The right organization will not succeed without the required leadership. Admiral Crowe was the chairman when Goldwater-Nichols became law; however little changed. When General Powell became chairman, he took the bold action required to institute what Congress had legislated.

There are lessons to be learned from other events that also bear on the issue of organizing and a few merit mention here.

The flawed response to Katrina points out the imperative for people in positions of responsibility to actually understand their statutory authorities and responsibilities, as well as the organizational mechanisms put in place for fulfilling those responsibilities. They also need to have some level of operational competence. Michael Brown did not understand FEMA’s authorities or responsibilities or the National Response Plan, or what it takes to mount an effective response when subordinate levels of government are overwhelmed. In contrast, the Coast Guard in Katrina was populated by men and women at all levels who understood their authorities, responsibilities and capabilities and knew how to operate. Some 33,000 Americans survived Katrina because the Coast Guard had that kind of professionalism and operational competence. And it still does.

The outcome of the failed Desert One hostage rescue mission in Iran makes clear the importance of structuring an operation for success rather than so that everyone gets a shot at shared glory. I am not one prone to quoting Navy flag officers when a pearl of wisdom is needed, but a quote I have heard attributed to Admiral William “Deke” Parsons gets it right – “There is no end to the good a man can do, provided he cares not who gets the credit.” What is important is getting the job done, not who does it or who gets credit for it. Of course, getting the job done requires that someone with the right tools and skills actually gets invited to the party.

The difficulties encountered in the response to the Deepwater Horizon oil spill point out the importance of ensuring that the available response mechanisms are properly scaled to the potential size of the event. The Oil Pollution Act of 1990, written in response to the EXXON VALDEZ oil spill, was scaled for events up to a major ship-sized spill and was extremely effective in that domain. But many of the statutory requirements in OPA ’90 and much of the response planning and preparation under it were inadequate for a spill of the size of Deepwater Horizon. The point here is that the enabling authorities have to be adequate for event, and they have to be available at the outset. Waiting for after-the-fact emergency legislation or executive Orders is guaranteed to lead to failure. However, having adequate authorities available at the start is not enough. As certain aspects of the Deepwater Horizon response show, it is imperative that political leaders and others in positions of authority actually know enough about the authorities, responsibilities and preparations already in place so that they don’t inadvertently act in such a way that an existing response regime is effectively nullified and a vacuum created in its place. There are provisions of OPA ’90 that would have been adequate in the Deepwater Horizon event but they were not allowed to be used because ill-considered actions by politicians at all levels preempted or precluded their use.

Organization is unimportant and it is all important. It is unimportant in that there are many ways of organizing for success. It is also all important in that you can organize so as to preclude the possibility of success. However, having a “right organization” on paper does not mean that you will succeed. You must also have the wherewithal, most especially properly skilled and experienced people, to enable said “right organization” to operate effectively.

Mr. Leitenberg’s comments on the potential for a terrorist bioweapon appear to be based on observations of state programs, such as that in the former Soviet Union, to produce militarized biological weapons for the battlefield. But to be useful in a battlefield setting, a biological weapon would need to be ruggedized, mated to a suitable delivery system (e.g., artillery), with quantities sufficient to be deployable over a large area in the field, and with effectiveness sufficient to affect battlefield outcomes (i.e., a casualty rate in excess of 25% or so). Meeting these requirements is, as Mr. Leitenberg has correctly noted, not easily done, even for a state with the capabilities of the former Soviet Union. Or the United States for that matter.

The requirements for a battlefield weapon, however, are very different than those for a terrorist weapon. A terrorist bioweapon would not have to be ruggedized for the battlefield, nor would it have to cover a large area in order to be effective. It would also not have to be nearly as effective as a battlefield weapon in order to be effective as a TERROR weapon.

In short, by failing to take the differences between state programs aimed at the battlefield and a potential terrorist biological weapon, together with recent developments in global biological science capabilities into account, Mr. Leitenberg is leaping heroically to unsupportable conclusions.

Why the third stage of Michael Montague’s plan and not the first? The barriers for creating a national bio-surveillance system that reaches a representative selection of the US population are considerable and varied, and by-enlarge, not bio-technological in nature.

The first and most severe such barrier is public fear which in turn drives policy. The US is a nation that has so far resisted even the elementary step of a unified national ID card even to the point of States refusing to cooperate with the federal Real ID Act. Video surveillance systems that would be introduced in other parts of the developed world with little or no thought for privacy are strongly resisted in the US. This strong distrust by the public of anything that could be called “government surveillance” remains very alive even after 911. One of the many consequences of this fear is the creation of government policies to address it. There are a large number of laws and regulations, including but not limited to HIPAA, that impose complex and stringent regulation concerning the handling of patient data and samples. Pooling samples and getting a read-out of viruses resident in a clinical population might have been legal in 1970′s, when such technology was being developed at Oak Ridge, but is now something that would, by law, require significant administrative oversight. Such oversight would need to be in place before, not after, the technology-component was in place otherwise fear-mongers on the grass-roots and political levels would kill such a bio-surveillance effort before it could begin. This is one of the reasons that Michael Montague’s previously stated plan does not start with the introduction of new or old technology, but rather with an administrative framework using only data that is already being collected.

Another barrier to creating a useful bio-surveillance program is data management and analysis. When was a sample taken? When was it analyzed? When was the related data transmitted to a central database? Where is it from? Is that the location of the patient’s home? Of the hospital? Was the analysis performed at one of those locations, or at a third location? Each of these questions alone, and for a single specimen, are easy. However, managing and characterizing the answers to all of these questions at the same time, and for thousands to millions of specimens, and doing so without causing privacy concerns, see above, and doing it in anything like a real-time manner is NOT easy. This is the other reason why Michael Montague’s plan focuses upon building a central database using existing data first, and creating new forms of data to populate it only later. Without a firm handle on the meta-data associated with a pathogen detection, such a detection is all but useless.

This explains why would Dr. Anderson’s pooling and centrifuging technology can not be the the first stages of a bio-surveillance program, but why shouldn’t it be the last? In essence, Dr. Anderson’s proposal is a metagenomic study of the viral fraction of pools of clinical samples. As such, we can expect all of the traditional difficulties that have been observed with other metagenomic studies:
Detection by sequencing suffers from numerous problems. Even with immuno and hybridization based subtraction of known viruses, many rounds of sequencing will be required to achieve anything like a complete characterization of the pooled sample. Without such subtraction, the most populous species in the population will be sequenced many times consuming output bandwidth. Consumption of bandwidth prevents rare species in the pool from being sequenced at all. Next generation sequencing technology has not been able to add enough bandwidth to directly overcome this. Immuno-subtaction, and subtractive-hybridization could eventually overcome this, but only with multiple rounds of sequencing. Initial rounds of sequencing are needed to determine the most populous viruses in the pool. Only then would one know which viruses to subtract out from subsequent rounds of sequencing. Multiple rounds of sequencing followed by subtraction by antibodies and/or hybridization can rapidly become extremely expensive, and is always very slow because libraries must be remade. The result is that, after the centrifuge step, each pool would take many weeks or even months to analyze (and that’s without any effort to assemble the resulting reads). Thus, with current methods, data-sets from pooled samples analyzed by sequencing, would require vast resources to be available in anything like real-time. With the removal of the sequencing detection method and the introduction of a multiplex PCR coupled with microarrays, and/or an ELISA-on-a-chip detection method in it’s place, something like Dr. Anderson’s centrifuge purification of the viral fraction of pooled samples would be quite useful. This is exactly the sort of thing described in the third stage of Michael Montague’s plan. Of course, not all biological threats are viral, so centrifuge based purification could only be one part of a larger detection strategy even at the third stage of the plan.
However, from an epidemiological point of view, pooled samples provide an imperfect data-set regardless of the technological details of how they are analyzed. This is because the viral load of a given infection is highly variable from patient to patient and at different points during the infection. The consequence is that there is no definitive way to distinguish between 1% off the contributors to a pool being positive for a given pathogen, and 100% being positive or anything in between. Also pooling samples imposes a timing penalty since the oldest sample to be added to a pool is delayed waiting for the last sample. For periodic but infrequent snap-shots of the circulating pathogens this might not be a major concern, however, the detection of a natural epidemic or a biological attack is not something that can wait. Look at how rapidly the swine flu situation developed. This is why Michael Montague’s plan does not stop at just pooled samples (the third stage of the plan), but proceeds toward a larger goal of cheap, fast, individual, broad-spectrum detection with anonymous national data gathering and analysis.

In reference to Dr. Montague’ comments:

Global Screening for Human Viral Pathogens has been described in detail in http://www.cdc.gov/ncidod/eid/vol9no7/03-0004.htm. Briefly the procedure includes nationwide routine collection of both normal and diagnostic sera, shipment of these to centralized laboratories for analysis, pooling of excess diagnostic sera now routinely discarded (amounting to hundreds of liters per week), recovery of the viral loads from
100 liter batches using the K-II centrifuge (which I developed in collaboration with the Gas Cenrifuge program at Oak Ridge), further concentration and purification using microgradient ultracentrifuges recently developed, shotgun sequencing of the concentrates, and data reduction and sequence reconstruction. Assuming 1 ml per originall donor, and ten centrifuges in parallel, one million cases can be scanned per run, assuming sufficient collection. The total viral load is concentrated down to less than the average volume of one original sample, hence the final concentration can approach that in each original viremic donor. In general viremia peaks with fever, hence the importance of obtaining samples on admission, as can be done here. The methods apply equally well to urine, and modifications apply to tissues. A complete concentration run takes less than three days. The objective is a running inventory of all viruses in circulation in man. The K-II centrifuge is used world wide to purify commercial vaccines, especially those for influenza. Much of this work depends on studies done on marine viruses. Organization of this work is proceeding in China.