Wednesday, July 22, 2015

CDC Director Calls for another COMPREHENSIVE REVIEW of lab safety six months after the last one


UPDATE:   575 shipments, 192 total labs received live, incompletely irradiated Dugway anthrax.  Congressional hearing held 7/28/15.

(The subjects in my Cheer! below are among those mentioned by USAT on July 21, 2015--Nass)

The CDC Cheer 

When anthrax spores are flying through its halls, whaddaya do?

You know what to do:  It's a Comprehensive Review!

If the House is holding a hearing, whaddaya do, whaddaya do?

You know what to do:  It's a Comprehensive Review!

If USA Today is asking questions, whaddaya do?

You know what to do:  It's a Comprehensive Review!

When CDC hides Dugway's woes, whaddaya do, whaddaya do?

You know what to do:  It's a Comprehensive Review!

When 100 labs you regulate get cited, whaddaya do?

Do a Review!

Do a Review!

Do a Review!
Here is the last review of lab safety at CDC** also requested by the Director, dated January 13, 2015.  The ink is barely dry.  But since it was so much fun, why not do it again?

Posted: Jul 21, 2015 1:13 PM EDTUpdated: Jul 21, 2015 1:13 PM EDT
(USA TODAY) - The Centers for Disease Control and Prevention is launching a comprehensive review of how it regulates safety and security at bioterror labs in the wake of an ongoing USA TODAY Media Network investigation that has prompted congressional probes into the agency’s effectiveness.
CDC Director Tom Frieden ordered the review last week as USA TODAY prepared to report on newly obtained documents showing that the agency’s inspectors have allowed labs to keep experimenting with bioterror pathogens despite failing to meet key requirements on inspection after inspection, sometimes for years. The action also comes as the agency faces a hearing in the House next week.
“This review will be wide-ranging and includes a review of regulatory authority and the exercise of that authority so that we can identify potential modifications to the methods used to inspect labs,” the CDC said in a statement this week...
“We hope this latest review signals that the agency is finally taking this issue seriously," the bipartisan leaders of the subcommittee and full committee said in a statement late Tuesday about CDC's examination of its lab inspection program. "While we applaud CDC’s intent to investigate this matter, previous assessments have failed to meaningfully address the root causes of why these safety lapses keep happening..." 
And this story as reported by U Minnesota's CIDRAP
**   from the earlier review:  **  CDC lacks a culture of safety.  Just 6 months ago, an advisory committee to the CDC Director issued its recommendations to improve safety at CDC.  The report began with the following words: "Observation: Leadership commitment toward safety has been inconsistent and insufficient at multiple levels. Safety, including lab safety, is viewed by many as something separate from and outside the primary missions of public health and research.

The committee's final observation began: "We are very concerned that the CDC is on the way to losing credibility. The CDC must not see itself as "special." The internal controls and rules that the rest of the world works under also apply to CDC."  

Monday, July 20, 2015

21st Century Cures Act Dismantles Meaningful Federal Regulation of Drugs and Devices

The 21st Century Cures Act was passed (unanimously) out of Committee on July 7, 2015 and passed by the House on July 10, by a vote of 344 to 77.  

It could have been called the Stealth Act:  There was very little preceding discussion of this bill, despite its potentially huge effects on US healthcare.  TV's Katie Couric, having been affected by cancer, "wrote" a piece in the HuffPo about the bill's importance, published one day before the vote.  Forbes opined against the bill, discussing Jerry Avorn's piece in the NEJM.  That was about the extent of discussion in the media.

Jerry Avorn, a Harvard med school professor and drug industry critic, noted for example:

An underlying premise of the bill is the need to accelerate approval for new products, but this process is already quite efficient. A third of new drugs are currently approved on the basis of a single pivotal trial; the median size for all pivotal trials is just 760 patients. More than two thirds of new drugs are approved on the basis of studies lasting 6 months or less... 
More problematic proposals include encouraging the use of “shorter or smaller clinical trials” for devices and the request that the FDA develop criteria for relying on “evidence from clinical experience,” including “observational studies, registries, and therapeutic use” instead of randomized, controlled trials for approving new uses for existing drugs...
The bill would also encourage the FDA to rely more on biomarkers and other surrogate measures rather than actual clinical end points in assessing the efficacy of both drugs and devices. The FDA already uses surrogate end points in about half of new drug approvals...
Another section would allow device makers to pay a third-party organization to determine whether the manufacturer can be relied on to assess the safety and effectiveness of changes it makes to its devices, in place of submitting an application to the FDA. Thus certified by the external company, a device maker would be authorized to continue to assess its own products on an ongoing basis... 
The effects of this bill would force untested and unregulated drugs and medical devices on the public.  It would dismantle much of pharmaceutical regulatory science and practice in the US. 

This bill's provisions exemplify 'regulatory capture' on steroids.

This single bill--just one law approved by 82% of our federal House members-- would dismantle in one step patient protections that have been established over a century, established in response to medical disasters that killed thousands of Americans, and which are accepted worldwide.

Perhaps we should be grateful that the corruption in Washington has become so naked, and so bold.

How Not to Fix the F.D.A./ NYT explains that the Cure is Worse than the Disease: 21st Century Cures Act passes House

Another giveaway to health industries (and woe to patients) is embodied in the so-called 21st Century Cures Act.   It passed the House of Representatives this week before you knew it existed.

Usually industry's best friend, the NY Times surprisingly editorialized against this shameful bill today.  Here is what the Times wrote:

"A bill passed by the House and ostensibly designed to streamline the Food and Drug Administration is loaded with bad provisions and may not even be necessary. The Senate should either eliminate or rewrite the flawed provisions before passing its version of the legislation.
The bill would weaken the F.D.A.’s already flimsy regulation of medical devices, posing a threat to future patients who have devices implanted that cannot easily be removed if found defective. It would allow a drug to be tested on humans based on only limited evidence that it is safe and effective.
It would expedite the use of new antibiotics by providing financial incentives to hospitals to use them — benefiting manufacturers but also driving up costs and encouraging overuse, potentially breeding resistant superbugs. It would extend exclusive rights for manufacturers to market high-priced, brand-name drugs if they gain a new approval to treat a rare condition. And it would open a wide loophole in rules requiring companies to report payments they make to doctors to get them to prescribe their drugs.
While the bill has some valuable provisions — like making experimental drugs available more quickly to patients who have illnesses that cannot be cured, and promoting the development of treatments based on an individual’s genetic data — those elements don’t justify the bill’s passage in its current form.
The F.D.A. was once routinely vilified for sluggishness and timidity, but with the help of industry funding it has made enormous progress in speeding up its reviews and approvals. The agency testified in April that its drug review times are consistently faster than those of all other advanced regulatory agencies around the world, with the result that American patients receive new drugs sooner than people elsewhere. In 2014, the F.D.A. approved the largest number of new drugs in almost 20 years and also reduced the review times for devices.
A big reason the bill won bipartisan support in the House is that it would increase funding for the National Institutes of Health by $8.75 billion over the next five years, ending a decade of mostly stagnant funding. And any improved Senate version should certainly include new money.
Special interest money also played a role, with many of the top supporters of the legislation having received hundreds of thousands of dollars in contributions from the pharmaceutical industry and the medical device industry last year, according to the nonpartisan Center for Responsive Politics.
The Senate will take up a similar bill later this year. When it does, it needs to cure its many flaws, while also providing sufficient funds to the F.D.A. to meet its ever-increasing workload.

U.S. Health Department *Retracts* Statement on Emergent (anthrax vaccine mfr) getting an Ebola contract/ Bloomberg and WaPo

Jul 16, 2015 4:40 pm ET

USG gives contract to anthrax vaccine manufacturer to develop an Ebola drug/ Bloomberg

Recall that the current anthrax vaccine manufacturer has never developed and brought to market a single drug.  The anthrax vaccine was developed by the US army.  The company has purchased other companies, such as Cangene, that do have a few marketable products, though the market for them is small. It is also marketing a nerve gas decontamination skin cream developed by the Canadian government.

But Emergent BioSolutions, the anthrax vaccine manufacturer, has understandably high hopes and great expectations.  The company has been repeatedly smiled upon by the US government, earning billions of dollars for anthrax vaccine itself, for testing the vaccine, for developing new vaccines, for storing the vaccine, and for promises.  Now the company is making another promise, to produce drugs for Ebola.  You see, the company gets paid for the promise to try and develop such a product. The company will earn considerably more if a product actually emerges and is manufactured.  But so far, all the other products EBS was paid to develop have not panned out. 

But why should that get in the way of giving them yet another contract to develop a desperately needed product?  From Bloomberg:
Emergent BioSolutions, the maker of an anthrax vaccine, will develop and produce an experimental Ebola drug, the US government said Wednesday.   
The Department of Health and Human Services reached a two-year agreement that gives Emergent $19.7 million to develop the drug for clinical trials and, if successful, to scale up production for potential stockpiling, the agency said in an e-mailed statement.
Emergent, based in Gaithersburg, Maryland, makes the only anthrax vaccine cleared by the U.S. Food and Drug Administration, according to the product website. It also makes treatments for patients with blood disorder hemophilia B and hepatitis B.
The Ebola drug to be developed is similar to ZMapp, the experimental drug made by San Diego-based Mapp Biopharmaceutical Inc., which was given to American health worker Kent Brantly and other Ebola victims last year until supplies ran out.
ZMapp is a cocktail of three antibodies grown in modified tobacco plants. Emergent’s version uses the same antibodies but will grow them in mammalian cells, which can produce higher quantities of the molecules.
HHS and Emergent didn’t immediately respond to requests for comment on when human trials may begin.

Monday, July 6, 2015

XKeyscore/ The Intercept

What information exactly does the NSA (and its Five Eyes partners) have access to?  At least as much as noted below.  How long is the information stored?  Maybe that is a function of the storage available, which we know is increasing rapidly. From The Intercept:
One of the National Security Agency’s most powerful tools of mass surveillance makes tracking someone’s Internet usage as easy as entering an email address, and provides no built-in technology to prevent abuse. Today, The Intercept is publishing 48 top-secret and other classified documents about XKEYSCORE dated up to 2013, which shed new light on the breadth, depth and functionality of this critical spy system — one of the largest releases yet of documents provided by NSA whistleblower Edward Snowden...
These newly published documents demonstrate that collected communications not only include emails, chats and web-browsing traffic, but also pictures, documents, voice calls, webcam photos, web searches, advertising analytics traffic, social media traffic, botnet traffic, logged keystrokes, computer network exploitation (CNE) targeting, intercepted username and password pairs, file uploads to online services, Skype sessions and more...

Sunday, July 5, 2015

CDC Says USA Today Will Have to Wait 3 Years to Learn About CDC's Pathogen Mishandling

From USA Today
The Centers for Disease Control and Prevention — which has publicly disclosed three serious laboratory accidents during the past year involving Ebola, anthrax and a deadly strain of bird flu — says it will take three more years before it will release copies of all incident reports for the agency's labs in Atlanta and Fort Collins, Colo...The agency initially said it anticipated responding by June 4...
But OTOH, CDC has time to redact a 14 page report, if USAT will accept that instead! 
On May 26, the CDC sent a letter to USA TODAY offering to provide a redacted version of the 14-page lab-incident summary report instead of the full incident reports the newspaper asked for in January. "If you are amenable to accepting these records as a final response please let us know and we will send these records to you immediately... "
For full coverage of USA TODAY's investigation of safety at high-containment laboratories, go to:

Public Health Gone Awry: Birth Dose of Hepatitis B Vaccine (IOM chimes in on lack of good vaccine data)

Hepatitis B is a serious disease.  It is highly prevalent in many countries in Asia (nearly 10% of Chinese carried the illness in 1992), but fortunately is of low prevalence in the US.  Per CDC, the overall reported US incidence rate for 2013 was 1.0 case per 100,000 population. After adjusting for under-ascertainment and under-reporting, an estimated 19,764 acute hepatitis B cases occurred in the US in 2013. 

Hepatitis B is due to a virus transmitted by sex, vertical transmission from mother to newborn, from blood products and iv drug abuse primarily. There is no casual transmission. The graphs below show that disease rates in all age groups were dropping even before hepatitis B vaccine was recommended for children with no risk factors, in late 1991.

Acute hepatitis B cases in children are now extraordinarily low: according to CDC, they have fallen "from 1.2 cases per 100,000 population in 1990 to 0.02 cases per 100,000 population in 2007," or one new, acute case per 5 million children per year.  (The same CDC report notes there were 87 perinatal cases reported from 22 states in 2007, a higher incidence. I am guessing that the perinatal cases were detected via maternal screening, while the prior estimate was derived from new clinical cases in older children.)

The reduction in disease incidence is fantastic. CDC's recommendation that all pregnant women be screened for hepatitis B in 1988, and that they and their newborns be treated, is likely the major reason for the decline in pediatric and young adult cases.

But CDC didn't stop there.  CDC made stepwise recommendations for hepatitis B vaccinations for all children (who were by age at lowest risk of hepatitis B) during the 1990s, and specified a dose at birth for all newborns in 2002, even though the risk to newborns with hepatitis B negative mothers was close to zero even then. (A well-publicized controversy in France over hepatitis B vaccine-induced multiple sclerosis in the mid 1990s had affected vaccination acceptance here.  The multiple sclerosis issue was never fully resolved, while the birth dose of hepatitis B vaccine may have contributed to greater vaccine uptake in the US, according to CDC.)

What do other countries with low prevalence of the disease do with respect to vaccinating newborns, a strategy that only helps those from Hepatitis B-infected families? Data on vaccine policy for all countries in Europe can be found on the ECDC website. 

Only 5 of europe's 31 countries recommend a dose of hepatitis B vaccine for newborns whose mothers are Hepatitis-B negative: Estonia, Lithuania, Poland, Portugal, and Romania.

Incidence* of acute hepatitis B, by age group and year --- United States, 1990--2007
Incidence* of acute hepatitis B, by age group and year --- United States, 1990--2007
* Per 100,000 population.

Incidence* of acute hepatitis B, by sex and year --- United States, 1990--2007
Incidence* of acute hepatitis B, by sex and year --- United States, 1990--2007
* Per 100,000 population.
 The bars indicate the rate per 100,000 (left y-axis) by sex; the line is the ratio (right y-axis) of the incidence rate among males compared with that among females.

But here's the thing:  

Public health decisions must balance risk and benefit to the entire population when determining policy.  In the case of vaccinations, it can be devilishly difficult to ascertain vaccine causality: the true rates, types and severity of adverse reactions remain questionable, since they may be delayed by weeks, months or even years following a vaccination. (Local reactions, rarely severe, such as redness, swelling, or tenderness at the injection site are easy to assign to a vaccine, while systemic reactions are not.)

When a disease is common in the population, in order to reduce its incidence via vaccinations, one can accept a certain degree of (estimated) adverse events due to vaccinations.  

When a disease is rare, but you are still vaccinating the same number of people, the number of  vaccine-induced adverse events does not drop--but your population benefit is reduced, since you are preventing fewer cases.  Given the reduced benefit, the adverse reactions may no longer be counterbalanced by the population benefit.  But have CDC's public health professionals reevaluated their hepatitis B vaccine policy in light of current disease rates? 

There is a big, big problem at the heart of vaccination policies: there simply are no reliable adverse reaction data.  In the specific case of hepatitis B vaccine, a newborn gets vaccinated on the first day of its life, and since the parents have no prior experience with that baby, it is especially difficult to identify a systemic adverse reaction to the initial dose of vaccine.

One "non-systematic" review reported:  "After reviewing the literature, we observed that complications seen after Hepatitis B vaccination are sudden infant death syndrome, multiple sclerosis, chronic fatigue syndrome, idiopathic thrombocytopenic purpura, vasculititis, optic neuritis, anaphylaxis, systemic lupus erythematosus, lichen planus and   neuro-muscular disorder."  Observed.  Not measured.  Who knows what it means?

The label for Glaxo's Engerix-B vaccine is vague regarding causality and severity of adverse events. A WHO information sheet on Hepatitis B adverse reactions is equally troubling, as the literature it cites is full of contradictions. Hand-waving by WHO to dismiss unwanted findings is unconvincing, when a vaccination policy appropriate for reducing hepatitis B transmission to newborns in low resource areas of the world (areas without assured screening during pregnancy) has been imposed in the US on our high resource, highly screened population of mothers and infants.

I know that what I am writing seems difficult to believe.  How could vaccines be licensed by FDA without good adverse event data?  But the fact is that when they are licensed, all the data FDA evaluates have been generated by the manufacturer.  Later, it is usually not beneficial to the manufacturer to actively seek evidence of harm.

The US government requests advice from the Institute of Medicine (founded in 1970 and part of the National Academy of Sciences, chartered by Congress in 1863) regarding issues of public health.

In 2012, an Institute of Medicine which had been asked to investigate the adverse event literature for Hepatitis B and other vaccines, issued this report

Adverse Effects of Vaccines: Evidence and Causality


Committee to Review Adverse Effects of Vaccines; Institute of Medicine; Stratton KFord ARusch EClayton EW, editors. Washington (DC): National Academies Press (US); 2012.
The report's conclusions state:
The committee acknowledges that some readers may have concerns about two aspects of the report. First, the committee does not make conclusions about how frequently vaccine adverse events occur. Secondly, the committee concluded, for most analyses, that the evidence is inadequate to accept or reject a causal relationship and some readers might interpret the committee's language in different and inaccurate ways. The committee offers concluding comments to address these two issues.
This report is not intended to answer the question “Are vaccines safe?”. The committee was not charged with answering that question. Other bodies make that determination and contribute to ongoing safety monitoring, including governmental agencies, care providers, and industry, as they determine the benefits and risks of marketing a product. At all levels, policy determining vaccine use requires a balancing of risks and benefits. As described in Chapter 1 and the Preface, that is outside the bounds of this committee's assignment. It should also be noted that where the committee has found evidence of a causal relationship, it does not make conclusions about the rate or incidence of these adverse effects.
Determining the rate of specific adverse events following immunization, in the general population or a subset thereof, is challenging. It would be possible, for example, to estimate a rate of the occurrence of a specific adverse effect in a vaccinated population or susceptible subgroup of interest. This could be done using a summary relative risk or absolute risk difference (e.g., estimated from a set of consistent reports reviewed by the committee) if there were large population-based studies of the occurrence of the adverse event in unvaccinated individuals (e.g., in the general population or susceptible subgroups of interest) who do not substantially differ from those vaccinated on any known, important confounders (e.g., age and exposure to other vaccinations or other agents or factors known to cause the adverse event). None of these preconditions is fully met for the adverse events reviewed in this report.
The committee also notes here that large epidemiologic studies that report no cases of the adverse event of interest in vaccinated study participants, if included in our analyses, raise particular concerns. If at least some cases of the adverse event occurred in a study's unvaccinated comparison population, an upper limit of the 95% confidence interval (CI) for the study's relative risk or absolute risk difference could be estimated, but one would be unable to rule out a possibly increased risk unless the vaccine was significantly protective against that particular adverse effect. Also, including such studies may have exacerbated problems with detection biases unless precautions were taken to ensure equal surveillance for the adverse event in the unvaccinated and vaccinated populations being compared...

So there it is.  In the absence of good data, it is hard to make good public health decisions--but they get made nonetheless, and the decision-making is population-based, independent of any individual's unique risk-benefit profile.

But for an individual, you can make an assessment that includes your risk factors for the disease, the vaccine efficacy (very good for Hepatitis B vaccine, although duration of protection is uncertain)
 and see how that balances with the (unknown) degree of risk from the vaccination.  If you are at more than infinitesimal risk for the disease, include a factor for the considerable health risks inherent in the disease, were you to develop it in the absence of vaccination. Caveat emptor.

Thursday, June 18, 2015

Dugway does not just make anthrax. What else got sent out live?

USA Today reported that a CDC study found that anthrax spore killing had not been standardized using control spore samples at Dugway.  Tests of different spore concentrations and volumes had not been tested against different radiation doses to ascertain the degree of lethality of the process under varying conditions.

It seems remarkable to me that this could actually go on for ten or more years.  But putting my doubts aside, there is another issue:  what else was irradiated and shipped out with live pathogens?

All the select agents come to mind, including Ebola, Marburg, and anything else that many US labs are creating defenses against, and for which they are developing better and quicker detection methods.  This is a considerable collection of bad bugs.  So anthrax aside, what else went out "live" and what happened as a result?  Presumably gamma killing of the rest was not standardized or tested either, right?

Why do only anthrax scientists keep getting thrown under the bus?

UPDATE: Great source on Ivins' emails and the irradiation problem.  Ivins thought the problem was due to a new irradiation machine.

An Anonymous made a comment that Dugway is only approved as a BSL 3, not a BSL 4, which is required for work with Ebola and Marburg, and thus they do not work with those viruses. When meaning to approve the comment I erased it by mistake.

I certainly could have been wrong about which pathogens are present at Dugway, but my recollection is that Dugway did have BSL 4 status.  However, I think this is based on a document from the 1980s. It comes from an environmental impact statement for a proposed lab, which is discussed in this book. However, I also find links to army statements that Dugway has only BSL 3 labs.  USA Today claims there is a BSL-4 at Dugway.  It seems I can't resolve the discrepancy tonight.

My original point stands, which is that if Dugway's gamma irradiation did not inactivate all anthrax spores, the gamma irradiation of other pathogens was likely inadequate as well.

Thursday, June 11, 2015

USA Freedom Act: Lies the Government is Telling You/ Judge Andrew Napolitano

From the Washington Times:

Last week, Republicans and Democrats in Congress joined President Obama in congratulating themselves for taming the National Security Agency’s voracious appetite for spying. By permitting one section of the Patriot Act to expire and by replacing it with the USA Freedom Act, the federal government is taking credit for taming beasts of its own creation.
In reality, nothing substantial has changed.
Under the Patriot Act, the NSA had access to and possessed digital versions of the content of all telephone conversations, emails and text messages sent between and among all people in America since 2009. Under the USA Freedom Act, it has the same. The USA Freedom Act changes slightly the mechanisms for acquiring this bulk data, but it does not change the amount or nature of the data the NSA acquires.
Under the Patriot Act, the NSA installed its computers in every main switching station of every telecom carrier and Internet service provider in the United States. It did this by getting Congress to immunize the carriers and providers from liability for permitting the feds to snoop on their customers and by getting the Department of Justice to prosecute the only CEO of a carrier who had the courage to send the feds packing.
In order to operate its computers at these facilities, the NSA placed its own computer analysts physically at those computers 24/7. It then went to the U.S. Foreign Intelligence Surveillance Act (FISA) Court and asked for search warrants directing the telecoms and Internet service providers to make available to it all the identifying metadata — the times, locations, durations, email addresses and telephone numbers used — for all callers and email users in a given ZIP code or area code or on a customer list.
The first document revealed by Edward Snowden two years ago was a FISA court search warrant directed to Verizon ordering it to make available to NSA agents the metadata of all its customers — more than 113 million at the time. Once the court granted that search warrant and others like it, the NSAcomputers simply downloaded all that metadata and the digital recordings of content. Because the FISA court renewed every order it issued, this arrangement became permanent.
Under the USA Freedom Act, the NSA computers remain at the carriers’ and service providers’ switching offices, but the NSA computer analysts return to theirs; and from there they operate remotely the same computers they were operating directly in the Patriot Act days. The NSA will continue to ask the FISA court for search warrants permitting the download of metadata, and that court will still grant those search warrants permitting the downloading. And the NSA will continue to take both metadata and content.
The Supreme Court has ruled consistently that the government must obtain a search warrant in order to intercept any nonpublic communication. The Constitution requires probable cause as a precondition for a judge to issue a search warrant for any purpose, and the warrant must “particularly [describe] the place to be searched, and the persons or things to be seized.” Because this is expressly set forth in the Constitution itself, Congress and the president are bound by it. They cannot change it. They cannot avoid or evade it.
Probable cause is evidence about a person or place sufficient to permit a judge to conclude that evidence of a crime will probably be found. Both the Patriot Act and the USA Freedom Act disregard the “probable cause” standard and substitute instead a “government need” standard. This is, of course, no standard at all, as the NSA has claimed under the Patriot Act — and the FISA court bought the argument — that it needs all telephone calls, all emails and all text messages of all people in America. Today it may legally obtain them by making the same claim under the USA Freedom Act.
When politicians tell you that the NSA needs a court order in order to listen to your phone calls or read your emails, they are talking about a FISA court order that is based on government need — not a constitutional court order, which can only be based on probable cause. This is an insidious and unconstitutional bait and switch.
All this may start with the NSA, but it does not end there. Last week, we learned that the FBI is operating low-flying planes over 100 American cities to monitor folks on the streets and intercept their cellphone use — without any search warrants. Earlier this week, we learned that the Drug Enforcement Administration has intercepted the telephone calls of more than 11,000 people in three years — without any search warrants. We already know that local police have been using government surplus cell towers to intercept the cellphone signals of innocent automobile drivers for about a year — without search warrants.
How dangerous this is. The Constitution is the supreme law of the land. It applies in good times and in bad, in war and in peace. It regulates the governed and the governors. Yet if the government that it regulates can change it by ordinary legislation, then it is not a constitution but a charade.
Suppose the Congress wants to redefine the freedom of speech, the free exercise of religion or the right to keep and bear arms, just as it did the standards for issuing search warrants. What is the value of a constitutional guarantee if the people into whose hands we repose the Constitution for safekeeping can change it as they see fit and negate the guarantee?
What do you call a negated constitutional guarantee? Government need.

Tuesday, June 9, 2015

As the Anthrax Story Keeps on Coming: 68 labs, 5 countries

On June 9, two weeks since this story first burst forth, we are up to 68 labs that likely got some live anthrax from Dugway.  And another country has been added, the UK.

If the story is accurate as told so far, what probably happened is that there was incomplete inactivation due to inadequate doses of gamma irradiation.  Those responsible for the inactivation process (usually exposing spores to cesium or cobalt sources of gamma rays) may not have recalibrated the radiation dose for larger collections of spores, and for different containers, media, etc. Bacterial killing is not like killing cows.  A cow is either alive or dead.  But collections of bacteria die at log rates, and killing that very last spore can require a much higher dose of radiation than is needed for the first 99.99% of the batch.

The good news is that it takes, in general, many thousands of inhaled spores to produce an infection. So small numbers of live spores won't generally make anyone sick.  Though even one can be used to grow a deadly batch of new anthrax spores.

Live Anthrax Sent to 66 Labs in 19 States, Washington DC and 3 Countries: But Nobody Discovered This for Years? It Strains Credulity.

I will be writing more about the US DoD assertion that up to 66 laboratories in 19 states, the District of Columbia and three countries  (Australia, South Korea and Canada) received live anthrax spores by mistake from an Army lab at Dugway Proving Ground in Utah. The June 4 WSJ (behind a paywall) says the problem has existed for "over a decade".

The story seems improbable to me, since the mistake should have been caught fairly quickly, not many years later.  Scientists who work with potentially deadly organisms generally don't take claims of their inactivation by others, elsewhere, on faith:  they plate them out and incubate them and check whether there is growth, to be sure there are no live spores, before exposing themselves to a deadly agent.  To imply that scientists at 66 laboratories all failed to perform this procedure, which is SOP, strains credulity.

In 2014 it was found that CDC had a similar issue: it was reported that anthrax spores had been 'inactivated' using a chemical procedure that was sufficient for anthrax in its vegetative form, but not in its spore form. This was said to have exposed about 80 people at CDC to potentially aerosolized spores.  The mistake was discovered when plates were left by chance for a week in an incubator, and late growth was discovered.

The story was that after the chemical treatment, spore growth on plates (into vegetative cells) was delayed but not prevented.  The incident exposed several levels of incompetence. Any idiot working with anthrax should have understood that anthrax' niche as a bioweapon stems from its ability to retain growth potential even after being exposed to extremes of pressure, temperature and dryness (dropped from bombs or airplanes), while in spore form. A spore is anthrax in 'suspended animation.' But during active growth, in the vegetative stage, anthrax is very easily killed.  (Though you must be sure none of it forms spores before it is killed.) As a spore, anthrax is inactivated only with great difficulty.  Which is reflected by how it can start to grow, given the right conditions, even after spending one hundred years or more in spore form.

The CDC mishap informed researchers that they should be alert for delayed growth, when anthrax has been exposed to a procedure intended to kill or damage it, so plates testing anthrax growth should be incubated for longer than normal.  

Below are excerpts from 2 abstracts pointing out that irradiation of spores may not always kill them.  Many factors influence the dose of radiation required to kill all spores in a bundle, including whether spores are wet or dry, the type of diluent, the geometry of how spores are packaged together during irradiation, type of packaging and spore concentration. These factors are only partly understood.  Furthermore, bacteria and spores undergo log killing (as opposed to an all-or-nothing process): a low radiation dose allows, for example, 1/1,000 spores to survive, while a higher dose only allows 1/1,000,000 to survive.

But that is why you test your batch to ensure it is fully inactivated before you expose yourself to it. And Dugway would have been required to do so before shipping it out to others.  Dugway produced most of the anthrax that was stored in Bruce Ivins' flask RMR1029.  Dugway has been making large production runs of anthrax for many years. It is not a newcomer to this enterprise.

Also note that when spores are shipped, their packaging within packaging is supposed to prevent any leakage of contents, no matter what type of indignities the package may be subjected to, en route. (There are federal rules that were enacted after leakage many decades ago.) And packages must be tracked carefully as well.

For example:  here is part of an SOP published by University of Pittsburgh investigators on what it takes to approve a method for inactivation of select agents (those microbes, like anthrax, designated as high threat agents for bioterrorism):

Standard Operating Procedure for Obtaining Approval and Safety Testing of a Sample Inactivation Method
  • 1. For all sample inactivation procedures, the investigator  and  his  or  her  staff must  notify the  Team  of the intent to  inactivate  biological  materials  for  removal  from  the  RBL  BSL­3/registered Select Agent facility. 
  • 2. The proposed inactivation procedure must be discussed  either at a strategy meeting prior to initiation of a project or  at  the  investigator’s  standing  monthly  meeting  with  the  Team. 
  • 3. Each proposed inactivation method must be described  in  detail,  along  with  corresponding  safety  testing  procedures that demonstrate the lack of viable infectious material  after the inactivation procedure. 
  • 4. An investigator may use an original inactivation procedure, or  he  or  she may  use an existing inactivation  procedure published elsewhere or developed by another investigator and listed in this SOP. 
  • 5. Once  the  Team  has  been  notified  of  the  inactivation  procedure,  the  investigator  may  proceed  with  performing  safety testing on the inactivated materials. Safety testing is  required  for  both  original  inactivation  procedures  and  for  existing inactivation procedures developed by other investigators or published in the literature. 
  • 6. If  an inactivation method is to  be  used  for more than  one pathogen, safety testing data must be provided for each  pathogen or type of pathogen. 
  • 7. It is  recommended to  use  a  high­ titer  or  concentrated stock of infectious agent in the safety testing to provide the  most rigorous challenge to the inactivation procedure...
1.    2006 Sep;101(3):514-25. 
Spores of Bacillus subtilis: their resistance to and killing by radiation, heat and chemicals.
Setlow P1.
A number of mechanisms are responsible for the resistance of spores of Bacillus species to heat, radiation and chemicals and for spore killing by these agents... Both UV and gamma-radiation also kill spores via DNA damage. The mechanism of spore resistance to gamma-radiation is not well understood, although the alpha/beta-type SASP are not involved...  Given the importance of the killing of spores of Bacillus species in the food and medical products industry, a deeper understanding of the mechanisms of spore resistance and killing may lead to improved methods for spore destruction.

2.    2008 Jul;74(14):4427-33. doi: 10.1128/AEM.00557-08. Epub 2008 May 30

Gamma irradiation can be used to inactivate Bacillus anthracis spores without compromising the sensitivity of diagnostic assays.

Dauphin LA1Newton BRRasmussen MVMeyer RFBowen MD

The use of Bacillus anthracis as a biological weapon in 2001 heightened awareness of the need for validated methods for the inactivation of B. anthracis spores. This study determined the gamma irradiation dose for inactivating virulent B. anthracis spores in suspension and its effects on real-time PCR and antigen detection assays. Strains representing eight genetic groups of B. anthracis were exposed to gamma radiation, and it was found that subjecting spores at a concentration of 10(7) CFU/ml to a dose of 2.5 x 10(6) rads resulted in a 6-log-unit reduction of spore viability... 

Thursday, May 14, 2015

HR 2322: A One-Size-Fits-All Bill to Vaccinate Every American Child With Every Vaccine CDC/ ACIP Recommend

Wow!  Who saw that coming?  The Constitution did not specify that medical care was a federal responsibility, so for over 200 years it has been left to the states.  Yes, fifty years ago we got Medicare and Medicaid, and now the Affordable (for whom?) Care Act, but the specifics of what drugs and vaccines people receive has been left to the states... and to doctors and patients working collaboratively.

Now we have HR 2232 that says every child, all the time, must receive whatever vaccines a group of industry insiders (CDC's Advisory Committee on Immunization Practices) add to the vaccine schedule.  Is this bill going to be attached as a rider in the dead of night to some other bill and passed before we know it?  The bill is an extraordinary overreach, and it is sad that a black Congresswoman, Frederica Wilson, introduced it.  However, one does not need to look very far to find the long arm of Pharma behind it:  Representative Wilson's senior advisor Kenneth Austin previously worked for Abbott, a pharmaceutical company, and GlaxoSmithKline, a major vaccine manufacturer.

At least the W.H.O. still knows that vaccination decisions should be made through risk-benefit assessment, not one-size-fits-all, shotgun approaches that benefit industry primarily.  We already have the 1995 Vaccines for Children Act that provides vaccines to every child in the country (55%) who might not afford them.  From W.H.O.:

Key point
Risk/benefit assessments should be applied to most situations relating to the efficacy or safety of vaccines to ensure public safety and public health.