Tag Archives: NIH

Controversy Over H5N1 Flu Continues

Just when it seemed like consensus existed on how to handle the hot potato of mammalian-transmissible H5N1 influenza, the public release on Friday afternoon of a letter sent April 12 from the respected influenza and public health researcher Dr. Michael Osterholm to a National Institutes of Health official collapsed the apparent consensus like a house of cards.

To recap: On March 29 and 30, the U.S. government’s National Science Advisory Board for Biosafety (NSABB), organized by the NIH’s Office of Science Policy, met to reconsider the NSABB’s original decision last December that said the paper written by Dr. Yoshihiro Kawaoka and another paper by Dr. Ron Fouchier on their respective efforts to produce and study H5N1 mutants transmissible by air from ferret to ferret should only be published without the methods sections, a way to prevent release of the details on how they developed these potentially dangerous mutant strains. The initial NSABB recommendation to allow publication of only the redacted papers failed to win support from a panel convened by the World Health Organization in February, creating a conflict between the NSABB (and hence the NIH) and the WHO. Claiming that new data first revealed to the WHO group led to the different outcome, Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases — the U.S. agency that sponsored the work of both Dr. Kawaoka and Dr. Fouchier — called on the NSABB to rethink its initial decision, which resulted in the NSABB reversing itself on March 30 and supporting full publication, in a unanimous vote for Dr. Kawaoka’s work, and in a 12-6 vote for Dr. Fouchier’s. So, by early April, the NSABB (and hence, pending official U.S. policy) and the WHO agreed that full H5N1 publication could proceed. Peace reigned across the land.

Dr. Michael Osterholm

Until 2 weeks later, when Dr. Osterholm an NSABB member, upset the tranquility by writing his bombshell letter to Dr. Amy Patterson, NIH’s associate director for Science Policy. In it, Dr. Osterholm took vigorous swipes at how the NIH set up the NSABB’s reconsideration session and detailed his grave concerns about public release of how the H5N1 work was done. Both “Science” and “Nature” received the letter on April 13, and according to a report in “Nature,” Dr. Osterholm said he was not the source for the leak.

“I believe the agenda and speakers for the March 29 and 30 NSABB meeting as determined by the Office of Biotechnology Activities [part of the NIH’s Office of Science Policy] staff and other U.S. government officials was designed to produce the outcome that occurred,” Dr. Osterholm charged in his letter. “It represented a very ‘one-sided’ picture of the risk-benefit of the dissemination of the information in these manuscripts. The agenda was not designed to promote a balanced reconsideration of the manuscripts.”

A major problem, he said, was that the “experts that addressed [the March NSABB session] have a real conflict of interest in that their laboratories are involved in this same type of work and the results of our deliberations directly affect them too.” The same problem occurred at the WHO meeting in February, he added.

Dr. Osterholm tempered his charge by saying he did not “suggest that there was a sinister motive by the U.S. government,” but still leveled a hefty blast, saying “I believe there was a bias toward finding a solution that was a lot less about robust science- and policy-based risk-benefit and more about how to get us out of this difficult situation.”

The upshot was that in the revised decision NSABB, U.S. policy makers, and researchers failed to “come to grips with the very difficult task of managing dual-use research of concern and the dissemination of potentially harmful information to those who might intentionally or unintentionally use that information in a harmful way.” His worry is — if not in this case — “will the Board ever find a bright line for redacting publication” of any future research that could potentially threaten public health?

Dr. Osterholm cited a major danger if details of this research became fully public: “A ferret-to-ferret experiment is expensive and technically demanding, and could only be done by a handful of labs in the world. Once the mutations are public, individuals … in many other labs could generate the mutants in a few weeks given several thousand dollars for gene synthesis,” using reverse genetics.

Finally, Dr. Osterholm questioned the public-health benefit from full release of the methods sections of the two H5N1 papers. “The most important aspect of the results in these two studies on surveillance and control has already been accomplished namely alerting the world to the possibility that H5N1 influenza virus surely can become a mammalian-transmitted virus and poses real pandemic potential.” Publication of more details from the research will not add to that alert, nor would it immediately help in the development or production of countermeasures against a potential H5N1 pandemic, he said.

Despite his concerns over full disclosure of the methods, Dr. Osterholm affirmed his overall support for this H5N1 research in a comment to “Nature” on Friday.  “I have been and continue to be a supporter of this kind of research,” he told the journal.

—Mitchel Zoler (on Twitter @mitchelzoler)

Leave a comment

Filed under Blognosis, Health Policy, IMNG, Infectious Diseases, Internal Medicine

N.Y. Times Slams Air-Borne H5N1 Research

The New York Times looked at air-borne H5N1 research, and saw it wasn’t good.

The Times devoted it’s lead Sunday editorial in its Jan. 8 edition — the paper’s place for its highest profile editorial pronouncements, usually focused on politics, economics, or international relations — to its official opinion on  controversial research in which two labs, one in Madison, Wis., and one in Rotterdam, made strains of the deadly H5N1 avian influenza that were transmissible in the air from ferret-to-ferret.

H5N1 virus/image courtesy Cynthia Goldsmith, CDC Public Health Image Library

In the editorial, the newspaper declared that “the research should never have been undertaken because the potential harm is so catastrophic and the potential benefits from studying the virus so speculative.” And that “the consequences, should the virus escape, are too devastating to risk.”

These statements were startling not only because the Times rarely takes an editorial stand on the specifics of biomedical research, but also because, as the editorial itself admitted, “we nearly always champion unfettered scientific research and open publication of the results.” So why the uncharacteristic stand?

The editorial cited two major reasons: the underlying danger from the new virus that’s been created, and the questionable research benefits from this line of work. The newspaper called the potential benefit from studying the newly made H5N1 variant “speculative” and questioned the level of security currently in place to safeguard the new virus.

But the Times’ concerns strikingly contrast with recent statements from officials at the National Institutes of Health, which co-sponsored this H5N1 research, as well as from officials at the World Health Organization.

On Dec. 30, an opinion piece in The Washington Post by Anthony Fauci, Gary Nabel, and Francis Collins of the NIH strongly defended the research and provided a simple, but unequivocal scientific rationale for it. “New data provide valuable insights that can inform influenza preparedness and help delineate the principles of virus transmission between species,” they wrote. “Identifying threatening viruses can also facilitate the early stages of manufacturing vaccines that protect against such a virus in advance of an outbreak…Decades of experience tells us that disseminating information gained through biomedical research to legitimate scientists and health officials provides a critical foundation for generating appropriate countermeasures and, ultimately, protecting the public health.” These NIH officials also defended the security in place, noting “the engineered viruses developed in the ferret experiments are maintained in high-security laboratories.”

The WHO issued its endorsement the same day, saying : “Studies conducted under appropriate conditions must continue to take place so that critical scientific knowledge needed to reduce the risks posed by the H5N1 virus continues to increase.” Although the WHO statement cautioned that the organization was “deeply concerned about potential negative consequences” of the research, it firmly stated that “research which can improve the understanding of these viruses and can reduce the public health risk is a scientific and public health imperative” that “must continue.”

The Times has been notable among U.S. papers in its thorough, thoughtful, and informative reporting covering several facets of the air-borne H5N1 story since it broke on Dec. 20. The big story initially centered on the suppression of details of how the ferret experiments were done, but since then the issue appropriately shifted to why the research was done and whether it had scientific merit. The Times greatly added to this discussion by publishing an interview with the head of the Rotterdam research team, and follow-up articles that examined the balance of potential benefits and risks from the work, as well as some of the underlying science behind avian flu transmission. Their interview with Dr. Fouchier, head of the Rotterdam group, included a memorable quote where he explained why he thought the research was so vital despite its danger: “In our opinion, nature is the biggest bioterrorist,” he said.

After producing such helpful and meaningful reporting over the past 2 weeks, it seems particularly curious that the Times’ editorial board looked at the totality of what’s been said on the subject and came down against the research, especially after it received renewed votes of confidence from several respected NIH leaders and from the WHO. It makes you wonder which infectious disease experts stand behind the Times’ position.

—Mitchel Zoler (on Twitter @mitchelzoler)

Leave a comment

Filed under Blognosis, Family Medicine, Health Policy, IMNG, Infectious Diseases, Internal Medicine, Internal Medicine News, Primary care

H5N1: Keep That Genie in the Bottle

Throw out a hint of some meaty research and say “Don’t Ask! Don’t Tell!”  You might as well draw a map to the Christmas cache and tell the kids, “Don’t follow this trail!”

The U.S government seems to be engaging in the worst kind of this delusion by asking the journals Science and Natureto withhold the methodology sections of two important papers on H5N1 viral mutation.

Michele G. Sullivan/Elsevier Global Medical News

The papers, one by University of Wisconsin-Madison veterinary virologist Yoshi Kawakoa and one by Dr. Ron Fouchier of Erasmus Medical Center in Rotterdam, Netherlands, detail their work on avian flu H5N1 mutation. Each describes genetic engineering that created a new strain almost 100% lethal to ferrets — generally considered the best animals to model a human respiratory infections.

Presumably, Drs.  Kawakoa and Fouchier conducted their experiments with the goal of helping to protect mankind against the virus’ inevitable change. But the National Science Advisory Board for Biosecurity sees a dark side. The agency’s official plea to both journals suggests that publishing “the  methodological and other details … could enable replication of the experiments by those who would seek to do harm.”

Their concern is not unfounded: It goes without saying that an individual, or even  a country, could use this with evil intent.  A weaponized bird flu with a 90% or higher mortality rate would make the anthrax letters of  2001-2002 look like a scuffle in a kindergarten sandbox.

But is censoring going to keep this knowledge hidden?

Scientific discoveries almost always build upon prior knowledge in a long, nearly unbroken, chain of meticulous research. Researchers publish long strings of studies on the same topic, each one evolving just slightly from the last. Others with a passion for the same topic climb on board as well, so that eventually everyone benefits.

A clear representation of this? At least some of the research that so troubles our government has already been disseminated.

Colorized transmission electron micrograph of Avian influenza A H5N1 viruses (seen in gold). Courtesy the Centers for Disease Control and Prevention

Last year, Dr. Kawakoa described his lab’s creation of an H5N1 mutation almost universally lethal to ferrets.  The study describes his work with the two most virulent forms of H5N1, both isolated from humans and both with a human kill rate of up to 80%. Dr. Kawakoa and his colleagues manipulated the genes in both to create a novel virus that appeared even more lethal, killing all of the intranasally inoculated ferrets.

The paper not only identifies the genes — hemagglutinin (HA) and nonstructural protein (NS) — but the method of reverse engineering and  the modifications’ chromosomal positions. Its purpose was not to create a super-pandemic among humans, but to identify the genes and loci that most contribute to H5N1’s uniquely dangerous potential.

His new paper, according to the National Institute of Health’s  comment,  shows “that  the H5N1 virus has greater potential than previously believed to gain a dangerous capacity to be transmitted among mammals, including perhaps humans.”

Last September, Dr. Fouchier presented his now-to-be-edited work at the Fourth ESWI Influenza Conference. During an oral presentation, he described work that resulted in some potent H5N1 mutations. According to the conference daily, the researchers infected ferrets with the new H5N1, also formed by plasmid reverse engineering and also manipulating hemagglutinin.  The infected ferrets died, but didn’t transmit the virus.

The team then let the virus do its own thing,  just moving it repeatedly from a sick ferret’s nose to a healthy nose without tinkering – the way a virus would naturally mutate by adapting to each new host.  Dr. Fouchier found a new H5N1 with new mutations: It became an airborne form after 10 transmissions, suggesting that avian flu can mutate within one species, rather than requiring a “mixing bowl” animal, like a pig.

“This virus is airborne and as efficiently transmitted as the seasonal virus,” the paper quoted Dr. Fouchier as saying. “This is very bad news, indeed.”

The meeting wasn’t secret. Journalists were there, and some even wrote about it. New Scientist ran a piece about the research, as did Scientific American.

If this much information is already out there, might it just be possible that a “rogue scientist” could come up with much, much more? And is the National Science Advisory Board for Biosecurity really suggesting that only two scientists in all the world have so advanced this virus?

It might even be possible that there are labs in other countries working on the same thing. And that some of those countries might want to suppress important findings — holding them close the vest to “protect” the populace.

We wouldn’t want that now. Would we?

—Michele G. Sullivan

Leave a comment

Filed under Epidemiology, Genomic medicine, Health Policy, IMNG, Infectious Diseases

At 25 Years, NIAMS Celebrates Progress, But Has a Long Way to Go

It’s been 25 years since the establishment of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and great strides have been made in diagnosis, treatment, and management of numerous conditions, “but you ain’t seen nothing yet,” said Dr. Francis Collins, director of the National Institutes of Health.

Opportunities for medical research have never been as great as they are today, said Dr. Collins, who gave the welcome address for NIAMS’ 25th anniversary at the NIH campus in Bethesda, Md.

Although prominent researchers in the field agreed that research has come a long way in the past 25 years, they stressed that there is still a long way to go. Currently, the molecular basis for 4,000 diseases is known, said Dr. Collins. “But we have effective treatment for only 200.”

In broad strokes, the day-long event touched on the past, present, and future of major diseases of bones, joints, muscles, and skin – including muscular dystrophies, osteoporosis, rheumatoid arthritis, and lupus – through panels and discussion involving prominent researchers, physicians, and patient advocates.

“These diseases are chronic, crippling, and common,” said Dr. Stephen Katz, director of NIAMS, in his opening address. “They affect every family in the United States.”

Among the attendees were many researchers and clinicians who said they felt loyalty and appreciation for receiving funding from NIAMS at some point in their career. For some, the progress in the past 2 decades was quite tangible.

“Public investment in osteoporosis research has really changed how we take care of the patients,” said Dr. Sundeep Khosla, president of the American Society for Bone and Mineral Research. Dr. Khosla, professor at the Mayo Medical School, Rochester, Minn., recalled a time more than 2 decades ago when calcium, vitamin D, and estrogen were the only options he could offer to patients with osteoporosis.

A few years later, bisphosphonates became available, then came anabolic drugs, and now more drugs are in the pipeline. Patient diagnosis also has advanced, he said. Although he agreed that the field still has a long way to go, he was optimistic about more progress. “Who knows what will happen in the next 25 years?” he asked.

There was talk of individualized therapy, balancing research and treatment, and a closer collaboration among scientists, all in the spirit of bringing better diagnosis and treatment to patients.

“We’re in a different world from when all we had was aspirin,” said Dr. Daniel Kastner, a scientific director at the National Human Genome Research Institute. “But what we really want is a cure. And we’re not there yet.”

Naseem S. Miller (@ReportingBack)

Leave a comment

Filed under Allergy and Immunology, Dermatology, Family Medicine, Genomic medicine, IMNG, Internal Medicine, Primary care, Rheumatology, Video

An Itch to Treat Itching More Effectively

Never underestimate the power and the agony of itching, or our inability to stop it.

Image by flickr user janhatesmarcia (Creative Commons)

I learned that many years ago at the impressionable age of 18, as I shared a hospital room with an elderly patient who suffered chronic, severe vaginal itching. If the thought of that doesn’t make you wince, this might – I could hear the attending and resident physicians standing just outside the door of our room talk about her as if we, the patients, weren’t there. They didn’t have a clue how to help her. So they decided the problem must be all in her head. One said in an irritated voice, “Let her go home and itch.”

That was 1974. Oh, how times have changed. Today, physicians and researchers are recognizing that chronic itch is like chronic pain – once it is present, it can permanently change the central nervous system to make treatment much more difficult, Dr. Timothy Berger explained at Skin Disease Education Foundation‘s Las Vegas Dermatology Seminar. We might begin to see treatments that act not just peripherally but centrally.

Photo by flickr user fifikins (Creative Commons)

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) on Oct. 29, 2010, held its first roundtable discussion on pruritus (itching), said Dr. Berger, of the University of California, San Francisco. A summary of the meeting and a list of attendees will be posted on the NIAMS Web site before the end of 2010, NIAMS media liaison Trish Reynolds told me.

Pruritus experts have expressed interest in following the example set by some European centers to create major referral centers for itch, much like pain referral centers, Dr. Berger said. Patients with difficult itching would be referred to these centers, which would collect and analyze data, store tissue samples, and tackle pruritus in a much more organized and – one hopes – successful way.

“We’re now at the point where we might be able to do something about itch,” he said.

Now, that’s what I call relief.

–Sherry Boschert

Disclosure: Skin Disease Education Foundation and my employer, International Medical News Group, are both owned by Elsevier.

Leave a comment

Filed under Allergy and Immunology, Anesthesia and Analgesia, Dermatology, Family Medicine, IMNG, Internal Medicine, The Mole, Uncategorized

Radiation’s Double-Edged Sword

Image courtesy of IAEA

—from the International Stroke Conference in San Antonio 

Ionizing radiation—useful for imaging and therapy—has undoubtedly been a boon to medicine.  The ability to quickly and noninvasively peek inside the body has not only led to faster diagnoses, but more accurate ones.  The ability to target cancerous tissue with a beam of radiation has improved therapeutic options for many cancer patients. 

However, it comes with a cost.  In the past few months, newspaper headlines have detailed cases of accidental exposure of patients to dangerously high doses of ionizing radiation for both imaging and radiotherapy.  The cases were alarming enough that members of the  House Energy and Commerce Committee’s Subcommittee on Health called radiology organizations, manufacturers, and experts to testify on ways to improve the safety of medical technology involving ionizing radiation to prevent accidents like those in the headlines. 

As that hearing occurred in Washington, data presented at the ISC was a stark reminder that even if  procedures using ionizing radiation meet safety requirements, patients could be exposed to concerning levels of ionizing radiation over the course of diagnosis and treatment of just one condition.  At the ISC,  Dr. Venkatesh Aiyagari, a professor of neurology at the University of Illinois, presented data on cumulative radiation exposure for patients with subarachnoid hemorrhage (SAH) over the course of their hospital stay. 

In the retrospective study 107 patients with SAH underwent 1,458 CT scans.  The researchers looked at cumulative effective dose, a term which refers to the radiation risk averaged over the entire body.  Over the course of treatment, 24% received moderate effective doses (>3-20 mSv), 39% received high effective doses (>20-50 mSv), and 35% recieved very high effective doses (>50 mSv). 

Let’s put that into perspective.  The U.S. Nuclear Regulatory Commission estimates the average annual radiation exposure from natural sources to an individual in the United States is about 3 millisieverts.  The NRC requires that its licensees limit maximum radiation exposure to individual members of the public to 1mSv per year and limit occupational radiation exposure to adults working with radioactive material to 50 mSv per year. 

Of course, Dr. Aiyagari’s study looked only at effective doses for one condition.  The effects of ionizing radiation are cumulative, so all of those dental x-rays, chest x-rays, and CT scans add up.  Right now, no one is tasked with keeping track, though that may change.  Earlier this year the NIH’s Clinical Center announced that radiation exposure for procedures at the center would be documented in the patient’s EHR.   Around the same time, FDA announced an initiative to reduce unnecessary radiation exposure from CT, nuclear medicine studies, and fluoroscopy.  Possible steps may include requiring manufacturers to display, record, and report equipment settings and radiation dose. 

It seems clear that physicians can expect changes in the way that medical radiation is tracked and some rethinking about how necessary some scans are. 

—Kerri Wachter ( @knwachter on Twitter) 

Bookmark and Share

1 Comment

Filed under Health Policy, IMNG, Nuclear Medicine, Radiology

Health Literacy Lesson: Education Does Not Equal Understanding

detail from painting, Changes and Communications, by Alfred Julio Jensen, photo by Heidi Splete

detail from painting, Changes and Communications, by Alfred Julio Jensen, photo by Heidi Splete

From the National Library of Medicine, Bethesda, Md.

This week I participated in a journalism fellowship at the National Institutes of Health’s National Library of Medicine, and communication was a recurring pattern. The NLM is taking several steps to improve how it communicates medical information to the public, with online initiatives including the consumer-oriented Medline Plus database and the Genetics Home Reference. But not everyone has online access, obviously. Dr. Donald A.B. Lindberg, NLM director, discussed the federal government’s investment–despite the high cost of printing–in producing NIH MedlinePlus, a magazine distributed free of charge to doctors’ offices across the U.S. as a way to get more medical information to patients. Health literacy isn’t only a function of whether you own a computer, though. Dr. Lindberg also commented that many brilliant individuals don’t automatically understand what’s under their skin.

Part of the goal of the fellowship was to learn about tools that the NLM has to help journalists communicate more effectively with our readers, and I had another reminder that education does not always equal understanding. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said that he had found it challenging to clearly communicate the details of the current pandemic H1N1 influenza virus to a group of parents whose children attend private schools in Washington, D.C. They are, he said, some of the most educated parents in the country.

Our physician readers face communication challenges every day as they try to help their patients get well and stay well. Our challenge is to give them the most useful and understandable information we can, so they can pass it on.

—Heidi Splete (on Twitter @hsplete)
Bookmark and Share

Leave a comment

Filed under Practice Trends, Primary care

What exactly IS translational medicine?

Courtesy NIH

Courtesy NIH

From the annual Academic Surgical Congress in Ft. Meyers, Florida

I’ve spent 2 days listening to presentations that fall into primarily two categories: basic science animal studies and retrospective reviews of large patient databases.  My perception was that the basic science people attended the basic science talks and the clinical people attended the clinical talks. 

The term translational medicine is bandied about a lot these days but the breakdown of these presentations got me to wondering: what exactly is translational medicine anyway?  How do you get from bench to bedside?

So I did a little digging.  According to the NIH initiative Re-engineering the Clinical Research Enterprise,

Scientists are increasingly aware that this bench-to-bedside approach to translational research is really a two-way street. Basic scientists provide clinicians with new tools for use in patients and for assessment of their impact, and clinical researchers make novel observations about the nature and progression of disease that often stimulate basic investigations.

Thinking about the sessions that I sat through over the past 2 days, I have to wonder how ‘two-way’ that street really is.  It seemed to me that basic scientists and clinicians talk more at each other than with each other.  There just doesn’t seem to be much overlap between the two worlds.

What can be done to change this in real terms, not in grand initiative terms?  Could it be as simple as listening and not just talking?

—Kerri Wachter


Filed under Practice Trends, Surgery

Unusually Full Disclosure …


From the NARSAD Symposium, New York:

A funny thing happened while I was covering the NARSAD (previously the National Alliance for Research on Schizophrenia and Depression) symposium in New York City. It had nothing to do with the research or science presented. During the last presentation of the day, Dr. Dan W. Haupt, an assistant professor of psychiatry at Washington University School of Medicine in St. Louis, caught my attention by spending more than the usual passing moment reviewing his financial disclosures. It didn’t seem all that remarkable at first– he’s a consultant for a handful of pharmaceutical companies– until you remember that at virtually every other scientific meeting, the speakers race through their disclosure slides and give them litle attention or care.  

So why the focus on disclosures by Dr. Haupt? As he explained it, the Washington University School of Medicine has a strict and comprehensive policy on conflict of interest and financial disclosures (http://medcoi.wustl.edu/medadmin/coisite.nsf/) that exceeds the requirements of the National Institutes of Health. And even when the university has determined that a consulting relationship doesn’t create a conflict, investigators are required each year to justify the interactions and state how they could affect clinical decision making, Dr. Haupt said.

Financial relationships with industry are increasingly a hot topic as Congress and the NIH call for tighter scrutiny of those ties. Recently, the NIH imposed new disclosure requirements on all grants to Emory University as it investigates whether one of the university’s scientists fully disclosed his financial ties with a pharmaceutical company. Emory officials outlined the new conditions in a letter to the research community (http://www.osp.emory.edu).

So my experience at NARSAD leaves me wondering, will I soon see more presentations like Dr. Haupt’s?

— Mary Ellen Schneider

Leave a comment

Filed under Practice Trends, Psychiatry