader stopped beating but Comrade Kim Jong-Il lives with us forever... to give blessings for the bright future of our people," the ceremonial head of state Kim Yong-Nam said in a speech.

"The successful launch of our Kwangmyongsong-2 satellite is also another victory achieved by our military and people, by faithfully following the teachings of the great leader (Kim Jong-Il)," he said.

It was unclear what memorial events were scheduled on Monday, the anniversary day.

The North said the apparently successful launch -- its second after a much-heralded but botched mission in April -- was a scientific project to put a weather satellite into orbit.

But the United States and other nations viewed it as a disguised ballistic missile test banned under UN resolutions triggered by its past nuclear tests in 2006 and 2009.

The Security Council Wednesday condemned the launch and said members "will continue consultations on an appropriate response".

The impoverished but nuclear-armed nation apparently timed the launch to mark the death anniversary and to drum up more support for the young and inexperienced Jong-Un.

Choe Ryong-Hae, the head of the political bureau at the North's military, vowed to "hit back immediately" if rival South Korea or the United States provokes the nation, and reaffirmed loyalty to the young leader.

"Our whole army stands ready for battle under the teachings of Kim Jong-Un while the US and South's enemy forces are going amok to destroy our system," he said in a speech.

"It is our firm determination to hit back immediately at provocations...and we solemnly pledge again to faithfully serve our dear supreme commander (Jong-Un)," Choe said to big applause from the crowd.

Mass rallies are being staged nationwide to celebrate the rocket launch, the ruling party newspaper Rodong Sinmun said on Sunday.

Officials, students, workers and soldiers in three northern provinces rallied Saturday to give speeches and sing songs in memory of the late ruler and to praise his son for leading the successful launch, it said.

- AFP/xq

Read More..

Google will alter search to end FTC antitrust inquiry, says report

The Federal Trade Commission may bring its two-year antitrust investigation of Google to a close by allowing the company to make voluntary changes to its search business, according to a report.

The search giant is said to be readying an announcement about changes to its use of "snippets," bits of text culled from sites such as Yelp and TripAdvisor and displayed in search results, Politico reports, citing unnamed sources. Yelp and others had charged Google with using their content without permission.

Google will also makes tweaks that will allow for easier porting of search-ad campaigns from Google to rival search services, Politico's sources said.

Politico suggested on Tuesday that the FTC may leave the search-related case to the European Commission, which has mounted an investigation of its own. Reuters reported on Tuesday that some Google competitors, sensing a possible defeat, are taking the case to the Justice Department.

Google and the FTC also look to be close to a settlement in a case involving so-called frand -- or standard essential -- patents owned by Google.

Politico said the FTC declined to comment on today's report about the search tweaks, and it said Google would provide only the following statement: "We continue to work cooperatively with the Federal Trade Commission and are happy to answer any questions they may have."

Read More..

Space Pictures This Week: Frosty Mars, Mini Nile, More

Photograph by Mike Theiss, National Geographic

The aurora borealis, also known as the northern lights, illuminates the Arctic sky in a recent picture by National Geographic photographer Mike Theiss.

A storm chaser by trade, Theiss is in the Arctic Circle on an expedition to photograph auroras, which result from collisions between charged particles released from the sun's atmosphere and gaseous particles in Earth's atmosphere.

After one particularly amazing show, he wrote on YouTube, "The lights were dancing, rolling, and twisting, and at times looked like they were close enough to touch!" (Watch his time-lapse video of the northern lights.)

Published December 14, 2012

Read More..

Conn. Victim's Father Remembers 'Loving' Daughter

(Image credit: Emilie Parker Fund/Facebook)

Emilie Parker, the little girl with the blond hair and bright blue eyes, would have been one of the first to comfort her classmates at Sandy Hook Elementary School, had a gunman’s bullets not claimed her life, her father said.

“My daughter Emilie would be one of the first ones to be standing and giving support to all the victims because that’s the kind of kid she is,” her father, Robbie Parker said as he fought back tears, telling the world about his “bright, creative and loving” daughter who was one of the 20 young victims in the Newtown, Conn., shooting.

“She always had something kind to say about anybody,” her father said.  ”We find comfort reflecting on the incredible person Emilie was and how many lives she was able to touch.”

Emilie, 6, was helping teach her younger sisters to read and make things, and she was the little girls would go to for comfort, he said.

“They looked up to her,” Parker said.

READ: Complete List of Sandy Hook Victims

Parker moved his wife and three daughters to Newtown eight months ago after accepting a job as  a physician’s assistant at Danbury Hospital. He said Emilie, his oldest daughter, seemed to have adjusted well to her new school, and he was very happy with the school, too.

“I love the people at the school. I love Emilie’s teacher and the classmates we were able to get to know,” he said.

      (Image Credit: Alex von Kleydorff/AP Photo)

The family dealt with another tragic loss in October when Emilie lost her grandfather in an accident.

“[This] has been a topic that has been discussed in our family in the past couple of  months,” Parker said. “[My daughters ages 3 and 4] seem to get the idea that there’s somebody who they will miss very much.”

Emilie, a budding artist who carried her markers and pencils everywhere, paid tribute to her grandfather by slipping a special card she had drawn into his casket, Parker said.  It was something she frequently did to lift the spirits of others.

“I can’t count the number of times Emilie would find someone feeling sad or frustrated and would make people a card,” Parker said. “She was an exceptional artist.”

The girl who was remembered as “always willing to try new things, other than food” was learning Portuguese from her father, who speaks the language.

(Image Credit: Emilie Parker Fund/Facebook)

On Friday morning, Emilie woke up before her father left for his job and exchanged a few sentences with him in the language.

“She told me good morning and asked how I was doing,” Parker said. “She said she loved me, I gave her a kiss and I was out the door.”

Parker found out about the shooting while on lockdown in Danbury Hospital and found a television for the latest news.

“I didn’t think it was that big of deal at first,” he said. “With the first reports coming in, it didn’t sound like it was going to be as tragic as it was. That’s kind of what it was like for us.”

CLICK HERE for full coverage of the Sandy Hook shooting.

Parker said he knows that God can’t take away free will and would have been unable to stop the Sandy Hook shooting. While gunman Adam Lanza used his free agency to take innocent lives, Parker said he plans to use his in a positive way.

“I’m not mad because I have my  [free] agency to use this event to do whatever I can to make sure my family and my wife and my daughters are taken care [of],” he said. “And if there’s anything I can do to help to anyone at any time at anywhere, I’m free to do that.”

(Image credit: Emilie Parker Fund/Facebook)

Friday night, hours after he learned of his daughter’s death, Parker said he spoke at his church.

“I don’t know how to get through something like this. My wife and I don’t understand how to process all of this,” he said today. “We find strength in our religion and in our faith and in our family. ”

“It’s a horrific tragedy and I want everyone to know our hearts and prayers go out to them. This includes the family of the shooter. I can’t imagine how hard this experience must be for you and I want you to know our family … love and support goes out to you as well.”

Read More..