Feeds:
Posts
Comments

Posts Tagged ‘NIH’

Reporter: Aviva Lev-Ari, PhD,RN

 

Functional Genomics Screening Strategies: Part One

Utilizing RNA Interference (RNAi) Screens

to Explore Drug Targets and Cellular Pathways

Boston, MA | September 24-25, 2013

Dr. Scott Martin, Team Leader for RNAi Screening at NIH’s Chemical Genomics Center, to Present “Swimming in the Deep End – Sources Leading to a False Sense of Security in RNAi Screen Data” at Functional Genomics Screening Strategies Conference

There has been a growing skepticism surrounding RNAi data and the validity of hits arising from largescale RNAi screens. Much of this comes from a lack of agreement between screens conducted in similar biological systems and difficulty in validating published screen hits. In light of these realities, we must rethink some widely held beliefs about screening and validation strategies. These issues and relevant data will be discussed.

 

Functional Genomics Screening Strategies: Part Two

Exploring Novel Screening Platforms and Cellular

Models for Next-Generation Screens

Boston, MA | September 25-26, 2013

The second half of Functional Genomics Screening Strategies will explore the use of chemical genomics screens, microRNA (miRNA) and long non-coding RNA (lncRNA) screens and the transition into advanced cellular models such as, 3D cell cultures, co-cultures and stem cells that will launch the next generation of functional screens. Screening experts from pharma/biotech as well as from academic and government labs will share their experiences leveraging the utility of such diverse screening platforms and models for a wide range of applications.

 SOURCE

 

Read Full Post »

Impact of Sequestration on the National Institutes of Health

Reporter: Aviva Lev-Ari, PhD, RN

Article ID #59: Impact of Sequestration on the National Institutes of Health. Published on 6/4/2013

WordCloud Image Produced by Adam Tubman

UPDATED 6/5/2013

GenomeWeb Feature: Researchers Weigh in on Grants in the Time of Sequester

June 05, 2013

NEW YORK (GenomeWeb News) – When Nicholas Navin’s R01 grant to use single-cell sequencing to study tumor evolution in breast cancer was first funded in 2012, it was funded at 83 percent of the requested budget.

Because of the sequester, Navin’s grant now will be cut a further 6 percent. In addition, he has only been given funding for the next three months.

“After those three months, I assume that it will continue to be funded for the rest of the year,” said Navin, an assistant professor at the University of Texas MD Anderson Cancer Center, “but they only give you enough funding to support you for three months.”

The sequester — the across-the-board cuts to the US budget that were implemented at the beginning of March — has led to budget decreases across the federal government, including at research funding agencies like the National Institutes of Health and the National Science Foundation. The cuts exacerbated what was seen by many as an already tight funding situation that was not keeping pace with inflation, making it increasingly difficult for researchers to fund their work.

Steven Salzberg, a professor at Johns Hopkins University School of Medicine, recently had a grant rejected that was ranked in the top 11th percent of applications. In the past, he’s had grants funded that were in the 16th percentile or 17th percentile.

“They are funding, one would hope, grants at the 11th percentile, but not this particular one,” he said. “So you have to resubmit it or you can give up. Those are your two choices.”

As budgets decline and competition for grants increase, researchers are submitting more proposals and are beginning to look elsewhere for funding. At the same time, they are wondering what the effect of sequestration will be on science and scientists, particularly early career investigators. Still, there are steps investigators can take to try to get their proposal to stand out.

Cuts and effect

Because of the sequester, both NIH and NSF have seen their budgets fall about 5 percent. For this fiscal year, NIH’s budget is about $29.15 billion, as compared to $30.86 billion for fiscal year 2012. At the same time, NSF has about $6.9 billion for 2013, compared to last year’s $7.0 billion.

To cope with these decreases, NIH has cut all noncompeting renewals by 4.5 percent, but other changes were mostly left up to the various institutes that comprise NIH. For example, NHGRI, like other parts of NIH, is cutting noncompeting renewals, but it is not touching small grants, which it defines as ones with commitments of $250,000 or less and that typically are funded through R03 or R21 mechanisms. In addition, NHGRI won’t be giving future inflationary increases to competing applications.

“NHGRI deals with such a relatively small number of grants that we can look at each one individually and make decisions on the basis of how that particular application addresses institute aims and what the application needs in order to be successful,” Mark Guyer, the deputy director of NHGRI, told GenomeWeb Daily News. “Almost everything we do is really on a case-by-case basis beyond the across-the-board cuts to non-competing.”

The sequester, though, comes on the heels of years of small increases to funding agencies’ budgets. While the NIH budget went through an unprecedented doubling between about 1998 and 2003, it has since languished, with increases that typically did not keep pace with inflation.

“The field generally was in dire straits [heading into the sequester], given the very low payline by NIH, for example, and even NSF,” said Sarah Tishkoff, a professor at the University of Pennsylvania.

Salzberg noted that the two NIH R01 grants that he already has — awarded prior to the sequester — were cut about 15 percent to 20 percent. This, he added, was done “administratively because of budget reasons, not because of the peer review.”

“Now [the sequester] comes along and makes it even worse,” Tishkoff added.

Overall, NIH has estimated that it will fund nearly 8,300 competing research grants for FY2013, a decrease of about 700 from last year.

NHGRI also said that, in the face of the sequester, it is aiming to keep the average size of the awards it makes for FY2013 similar to the sizes of those it gave out in FY2012 — meaning that it will be giving out fewer total awards. Competition for grants, then, will become increasingly competitive.

“The [scientific] opportunities over the last decade at least and certainly into the foreseeable future are increasing hand over fist … and available funding is not keeping up with that,” Guyer said. “So necessarily things have gotten more competitive, and the sequester approach to managing the federal budget has only exacerbated the competitive aspects of things.”

As fewer proposals get funded and there’s less money to go around, many investigators may find themselves submitting more proposals to a number of funders.

“I am looking at submitting [more] proposals because it looks like funding is tight, and it is going to remain tight,” Salzberg told GWDN. “Unfortunately this produces a vicious cycle where many of us feel like our chances of getting funded are lower, therefore we should submit more proposals, but that then in return reduces the percentage that gets funded.”

It also increases the amount of time researchers spend reviewing proposals.

Others are looking to supplement their funds by turning to alternative funding sources. Navin, for example, is looking at private foundations and other organizations that fund cancer research, such as the Susan G. Komen Foundation or the Damon Runyon Cancer Research Foundation.

There, he said, he may have a few options given that he studies breast cancer. Other researchers, he noted, may not have such options. “I know some of my colleagues that work on colon cancer or some of the more rare cancers like testicular cancer or bladder cancer, they really have a hard time finding funding now,” he said.

In addition, cuts and uncertainty about future reductions in funding could make a lab a precarious place. After such budget cuts or in anticipation of cuts, some labs have slowed down their growth or have even begun to let people go.

Salzberg said that, as a computational biologist, his main expenses are the salaries of the students, postdocs, and staff who power his lab.

“[The funding situation] also makes me much more reluctant to hire postdocs or any new staff because I don’t have any more money coming in. You need more money to hire new people,” he said. He added that he still gets a number of requests from people looking for positions, but “I don’t have the funding for a new postdoc. Until I get some new funding that’s what I’ll keep saying.”

“I’ve seen [colleagues’] grants just get slashed by huge amounts,” Tishkoff added, noting that she’s seen technicians beginning to lose their jobs.”[Investigators] either have to cut some of the staff or they have to cut one of the aims.”

And as grant budgets are cut, researchers have to accomplish their research aims with less, and this often means cutting back on some of the science they would like to have done.

“Because they cut the budget, you have to cut the scope,” Salzberg said. “You still do the work, but you don’t do all the things that you want to do.”

Navin, for example, is looking to use a smaller study size, even though that’ll affect the statistical power of his work.

And that’s for the grants that get funded.

“Some projects just aren’t getting done,” Salzberg added. “[My grant] that wasn’t funded was a different project and we’re not going to do it.”

This, he said, may lead to delays in improvements to healthcare. New treatments and drugs will come, he said, but it may be in 20 years rather than in 10 years or 15 years.

Concern for new investigators

One common fear is that the sequester will disproportionately affect new investigators as they try to start labs and fund them or even dissuade them from pursuing a career in academia.

“It looks like it is disturbing a lot of young people and influencing the way that they are thinking about a potential career,” Guyer said.

Tishkoff added that she is worried that junior scientists will see how the more senior people are struggling to find funding, and opt out. “[New investigators] have to get grants if they want to get tenure. They have to get grants to be successful and to continue to be a scientist in the future,” she said.

“That’s the question that I get over and over again” from students and postdocs, Navin added. “What’s it going to be like in … five to 10 years?”

“I try to stay optimistic and tell them that there will be funding, but it is hard to predict the future,” he said.

Still, junior scientists may look for careers in industry or outside of the research realm.

“I think that when they hear all of this gloom and doom talk going on, it is really discouraging them. And that makes me really worried that we are losing talented scientists,” Tishkoff said. She added that she’s noticed that people with computational biology or bioinformatic backgrounds seem to be heading to industry.

Salzberg added that the field may never even know what it is losing. “People will leave the field — they won’t announce it — they just go get a job doing something else,” he said. “Generally, you lose that [talent] forever because that person doesn’t come back.”

Funding agencies like NIH do have mechanisms in place to try to help new investigators get grants. For example, proposals from new investigators are reviewed separately from ones submitted by established PIs. That way, early-career researchers compete against each other, rather than against those with more experience.

Further, in its policy statement for this fiscal year, NIH said that it would continue to support new investigators applying for R01 grants with success rates similar to those of established PIs.

“I really think they are doing as much as they can, but there is a bottom line,” Tishkoff noted. “If you do not have the money to give out, then it is going to be more and more and more competitive. That’s just how it is.”

NHGRI, in its own policy statement, said that it is “very flexible” in supporting early-stage investigators by not reducing recommended budgets if possible, by giving special consideration when applying for renewals to avoid gaps in funding, and by its Pathway to Independence Awards, which are targeted to postdocs who are moving toward running their own lab.

Outside of federal support, there are also a number of grants that specifically fund new investigators, such as the David and Lucile Packard Foundation Fellowships for Science and Engineering, Burroughs Wellcome Fund Career Awards, or the Sloan Research Fellowship, among others.

Tips for getting a grant

With increased competition for a smaller pot of money, submitting a well-crafted grant proposal might help it stick out from the rest in the pile. While some researchers may be quickly churning out as many proposals as they can, Tishkoff said that approach may not be the best one.

“The fact is it’s now even more competitive, it is even more important that people are taking time to really work on the grants carefully and not try to rush through them,” she told GWDN.

Still, submit a proposal quickly. “Don’t wait to apply for your first grant,” Salzberg said. “Very few people get funded on their first time around. You learn a lot from the reviews you get back.”

For his first grant, Salzberg partnered with a senior colleague to be a co-PI on the grant. “You can learn a lot about grantsmanship that way,” he said. “And then if the senior colleague gets funded, then you get some money out of that.” In addition, “you also learn some of the administrative hoops.”

Once on a grant, investigators begin to be invited to review panels that evaluate such grant proposals. “That’s a very valuable experience,” Salzberg said. “The first couple of times you are on a review panel, you learn a tremendous amount because you see a lot of other people’s grant applications and you see what the reviewers are saying about them.”

Tishkoff said one common problem she’s seen, particularly among new investigators, is that the proposals can feel hurried and too full of jargon. “You’ve got to take your time, write clearly in a manner that a general scientist can understand,” she said, adding that investigators have to sell their idea to a “broad scientific audience [and] make the point of why it is cutting edge and important and advances the field.”

Having other, more senior people look over a proposal is often a key step, she added, saying that she’s seen applications in which there were simple errors like numbers not adding up that could have easily been avoided by having someone else take a look at it.

An oft-overlooked step, by new and established PIs alike, is getting in touch with their program officers. “Start out talking to NIH program people as soon as possible,” Guyer said.

Program officers can provide information on funding mechanisms, initiatives, and budgets, and offer feedback on how project ideas fit within institutes’ priorities. “And we think, at least we tell ourselves, that it can help save people a lot of wasted time,” he added.

Tishkoff said that she typically calls up her program officer when she’s thinking about and applying for a grant to see how her idea fits with what the institute is interested in funding and to discuss a potentially reasonable budget.

“You could say, ‘I am thinking about applying for this, this, and this. Is that something that you or this institute would be interested in funding?'” she said. “And so you can try to aim to make your proposal fit with what their goals are at the moment.”

“Secondly, I always tell them, ‘OK, here’s the budget I have in mind. Is that going to be realistic or not?'” she added.

And once, she said, she was told her budget for what she called an “all-in-one, big giant grant” was too high to be funded. Instead, Tishkoff broke that large, all-inclusive grant into smaller, more focused projects, and she stripped the budgets to the bare bones.

However, not all proposals will be funded, even well-written ones. “There’s no magic bullet here, though, it’s just times are tough,” Salzberg added. “If they are only funding 10 percent of proposals, then whatever happens, 90 percent of them are going to be rejected, so try to be in the top 10 percent, but we can’t all be in the top 10 percent all the time.”

Navin added that those who get rejected should not give up and should keep submitting. “I just think you have to be very optimistic, be an eternal optimist and just keep submitting your grants to as many different funding agencies as possible,” he said. “And eventually, if it is a good idea, it’ll get funded.”

The next fiscal cycle

While fiscal year 2013 is more than half over, the US federal budget for fiscal year 2014 isn’t yet set, so what is in store for research funding — and whether the sequester will continue —isn’t clear.

The Obama administration released its budget proposal for FY 2014 in April, which would replace the sequester. It called for $31.3 billion for the National Institutes of Health — an increase of 1.5 percent over the FY 2012 budget — and $7.6 billion for the National Science Foundation — an 8.4 percent increase over its FY 2012 appropriation.

The budget, though, needs to pass Congress.

“We’re making plans for FY ’14 on the basis of what the administration presented as a budget,” Guyer said. “We’re hoping the Congress can do better than that. On the other hand, we are realistic.”

Ciara Curtin is GenomeWeb’s science features editor as well as the editor of the Daily Scan and Careers blogs. E-mail Ciara Curtinand follow @DailyScan, and @CareersGW on Twitter.

Fact sheet: Impact of Sequestration on the National Institutes of Health

The National Institutes of Health is the nation’s medical research agency and the leading supporter of biomedical research in the world. NIH’smission is to seek fundamental knowledge about the nature and behavior of living systems and apply that knowledge to enhance health, lengthen life, and reduce the burdens of illness and disability. Due in large measure to NIH research, a person born in the United States today can expect to live nearly 30 years longer than someone born in 1900.

More than 80 percent of the NIH’s budget goes to over 300,000 research personnel at more than 2,500 universities and research institutions throughout the United States. In addition, about 6,000 scientists work in NIH’s own Intramural Research laboratories, most of which are on the NIH main campus in Bethesda, Md. The main campus is also home to theNIH Clinical Center, the largest hospital in the world totally dedicated to clinical research.

Sequestration:

On March 1, 2013, as required by statute, President Obama signed an order initiating sequestration. The sequestration requires NIH to cut 5 percent or $1.55 billion of its fiscal year (FY) 2013 budget. NIH must apply the cut evenly across all programs, projects, and activities (PPAs), which are primarily NIH institutes and centers. This means every area of medical research will be affected.

NIH FY2013 operating plans:

NIH FY2013 Operating Plan

NIH FY2013 Operating Plan Mechanism Table

NIH Guide Notice: Fiscal Policy for Grant Awards FY2013

NIH Institutes and Centers FY2013 Funding Strategies

The estimated numbers:

(FY 2013 figures compared to FY 2012)

While much of these decreases are due to sequester, NIH funding is always a dynamic situation with multiple drivers:

  • Approximately 700 fewer competitive research project grants issued
  • Approximately 750 fewer new patients admitted to the NIH Clinical Center
  • No increase in stipends for National Research Service Award recipients in FY2013

The impact:

  • Delay in medical progress:
    • Medical breakthroughs do not happen overnight. In almost all instances, breakthrough discoveries result from years of incremental research to understand how disease starts and progresses.
    • Even after the cause and potential drug target of a disease is discovered, it takes on average 13 years and $1 billion to develop a treatment for that target.
    • Therefore, cuts to research are delaying progress in medical breakthroughs, including:
      • development of better cancer drugs that zero in on a tumor with fewer side effects
      • research on a universal flu vaccine that could fight every strain of influenza without needing a yearly shot.
      • prevention of debilitating chronic conditions that are costly to society and delay development of more effective treatments for common and rare diseases affecting millions of Americans.
  • Risk to scientific workforce:
    • NIH drives job creation and economic growth. NIH research funding directly supports hundreds of thousands of American jobs and serves as a foundation for the medical innovation sector, which employs 1 million U.S. citizens. Cuts to NIH funding will have an economic impact in communities throughout the U.S. For every six applications submitted to the NIH, only one will be funded. Sequestration is reducing the overall funding available for grants. See the history of NIH funding success rates.

Frequently asked questions:

How many fewer grants will be awarded?
Approximately 700 fewer research project grants compared to FY 2012.

Have the institutes and centers announced their adjusted paylines based on these cuts?
The adjusted NIH Institute and Center (IC) paylines and funding strategies can be found here:http://grants.nih.gov/grants/financial/index.htm#strategies

What percent cut will be made to existing grants?
Reductions to noncompeting research project grants (RPG) vary depending on the circumstances of the particular IC. The NIH-wide average is -4.7 percent.

Will the duration of existing grants be shortened to accommodate the cuts?
In general, no.

Will all grants receive the same percentage cut or will some grants be cut more than others?
Institutes and centers have flexibility to accommodate the new budget level in a fashion that allows them to meet their scientific and strategic goals. As noted above, there are different percentages for different ICs, and in some cases for different mechanisms within an IC (RPGs, Centers, etc.). In addition, there may be reductions to grants for reasons other than sequestration, as is the case every year.

Will certain areas of science that are at a critical juncture be affected by these cuts? 
All areas of science are expected to be affected.

Will some areas of science be affected more than others?
The sequester does not stipulate the precise reduction to each scientific area. However, it is likely that most scientific areas will be reduced by about 5 percent because the sequester is being applied broadly at the NIH institute and center level.

What will be the impact of these cuts to NIH’s intramural research at its Bethesda campus and off-campus facilities?
The impact on NIH’s intramural research is substantial, especially because it applies retroactively to spending since Oct. 1, 2012. That can double the effect — a full year’s cut has to be absorbed in less than half a year.

Will NIH be furloughing or cutting employees at its NIH campus and off-campus facilities?
There are no current plans to do so. At present, HHS is pursuing non-furlough administrative cost savings such as delayed/forgone hiring and reducing administrative services contracts so that furloughs and layoffs can be avoided. Additionally, employee salaries at NIH make up a very small percentage (only 7 percent) of the NIH budget.

How will current patients at the NIH Clinical Center be affected?
Services to patients will not be reduced.

Will the NIH Clinical Center see fewer patients because of the cuts?
Approximately 750 fewer new patients will be admitted to the NIH Clinical Center hospital in 2013 or a decrease from 10,695 new patients in 2012 to approximately 9,945 new patients in 2013. While much of this decrease is due to funding, clinical activity is always a dynamic situation with multiple drivers.

Will the sequester cut need to be applied to the FY 2014 budget?
The President’s FY 2014 Budget would replace sequestration and reduce the deficit in a balanced way. The President is ready to work with Congress to further reduce deficits while continuing to make critical investments.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health®

Read Full Post »

Reporter: Aviva lev-Ari, PhD, RN

Rock Talk

Helping connect you with the NIH perspective


Diversifying the Training Experiences of the Biomedical Research Workforce

Posted on March 8, 2013 by 

I’m eager to tell you about another important biomedical workforce-related initiative that NIH is launching based on the Advisory Committee to the Director (ACD) working group recommendations. This initiative seeks to expand existing research training and allow research institutions to best prepare their trainees for a variety of research-related career outcomes. The ACD working group report showed that while almost half of US-trained doctorates work in academia, an increasing proportion of newly trained doctorates finds employment opportunities in non-academic sectors and in other research-related occupations.

US-trained doctorates post-training employment as of 2008: 18% non science related, 18% science-related non-research, 6% government research, 18% industry research, 43% academia. NSF Survey of Earned Doctorates data based on 130,000 individuals which is an underestimate of total biomedical research workforce

Especially in challenging financial times, it is important to not only prepare trainees for a diverse set of career outcomes, but to leverage existing resources and enlist additional support from the potential beneficiaries of NIH-supported training – the employers of PhD scientists. TheBroadening Experiences in Scientific Training (BEST) program aims to do just that.

The BEST awards will be piloted through the NIH Common Fund, and support the development of new and innovative methods for preparing graduate students for the full breadth of research and research-related careers in the biomedical, behavioral, social, or clinical sciences. How applicant research institutions choose to approach this may vary. For example, scientific research institutions might initiate mutually beneficial collaborations with schools of business, public policy or economics, or might propose developing partnerships beyond academia and engaging the private sector or non-profit entities. But all programs should introduce students and postdoctoral scientists to the wide array of biomedical careers early in their training, and provide them with experiences in the career they plan to pursue, in addition to their PhD studies and traditional postdoctoral training.

BEST intends to change the culture of biomedical graduate education by seeding the development of diverse training experiences. Up to 15 BEST awards will be made in fiscal year 2013 to support research institutions’ program and administrative needs during the initial stages of development, and to create self-sustaining programs in collaboration with external support. Communication among awardees and rigorous monitoring of outcomes are essential aspects of this award program so that effective and proven models for training can be shared with universities across the United States.

We plan to review applications to the BEST funding opportunity this summer. An informational webinar to advise applicants will be held in March, letters of intent are due in April, and applications are due in May of this year; more details on the program are in the NIH GuideNotice and on the program website.

As the centerpiece of all the ACD biomedical workforce recommendations, this program is an important part of supporting the biomedical research enterprise as a whole, at all stages of the scientific process. This investment is just the beginning of how we prepare biomedical research trainees for a broader set of career options, and I look forward to following the work of BEST awardees as they pioneer these diverse training programs.

 

3 THOUGHTS ON “DIVERSIFYING THE TRAINING EXPERIENCES OF THE BIOMEDICAL RESEARCH WORKFORCE”

  1. It’s fantastic that the ACD is recognizing the need for training and experiential learning outside of pure academic career tracks! I am part of a group of graduate students and postdocs at Washington University School of Medicine who, while looking for an opportunity to gain training and experience, formed a nonprofit consulting company that forms collaborations between early and late stage life sciences companies and small groups of graduate students and postdocs. Through these team strategic consulting projects, all participants whether academic or non-academic focused, receive hands-on, real-world learning experiences. These opportunities train participants in becoming effective communicators, collaborators, leaders, and managers—skills that are often under-developed in many recent graduates and aspiring principal investigators. The group has had tremendous success over the past two years working with 32 companies and 140+ student consultants, many of whom have gone onto academic and non-academic careers and even started their own company. The group also earmarks a significant portion of their revenue for outreach initiatives to support science and career development throughout the community. Importantly, because these projects are inexpensive, the demand for the services is high throughout the country, opening up a huge opportunity for similar initiatives to develop at other universities. Indeed, several groups of graduate students around the U.S are currently taking steps to creating similar initiatives at their institution. We hope the BEST program can foster similar self-sustaining initiatives.

  2. Could anyone from the Rock Talk Blog team comment on why NSF survey data from 2008 is being shown here instead of data from 2011 which was released in December? It would seem to me that the 2011 data would be much more relevant given that 2008 was the start of the recession and that 2% unemployment number back then must have surely risen since then. I would also be curious to see how the percent of people in “Academia” and “Industry research” has changed from 2008 to 2011. My guess is that in the three years from 2008-2011 there have been some dramatic changes in these percentages with “Academia” and “Industry research” comprising now less than 40% combined.

 

Read Full Post »

Larry H Bernstein, MD, FCAP, Reporter

Laboratory

NIH-Funded Tissue Chips would Predict Drug Safety
Published: Friday, August 31, 2012
Last Updated: Friday, August 31, 2012

Researchers from Cornell University will develop microphysiological modules to model the nervous, circulatory and gastrointestinal tract systems.
Cornell’s Michael Shuler has received National Institutes of Health (NIH) funding to make 3-D chips with living cells and tissues that model the structure and function of human organs and help predict drug safety.

Shuler, the James and Marsha McCormick Chair of the Department of Biomedical Engineering, and James Hickman of the University of Central Florida (UCF) jointly received one of 17 NIH grants for tissue chip projects.

Shuler and Hickman’s grant of approximately $9 million over five years includes subcontracts to UCF, RegenMed, GE, Sanford-Burnham and Walter Reed Army Institute. It will support their work in microphysiological systems with functional readouts for drug candidate analysis during preclinical testing.

The researchers also plan to build a 10-organ system designed to be low-cost yet highly functional to use in drug discovery, toxicity and preclinical studies.

With the funds, the NIH is supporting bio-engineered devices that will be functionally relevant and will accurately reflect the complexity of a particular tissue, including genomic diversity, disease complexity and pharmacological response.

The NIH tissue chip projects will be tested with compounds known to be safe or toxic in humans to help identify the most reliable drug safety signals — ultimately advancing research to help predict the safety of drugs in a faster, more cost-effective way.

The initiative marks the first interagency collaboration, with the Defense Advanced Research Projects Agency, launched by the NIH’s recently created National Center for Advancing Translational Sciences. The NIH plans to commit up to $70 million over five years to the program

NIH Funds Development of Tissue Chips to Help Predict Drug Safety
Published: Wednesday, July 25, 2012
Last Updated: Wednesday, July 25, 2012

DARPA and FDA to collaborate on therapeutic development initiative.

Seventeen National Institutes of Health grants are aimed at creating 3-D chips with living cells and tissues that accurately model the structure and function of human organs such as the lung, liver and heart.

Once developed, these tissue chips will be tested with compounds known to be safe or toxic in humans to help identify the most reliable drug safety signals – ultimately advancing research to help predict the safety of potential drugs in a faster, more cost-effective way.

The initiative marks the first interagency collaboration launched by the NIH’s recently created National Center for Advancing Translational Sciences (NCATS).

Tissue chips merge techniques from the computer industry with modern tissue engineering by combining miniature models of living organ tissues on a transparent microchip.

Ranging in size from a quarter to a house key, the chips are lined with living cells and contain features designed to replicate the complex biological functions of specific organs.

NIH’s newly funded Tissue Chip for Drug Screening initiative is the result of collaborations that focus the resources and ingenuity of the NIH, Defense Advanced Research Projects Agency (DARPA) and U.S. Food and Drug Administration.

NIH’s Common Fund and National Institute of Neurological Disorders and Stroke led the trans-NIH efforts to establish the program. The NIH plans to commit up to $70 million over five years for the program.

“Serious adverse effects and toxicity are major obstacles in the drug development process,” said Thomas R. Insel, M.D., NCATS acting director.

Insel continued, “With innovative tools and methodologies, such as those developed by the tissue chip program, we may be able to accelerate the process by which we identify compounds likely to be safe in humans, saving time and money, and ultimately increasing the quality and number of therapies available for patients.”

More than 30 percent of promising medications have failed in human clinical trials because they are determined to be toxic despite promising pre-clinical studies in animal models.

Tissue chips, which are a newer human cell-based approach, may enable scientists to predict more accurately how effective a therapeutic candidate would be in clinical studies.

 

Read Full Post »

 

Reporter: Aviva Lev-Ari, PhD, RN

Gordon H. Sun, M.D., Jeffrey D. Steinberg, Ph.D., and Reshma Jagsi, M.D., D.Phil.

N Engl J Med 2012; 367:687-690   August 23, 2012

Since the founding of the National Institutes of Health (NIH) and the National Science Foundation (NSF) more than six decades ago, the United States has maintained a preeminent position as a government sponsor of medical research. That primacy is being tested, however, by potent economic challenges. The NIH’s proposed budget for fiscal year 2013 would freeze baseline funding at 2012 levels, continuing a decade-long failure to keep pace with the rising costs of conducting medical research. Across-the-board cuts mandated by the Budget Control Act (BCA) of 2011 will also affect medical research, with the NIH, NSF, and other federal research sponsors sustaining budgetary reductions of about 8% next year.

Cuts to government-funded research will have adverse long-term effects on the health care system and the economy and may irreversibly compromise the work of laboratories long accustomed to receiving stable federal support. Moreover, many medical researchers could transfer their knowledge and resources abroad. In fact, five emerging Asian economic or technological powers — China, India, South Korea, Taiwan, and Singapore — already have medical research policies in place that are filling the void being created by ever more restrictive U.S. funding.

Several U.S.-based economists have justified increasing research budgets on the premise that medical discoveries have intrinsically high economic value. For example, Murphy and Topel have suggested that eliminating deaths related to heart disease had an estimated worth of $48 trillion, and a 1% reduction in cancer-related mortality could save $500 billion.1 Beyond these ambitious goals, however, are more practical arguments favoring support for medical research.

Local and regional economic benefits are one example. A June 2008 analysis by Families USA showed that during the NIH’s fiscal year 2007, nearly $23 billion in grants and contracts supported more than 350,000 jobs, with each dollar generating more than twice as much in direct state economic output in the form of goods and services. The NIH reported that almost 1 million Americans worked in for-profit medical businesses in 2008, earning $84 billion and generating $90 billion in goods and services, reinforcing the importance of preserving the U.S. position as a “knowledge hub” for medical research.2 Nevertheless, BCA cuts next year could result in at least 2500 fewer NIH grants, 33,000 fewer jobs, and a $4.5 billion loss in economic activity.3 Since the NIH’s budget represents less than 1% of overall federal spending, policymakers must reconsider whether shaving 8% from NIH outlays will have a noticeable positive effect on the national deficit or economy.

Fallout from funding cuts could include shifts in the U.S. medical research workforce. In 2000, the National Research Council noted both an overall shortage of medical researchers and inadequate funding for scientists working in the United States, which coincided with a decline in the number of funded NIH grant applications from 31% in fiscal year 2002 to 19% in 2010. This change is particularly critical for postdoctoral researchers, who represent the majority of the U.S. biomedical science workforce. According to the NSF, nearly half the 14,601 new postdoctoral-level researchers who were trained in the United States in 2009 were not U.S. citizens or permanent residents. If U.S. institutions are willing to devote money, training, and infrastructure to support talented, committed researchers, it would be an illogical waste of resources and poor long-term strategy to reduce federal grant mechanisms and wipe out potential job opportunities. Indeed, declining financial support may well encourage medical researchers to seek employment elsewhere.

As compared with the United States, China, India, South Korea, Taiwan, and Singapore have taken a sharply different view of medical research and have developed policies that foster medical research as an engine for economic growth and intellectual innovation (see tableMajor Government Agencies in Asia and Their Budgets for Medical Research.). Their national budgets are heavily based on scientific research and development, and funding is increasing, with budgetary targets ranging from 2 to 5% of their gross domestic products (GDPs). India’s funding goal for medical research alone is 2% of its GDP.

Increased funding for research infrastructure attracts scientists and organizations interested in high-quality research, including clinical trials. During the past two decades, increasing numbers of clinical trials have moved overseas, where benefits can include decreased costs of doing business, fewer administrative regulations, and greater enrichment of international relationships among researchers. The average annual rate of growth in clinical trials has been highest in China — 47% — while the number conducted in the United States has decreased by an average of 6.5% annually.4 In addition, the increased attention paid to Asia by private firms and other nongovernmental organizations has spurred rapid policy-level responses to concerns about the lack of informed consent, transparency, and other ethical issues, thus further strengthening the appeal of conducting research in the region.

Asian policies reflect a recognition of the extrinsic economic benefits of medical research. China and India have advocated for more government-funded medical research to improve health-related outcomes. China has espoused increased spending as part of achieving xiaokang, a Confucian term meaning a moderately prosperous society. In 2007, India inaugurated its Department of Health Research, which coordinates biomedical science and health-services research programs and translates their findings to address public health concerns. Since the signing of the Korean War Armistice Agreement in 1953, South Korea has leaned heavily on government-funded research to reduce poverty, allowing the country to gradually acquire advanced technologies and expertise. Medical research is part of at least two core technology areas in South Korea’s “577 Initiative”: medical technologies, such as neuroimaging, to address the needs of an aging population and research on issues pertaining to national safety and public health, such as infectious-disease preparedness and food safety.

National research and development programs have been a fundamental component of Taiwan’s economic policy for at least five decades. In 2005, the country began developing “intelligent medical care” — similar to earlier U.S. initiatives — which integrates medical information technology with quality-improvement measures. In Singapore, medical research and economic oversight are administratively linked. For example, the Biomedical Sciences Group of the Economic Development Board supports researchers financially and designs strategies that enhance Singapore’s status as a knowledge center, and the private firm Bio*One Capital invests directly in promising medical technologies.

The diverse strategies outlined above allow Asian countries to systematically recruit medical researchers from both home and abroad. China is particularly proactive in enticing Chinese-born, U.S.-educated researchers to return to their native country by offering generous financial and material incentives under its Knowledge Innovation Program. As the vice president of the Chinese Academy of Sciences stated more than a decade ago, modern “research and development is actually a war for more talented people.”5 In 2000, Singapore jump-started its Biomedical Sciences Initiative to attract medical researchers worldwide with a direct $2 billion investment, as well as with tax incentives for internal biotechnology start-ups and global pharmaceutical firms. In Singapore and India, English is the primary language for scientific communications, which alleviates concerns about language barriers.

For two decades, emerging Asian countries have been designing long-term strategies to reap the benefits of medical research. Meanwhile, the United States is relying on short-term solutions to support its medical research infrastructure, such as those offered by the Patient Protection and Affordable Care Act and the American Recovery and Reinvestment Act. Decreased investment in U.S. medical research could lead to long-term economic damage for the United States and the loss of its stature as a global leader in the field. Powerful incentives that can retain an elite biomedical-research workforce are necessary to strengthen the U.S. health care system and economy.

The views expressed in this article are those of the authors and do not necessarily reflect those of the Robert Wood Johnson Foundation, the Department of Veterans Affairs, or the Agency for Science, Technology, and Research.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

SOURCE INFORMATION

From the Robert Wood Johnson Foundation Clinical Scholars Program (G.H.S., R.J.), the Department of Otolaryngology (G.H.S.), and the Department of Radiation Oncology (R.J.), University of Michigan, and the Health Services Research and Development Service, VA Ann Arbor Healthcare System (G.H.S.) — both in Ann Arbor, MI; and the Singapore Bioimaging Consortium, Agency for Science, Technology, and Research, Singapore (J.D.S.).

http://www.nejm.org/doi/full/10.1056/NEJMp1206643?query=TOC

 

 

Read Full Post »

Reporter: Aviva Lev-Ari, PhD, RN

The information below is posted on our Scientific Web Site in solidarity with all the Young Life Sciences Scientists in the US, Canada and around the Globe regarding the discrepancy in the marketplace between high supply of highly qualified young scientists and the low demand for their talent by Academia and by the Pharmaceutical and Biotech Industries as evidenced by few jobs for that valuable talent.

The matter has been address by the NIH and was reported in my post on June 27, 2012

Picturing US-Trained PhDs’ Paths and Pharmaceutical Industry’s Crisis of Productivity: Partnerships between Industry and Academia

http://pharmaceuticalintelligence.com/2012/06/27/picturing-us-trained-phds-paths-pharmaceutical-industrys-crisis-of-productivity-partnerships-between-industry-and-academia/

Related matters on that subject are addressed in the following Posts by Dr. Jonathan Thon

Dr. Thon holds joint appointments within the hematology division at Brigham and Women’s Hospital, and Harvard Medical School in Boston, and is an American Society of Hematology Scholar.

The truly bleak job prospects for young scientists in the life sciences

Posted on July 30, 2012 by Jonathan Thon

The following is my response to a letter from Canada’s federal minister of health, Leona Aglukkaq, who was in turn responding to an earlier letter from me:

Honourable Leona Aglukkaq,

Thank you first and foremost for taking the time to respond to my letter on February 7, 2012, regarding the lack of opportunity for early-career scientists in Canada (see the health minister’s response here). While the Canadian Institutes of Health Research (CIHR) is taking positive steps to meet its stated goals of attracting and retaining the best researchers, the Canadian government is failing to acknowledge how truly bleak the job prospects for young scientists are in the life sciences. While resources will always be limiting, the government needs to appreciate that current federal investment in biomedical science is insufficient to maintain the present rate of scientific advancement and falls short of supporting a sustainable pipeline of talented new health researchers. What’s more, this country’s overabundance of PhDs has kept postdoctoral salaries at a rate of $38,000 per year, which is shockingly low when one considers that a four-year undergraduate degree and five-year graduate program are required to fill the role. Worse still, it has extended postdoctoral fellowships (considered neither “student” nor “faculty” positions in Canada) to between four and eight years, creating a temporary “holding pattern” from which most young scientists ultimately transition to other careers.

If Canada is not prepared to make the necessary investment in academic biomedical research, universities must not be permitted to continue to push PhD students and postdoctoral fellows through the present system blindly, with complete disregard to the lack of academic career opportunities that await them. By failing to adapt to current labour market trends, the Canadian people are investing a significant amount of time and money into training highly-educated life scientists to take up positions that simply do not exist, forcing them into under-employment in the private sector. Not only does this represent a terrible return on investment, but it is stunting economic growth. The number of graduate students being trained for academic science positions that 80 percent of them will never fill needs to decrease significantly and the focus needs to shift from academic professorships to alternative professions as support scientists and consultants in neighbouring industries including medicine, finance, teaching and law.

Recently, both the U.S. National Academies and the National Institutes of Health’s Biomedical Workforce issued reports exhorting universities to “improve the capacity of graduate programs to attract talented students by addressing issues such as attrition rates, time-to-degree, funding, and alignment with both student career opportunities and national interests.” To accomplish this, the U.S. National Academies recommend that institutions “restructure doctoral education to […] shorten time-to-degree and strengthen the preparation of graduates for careers both in and beyond the academy.” The NIH concurred, citing the need to “involve relevant employers in the public and private sector in designing and training paths for students.” Among the reforms called for are:

  • Information and guidance about career opportunities and training in skills relevant to non-academic jobs to be provided to all graduate students and post-doctoral fellows on fellowships or principal investigator grants as normal parts of their programs.
  • Limitations to the period any individual can spend as a graduate student of post-doctoral fellow, which must be covered in its entirety under “any combination of training grants, fellowships and research project grants.”
  • Increasing the proportion of graduate students and post-doctoral fellows that receive support through fellowships and training grants versus faculty research grants, to shift the focus from the principal investigators’ labour needs to young scientists’ professional development. The report emphasizes that the overall number of young scientists supported should not increase.
  • Institutional tracking over time of career outcomes for all their graduate students and post-doctoral fellows, which should be made publicly available.

The last two recommendations are perhaps the most important and I have separated them here for added emphasis.

  • To improve career opportunities and limit the overproduction of transient trainees, labs should replace many of their post-doctoral fellow slots with permanent staff scientist positions.
  • Post-doctoral pay and benefits must improve. The Biomedical Workforce proposes implementing a starting salary of $42,000 (which I still consider to be a discouraging return on the increasingly lengthening 5-year investment necessary to earn a PhD), with a “large jump between [post-doctoral] years 3 and 4” intended “to incentivize principal investigators to move fellows to permanent positions.” Given the current state of academic science, the Biomedical Workforce felt it necessary to add that “all NIH-supported postdoctoral researchers on any form of support (training grants, fellowships, or research project grants) [should] receive benefits that are comparable to other employees at the institution,” including paid vacation, parental leave, healthcare, and retirement plans.

The government of Canada has done little to acknowledge and less to address the current overabundance of highly-trained young PhD scientists in low-paying dead-end jobs whose expertise will ultimately (after a significant period of re-training) be better served in other industries. While the CIHR’s efforts to improve current funding practices are necessary, they will not prove sufficient to resolve this issue. The current approach to training scientists and moving them through the labour force is frighteningly inefficient. Training more research scientists than we have the funds to support is not the solution – it is the problem. Acknowledging that we are facing a crisis and implementing the aforementioned recommendations will dramatically improve working conditions for young scientists while curbing inefficiencies in our labour market that are serving to limit economic growth.

Post to Twitter

In a concerted effort to practice what I preach, I write often to the Office of the Prime Minister to highlight issues facing early-career scientists in Canada. To their credit, I always receive a response. Below is a transcript of the most recent letter I received from the Minister of Health, Leona Aglukkaq. Please see ‘Bring home the scientific troops’ to review previous transcripts.

Dear Dr. Thon:

The office of the Prime Minister has forwarded to me a copy of your correspondence of February 7, 2012, concerning opportunities for young scientists in Canada.

The Canadian Institutes of Health Research (CIHR) recognizes the role that new and early career investigators play in creating a sustainable foundation for Canadian health research. In its second strategic plan entitled Health Research Roadmap: Creating innovative research for better health and health care, the CIHR stated its intention to build capacity to attract and retain the best researchers by working with partners at all levels, including teaching hospitals, other federal funding agencies and federal departments. This will involve, among other things, ensuring that sufficient operational support is provided by rectifying the inconsistencies in postdoctoral funding and reviewing the level and form of financial assistance provided.

As part of the CIHR’s commitment to ensuring the long-term sustainability of its contribution to the Canadian health research enterprise, the CIHR has also initiated a process to design a new open suite of programs and peer review system. The new design responds to concerns such as yours from the health community that we need to be providing more support for new and early career investigators.

In the new open suite of programs, the CIHR is considering specific support to new and early career investigators with excellent training and early career productivity to ensure that these researchers have an opportunity to build promising programs of research and knowledge translation. In a new scheme that focuses on projects, the CIHR is considering giving priority in the first stage of review to the quality of the idea with limited information about the track record of the applicant. This would remove some of the biases or barriers (real or perceived) for new and early career investigators.

The CIHR’s direct training programs are not changing as part of this process and will continue to be a part of the CIHR’s strategy to support a sustainable pipeline of talented new health researchers into the health research enterprise.

It should also be noted that the CIHR’s Strategy for Patient Oriented Research also has a focus on developing the talent pool for clinical research in Canada. You can follow the development of this important strategy on their website athttp://www.cihr-irsc.gc.ca.

With regard to your concern about the low levels of successful applications in the CIHR’s Open Operating Grants Program, it should be noted that in February 2008, the CIHR pledged to create and maintain a stable Open Operating Grant Program. This included a commitment to fund at least 400 new grants per competition (800 per year). This commitment will be maintained with the new program structure.

The CIHR currently funds some 14,000 researchers and trainees. In designing the new funding program, the CIHR’s intent is to continue supporting a similar number of investigators and trainees. Furthermore, the CIHR is committed to ensuring that approximately 70 percent of the grants and awards budget continues to be allocated to support investigator-initiated research.

I appreciate having had this opportunity to respond to your concerns.

Sincerely

Leona Aglukkaq

c.c. Office of the Prime Minister

I will be responding to Ms. Aglukkaq’s letter in my following post – and I encourage you to do the same. You can contact the Honourable Leona Aglukkaq at:

House of Commons
458 Confederation Building
Ottawa, Ontario
K1A 0A6

Tel: (613) 992-2848
Fax: (613) 996-9764
Email: Leona.Aglukkaq@parl.gc.ca

The research bottleneck – flying blind

Posted on June 25, 2012 by Jonathan Thon

Post to Twitter

The Bridges to Independence report (NRC, 2005) reveals that the number of PhD-trained life scientists in the United States ages 35 and younger increased by 59 percent between 1993 and 2001 while the number of these scientists in tenure-track positions increased by only 7 percent. At research institutions this number decreased by 12 percent over the same period of time. Studies by Michael S. Teitelbaum (Research funding: structural disequilibria in biomedical research. Science 321, 644-645. 2008) and Cyranoski, D. et al. (The PhD factory: the world is producing more PhDs than ever before. Is it time to stop? Nature 472, 276-279. 2011) support these observations and show that the supply-demand gap continues to grow.

Studies from the National Association of Teachers in Further and Higher Education, the British university and college lecturer’s union, and the BETT Report, published in June 1999 by the Independent Review of Higher Education, Pay and Conditions, paint a similar picture for scientists in the United Kingdom and suggest a similar situation worldwide. With limited employment opportunities in academia as it is (Improving graduate education to support a branching career pipeline: Recommendations based on a survey of doctoral students in the basic biomedical sciences. 2011.), this statistic reflects a bad situation only getting worse.

To better assess the magnitude of this problem and compel academic institutions to address it, I suggest federal departments require universities to submit a detailed account of the placement histories of their recent graduates, which should be made available freely online. Another statistic worth tracking is the percentage of graduate students or research fellows training under principal investigators that now support independent research programs of their own. Comparing these figures to research investment practices that have traditionally focused on graduate and postdoctoral funding while avoiding the larger issue of subsequent employment should let us measure the effect these policies have on the knowledge market and provide the impetus to change them. At the very least, it would let prospective scientists know what they were getting into.

Because I am not the first to suggest that dissatisfaction later in their career has less cogency if students investing in a bioscience research career when they choose graduate training are made aware of the risks pursuant, a recent NRC Committee on Trends in the Early Career Patterns of Life Scientists recommended in 1998 “that accurate and up-to-date information on career prospects … and career outcome information … be made widely available to students and faculty. Every life science department receiving federal funding for research training should be required to provide its prospective graduate students specific information regarding all pre-doctoral students enrolled in the graduate program during the preceding 10 years.”

While this is a clear step in the right direction, a recent survey of 10 leading biology departments (experimental group) and professional schools (control group) in the United States concerning the information available to students considering a career in the biosciences showed striking differences between the two groups (Careers and Rewards in Bio Sciences: the disconnect between scientific progress and career progression). As a rule, biology departments had information about time to degree and percentage of matriculating students who obtained their PhD, but not about job placement. No biology department had a job placement adviser, although career counseling offices at some universities did try to help students leaving academic science find non-academic jobs.

By contrast, all of the professional schools – law, business, medical – tracked the salary and position of their graduates through Student Affairs or Career Services Offices. More often than not this information was advertised on school websites. The inaccessibility of specific information regarding pre-doctoral biosciences students enrolled in graduate programs over the last 10 years means that federal funding agencies regulating scientific development and growth are unequivocally flying blind.

Introducing career streams into academic research

Posted on June 4, 2012 by Jonathan Thon

Post to Twitter

In the 1990s the typical PhD in biological sciences entered the job market in their mid 30s, after spending approximately 3.8 years as a postdoctoral fellow (National Academy of Science, Enhancing the Postdoctoral Experience for Scientists and Engineers). This is 3.6 years longer than it was in 1970 (National Research Council, Trends in the Early Careers of Life Scientists) and roughly 10 years shorter than what it is today.

It is not surprising then that so few PhDs continue into academic positions after receiving their graduate degree. A major failing of our graduate school system is that despite their program choices both Master’s and doctoral students are exclusively trained to become academic investigators. This is a problem when only 20 percent of doctoral students will ultimately become professors and the average age of independence in academic research is now in the mid-40s (A deeper look into the 80 percent of PhDs who do not become professors, and A new era of science funding – Part 4: Speaking up in support of federally funded research). Meanwhile, industries such as biotechnology, drug development, policy development, and scientific writing (amongst others) employ the remainder.

Indeed, a recent study by Fuhrmann et al. have found that at the University of California, San Francisco, nearly one-third of students midway through their graduate training intend to pursue a non-research career path (Improving graduate education to support a branching career pipeline: Recommendations based on a survey of doctoral students in the basic biomedical sciences. 2011. In other words, we are training our graduate students to excel at professions they will never hold. To support the growing number of research PhDs universities are graduating yearly for which faculty positions are not available, we have extended the duration of the postdoctoral research fellowship position. Originally intended to allow for furthering expertise in a specialist subject, acquiring new skills and methods, and developing one’s ability to run an independent research program by apprenticing under an established professor, this has become a repository of misallocated talent that delay a scientist’s entry into their first “real” jobs by more than five years (Careers for Postdoctoral Scientists: The Ever-Aging Postdoc).

For the majority of scientists that are forced to transition into other industries, the postdoctoral fellow stage represents a significant waste of time that does not adequately prepare them for the career they will ultimately elect – and yet, because of the enormous number of postdoctoral fellows feeding into these professions, it has become a prerequisite for most of these positions. As with any new profession, employment in an altogether different field carries with it its own learning curve, further delaying the career advancement of the scientist.

A significant departure from the current trend of expanding the supply of research scientists without evidence of imminent shortages in either the private or academic sectors is necessary (Supply Without Demand), and could be addressed by implementing career streams at the graduate and postdoctorate levels. While this is not a new idea (Elizabeth Marincola and Frank Solomon. The career structure in biomedical research: Implications for training and trainees, The American Society for Cell Biology on the State of the Profession. Molecular Biology of the Cell. 9:3003-3006. 1998), research institutions such as Harvard are increasingly deciding to go the other way, creating additional temporary, non-tenure-track Instructor and Research Associate positions that are in every way equivalent to a postdoctoral research fellow designation and meant to follow postdoctoral training.

In my next post I will tell you why this is a problem.

A call to arms

Posted on May 17, 2012 by Jonathan Thon

Post to Twitter

Scientific research is a marathon, and if we fall behind now, while we are leaders in health innovation, the cost of recovering our position, in light of emerging economies with which we compete, will become progressively more expensive. Sustained increases in National Institutes of Health and Canadian Institutes of Health Research funding are critical to maintain North America’s innovation engines at a crucial time for research and the economy, and most importantly to improve the health and well-being of our populations.

Now is the time for scientists to advocate most strongly for national investment in biomedical research. Members of Parliament, Members of Provincial Parliament and Members of the Legislative Assembly in Canada, as well as senators and congresspersons in the United States are the decision-makers you elect to represent you – write to them. You can go to http://www.canada.gc.ca/directories-repertoires/direct-eng.html and enter your postal code (in Canada), orhttp://www.house.gov and enter your zip code (in the United States) to access your representative.

Things to remember when composing your letter:

  • Identify yourself as a constituent and a member of the scientific community
  • Ask that the legislator support sustainable funding priorities for your federal funding agency.
  • Briefly explain why these issues are important to you.
  • Acknowledge the efforts that are being made by their party
  • Give them your contact information and ask to be informed about the actions their office takes in response to your request.

Letters need to be kept simple and as personal as possible, with tangible examples of actions MPs, MPPs, and MLAs can take to change the landscape of how biomedical research is supported in Canada. These should be provided to the legislator in the form of a one-page cheat-sheet with your contact information included for reference. If dealing with your senator or congressperson in the United States you will need to ask to speak/meet with your representative’s health legislative assistant who handles health care issues in the district or state.

Giving opposition members speaking points against current government policies, emphasizing the economic relevance/importance of your position, and holding legislators accountable for providing examples of and justifying actions they have taken on their own promises are all good ways of having your opinions considered. After the meeting it is important to follow up with your representative within the week, whether or not the representative was supportive of your position. This is your chance to remind them of what you discussed and further emphasize the importance of their involvement on this issue.

Canada-specific:

  • Major research funding in Canada is done federally, but provinces are responsible for health spending and many provinces (e.g.: BC, Ontario, Quebec) have contributed to major infrastructure projects.

U.S.-specific:

  • States often put aside money for research into targeted areas (e.g. California’s support of stem cell research) and are generally more independent than Canadian provinces.
  • Many federal representatives will have specific assistants/aides for health related issues -ask to speak/meet with them

Example speaking points:

  • Low funding rates (NSERC PDFs, CIHR operating grants, etc.)
  • Low postdoctoral fellow salaries compared to other countries
  • Plus, 4 or 5 more good statistics that show why basic health research is a good investment or is currently underinvested.

While the argument for the government to prioritize an industry where the number of clinical advances, drug developments and cures is proportional to total research investment is not a difficult case to make – it needs to be made. I and others at The Black Hole continue to work at concentrating and contextualizing some of the more important issues facing early career scientists in Canada and abroad.

Take advantage of this resource and use hard numbers to emphasize your points. Addressing these concerns forces the issue to light, and commits politicians to publicly defensible positions for which they can subsequently be held accountable. Government agencies cannot lobby for themselves and policy makers do not share your unique perspective. Our health, economy, and the future of scientific progress are at stake, so step up and speak out.

Show me the money!

Posted on May 4, 2012 by Jonathan Thon

Post to Twitter

It falls to scientists to speak up in support of federally funding research and in this third installment of a four-part series, I explore the economic cost of doing research in a cash-strapped system and the burden this is placing on young investigators.

To bring yourself up to speed, installements 1 and 2 are referenced below:

  1. Biomedical Research and Broken Clocks: All the Parts, but No Instructions
  2. A Difficult Pill To Swallow: The Harsh Realities of a 15% Funding Rate

As has been discussed here on and off for quite some time, 80% of PhDs in the US will not become professors. For the majority of these scientific investigators, the inability to secure a faculty position has meant that they must languish in a series of post-doctoral positions supported by grant-funded professors who are increasingly finding themselves with limited resources. The average age of independence in research is now in the mid-40s, a testament to the bleak prospects facing young scientists (PDF).

Given this highly unstable state of academic funding, it is not surprising that many investigators have chosen to transition into more secure professions like teaching, medicine or law. For an in-depth review of the career prospects of a post-doctoral research scientist please see Careers and Rewards in the Bio Sciences: The Disconnect Between Scientific Progress and Career Progression(PDF). The loss hurts our competitiveness in biomedical research and forces industry abroad.

Given our current economy, it is imperative that efforts to improve the nation’s fiscal stability be grounded in the long-term competitiveness of industries we currently head, and that we leverage our expertise in medical science and capacity to do high-tech research. This does not need to come from increased government spending alone. Whereas academic medicine cannot build R&D into the pricing of its services, universities profit directly from tuition fees, patents and personal endowments.

Since these revenues are derived from faculty teaching loads, the scientific success of their investigators, and established reputation of their research program, faculty support must be factored into departmental operating budgets, freeing up tax dollars to directly support research innovation. Another idea would be to create tax breaks for private donations to federal funding agencies in an effort to reduce their dependence on public dollars and incentivize industry investment in national research programs. In the United States (the same nation that passed the Bayh-Dole Act to spur commercialization of university research), government funding of university research exceeds business funding by an order of magnitude, and business investment in university research is nearly half that of Canada (PDF).

Finally, limiting the number of federal awards issued per investigator, most of which are held by senior faculty (PDF), would open up more funding opportunities to help support young investigators and significantly lower the age of independence. While the debate of whether to preferentially support established labs with proven track records over younger faculty with new ideas is ongoing, without early career support junior researchers will not succeed.

If we are unwilling to prioritize young faculty and share what wealth there is, perhaps the better question is “Should we continue training so many of them?”

Read Full Post »

 

Reporter: Aviva Lev-Ari, PhD, RN

July 20, 2012

The 2012 Intelligent Systems for Molecular Biology conference held this week in Long Beach, Calif., marked the 20th anniversary of what is considered the largest meeting in computational biology.

As part of the festivities at this year’s meeting, two founding members of the International Society for Computational Biology, which plans and manages ISMB, presented an anniversary keynote.

Lawrence Hunter, who directs the computational bioscience program and the center for computational pharmacology at the University of Colorado School of Medicine, and Richard Lathrop, a professor in the department of computer science at the University of California, Irvine, delivered the keynote, which traced the early days of the meeting, with its initial focus on artificial intelligence, to its current focus on computational biology.

BioInform caught up with Hunter, who was the first president of ISCB, after his talk to discuss the history of the conference and possible future directions for the community. What follows is an edited version of the conversation.

It’s been 20 years since the first ISMB. How has the meeting evolved over the years?

ISMB has gone through several stages. In the very beginning it was almost entirely computer scientists and there were really clear themes that emerged from the meeting. [For example, at] the third meeting … half of the papers were about hidden Markov models. As the field has grown and changed, there is a much less clear division between the computer scientist and the biologist. We’ve really become computational biologists and so the level of biological sophistication has gone up and the field has diversified so that there is really rarely a clear theme anymore; it’s multifaceted and diverse.

Another thing that’s changed is the orientation toward medicine. In the early days of the field, we were grappling with much more basic science problems and while there is still a lot of that, there is a much higher proportion of work that’s translational or clinical. Whether it’s drug repositioning, where I think there is real potential to change the pharmaceutical industry based on the kind of informatics work that’s done here, to an increase in the use of clinical data in the techniques that are being proposed here — whether it’s text mining or patient records or formalin-fixed, paraffin-embedded samples and the challenges in doing transcriptomics in those kinds of clinical samples — we are much more tightly connected to human health than we were 20 years ago.

Is that a good thing? Does the focus on health mean that bioinformatics tool development in other areas is being neglected?

I think it’s a good thing. Everybody wants to be relevant. Scientists don’t want to do things in the abstract; they want to do things that make a difference in people’s lives. One of the biggest ways to make a difference in people’s lives with bioinformatics is through medicine or pharmacology. There has never been a big contingent of folks working in agriculture but there are always a few … so far, the agricultural impacts have been smaller than the medical ones. And there are plenty of people doing basic science who are trying to understand how life works, [and] not so much trying to affect disease. I think there is a good balance and it will shift around from time to time. It would be great if there were more agricultural kinds of applications … [but] there is much more funding for things with medical applications than there are for ones with ag applications.

Following up on comments about funding, do you find that researchers have gotten better at including a budget for informatics in their grant proposals?

I think reviewers demand pretty sophisticated informatics in a lot of grants. For NIH grants, especially for the bigger, more prestigious ones — R01s or program projects or the [Clinical and Translational Science Awards] — all of those require a pretty good degree of informatics sophistication, I think, in order to do well. Looking over the last 20 years, one thing that has improved, although it could still use work, is study sections at [the National Institutes of Health], the review panels, becoming more sophisticated about computation. For a long time there was no standing study section at NIH that was specifically computational. Now there are two. There is also increasing sophistication on other study sections, so if you sit on an NIGMS panel, for example, there are going to be at least a couple of people who are pretty sophisticated about the informatics looking at those applications.

For the really large center proposals, and I am thinking now about the CTSA awards, there was such an emphasis on the informatics in the program announcement from the NIH that it changed institutions. Medical schools started adding divisions or departments of biomedical informatics in response to NIH requirements that the grant proposals be more sophisticated.

You mentioned earlier that ISMB has evolved since it first launched. Do you think that the meeting and ISCB in general have stayed true to their initial mandates?

It’s evolved. When we first put it together, we were thinking about artificial intelligence and robotics in molecular biology. It was much narrower. There were already conferences on, say, biological databases and we didn’t think that it was our topic. There was also the RECOMB [Conference on Research in Computational Molecular Biology] community, the algorithms community, and we separated from them too so that original vision was much narrower. ISMB has turned into a much more inclusive conference and ISCB a more inclusive society.

ISCB and ISMB both start with ‘IS’ but the ‘IS’es are different. ISMB, the conference, was about intelligent systems, that is, about AI. ISCB is the International Society for Computational Biology; it’s a much broader mandate. It includes databases and algorithms and visualization and all kinds of things that aren’t intelligent systems. That’s been a big change from the initial vision and, I think, ultimately a good one. I think the boundary lines were not productive and while I am still very interested in the artificial intelligence question, the blending of people working from different areas of computer science all sort of pulling towards solving problems motivated by biology has really been productive and so I am glad we’ve changed a bit from the initial vision.

Is there still room for AI?

The AI stuff has never gone away. There is tons of machine learning here, text mining, ontology, and knowledge representation here. One of the reasons I think this conference and this field and the original AI in molecular idea has been so successful is the technology works. It works in molecular biology almost better than it works in any other application area. So there is no shortage of intelligent systems at ISMB. It’s just more than that now.

Are there any computational issues that the community was dealing with 20 years ago that are still being dealt with today?

We go in cycles. If you go back to the very early ISMBs there was a lot of sequence analysis and alignment questions and relatively little dynamics. Fast forward 10 years, everything was microarrays and time series and concentration levels and sequence analysis was a boring solved problem. Fast forward 10 more years and we’ve gone back in a circle. Right now, microarrays are kind of a boring solved problem and sequence analysis is really interesting and hot again. The technology changes and so the problems change, nothing ever seems to stay solved. Either our ability to peer into the biology lets us know that we were naïve or over simplistic about something that we now need to go back and look at much more carefully. For example, the assumption that only protein-coding bits of the genome were transcribed underlay a lot of science for a long time. Now it turns out that a huge portion of the genome is transcribed and there is a lot of action going on in RNA editing and mircoRNAs and long non-coding RNAs are starting to look interesting again. As you look deeper, more interesting problems come up that you didn’t notice when you were making assumptions about how biology works.

It’s rare in our field that we prove some technique optimal. The best we can do is prove that my way of doing it is better than X,Y, and Z and so it’s a step forward but that always leaves the possibility that there is yet a still better way to do it and we still see people who are working on topics that have been well studied for a long time [such as] splice site identification, transcription start sites, structure prediction, function prediction problems that have been studied for a long time, yet new methods that are generally better come out. Even after working on it for 20 years, there is still the potential to do better.

Looking ahead 20 years from now, what do you see as the future of bioinformatics?

Let me take [a prediction] from my keynote. I think that we will see computer programs as increasingly independent and individuated intellectual partners. Right now, everybody using, say, Cufflinks uses the same version and it does the same thing every time. 20 years from now, I would expect that my computer program would be so customized to my way of thinking and what’s going on in my lab that the same computer program would do something different in somebody else’s lab. That doesn’t mean it’s not reproducible, we’ll know what it did and why, but that rather than having tens of thousands of copies that do the same thing, it’ll be more like having a computational member of the lab. It will know what we are after and what our interests are and what my collaborators want and who my competitors are and be much more individualized. I am not going to say that we’ll have a program that everyone thinks is a mind 20 years from now … but I think along the path to developing genuine artificial intelligence, all minds are unique, everybody is different, and that’s going to be increasingly true to programs too.

http://www.genomeweb.com//node/1108711?hq_e=el&hq_m=1314078&hq_l=7&hq_v=e1df6f3681

Uduak Grace Thomas is the editor of GenomeWeb’s BioInform. She covers bioinformatics, computational biology, and life science informatics. E-mail her here or follow her GenomeWeb Twitter account at @BioInformGW.

 

Read Full Post »

Reporter: Venkat Karra, Ph.D,

Recently studies on structural abnormalities of chromosomes (Mosaicism) were conducted by two consortia, one led by scientists at the National Cancer Institute (NCI), and one by Gene Environment Association Studies (GENEVA). This study was sponsored by the National Human Genome Research Institute (NHGRI).  These studies have found that mosaicism can be detected in a small fraction of people without a prior history of cancer. Mosaicism results from a DNA alteration that is present in some of the body’s cells but not in others. A person with mosaicism has a mixture of normal and mutated cells. “These two studies provide large population-based evidence that genetic mosaicism increases with age and could be a risk factor for cancer” which may mean that detection of genetic mosaicism could be an early marker for detecting cancer, or perhaps other chronic diseases,” said Stephen Chanock, M.D., co-author and chief, Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, NCI.

Scientists began observing an unexpected frequency of structural abnormalities in chromosomes during quality control checks of data from genome-wide association studies (GWAS) conducted in the GENEVA consortium and similar programs at NCI. These studies involve comparing hundreds of thousands of common differences across individual patients’ DNA to see if any of those variants are associated with a known trait, such as cancer. At first, these abnormalities were thought to be errors or outcomes of laboratory procedures. But they were found consistently at a low frequency, so the scientists wondered with what frequency these structural abnormalities occurred in the general population.

The NCI-led study observed that genetic mosaic abnormalities were more frequent in individuals with solid tumors (0.97 percent vs. 0.74 percent in cancer-free individuals). The NCI study also observed mosaic chromosomal abnormalities in slightly less than 1 percent of the study participants, but noted that the frequency of detectable genetic mosaicism increased with age. This was consistent with GENEVA results that found genetic mosaicism increased in those over the age of 50.

In both studies, scientists observed an increase in the detection of genetic mosaicism in patients with hematological cancers (leukemia, lymphoma and myeloma), for which DNA was collected at least one year prior to diagnosis, compared to cancer-free individuals. Results from the NCI study showed that risk of leukemia was also substantially higher among people with these chromosomal alterations while the GENEVA study showed that the risk of acquiring a hematological cancer diagnosis was 10 times higher for people who had mosaic chromosomal abnormalities. The results of both studies suggest that mosaicism, observed in older people, may be an asymptomatic condition — not often causing overt illness — that may predispose them to hematological cancer. However, GENEVA and NCI scientists stress that the event numbers analyzed are small, and additional studies are needed across a broader diversity of populations to establish the clinical significance of these findings.

NIH scientists say these findings will have important implications for the design and analysis of molecular studies of cancer, as well as ongoing studies looking at the characterization of cancer genomes, such as NIH’s The Cancer Genome Atlas and the International Cancer Genome Consortium.

NIH scientists recommended that additional analyses be conducted in groups of currently healthy people so that investigators may follow them over time for health outcomes.

The results of the studies were published online May 6, 2012, in Nature Genetics.

Read more….

Source:

http://www.genome.gov/27548594

Read Full Post »

« Newer Posts