Health Meaning

Although the 2015 agreement reached massive spending by Congress last night gives the National Institutes of Health (NIH) a flat budget, it contains modest increases for some programs within the agency. A companion report also contains a number of directives that the defenders of biomedical research are eyeing with suspicion.

The increase of $ 150 million, only 0.5% boost to $ 29.9 billion it received last year, still leaves NIH below its level of the budget in 2012, before the sequestration took a mouthful of 5%, noted defenders of biomedical research. It is far from an increase of $ 606 million a subcommittee of the Senate had approved expenditure and lower than the request of the White House for $ 211 million. "We appreciate any increase, but it is not doing the job. We are going backwards, "says Jennifer Zeitzer, deputy director of the Federation of American Societies for Experimental Biology Public Affairs office in Bethesda, Maryland.

The bill singles out some areas for larger increases. The National Institute on Aging gets an increase of $ 28.6 million, or an increase of 2.4% to $ 1.2 billion. "[A] substantial portion" of the new money should go to Alzheimer's disease based on the quality of grant proposals, said a report accompanying the bill. Some institutes also received a boost through an increase of $ 25 million for the BRAIN initiative of the Obama administration, which receives a total of $ 65 million.

The $ 12.6 million project also tags law for a new pediatric research initiative that Congress created earlier this year by passing the law on research Gabriella Miller Kids first. The program is supposed to be funded by a check-off box on tax returns that finance political conventions. But apparently, the Congress decided to get started by including the money in the budget of the NIH, said David Moore, director of government relations at the Association of American Medical Colleges in Washington, DC

in addition, the bill provides $ 238 million NIH to research and Ebola vaccine development as part of a $ 5.2 billion emergency bill across government for Ebola.

a recent concern about the NIH budget every year money is skimmed off for other Department of Health and Human Services (HHS) agencies-is addressed in the bill. He said the $ 700 million that the NIH is set to contribute to "exploit" this year will come back as $ 715 million for the agency. (After this accounting maneuver, NIH always receives only a total of $ 150 million more than last year, however.) Other HHS agencies that have already received part of their budgets to this faucet will instead get direct credits Moore notes.

The report also directs NIH to pay more attention to the age at which new NIH researchers receive their first research grant, now 42 on average. NIH "is directed to develop a new approach to taking action to reduce" this age. The language echoes a controversial proposal by the Representative Andy Harris (R-MD), a member of the Appropriations Committee of the House of Representatives that would require NIH to lower the age of the first R01 4 years within a decade, but not this specific objective.

lawmakers also are a constant concern: the amount of NIH dedicated to specific diseases ignores the burden that the disease creates or mortality rates. The report "urges NIH to ensure that research funds are invested in areas where American lives can be improved." It also indicates NIH "to prioritize federal funding for medical research on awareness and education," apparently a reference to a subsidy for a nutrition video game that Harris criticized as less important than the search for disease .

biomedical attorneys generally feel NIH should establish research priorities based on the quality of research proposals, not the burden of the disease or other criteria set by Congress. well that they worry about the aging of new researchers, they have reservations about Harris solutions. "what we see here is the committee expressing some concerns and set expectations," says Moore. "It is not certain that the next steps will be, but it is something that we will watch very closely"

More details.

• Complementary Medicine Institute NIH will receive a new name. Now called the National complementary and alternative medicine Centre, the bill replaces the last two words with "Integrative Health." the report says this is because interventions such as food supplements and therapy of spinal manipulation are now so widely used, they are not alternatives but are part of medical care.

• the report advises NIH to follow a report medicine Institute this past June recommend changes to the design and management of the national study of Special Education (NCS), a plan to track the health of 100,000 babies to adulthood. But the bill also says that 165 million $ allocated this year for the study could be spent on "research related to the goals and mission of the study" the NIH institutes.

The fate of the NCS will likely be decided later this week at a meeting of the Advisory Committee of the NIH director, in which a working group will recommend whether to launch the full study.

to see all our stories on the 2015 budget, click here

* Update, December 11, 10:42 :. increased $ 25 million in the Initiative BRAIN was added to this article.

Testosterone can be the key to manhood, but it also stirs the growth of cancer cells in the prostate . So, injections of the hormone may seem like the last thing a man with such needs in cancer. But a new study shows that the shots can slow the progression of tumors untreatable prostate in some patients.

Researchers have known since the 1940s that reducing the levels of testosterone and other male sex hormones may curb prostate tumors. Today, a common treatment for prostate cancers that have spread to other parts of the body is chemical castration, drugs that reduce the body's production of testosterone and related hormones. But cancer cells generally adapt to low hormone levels and resume growth. For example, they sometimes handle more receptor molecules stimulated by testosterone or upgrade to a version of the receptor that does not need testosterone to encourage growth. Although researchers have developed new treatments to counter this resistance, such as drugs that block the receptor for testosterone, tumors often develop resistance quickly too.

The studies of cancer cells in a dish and tumors in animals have revealed a paradox of the so-called prostate cancer resistant to castration. Cancer cells that thrive when testosterone is rarely often die when exposed to high levels of the hormone. The experiments suggest that additional hormone disrupts DNA replication and results in fractures of the DNA, which can be fatal to a cell. This paradoxical relationship means that doses of testosterone may be beneficial against resistant tumors.

medical oncologist Michael Schweizer, now at the University of Washington, Seattle, and colleagues at the Johns Hopkins University School of Medicine in Baltimore, Maryland, tested this strategy in 16 men whose prostate cancers had become resistant to chemical castration. Most of their tumors had spread, or metastasized. In the study, the men continued to receive treatment for chemical castration, but every 28 days, the researchers also have their testosterone injection. Each sharp shooting blood testosterone levels well above normal, but gradually declined until they were close to the level produced by chemical castration. The justification for these oscillations, Schweizer says, is that "you do not let the cancer cells of the prostate to get used to a testosterone environment." The peaks of hormones will kill cancer cells that have adapted to low testosterone, while the valleys will smother the cells that need testosterone to grow.

to assess the progress made by the subjects, the researchers measured the amounts of specific antigen prostate (PSA) in the blood, an indicator of the growth of prostate cancer. Two patients left the study after the first round of treatment because of side effects. In seven of the remaining subjects, PSA levels increased during the first three cycles of treatment, suggesting that they do not receive the injections. But PSA levels dipped in seven others, a sign that their tumors may be decreasing. "The fact that half the guys who got through three cycles [of treatment] showed a response is encouraging," said Schweizer.

He and his colleagues performed CT scans on 10 patients to check the size of their metastasis, or tumor colonies generated by the initial growth. in four patients, metastases had decreased, and in one patient, they had disappeared, reports the online team today Science Translational Medicine . the five men were in the group that showed PSA decreases.

over time, however, the benefits of testosterone injections decreased. PSA levels started to increase after about 7 months, suggesting renewed growth in tumors. But even a short-term response could prolong patients' lives, because prostate cancer resistant to chemical castration is usually incurable, Schweizer notes. Although some previous studies have attempted to assess the effects on prostate cancer to boost testosterone levels, they do not provide the high doses of hormone required to kill resistant cancer cells, he said. Thus, the new work "is a first step towards finding out who will benefit from this treatment."

For patients who remained in the study, treatment side effects included nausea and hair loss, and the two subjects developed blood clots in the lungs. Of the two people who left the test early, we fell ill with pneumonia and died of sepsis, inflammation of body-wide infections that often results. This is not a typical consequence of testosterone therapy, Schweizer said, so the researchers believe it was caused by a chemotherapy drug that the patients also took over part of the study.

Some researchers and doctors feared that the testosterone treatment may accelerate tumor growth, says Charles Ryan, cancer endocrinology researcher and physician at the University of California, San Francisco, who has not participated. But the study shows that "there is potentially a large number of patients for whom this treatment is not harmful, but may be beneficial." However, he is not ready to change the way it treats cancer patients prostate until researchers conduct studies that confirm the effects of testosterone and clarify the risks of treatment.

"They intriguing clinical data," says medical oncologist and cancer researcher prostate Christopher Logothetis from the University of Texas MD Anderson cancer Center in Houston, who also was not connected to the study. But he was disappointed that the team did not test the biopsy samples of subjects to determine how testosterone influenced tumors. This analysis is essential for researchers to understand how to predict which patients will benefit from treatment and which might be harmed, he said.

Two other studies of testosterone therapy in patients with prostate cancer resistant to castration began, Schweizer notes, so that researchers may soon have a better idea of ​​whether the treatment is superior to current approaches.

Call it a quirk or scientific medical miracle. A girl who grew up with a serious genetic immune disease was apparently healed in her 30s by one of its chromosomes breaking apart and reassembling. Scientists traced the improvement of woman removing a deleterious gene by the interference of DNA in one of its cells-a phenomenon recently identified strains of blood that until now had only been linked to cancer .

The woman, who lives in Cincinnati, Ohio, suffered from recurrent bacterial infections as a child. At the time, the doctors found that she had an abnormally low level of white blood cells needed to fight against invading microbes. 9 years of the disease, described in two reports in 1964 The New England Journal of Medicine , was the first known case of what is now called WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome. In this extremely rare disease only about 60 cases are known around the world-patients live into adulthood, but they can develop lung damage, hearing loss, and other health problems frequent infections. Those WHIM are also very sensitive to the human papillomavirus, which causes warts on the skin and genital areas that sometimes become cancerous.

In 03, researchers WHIM linked to a gene called CXCR4 , which encodes a cell surface protein that immune cells use to recognize chemical messengers called chemokines. In WHIM, patients have a normal copy CXCR4 and a defective copy that causes the receptor to be overactive he does not cut when it is supposed to. This causes a sort of white blood cells to "get stuck" in the bone marrow instead of entering the bloodstream, said Philip Murphy, an immunologist at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.

Murphy and his colleagues studied the WHIM patients at the National Institutes of Health (NIH) Health Clinical Center to better understand the disease and develop a possible treatment with a drug that inhibits CXCR4 . There are two years, they heard a woman who said she wanted to bring in his two daughters for evaluation because they had inherited the disease.

"Very interesting," says clinical geneticist George Diaz of Medicine Mount Sinai Icahn School in New York, who identified CXCR4 mutations as the cause of WHIM. He said the restoration of the woman reminds him of the history of the Berlin patient, an HIV-positive man who developed leukemia and became virus after receiving a bone marrow transplant from a donor lacks a chemokine receptor that HIV needs to enter cells. Improving engraftment in mice lacking a copy of CXCR4 , Diaz added, "certainly could have clinical applications downstream."

The World Health Organization (WHO) has approved the first rapid diagnostic test for Ebola. The test does not need electricity, only requires a few drops of blood from a finger prick, and can return results in 15 minutes. It will be a great help to health workers in remote areas.

tests based on the current PCR require a blood sample taken by the needle, the safe transport of blood to a well equipped laboratory with trained staff, and at least several hours to return results. Depending how far a suspect from a testing laboratory, it can take more than a day to receive the test results.

The new test, produced by Corgenix, a company in Broomfield, Colorado, uses antibodies to identify a specific protein of the Ebola virus. The list price will be about $ 15 per test, said Robert Garry, an expert haemorrhagic disease at Tulane University in New Orleans, Louisiana, who helped develop the test. But reductions are available, he said, for bulk purchases and suppliers for use in Africa.

In its announcement, the WHO declared that the test correctly identified 92% of people infected and 85% of those not infected. The test will be supported by PCR tests, Garry agrees. "A quick test is always going to be tested," he said. "And no diagnosis can replace the judgment of a health professional."

The number of Ebola cases has declined since the peak of the epidemic in September and October. But in Guinea and Sierra Leone, dozens of new cases continue to appear each week, many of which are unrelated to known chains of transmission. The rapid test will be useful for quickly identifying new hot spots, said Garry

* Ebola files :. Given the current Ebola outbreak unprecedented in terms of the number of people killed and the rapid geographic spread, science and Science Translational Medicine made a collection of research articles and news on the viral disease available for researchers and the general public.

There was a baffling case. The 2.5-year-old French girl was in good health, but in 2011, she was hospitalized because she had trouble breathing. After testing for a variety of bacterial and viral infections, her doctors diagnosed his illness as severe flu and began to deal with the drug Tamiflu. The girl lived, but she spent 20 days in hospital, some of that time on a ventilator to help him breathe.

Now, researchers have understood why the girl almost died of a disease that many of us get -and-survive each year. They identified a mutated gene that crippled its defenses against the flu virus. The study suggests that defective genes could explain other cases of fatal influenza.

You might think that your last fight flu was bad, but if it did not you land at the hospital, the doctors do not consider "severe." The number of people who come down with severe flu each year depends on the strain of flu virus that is in circulation, but young children and the elderly are usually the most susceptible. "These people would have died before the age of intensive care," the doctor Jean-Laurent Casanova at Rockefeller University in New York City. Although doctors have improved to save people with severe flu, researchers have not understood why most of them have become so bad in the first place.

In previous studies, Casanova and his colleagues discovered a number of mutations that alter the immune system's ability to fight certain infections, such as herpes encephalitis, a type of brain inflammation. To determine if the girl made all the mutations that could explain his illness, the researchers sequenced the part of his DNA that code for proteins. They found that the two copies of IRF7 girl gene were mutated. His mother and father carried different mutations in this gene. However, both parents also had a normal copy of IRF7 , so they were healthy. Because the girl inherited a defective version of the gene from each parent, she had no normal copy.

IRF7 is one of our immune system control switches. When viruses infect our cells, it cranks genes that code for antiviral proteins known as type III interferons name I and type. But the versions of IRF7 realized that the girl did not do their work, the researchers determined mutated. For example, the team tested the dendritic cells of the girl, usually a major source type I interferons and III. In response to the flu virus, activity type III type I interferon genes and abnormally low in the patient's dendritic cells, reports the online team today Science . The researchers also measured the production of type I interferon dendritic cells: α2 interferon. Its dendritic cells fact none of this antiviral protein.

Casanova and his colleagues also wanted to test how mutations of cells that are attacked by the virus affected. Influenza viruses invade the cells lining the lungs, but obtaining these patient cells is difficult. So the researchers translated some of the cells of the daughter of the skin stem cells, then coaxed to specialize in lung cells. Following exposure of these cells and the people of control healthy cells with influenza viruses, researchers were then tested for a viral protein. Compared to control cells, about twice as many lung cells were infected by the virus.

"severe influenza is not just a viral disease, there is also a genetic disease," says Casanova. The researchers identified mutations are extremely rare, so they probably are not many cases severe influenza among children. But researchers are looking for different mutations in IRF7 and other genes related immune system that children also lower defenses. He added that the results suggest the treatment children who have severe flu with interferon-α.

"It is a very elegant study," says immunologist Paul Thomas research Hospital St. Jude children in Memphis, Tennessee. " they show only one mutated gene can control the sensitivity "on severe influenza. Viral immunologist Jacco Boon of the University of Washington in St. Louis agrees." It is an excellent paper for the field "and provides "very convincing evidence" that these mutations have left the girl vulnerable to disease, he said.

The researchers studied patient is now almost 7, and n 't had another episode of severe influenza, with annual shots of the flu. But his good health poses a mystery. IRF7 offers protection against other viruses and the mice lacking the gene quickly succumb to viral infections. However, the girl did not become seriously ill. "The sensitivity to flu and not these other viruses is fascinating," said Boon. Casanova suggests that other genes could intervene to IRF7 to control these infections.

This week, officials of the US Food and Drug Administration (FDA) has taken a 15-hour incursion far outside current scientific . At a hearing of two days, the agency invited public comments on how it should regulate, a traditional healing practice homeopathy has been challenged by many scientific studies. For now, homeopathic remedies, largely sold over the counter, are considered drugs that can be marketed without FDA approval in the United States. But the agency can be prepared to rethink its policy.

"We have had phenomenal growth in the market and also security and emerging quality," Cynthia Schnedar, director of the Office of Compliance in the FDA's Center for Drug Evaluation and Research (CDER ) in Silver Spring, Maryland, said science Insider. "in light of this, we thought it was time to take another look."

The 0-year practice of homeopathy, estimated to be a multi-billion the United States-is based on two controversial principles: first, a substance that causes a particular symptom a healthy person can relieve the same symptoms in a sick person if consumed at a very low dose. Second, the dilution several times a substance actually makes a more powerful treatment, although no detectable molecules of the original substance remains.

The 37 speakers at the FDA hearing ran the gamut of true believers to skeptics and supporters of both camps sometimes seem to speak different languages.

"By its own definition, homeopathy can not work," Michael De Dora, director of public policy at the nonprofit Center for Washington, the investigative branch, said the panel in its presentation Monday. Several major metastudies, including a recent analysis by the Medical Research Council of Australia National Health and concluded that homeopathic remedies are no more effective than placebo for the treatment of any condition. "We should not spend much time on it," Dora said, "that the federal government is well aware of the scientific evidence against homeopathy."

But other doctors stakeholders and industry representatives he spent much of their time touting the value of medical treatments. And during the question period of 5 minutes after each presentation, the FDA panelists gently squeezed some of the speakers on their testimony.

"You strike me as someone who uses a lot of tools," Robert Nelson, deputy director of the Office of the FDA Pediatric Therapeutics in Silver Spring, Maryland, said Amy Rothenberg naturopathic physician before ask how she could be sure that his patients benefited from homeopathy alone. Rothenberg said she prescribes exclusively homeopathic treatments to about half of his patients, although some receive other forms of treatment other doctors.

Elaine Lippmann, the regulatory lawyer in CDER's Office of Regulatory Policy, asked the same question to several participants: "What about the scientific method to demonstrate the safety and effectiveness that our approval process that is inconsistent with homeopathy "

" it is like comparing apples and eggs, "said the homeopathic doctor Karl Robinson Houston, Texas. "Homeopathy is a science of observation," he said. Five patients with the same diagnosis official could receive five different treatments according to their mental, emotional and physical complexes. "It's a different paradigm, that's all."

The careful questioning tone reflects the unusual status FDA granted homeopathy. Since 1938, the agency has identified homeopathic products as drugs, partly thanks to US Senator and doctor Copeland Royal homeopath, who co-wrote the Federal Food, Drug and Cosmetic Act. since then, the FDA is based on a document known as the homeopathic pharmacopoeia name of the United States to determine what counts as a homeopathic drug. This list of substances now-1295 long articles is maintained by an independent industry body, the Convention Homeopathic Pharmacopoeia of the United States . the substances may be added to the list after they have had success "prove" to homeopaths trained, which determine how they affect the healthy subjects at various concentrations.

under FDA guidelines issued in 1988, a company can sell homeopathic products on the counter without demonstrating their safety and effectiveness, and unlike dietary supplements, packaging may include claims on the treatment of specific conditions, as long as they are "self-limitation" and not chronic. These conditions include sprains, colds or allergies.

But the FDA not ensure the quality and manufacture of homeopathic products, and recently raised several red flags. In 09 he issued a warning letter to Matrixx Initiatives when have been linked to a loss of smell among users high levels of zinc in several of its remedies against the Zicam cold. In 2010, he warned that homeopathic teething tablets produced by homeopathic Hyland contain potentially dangerous levels of toxic Solanaceae plant. And last month, he advised consumers not to rely on a variety of over-the-counter homeopathic remedies to control asthma attacks. FDA issued 40 warning letters to homeopathic product manufacturers since 09-up of nine letters between 02 and 08.

At the hearing, the agency requested data that would further assess risks and benefits of the products already on the market. Toxicologist Edward Krenzelok the Rocky Mountain Poison and Drug Center in Denver said that nearly 80,000 calls related to homeopathic regional poison control centers from 06 to 2013, 98% of callers reported no effect or side effects of the exposure. Most children-92% of calls -involved under 6.

This relatively clean safety record has been a starting point for many supporters of homeopathy talking. Pediatrician Robert Dumont Raby Institute for Integrative Medicine in Chicago, Illinois, who praised homeopathic remedies as "exceptionally versatile in many medical problems," assured the panel that he did not care about negative interactions with other drugs, because concentrations it generally recommends, "there is nothing in there to interact."

But others have argued that the real risk to public health emerge when consumers uninformed decide to use homeopathic remedies instead of proven medical treatments. Janine Jagger, a professor of medicine at the University of Virginia in Charlottesville and president of Familial Mediterranean Fever Foundation, described over-the-counter homeopathic remedies that list the same active ingredient as a prescription treatment for a rare genetic inflammatory disease. patients who believe that highly diluted substances is comparable to prescription medication may suffer serious harm, she said. "I need to explain more and more and more patients ... and there are cases that I will never have the chance to explain it," she said. "I would have with the FDA."

Just what kind of changes FDA would consider, if necessary, are not yet clear. Schnedar FDA is careful not to suggest that it plans to tighten regulations. "There is no preconceived options on the table," she said.

Several speakers made suggestions. Dora argued that the FDA should submit homeopathic products to the same process prior approval for marketing other drugs, a costly proposition for both regulators and manufacturers. others, including Adriane Fugh-Berman of Georgetown University in Washington, DC, suggested that FDA could at least clear product labels, for example, listing the concentrations of ingredients in milligrams rather than the number of times they were ritually diluted.

Fugh-Berman suspect that, after decades a policy essentially hands-off, the current popularity of homeopathic products can ultimately inspire FDA to draft new regulations. "There were several moments in history where people have simply ignored homeopathy because they thought he was dying, "she said," And it keeps coming.

The opium poppy may soon meet his first game. Researchers in the US and Canada report today they are closing in on a long-standing goal of engineering a complex set of genes in yeast that allow microbes to synthesize morphine, codeine and other drugs that have been harvested from the poppy since before recorded history began. The new work offers the prospect of being able to produce cheaply and easily widely used drugs with new features and fewer side effects. At the same time, political experts fear that new yeast strains could allow drug traffickers to convert sugar to morphine or heroin as easily as beer lovers create homebrew today.

"It really is the potential for screwing things," said Kenneth Oye, an expert from the biotechnology policy of the Massachusetts Institute of Technology in Cambridge. "If you get the built route for the synthesis of glucose pot to morphine, it's not controllable if it comes out. You better damn well get over it before it happens," said Oye which offers several ideas to increase surveillance of new biotechnology in a commentary published online today in Nature .

Morphine, heroin and other opiate poppy products are already causing a lot of havoc. Some 16 million people worldwide use illicit drugs. In the United States alone, nearly 14,000 people died from an overdose of heroin and other opioid analgesics between 2010 and 2012, according to data compiled from 28 states by the US Centers for Disease Control and prevention. Oye said the problem is that these numbers could skyrocket if the dealers and users can brew their own medicines.

Opiates are a class of compounds called alkaloids benzylisoquinoline (CADS), which together with the related families of molecules contains about 2,500 known compounds. In addition to morphine, these include thebaine, a precursor of the analgesic oxycodone and hydrocodone, and compounds commonly used antispasmodics, antibiotics and anticancer agents. BIA are multiringed complex structures that are difficult and expensive to synthesize in a laboratory. medicinal chemists have long sought a way easier and cheaper to prepare these compounds, in the hope that they might find new drugs. Health professionals have also sought versions that have fewer side effects, such as the risk of breathing and suppressed addiction that come with morphine. But until now, the engineering of opium poppy to produce new compounds proved difficult.

"Plants have slow growth cycles, so it is difficult to fully explore all possible chemicals that can be made from the BIA way," said William DeLoache, a bioengineering doctoral student the University of California, Berkeley, and lead author of the new work on the engineering yeast. "Moving the BIA way to microbes significantly reduces the cost of drug discovery. We can handle and adjust the yeast DNA and quickly test the results. "

a long way

efforts to insert the BIA way in yeast are ongoing for the better part of a decade . But it is a major challenge, said Vincent Martin, a microbiologist at Concordia University in Montreal, Canada, whose lab has worked on the project since 09. yeast engineered to produce morphine, Martin notes, requires the addition of genes to produce enzymes that carry a chain 15 distinct chemical transformations. However, one of the greatest successes of synthetic biology to-date synthesis of yeast antimalarial drug artemisinin necessary to give the genes perform only five chemical steps.

In reengineering yeast to SDAC, researchers generally divide the project into two parts. In the first part, the researchers splicing genes for enzymes that convert the amino acid tyrosine into an intermediate compound called S-reticulin; This step creates a key branch point that can lead to the synthesis of many different compounds BIA. A path leads to the morphine and codeine, while others lead to antibiotics and anticancer compounds. To create morphine, S-reticulin is first converted in a very closely related compound called R-reticulin, which is then converted in thebaine and ultimately to morphine.

Last year, researchers led by Christina Smolke, a synthetic biologist at Stanford University in Palo Alto, California, said they gave the yeast enzymes necessary for the implementation of thebaine to morphine steps at the end of the second part of the way. And last month, Martin and colleagues reported in PLOS ONE they had designed the yeast to complete all stages of the second half moving from R-reticulin morphine.

Meanwhile, the first part of the track was more difficult to remove in yeast. Tyrosine from glucose is easy: Yeast do this naturally. In 2011, Japanese researchers reported that they have obtained the first complete half way to work in Escherichia coli bacteria, transforming tyrosine S-reticulin. But so far that has established steps did not work well in yeast. The biggest obstacle was the first step: the conversion of tyrosine to a compound called L-Dopa. When the gene that directs this step is designed in yeast, bacterial enzyme works poorly at best, said Pamela Peralta-Yahya, a synthetic biologist at the Georgia Institute of Technology in Atlanta.

But John Dueber, a bioengineer at Berkeley; DeLoache; and colleagues took a break while working on a separate project to see if L-Dopa was present in some cells. The found that an enzyme called DOPA dioxygenase, converted into L-Dopa yellowish pigment. They quickly realized that they could use this enzyme as a color sensor for detecting whether another enzyme is capable of converting tyrosine to L-Dopa.

Then they teamed up with Martin and his colleagues Concordia. The group tested an enzyme from sugar beet called tyrosine hydroxylase. This beet enzyme is able to convert tyrosine to L-dopa in yeast, in the process turning the yellow Petri dish (see picture above), reports the team today Nature Chemical Biology . They were able to increase the production of L-Dopa nearly three times random mutation versions of the enzyme biosensor and using them to track those who have worked the best.

"It is nice work," said Smolke. For now, she added, the bacteria still produce higher yields of L-Dopa as yeast. "But he is preparing the ground to be able to integrate these channels in an organization," says Smolke.

For now, the stage is missing is being able to convert S-reticulin in R-reticulin, which connects the first and second halves of the full path. But apparently that's handy too. researchers at the University of Calgary have posted a summary of an online doctoral dissertation says that they have identified a plant enzyme that performs this S to R conversion, although the work has not been published yet. once it is, researchers will be able to insert the gene into yeast, filling the full path of morphine glucose. "I think it's doable in 2-3 years," said Dueber. "This area is moving much faster than we thought."

social and legal concerns

Given this speed, there is a year Dueber and Martin handed Oye, wondering if he would be willing to explore ideas how the scientific community can prevent Engineered yeast exacerbate the illegal drug trade. In their Nature comment, Oye and colleagues several recommendations. First, they suggest that businesses now that synthesize and distribute long stretches of DNA should consider carefully review applications for genes that code for key components drugmaking and block suspicious requests. These companies already undertake a process similar to the sequences of genes in microbes that could be used as biological weapons, and to report voluntarily requests of these genes to law enforcement agencies.

Other possible measures would compel researchers to design morphine producing yeast strains so they also produce unwanted toxins by homebrewers, or insert watermarks in genetic strains to make them more easy to follow if the strains fall into the hands of foreigners.

Although such measures may help deter criminals toxinmaking any watermarking or genes could also be removed by a trained and qualified microbiologist, Martin notes. Another option to slow the spread of the technology would be to request that newspapers do not provide all the genetic information of all organisms that can complement the complete transformation. (Dueber and Martin say that he has not received any request to omit data.)

At the end, a new technology for morphine production could have a profound impact on agencies Law application. But for now, agencies such as the FBI "did not recommend specific regulatory measures," said Edward You, supervisory special agent of the FBI biological weapons Countermeasures Unit of Mass Destruction Directorate in Washington, DC But he said the FBI is already part of an interagency working group, which includes representatives of the national Institutes of health and other research funding agencies, contemplating ways to keep the yeast strands modified on hands illicit drug manufacturers. And an ongoing commitment with scientists and policy analysts "will certainly facilitate these discussions," You said. "There is a window of opportunity here to negotiate security issues."

regulation play?

Yet some researchers fear that the hype around homebrewed heroin fears could cause harmful regulatory response. "I believe a thoughtful discussion of the risks, opportunities and regulatory requirements is important with this technology," says Smolke. However, she said she believes the comment Oye, for one, was "inflammatory." The new technology could in the long term, improvements on existing drugs trade led poppy and all the social ills it brings, she and others noted. laboratory-derived drugs, for example, might be easier for countries to regulate and reduce environmental damage, social unrest and violence associated with drugs derived from plants.

Smolke also notes that researchers are still a considerable distance to put together the complete chain of chemical transformations necessary for the yeast to make morphine. And if and when that happens, organizations will still be only infinitesimally small amounts of drugs. "In fact, it is more likely that a person can have easier access to morphine by dumping a lot of poppy seeds in their homebrew (or tea)," she said.

The question is how long this remains the case?