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Because of recent events and the fact that there is
so much misinformation being provided to the public from all sources,
ASA suggested to Prof. Meselson that we reprint this article with an
update from him to precede the reprint. The original ASA article received
outstanding comments from scientists all over the world.
Note Regarding Source Strength
by Professor Matthew Meselson
The "Note Regarding Source Strength" reproduced below
is the same as that published in the ASA Newsletter of June 8, 1995,
except for the correction of a typographical error (the omission of
"pi") in the equation for dose in Table 1.
Note
that source strength is defined as "the number of viable spores released
at the source that travel in the atmosphere as particles small enough
to initiate inhalation anthrax". Using this definition, the source strength
estimates in Table IV are given in milligrams,
taking the number of spores per milligram, as stated, as 109.
The question of whether the aerosol released at Sverdlovsk consisted
only of viable spores or also contained inviable spores and other material
is obviously not addressed in the present estimates. These estimates
should be regarded only as what they are: estimates of source strength,
as defined in the note, that follow from the stated assumptions regarding
atmospheric dispersion and regarding dose-response relations for the
infectious aerosol and the human population exposed to it.
Although
the present estimates follow from the assumptions made, the most relevant
dose-response data available are for non-human primates, not for any
human population, and none of it is for the low attack rates observed
in the Sverdlovsk outbreak. Neither do we know if the virulence of anthrax
spores in the aerosol released at Sverdlovsk was like that in aerosols
employed in published experiments with monkeys. And even the well done
experiments at Fort Detrick and Porton with monkeys gave ID50
values covering a more than twenty-fold range -- from 2,000 to 45,000
respirable spores. These uncertainties are only imperfectly addressed
by considering a number of different dose-response relations, as is
done in Table IV.
It
may be of interest that the estimates presented here have an antecedent
in an April 1980 memorandum I wrote for the US Interagency Sverdlovsk
Working Group. We had no reliable information about the geographical
distribution of attack rates. So we could only estimate what dose would
be inhaled at a given downwind and crosswind distance from an aerosol
release of a given number of spores under given atmospheric conditions.
My estimates of dose as a function of source strength, based on a Gaussian
plume model for a moderately stable atmosphere, were, as to be expected,
in good agreement with those in the present Table
II. Some members of the Working Group, apparently unfamiliar with
atmospheric dispersion models, thought my estimates of source strength
were far too low. The following month we received a memorandum from
Dugway Proving Ground with estimates in essential agreement with those
in my memorandum and in the present Table II.
By then, however, a very much higher estimate had already been briefed
to President Carter by Admiral Stansfield Turner, then Director of Central
Intelligence.
(The reprinted article)
Note Regarding Source Strength
by Professor Matthew Meselson
In
November 1994, Prof. Meselson described the size and source of a plume
of anthrax spores in Sverdlosk in 1979. The model employed and calculations
performed to estimate the concentration of spores is presented here.
Cambridge, Massachusetts.
This note
provides background information regarding the estimate of Meselson et
al. (Science 266: 1202-1208, 1994) that the aerosol that caused the
Sverdlovsk anthrax outbreak of 1979 contained between a few milligrams
and nearly a gram of anthrax spores. Figure and reference numbers correspond
to those in the Science article.
Estimating
source strength. We define the source strength as the number of
viable anthrax spores released at the source that travel in the atmosphere
as particles small enough to initiate inhalation anthrax. Source strength
may be estimated from knowledge of: (i) the attack rate among people
at a particular location; (ii) the dose D (number of spores inhaled)
corresponding to the attack rate, obtained from the dose-response relation;
(iii) the ratio R of the dose at the particular location to the source
strength, computed from the applicable atmospheric dispersion model
and the breathing rate of the exposed population. The source strength
is then D/R.
Atmospheric
dispersion model. The Gaussian plume model used in the article to
compute dose as a function of source strength at any downwind distance
(x) from the source and crosswind distance (y) from the cloud centerline
is given in Table I. The model employs sigma-x
and sigma-y values given by Briggs (21) for an atmosphere of neutral
stability (stability "D") on open terrain. The breathing rate is taken
as 30 L/min, as for a man engaged in light work (33).
Comparison
with other dispersion models. Table II gives
centerline doses for a source strength of 1010 spores calculated
from the atmospheric dispersion model and the breathing rate used in
the article and given in Table I. For comparison,
Table II also gives centerline doses calculated
from three other atmospheric dispersion models: Gaussian plume with
sigma values given by Briggs (21) for a slightly stable atmosphere (stability
"E") on open terrain; POINT V Gaussian puff model for stability "D"
with sigma values given in Table 2, page 17 in "Methodology for Chemical
Hazard Prediction" (Department of Defense Explosives Safety Board, Washington
DC, 1980); and the TNO "Yellow Book" Gaussian puff model for stability
"D" (TNO Defence Research, Rijswijk, The Netherlands). For each model,
it is assumed that there was no limit to vertical mixing. Depending
on the actual height of the mixed layer, the tabulated doses may be
subject to upward revision at large downwind distances.
Attack
rates. As described in the article, the attack rate at the ceramics
factory, circa 2.8 km downwind of the source and apparently intersected
by the cloud centerline, was about 2% (10/450) for pipe shop workers
and 0.8% (8/1,050) for those who worked in buildings west of the pipe
shop. The latter include anthrax patients who worked in the tile shop,
maintenance shop, and cafeteria. The overall rate was therefor 1-2%.
To calculate source strength, the article takes the attack rate 2.8
km directly downwind of the source as 2%.
Attack rates may also be estimated for two other locations, not considered
in the article. These are a residential section and an automotive maintenance
and repair center located, respectively, upwind and downwind of the
ceramics factory. The residential section had a population density of
10,000/km2. The part of it within the outermost constant
dosage contour of Figure 2 and bounded by the ceramics factory and Compound
32 covers 0.7 square kilometers. If 10% of the adult population were
at home at the time of cloud passage (including absentees, night workers,
pensioners, sick, unemployed, and vacationers), about 500 adults would
have been present. Ten patients were mapped within the area in question
(Figure 2), for an average attack rate of 2% or somewhat higher close
to the cloud centerline. An additional 8 patients resided in the area
but were mapped at their workplaces. If some of them were actually at
home when exposed, the average attack rate for the area could have been
about 3%.
The automotive maintenance and repair center, located about 3.9 km directly
downwind of the source, had three anthrax patients (Figure 2, patients
45, 46, and 62). From a cursory tour of the center, I estimate that
it had 200-300 employees. The corresponding attack rate would be about
1%, subject to errors of sampling and ascertainment.
It
appears from the above that the attack rate of 1-2% recorded at the
ceramics factory is consistent with the rates estimated for locations
upwind and downwind of it, providing some assurance that the ceramics
factory rate used in the article for source strength estimation is not
anomalous.
Dose-response
relation. The largest uncertainty in estimating the source strength
is not in the model of atmospheric dispersion or in the estimate of
the anthrax attack rate but in the relation between the number of viable
spores inhaled and the probability of contracting inhalation anthrax.
Even if there were an agreed dose-response relation for non-human primates,
which there is not, there would remain uncertainty regarding the relation
applicable to the actual population at risk and the particular aerosol
encountered at Sverdlovsk.
In
order to reflect the uncertainty, the article employs two different
dose-response relations. These are described in the text and in Table
III:
- Log-normal with a human LD50 of 8,000 spores (8) and
a slope of 0.7 probits per log dose (26,35). The LD50 comes
from a U.S. Department of Defense estimate that the human LD50
is 8000-10,000 spores (8). The probit slope is that reported by Glassman
(26, 35) for a large-scale experiment with cynomolgus monkeys.
- Independent spore action (38) with LD50 = 45,000. The
LD50 is that reported by Druett et al. for rhesus monkeys
(37).
A
log-normal relation allows for heterogeneity in susceptibility among
individuals in the exposed population. This is particularly important
at low attack rates, as at Sverdlovsk, since the more susceptible members
of the population will be over-represented among those who contract
anthrax.
The
independent action relation is based on the reasonable assumption that
spores act independently, not cooperatively, in the initiation of inhalation
anthrax. But the model assumes that there is no heterogeneity of susceptibility
in the population. At low attack rates, the neglect of heterogeneity
will cause the dose to be overestimated. The estimate from the independent
action dose-response relation, with a high LD50 (45,000 spores)
and no allowance for heterogeneity, is included in the Science article
in order to present an extreme high-end estimate.
Source
strength. Table IV gives source strengths, in
milligrams, calculated from three different dose-response relations
and two different atmospheric dispersion models for an attack rate of
2% at a distance of 2.8 km directly downwind of the source and a breathing
rate of 30 L/min.
In
addition to the two dose-response relations used in the article, the
table gives source strengths estimated on the basis of independent spore
action with LD50 = 8,000. The doses for a 2% attack rate,
calculated dose-response relations A, B, and C, are 9.3, 230, and 1300
spores, respectively. The number of spores per milligram is taken as
109 (39).
The
two estimates given in the Table for dose-response relations A and C
with the Briggs "D" atmospheric dispersion model are those given in
the Science article.
Matthew Meselson
Editor's Note: Prof. Meselson has been at Harvard long
enough to be classified a true New Englander and this evening his true
New England spirit was tested to the max. ASA cajoled the Professor
into going over this paper until almost 0200 hours on 12/17 (we had
to be at the printer at 0800). Matt - many thanks.
References:
Note: All numbered footnotes refer to the article listed below.
The Sverdlovsk Anthrax Outbreak of 1979
Matthew Meselson, Jeanne Guillemin, Martin Hugh-Jones, Alexander Langmuir,
Ilona Popova, Alexis Shelokov, Olga Yampolskaya
Science, New Series, Vol. 266, No. 5188. (Nov. 18, 1994),
pp. 1202-1208.
Stable URL: http://links.jstor.org/sici?sici=0036-8075%2819941118%293%3A266%3A5188%3C1202%3ATSAOO1%3E2.0.CO%3B2-1
TABLE I
BASIS OF DOSE CALCULATIONS
Atmospheric stability "D"
Wind speed circa = u = 5 m/sec at 10 m
Release height = 10 m
Source strength = Q spores
Deposition negligible
Infectivity independent of travel time
No mixing layer
Breathing rate = B = 5 X 10-4 m3/sec (= 30 L/min)
Dose = [QB][pusysz]-1exp[-(1/2)(y/sy)2]exp[-(1/2)(10/sz)2]
p = [3.18 X 10-5Q][sysz]-1exp[-(1/2)(y/sy)2]exp[-(1/2)(10/sz)2]
sy = [0.08x][1+0.0001x]-1/2
sz = [0.06x][1+0.0015x]-1/2
Downwind (x) and crosswind (y) distances are in meters.
TABLE II
CENTERLINE DOSE (SPORES) FROM FOUR MODELS
Wind speed circa = 5 m/sec
Breathing rate = 30 L/min
Source strength = 1010 Spores
|
Downwind
|
Briggs
|
Briggs
|
POINTV
|
TNO
|
|
distance
|
"D"
|
"E"
|
"D"
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"D"
|
|
1 km
|
106
|
219
|
317
|
281
|
|
2 km
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36
|
75
|
109
|
91
|
|
3 km
|
20
|
42
|
46
|
46
|
|
4 km
|
13
|
28
|
28
|
29
|
|
10 km
|
3.7
|
9.9
|
5.6
|
6.3
|
|
50 km
|
0.6
|
2.8
|
0.3
|
0.7
|
note: Stability "D" is neutral. Stability "E"
is slightly stable
TABLE III
DOSE-RESPONSE RELATIONS
|
LOG-NORMAL
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INDEPENDENT ACTION
|
|
LD50 = 8,000 spores
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LD50 = 45,000 spores
|
|
Slope = 0.7 probits/log dose
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Att.Rate = 1-(1/2)dose/LD50 = 1-exp[-0.69(dose/LD50)]
|
|
(Dose)
|
(Attack Rate)
|
(Dose)
|
(Attack Rate)
|
|
8000
|
.500
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8000
|
.115
|
|
4000
|
.417
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4000
|
.059
|
|
2000
|
.337
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2000
|
.030
|
|
1000
|
.264
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1000
|
.015
|
|
500
|
.200
|
500
|
.008
|
|
250
|
.146
|
250
|
.004
|
|
125
|
.103
|
125
|
.002
|
|
60
|
.068
|
|
|
|
30
|
.045
|
|
|
|
15
|
.028
|
|
|
|
8
|
.018
|
|
|
|
4
|
.011
|
|
|
|
2
|
.006
|
|
|
|
1
|
.003
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|
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Editor's Note: Using the first model of an LD50 of 8,000
spores and 0.7 probit/log dose, a dose of 9 spores would result in
the attack rate of 2% (the pipe shop workers). The high end estimate,
using the LD50 of 45,000 spores, based on rhesus monkies,
and the assumption that anthrax spores act independently, requires
a dose of just over 500 spores to result in an attack rate of 0.8%
(the number of workers affected west of the pipe shop).
TABLE IV
SOURCE STRENGTH ESTIMATES
A: LOG NORMAL WITH LD50 = 8,000, SLOPE 0.7.
B: INDEPENDENT SPORE ACTION WITH LD50 = 8,000
C: INDEPENDENT SPORE ACTION WITH LD50 = 45,000
|
DISPERSION
MODEL
|
RELATION A
DOSE = 9.3
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RELATION B
DOSE = 230
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RELATION C
DOSE = 1300
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BRIGGS "D"
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4 mg
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110 mg
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600 mg
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|
BRIGGS "E"
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2 mg
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50 mg
|
280 mg
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