CASE CLOSED … what really happened in the 2001 anthrax attacks?

* An important key to understanding the Amerithrax timeline during the relevant September-October 2001 period hinges on the documentary evidence still inexplicably being withheld.

Posted by DXer on March 25, 2011

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38 Responses to “* An important key to understanding the Amerithrax timeline during the relevant September-October 2001 period hinges on the documentary evidence still inexplicably being withheld.”

  1. DXer said

    “On July 18, 2007, a forensic psychiatrist completed a detailed review of Dr. ivins insurance billing records for medical appointments and prescriptions. Additionally, this psychiatrist was provided with an overview of Dr. Ivins’ social habits, interests, and obsessions.

    The forensic psychiatrist stated based on his experience, if Dr. Ivins was the mailer, it is quite possible that Dr. Ivins retained some kind of souvenir or references to the mailing events.”

    Wasn’t Dr. Saathoff, the long-time partner of FBI Quantico, this forensic psychiatrist?

    Does this mean the FBI has the insurance billing records that confirm that Dr. Ivins had a group therapy session scheduled on September 17, 2001?

    Why do journalists allow the FBI to characterize Ivins’ alibi as “crappy” when the FBI is withholding the relevant documents? Isn’t it the FBI’s document production that has been crappy?

    Haven’t identifiable individuals knowingly withheld Dr. Ivins’ contemporaneous lab notes written describing what he was doing in the lab on September 28, September 29, September 30, October 1, and October 2?

    Haven’t identifiable individuals knowingly withheld Dr. Ivins’ email to Mara Linscott on September 17, 2001?

    Will Dr. Ivins’ alibi look crappy when the FBI finally is forced to produce these documents — along with the autoclave log and the other documents relating to the death of the 12 rabbits between October 2 – October 5?

  2. anonymous said

    Scott Shane spews out the FBI’s word as gospel within 30 minutes. Meanwhile an apparently much more intelligent journalist actually seems to have some independent thoughts.

    http://www.miamiherald.com/2011/03/23/2130889/fbis-anthrax-suspect-is-likely.html

    While titillating, the latest analysis also fails to fully close the books on the case, because no one has produced clear forensic evidence showing that Ivins dropped the letters into a mailbox in Princeton, N.J., in September and October 2001.

    • anonymous said

      The FBI’s Behavioral Analysis Unit asked a longtime consultant, Dr. Gregory Saathoff, an associate professor of psychiatry at the University of Virginia, to review the records.

      Read more: http://www.miamiherald.com/2011/03/23/2130889/fbis-anthrax-suspect-is-likely.html#ixzz1HThcLmZY

      Did Shane even do any background on Saathoff?

      • anonymous said

        Saathoff, who apparently initiated the idea to delve into Ivins’ records, told a news conference Wednesday that after receiving them, he felt the case was so significant that he sought and obtained authority from the Justice Department to perform a comprehensive analysis.
        In early 2010, apparently after the expert panel secretly submitted its report to the court, the FBI formally closed one of the largest investigations in its history, electing to publicly declare Ivins’ guilt based on circumstantial evidence.
        The FBI’s case has since been called into question by a National Academy of Sciences panel, which found that the scientific evidence didn’t solely point to a flask in Ivins’ laboratory, and by scientists who worked with him at Fort Detrick who insist he couldn’t have done it. At the request of several members of Congress, the Government Accountability Office is conducting a separate inquiry.

        Read more: http://www.miamiherald.com/2011/03/23/2130889_p2/fbis-anthrax-suspect-is-likely.html#ixzz1HTi1zfcC

  3. DXer said

    Batches #22 – #39 are the emails that Dr. Saathoff mistakenly claims were deleted by Dr. Ivins.

    https://mrmc.amedd.army.mil/index.cfm?pageid=foia_reading_room.overview

    Dr. Saathoff indirectly is confirming that he in fact has not read them.

    So he did not interview Ivins and did not read the hundreds of emails from 2001 (that he mistakenly claimed were purged by Ivins).

    He should not only read them but have the FBI produce the 9/17 email to Mara.

    Dr. S. in particular should read the 10/5 email that amply demonstrates what Dr. Ivins was doing in the lab on the key long stretches on 10/3, 10/4, and 10/5.

    Then he should read Ivins’ contemporaneous lab notes on 9/28, 9/29, 9/30, 10/1, and 10/2 explaining what he was doing on those times.

    It is Dr. Saathoff’s failure to read (apparently unawareness) of these many dozens of emails that explains the disconnect between his narrative and the documentary evidence.

    • DXer said

      Are these the emails that Dr. Saathoff mistakenly thought Bruce Ivins had deleted? Was Dr. S aware that they were produced by USAMRIID?

      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: RE: Anthrax, mice, and CpG
      Date: Friday, August 31, 2001 8:47:03 AM
      I plan to leave about 10 am, so I’ll be there about 11 am. Could I get another parking exemption while
      I’m there? Also, we are running short of the FAV038 lot of AVA, so it would be greatly
      appreciated if we could get back any left over AVA after the experiment. Thanks! We are bringing you
      today:
      1) AVA (2 vials, 10 ml total)
      2) PA/Alhydrogel/PBS (10 ml total)
      3) Control – Alhydrogel/PBS (no PA) (10 ml total)
      If this is not OK, please let me know before I leave. Thanks!
      – Bruce
      —–Original Message—–
      From:
      Sent: Friday, August 31, 2001 8:30 AM
      To: ‘Ivins, Bruce E Dr USAMRIID’
      Subject: RE: Anthrax, mice, and CpG
      Bruce,
      We’ve cancelled lab meeting this morning, so I’m available at any time for
      the anthrax vaccine. Give a buzz before you leave to drop it off, so I can
      make sure I’m waiting for you.
      All the best,
      —–Original Message—–
      From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL]
      Sent: Tuesday, August 28, 2001 8:42 AM
      To: ‘
      Subject: RE: Anthrax, mice, and CpG
      Friday would be better for me, If you like, you could mail
      frozen samples to me, I could pick them up, or you could bring them up.
      Whichever you prefer is fine. Also, the American Society for Microbiology
      Annual Meeting will be next May, and I would like to present an abstract
      (with the two of us as the authors) with our guinea pig and (hopefully)
      monkey data. I would send the abstract to you for your comments, criticisms,
      suggestions, additions, deletions, etc., before submitting it. Would this be
      acceptable to you? I think it would be very well received at the meeting.
      I’ll see you Friday, a little before noon, if it’s convenient.
      – Bruce
      —–Original Message—–
      From:
      Sent: Tuesday, August 28, 2001 8:34 AM
      To: ‘Ivins, Bruce E Dr USAMRIID’
      Subject: RE: Anthrax, mice, and CpG

      Dear Bruce,
      Either one is fine. Just let me know what’s best.
      Since I feel bad about you having to run down here so often, how about I
      agree to bring the serum samples up to you when they’re all collected?
      —–Original Message—–
      From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL]
      Sent: Monday, August 27, 2001 7:38 PM
      To: ‘
      Subject: RE: Anthrax, mice, and CpG
      Hi,
      Is just before noon on Thursday or Friday better for you?
      – Bruce
      —–Original Message—–
      From:
      Sent: Monday, August 27, 2001 5:00 PM
      To: ‘Ivins, Bruce E Dr USAMRIID’
      Subject: RE: Anthrax, mice, and CpG
      Absolutely. Let me know how we can arrange it.
      —–Original Message—–
      From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL]
      Sent: Monday, August 27, 2001 3:20 PM
      To: ‘
      Subject: RE: Anthrax, mice, and CpG
      Can I get this to you on Thursday or Friday?
      – Bruce
      —–Original Message—–
      From:
      Sent: Monday, August 27, 2001 2:06 PM
      To: ‘Ivins, Bruce E Dr USAMRIID’
      Subject: RE: Anthrax, mice, and CpG
      Dear Bruce,
      Thanks for the offer. We’re on the schedule to boost the animals on
      Tuesday, Sept 4. Thus, if you could get us 18 doses of each type of vaccine
      (AVA and rPA vaccine) plus alum sometime the week before, that would be
      super.
      All the best,

      —–Original Message—–
      From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL]
      Sent: Saturday, August 25, 2001 7:07 PM
      To:
      Subject: RE: Anthrax, mice, and CpG
      I can get it to you this week, Please tell me the day you are
      planning to immunize. Also, how many doses of each (AVA and rPA vaccine)
      will you need. (Include any extra that you wish to have.) Thanks!
      – Bruce
      —–Original Message—–
      From:
      Sent: Thursday, August 23, 2001 4:43 PM
      To: ‘Ivins, Bruce E Dr USAMRIID’
      Subject: RE: Anthrax, mice, and CpG
      Dear Bruce,
      Hope you are well.
      The monkeys were immunized and bled. We need the second dose of both types
      of vaccine for the booster immunization ASAP. We’ll re-bleed a few times,
      then send you the serum for testing.
      All the best,
      —–Original Message—–
      From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL]
      Sent: Thursday, July 19, 2001 6:27 PM
      Subject: RE: Anthrax, mice, and CpG
      Hi, ,
      If you can get us 1 ml of serum, then we can probably go with that.
      – Bruce
      —–Original Message—–
      From:
      Sent: Thursday, July 19, 2001 5:41 PM
      To: Ivins, Bruce E Dr USAMRIID’
      Subject: RE: Anthrax, mice, and CpG
      Dear Bruce,
      I spoke too soon. Given that we plan to bleed the animals every 2 weeks,
      the vets won’t allow us to draw 5 ml each time (to get 2 ml of serum).
      Especially since we also want to do some serum chemistry and hematology on
      these animals.
      Can you make do with less serum? I’m only guessing, but when we studied
      mouse serum for anti-PA Abs by ELISA, the assay only took a few microliters
      of serum. More serum was needed for the neutralization assays, but if
      memory serves, the total volume required was approximately 300 ul. Thus, if
      you could get by with 0.5 – 1 ml of serum, everything will be OK.
      Otherwise, let me know, and we’ll figure something out.
      —–Original Message—–
      From:
      Sent: Thursday, July 19, 2001 4:08 PM
      To: ‘Ivins, Bruce E Dr USAMRIID’
      Subject: RE: Anthrax, mice, and CpG
      Will do. At least two 1 ml tubes of serum will be frozen down from each
      animal at each time point.
      —–Original Message—–
      From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL]
      Sent: Thursday, July 19, 2001 3:11 PM
      To:
      Subject: RE: Anthrax, mice, and CpG
      We draw blood into serum separator tubes, draw off the serum after
      clotting, aliquot the serum as we wish, then freeze it. For small (about 1
      ml or less) volumes, we use cryotubes. For larger volumes, we use 15-ml,
      screw-capped, conical polypropylene tubes. For bleed-outs (which I believe
      won’t be done in this experiment), we use 50-ml, screw-capped, conical
      polypropylene tubes. For each time-point in each monkey, we would like 2
      aliquots of 1 ml of serum (thus, 2 ml total). That is enough to cover both
      ELISA and TNA tests. After all the samples are taken, I can drive down and
      pick up the frozen serum, bring it back, and the ELISA and TNA assays will
      be run. Thanks. I’m eagerly looking forward to this experiment.
      – Bruce
      —–Original Message—–
      From:
      Sent: Thursday, July 19, 2001 1:57 PM
      To: ‘Ivins, Bruce E Dr USAMRIID’
      Subject: RE: Anthrax, mice, and CpG
      Dear Bruce,
      We’re all set for the monkey study. The animals are scheduled to be
      immunized on Tuesday, the day after the vaccine arrives. If memory serves,
      we’re injecting 0.5 ml intramuscularly. They’ll be re-immunized one month
      later. Bloods will be drawn every two weeks, and serum stored for you to
      test.
      In terms of collecting and storing the serum, I could use your advice. We
      do many of our ELISA assays in microtiter plates. If the same is true at
      your end, I could store the serum samples from each bleed in microtiter
      plates, making it easy to thaw them and do the assays using a multichannel
      pipetor. Alternatively, we could store each serum in a tube, separately.
      Which do you prefer? Also, what volume of serum do you need from each
      bleed? I’d like to generate several aliquots/animal/bleed, and want to
      store them in convenient volumes.
      Let me know.
      —–Original Message—–
      From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL]
      Sent: Wednesday, July 18, 2001 10:45 AM
      To: ‘
      Subject: RE: Anthrax, mice, and CpG
      Hi,
      I had planned to give you 10 ml (20 doses) of each vaccine. Would
      this be sufficient? I could give you more AVA if you like. I could also give
      you (individually) several hundred micrograms of PA, and several ml of PBS
      and Alhydrogel. Let me know and I’ll bring them to you when I bring the
      vaccines. Thanks.
      – Bruce
      —–Original Message—–
      From:
      Sent: Wednesday, July 18, 2001 10:33 AM
      To: ‘Ivins Bruce E’
      Subject: RE: Anthrax, mice, and CpG
      Dear Bruce,
      I don’t know how precious the two anthrax vaccines are. If you could spare
      additional material, I’d like to test it for the presence of DNA that might
      contain immunostimulatory or immunosuppressive sequences. We’d purify out
      the DNA and test it in vitro. This is part of an ongoing project in my lab
      where we test various vaccines for such agents.
      I’ll take anything you can spare.
      —–Original Message—–
      From: Ivins Bruce E [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL]
      Sent: Thursday, October 07, 1999 8:40 AM
      To: ‘
      Subject: Anthrax, mice, and CpG
      Hi, ,
      As you remember, in our first experiment with the mice, we got some
      time-to-death extension with CpG for mice challenged with virulent B.
      anthracis spores. In the second experiment, we demonstrated not only
      time-to-death extension, but also protection from death with the CpG. In
      this last experiment which we just concluded, we strangely got no protection
      at all, in terms of either survival or increased time-to-death. I believe
      that the main problem is that the mouse is such a generally poor and
      unpredictable model for anthrax. The guinea pig is a MUCH better model for
      anthrax infection/protection, and our guinea pig protocol for CpG has been
      approved, so I think the next step should be (when we get the funds
      released) to go into the guinea pigs. We’ll be able to look at specific as
      well as non-specific protection, and if we get some promising results, we
      can head into non-human primates. Hopefully we’ll get some money released
      within a few weeks and we can get started then. I’ll let you know. I’m sure
      that mice are an excellent animal model for a number of diseases, but
      anthrax isn’t one of them.
      – Bruce
      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: NGAV meeting at Pentagon, 23 AUG 01
      Date: Friday, August 31, 2001 3:45:43 PM
      Here are some notes from the NGAV meeting at the Pentagon on 23 AUG:
      1) – For NGAV funding, FY01 funds are going to be freed up for work on VEE. This will allow
      some money to be made available for rPA funds.
      2) – BDRP (nee SAIC; nee MARP) has made some untenable demands with respect to the rPA
      made for human use. They want $200,000 per year (without specifying the number of years) for
      indemnification. They want the government to cover the cost of lawsuits. They also want international
      indemnification. They are refusing to release the rPA unless the Army agrees to the above demands.
      said that if the rPA is not given to the Army, then we may have to go to AVANT and use E.
      coli rPA. It was pointed out that since the E. coli rPA differs in some respects from the B. anthracis rPA,
      a number of studies will probably have to be repeated, including stability and efficacy studies. This will
      extend the timeline for rPA going into humans. said that this issue “is a RIID issue.” Several
      individuals disagreed with him on this statement. told o have this
      issue resolved by the next meeting.
      3) A new GANTT chart will be constructed, in color, to show what has been done and what needs to be
      done.
      4) said that NIH people are doing a lot of tech base studies on rPA, including the need
      for an adjuvant, passive immunity studies, surrogate marker studies, and stability/potency testing. Some
      of these studies are being conducted with CDC and include AVA studies.
      5) asked for a RIID tech base update at the next meeting on Friday, September
      28, 9-10:30 am, in office. This update should cover timelines, start, end, and cost
      for: 1) formulation studies; 2) stability studies; 3) passive immunity studies (here and at Battelle); 4)
      surrogate marker and efficacy studies; 5) CpG studies. ( – I don’t think that wants reams of
      information, just some bullets about what we’ve done and what is to be done, also, timelines and
      funding for the projects.)
      6) Action Items for next meeting :
      1) will have resolved the rPA issue.
      2) A new GANTT chart will have been made.
      3) will discuss studies of AVA in humans.
      4) will discuss tech base studies including Battelle and RIID studies.
      – Bruce
      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: RE: Protocol modifications
      Date: Tuesday, September 04, 2001 2:01:53 PM
      Ninety-four rabbits won’t be a problem as far as the sub cu challenge goes, but will you have enough of
      each isoform to do the immunizations?
      – Bruce
      >—–Original Message—–
      >From:
      >Sent: Tuesday, September 04, 2001 8:36 AM
      >To:
      vins, Bruce E Dr USAMRIID
      >Subject: FW: Protocol modifications
      >
      >Re: animal protocol to study the contribution of rPA isoforms to protection against a lethal anthrax
      infection in rabbits. suggests we do 30 rabbits per group; see below. The change would
      result in 94 rabbits instead of 52 ($$$?). Please advise if we wish to accept his recommendations so I
      can make the changes. ( had originally suggested 16 per group). Thanks in advance.
      File: Rabbit isoform protocol23Aug.doc >>
      >>
      —–Original Message—–
      >From:
      >Sent: Friday, August 31, 2001 3:30 PM
      >To:
      >Subject: Protocol modifications
      >>>
      The isoform protocol is suggested to undergo the following statistical revisions. There are three
      reasons
      > for the revisions:
      >>
      1. This study is approaching the final formulation of the rPA anthrax vaccine candidate and thus
      must
      > adhere to stricter criteria.
      >>
      2. The stricter criteria involve the concept of “equivalency” testing. This means that we seek to
      reject
      > the hypothesis that the two isoforms are NOT equivalent with respect to survival and immune
      response
      > as measured by ELISA and TNA. Rejection of the hypothesis establishes the statistical evidence
      that the
      > isoforms are equivalent. This requires larger sample sizes than a test of the hypothesis that the
      two
      > isoforms are not different (a subtle difference), which is an early developmental hypothesis.
      >>
      3. Should this not be a strict GLP study due to the need for FDA approval of the decision that will
      > arise from it? We do not wish to have to repeat the study in the future under GLP standards.
      >>
      Revisions suggested:
      >>
      Page 3 replace objective with: “The hypothesis is that the two isoforms are NOT equivalent in
      survival rates
      > or immune response as measured by either ELISA and TNA. Equivalency is defined as a
      difference

      > in survival rates of no more than 20%, and a ratio of geometric mean ELISA titers and TNA
      titers of
      > no more than 4-fold respectively. The hypothesis will be tested at the 95% confidence level
      (2-tailed). Rejection
      > of the hypothesis establishes the equivalency of the survival and immune response of the
      two isoforms.
      > Failure to reject any of the hypothesis (survival or immune response) fails to establish the
      equivalency
      > of the two isoforms. Sex-specific tests will be done.”
      >>
      Page 11 replace Data Analysis with: “Sex-specific survival rates will be tested for equivalence using
      the method
      > of Farrington and Manning (ref). ELISA and TNA titers will be transformed to log10 and
      analyzed for
      > sex-specific equivalency based on the 95% confidence intervals (2-tailed) around the ratio of
      geometric mean titers.
      > Further analysis of survival correlations with sex, titers and isoform will use standard logistic
      regression.
      > Also, further analysis of titers will use multiple regression to test for sex differences and to
      test for
      > isoform differences. All tests will be at the 95% confidence level (2-tailed). All data will be
      automated
      > and verified prior to analysis. Statistical software package SAS (version 8.0 or greater) will
      be used
      > for analysis.”
      >>
      Page 11 Move the sample size justification to the page 5 and replace the statement there with:
      >>
      The test of equivalency of survival rates assumes 100% survival in both isoforms and a
      20%
      > maximum difference resulting in a sample size of 15 of each sex per isoform. The test of
      > equivalency of immune response assumes a log10 standard deviation of 0.50 logs and a
      > maximum ratio of geometric mean titers of 4-fold (0.60 logs) resulting in a sample
      > size of 12 of each sex per isoform. Therefore, 30 rabbits (15 male and 15 female) must be
      > tested at each isoform and with the combined isoforms as a control. The unprotected
      controls
      > will be set at a nominal 4 animals (2 of each sex) due to confidence in the 100% lethality
      > of the challenge dose.”
      >>
      Reference: Farrington CP and Manning G. Test statistics and sample size formulae for comparative
      > binomial trials with null hypothesis of non-zero risk difference or non-unity relative risk.
      > Statistics in Medicine, vol 9, 147-1454, 1990.
      >
      >
      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: Preparation of rPA vaccine + Alhydrogel
      Date: Wednesday, September 05, 2001 8:07:57 AM
      Dear ,
      Here is some of the information you requested. I am happy to provide it to you.
      Your fiend,
      Bruce
      >Here is how we prepare our rPA vaccine with aluminum hydroxide adjuvant:
      >
      >Materials:
      >>
      1) Dulbecco’s phosphate buffered saline (PBS) without calcium and without magnesium, pH 7.4 –
      sterile
      > 2) Aluminum hydroxide (Alhydrogel) (2% Aluminum oxide) – sterilized by autoclaving
      > 3) PA in ammonim acetate buffer, pH 8.9
      >
      >The PA we have been using has a concentration of 1.18 mg/ml. (This can be measured by absorbance
      at 280 nm, since 1.0 mg/ml of PA gives a reading of 1.0.) We dilute the commercial Alhydrogel stock
      above 1:10.64 (final dilution in vaccine) to get 0.5 mg of metallic aluminum per 0.5 ml dose of vaccine.
      (I believe that the maximum allowed is 0.85 mg per dose. The current human anthrax vaccine has
      about 0.725 mg aluminum per dose. Below is how we would make up ten 0.5-ml doses of vaccine
      containing 50 micrograms of PA per dose and 0.5 mg of aluminum per dose:
      >>>
      0.424 ml of PA (500 micrograms of the 1.18 mg/ml material)
      > 0.470 ml of Alhydrogel
      > 4.106 ml of PBS
      >
      >Add the Alhydrogel to the PBS in a sterile vaccine vial and mix by swirling until an even suspension is
      achieved. Add the PA and swirl immediately to mix. Put on ice and allow to stand from 1 hour to
      overnight on ice. If desired, a small, sterile stirring bar can be added to the PBS + Alhydrogel. While on
      a magnetic mixer, add the PA. (We’ve never had a problem doing it the former way, without a stirring
      bar.)
      >
      >Hope this has been helpful.
      >>
      – Bruce
      >
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      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: FW: August NGAV Meeting Moved Again to Wednesday, August 29th, 11 00-1 200 hrs
      Date: Wednesday, September 05, 2001 8:20:18 AM
      Attachments:
      Here you go,
      – Bruce
      —–Original Message—–
      From:
      Sent: Monday, August 27, 2001 10:39 AM
      To: ‘Ivins, Bruce E Dr USAMRIID’
      Subject: RE: August NGAV Meeting Moved Again to Wednesday, August 29th,
      11 00-1 200 hrs
      Bruce,
      The Read Ahead is provided to only. The minutes from July are
      attached.
      —–Original Message—–
      From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL]
      Sent: Monday, August 27, 2001 10:38 AM
      To:
      Subject: FW: August NGAV Meeting Moved Again to Wednesday, August 29th,
      11 00-1 200 hrs
      Can you send to me the attachments? I never got them. Thanks! I’ll
      see you on Wednesday morning, about 10:30 am.
      – Bruce
      > —–Original Message—–
      > From: Ivins, Bruce E Dr USAMRIID
      > Sent: Monday, August 27, 2001 8:54 AM
      > To:
      > Subject: RE: August NGAV Meeting Moved Again to Wednesday, August
      29th, 1100-1 200 hrs
      >>
      – Do you have the NGAV Final Minutes-23 July.doc and
      NGAV Read Ahead-Aug? Please forward them to me if you have them so that I
      can read them before I go to the Pentabon on Wednesday.
      > Thanks.
      > – Bruce
      >>
      —–Original Message—–
      > From:
      > Sent: Wednesday, August 01, 2001 12:25 PM
      > To:
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      > Subject: Approved Minutes for 23 July NGAV Meeting
      >>>
      Ladies and Gentlemen,
      >>
      Attached are the approved Minutes from the 23 July NGAV
      meeting. Please
      > note the new Action Items and the POC responsible to address
      them. I have
      > also attached a PowerPoint template to facilitate your
      response for the 30
      > August Meeting. The suspense for input to the Read Ahead
      for
      > will be NLT noon, Monday, 27 August. NOTE: the date of the
      August NGAV
      > meeting is 30 August, 0900-1030 hrs, Pentagon, Room 3C257.
      It does not
      > start at 0930 as previously mentioned at the last meeting.
      >>
      <> <>
      >>>
      >>
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      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: FW: Covance contract information
      Date: Wednesday, September 05, 2001 9:13:24 AM
      >—–Original Message—–
      >From:
      >Sent: Wednesday, September 05, 2001 8:17 AM
      >To: Ivins, Bruce E Dr USAMRIID
      >Subject: Covance contract information
      >>>>
      >Let me know when you plan to go and hopefully I can join you one day
      >
      >Thanks,
      >
      >>>
      >This contract is for the vaccination of 100 NZW rabbits on days 0 and 28. Includes prebleeds, im
      injections, terminal bleeds, maintenance, GLP study procedures, and cost of transportation and
      packaging.
      >
      >Pertinent Alores information for this contract is as follows:
      >Document No. W23MYC1159N015
      >APC 6R56
      >HR R8R
      >DAC
      >Purchase Order No. 01P0831
      >
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      From: Ivins, Bruce E Dr USAMRIID
      To: Ivins, Bruce E Dr USAMRIID;
      Subject: RE: Covance contract information
      Date: Wednesday, September 05, 2001 9:26:51 AM
      Addendum – in general, the best days for us are Mondays, Tuesdays and Thursdays. Wednesdays are
      usually full of animal work, and Fridays are frequently days of leave (use or lose). Other bad days –
      October 2, October 8, November 12, week of November 26.
      – Bruce
      >—–Original Message—–
      >From: Ivins, Bruce E Dr USAMRIID
      >Sent: Wednesday, September 05, 2001 8:34 AM
      >To:
      >Subject: RE: Covance contract information
      >
      >Dear ,
      >Let us know what days are especially bad for you (you’ll be on leave, at some wonderful meeting,
      etc.) or especially good for you. We’ll match that up with what days are good and bad for us and come
      up with a time to go. Thanks!!
      >- Brucie
      >>
      —–Original Message—–
      > From:
      > Sent: Wednesday, September 05, 2001 8:17 AM
      > To: Ivins, Bruce E Dr USAMRIID
      > Subject: Covance contract information
      >>>>>
      Let me know when you plan to go and hopefully I can join you one day
      >>
      Thanks,
      >>>>>>
      This contract is for the vaccination of 100 NZW rabbits on days 0 and 28. Includes prebleeds, im
      injections, terminal bleeds, maintenance, GLP study procedures, and cost of transportation and
      packaging.
      >>
      Pertinent Alores information for this contract is as follows:
      > Document No. W23MYC1159N015
      > APC 6R56
      > HR R8R
      > DAC
      > Purchase Order No. 01P0831
      >
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      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: FW: ABCNEWS.com: Researcher Infected With Bio-Warfare Agent
      Date: Wednesday, September 05, 2001 9:49:10 AM
      I thought you might find this story interesting – Bruce
      Researcher Infected With Bio-Warfare Agent
      http://abcnews.go.com/sections/living/DailyNews/biowarfare010725.html
      (b) (6)
      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject:
      Date: Wednesday, September 05, 2001 4:15:59 PM
      Hi,
      has just told me that she is beginning to think of career advancement, and she is starting to
      look at other openings in the research technician field, including positions at USAMRIID. We’ve told her
      that this position is finite in duration, although we haven’t told her that this will be her last year in the
      position, beacause the position will end this coming July. We will inform her about this in January. In
      the meantime, please keep your eye open for positions around here that she may be interested in, and
      let her know of any. If she finds one that requires her to leave before July, it will be OK, as long as she
      gives us some lead time on leaving. She has had some very good training with us, and she can enter
      the biocontainment suites, and that is a very big plus at USAMRIID.
      Thanks!
      – Bruce
      (b) (6)
      (b)
      (6)(b) (6)
      ( (b) (6)
      b
      )
      (
      6
      )
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      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: Ames spores
      Date: Thursday, September 06, 2001 9:42:11 AM
      Hi,
      I talked to in contracts here, and he said that everything is ready to go as far as
      the contract for the production of the Ames spores. We’re looking forward to getting them – we’re down
      to about 1/3 of the spore prep that you made previously – and then purifying them. Please let us know
      ahead of time when we should start to expect them.
      Thanks!! Hope you have a good fall!
      – Bruce

      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: FW: Ames spores
      Date: Thursday, September 06, 2001 10:17:03 AM
      Info on the Dugway Ames spores. – Bruce
      —–Original Message—–
      From:
      Sent: Thursday, September 06, 2001 10:28 AM
      To: ‘Ivins, Bruce E Dr USAMRIID’
      Subject: RE: Ames spores
      Hi Bruce,
      I’m getting ready to have some maintenance performed on the
      fermentor that we will use. We’ll probably start up in about a month. I’ve
      got a couple of other runs to do first. I’m having a wonderful introduction
      to Fall with my football team at 2 and 0 and the temperature starting to
      drop.
      —–Original Message—–
      From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL]
      Sent: Thursday, September 06, 2001 7:42 AM
      To: ‘
      Subject: Ames spores
      Hi,
      I talked to in contracts here, and he said that
      everything is ready to go as far as the contract for the production of the
      Ames spores. We’re looking forward to getting them – we’re down to about 1/3
      of the spore prep that you made previously – and then purifying them. Please
      let us know ahead of time when we should start to expect them.
      Thanks!! Hope you have a good fall!
      – Bruce

      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: Rabbit Immunizations
      Date: Monday, September 10, 2001 10:00:49 AM
      said that she has spoken to you about immunizing 100 more rabbits with recombinant
      B. anthracis protective antigen (with Alhydrogel adjuvant), 0.5 ml per intramuscular dose. We would like
      to bring the vaccine to you on Tuesday, September 18, and then 4 weeks later on Tuesday, October 16.
      We will give you 120 doses (60 ml total) to allow for a little extra.
      If these are not acceptable dates, please let me know. Thank you.
      – Bruce Ivins

      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: Anti-PA Human serum
      Date: Monday, September 10, 2001 12:43:05 PM
      Hi,
      We have Anti-PA IgG from humans which we are using in the mouse passive protection studies. Is
      there any human anti-PA serum (not human IgG) which we could use in these studies? We would need
      about 100 ml for each experiment.
      Thanks!
      – Bruce
      (b) (6)
      (b) (6)
      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: CpG progress update
      Date: Monday, September 10, 2001 1:23:05 PM
      Here is a progress update on CpG studies in animal hosts:
      1) In guinea pigs there is no non-specific protection afforded by CpG oligonucleotides against
      a parenteral challenge of virulent B. anthracis spores.
      2) In guinea pigs, there appears to be some enhancement of specific protection against
      parenteral challenge. At 0 and 4 weeks guinea pigs were immunized with AVA or AVA + CpG (100 or
      300 micrograms). The animals were challenged i.m. at 10 weeks with about 5,000 Ames spores.
      Results:
      GROUP SURVIVED/TOTAL (% SURVIVAL)
      Saline Controls 1/28 (4)
      AVA 15/32 (47)
      AVA + CpG (100 micrograms) 12/15 (80)
      AVA + CpG (300 micrograms) 11/16 (69)
      ____________________________________________________________________
      3) Currently, at CBER, an experiment is being conducted to see whether CpG specifically
      enhances the serological immune response of rhesus monkeys to PA with both AVA and rPA vaccines.
      Animals have been immunized with AVA, AVA + CpG, rPA vaccine, or rPA vaccine + CpG. Periodic
      bleeds will be taken and serum tested by ELISA and TNA for anti-PA titers.
      – Bruce

      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: Isoform studies information
      Date: Monday, September 10, 2001 2:28:33 PM
      Here is the information on the isoform studies. is writing the protocol. After
      determines the level of PA needed (2 doses) to give a mid-level protective response in rabbits, the
      same level of each of 2 PA isoforms will be used to immunize twice, at 0 and 4 weeks. At 10 weeks,
      the rabbits will be parenterally challenged with anthrax spores. Survival and anti-body titers will be
      determined. This experiment will hopefully demonstrate that the two isoforms are equally protective.
      This experiment is necessary in that two isoforms are found in purified preparations of rPA.
      – Bruce Ivins

      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: RE: update for rPA
      Date: Tuesday, September 11, 2001 7:49:40 AM
      Thanks,
      – Bruce
      >—–Original Message—–
      >From:
      >Sent: Tuesday, September 11, 2001 7:29 AM
      >To:
      >Cc: Ivins, Bruce E Dr USAMRIID
      >Subject: update for rPA
      >
      >Here is the portion of the progress report from and myself including the rPA stability study and
      isoform investigation. I understand Bruce has already sent you the animal part of the isoform study.
      >
      >A contract is being finalized with Battelle to perform a combined stability and efficacy study. The GMP
      rPA product will be formulated with Alhydrogel at neutral pH (no formaldehyde) and held at three
      temperatures (4 C, 25 C, 40 C) for various time intervals (including 3 days; 1 week; 1,3,6 & 12
      months), after which rabbits will be immunized with a single dose of this material (0.5 ml containing
      100 ug protein) and then challenged with 100 LD50 of B. anthracis Ames spores. The route of exposure
      still under discussion will either be aerosol, to follow the ORD, or subcutaneous, for better control of the
      delivery and statistical evaluation of the results. Animals will be monitored for general signs of health
      and blood drawn at weekly intervals for bioassay of titer by ELISA and activity by TNA. Protein at each
      interval will also be evaluated for biophysical integrity by assaying rPA that is spontaneously and actively
      desorbed from the aluminum hydroxide.
      >
      >rPA isoforms will be purified by tandem anion exchange chromatography for use biological and
      biophysical tests. The composition of each of two isoforms will be investigated to identify the source of
      charge micro-heterogeneity. Amino acid modification including deamidation will be investigated using
      available methods including chemical stains and ESI-LC-MS/MS analysis of tryptic fragments.
      (b) (6)

      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: FW: Anthrax, mice, and CpG
      Date: Tuesday, September 11, 2001 8:38:43 AM
      —–Original Message—–
      From:
      Sent: Tuesday, September 11, 2001 8:37 AM
      To: ‘Ivins Bruce E’
      Subject: RE: Anthrax, mice, and CpG
      Dear Bruce,
      I’ve been invited to deliver a lecture on the protective activity of CpG ODN
      in mid October. They’ve requested an abstract be submitted by the end of
      this week. Is the following OK with you?
      The ability of synthetic oligodeoxynucleotides (ODN) containing
      immunostimulatory “CpG” motifs to trigger an innate immune response capable
      of improving host survival following bacterial, viral and parasitic
      infection was investigated. Initial studies showed that normal mice treated
      with 5 – 50 ug of CpG ODN were protected for approximately 2 weeks from
      subsequent infection by >1,000 LD50 of Listeria monocytogenes or Francisella
      tularensis, or from 100 leishmania parasites. Subsequent studies
      established that higher doses of CpG ODN prolonged and/or enhanced the
      survival of mice challenged with biothreat agents such as inhaled anthrax
      and mouse-adapted Ebola virus. In each challenge model, protection was
      critically dependent on the CpG motif, being lost when the CpG dinucleotide
      was inverted or methylated.
      Two strategies were pursued to extend the protection conferred by
      CpG ODN. In the first, mice were treated with CpG ODN every two weeks for
      up to 4 months. Protection against L. monocytogenes and F. tularensis was
      induced and maintained for the duration of therapy. In the second, mice
      were injected with CpG ODN encapsulated in cationic stealth liposomes (CSL).
      CSL encapsulation significantly improved the uptake of ODN by cells of the
      immune system and increased the magnitude and persistence of the resultant
      immune response. Mice treated with encapsulated CpG ODN were protected
      from L. monocytogenes and F. tularensis for >4 weeks.
      To determine whether CpG ODN would be effective immunoprotective
      agents in humans, we examined the response of PBMC from >100 normal human
      donors to a large panel of ODN. Two distinct classes of CpG ODN were
      identified that activated human PBMC. The first (“K” type) ODN have a
      phosphorothioate backbone and multiple TCGTT and/or TCGTA. “K” ODN
      primarily stimulate B cells and monocytes to proliferate and secrete IgM,
      IL-6 and IL-10. The second (“D” type) ODN have a mixed phosphodiester/
      phosphorothioate backbone and contain a single hexameric
      purine/pyrimidine/CG/purine/pyrimidine motif flanked by self-complementary
      bases that form a stem-loop structure capped at the 3′ end by a poly G tail.
      “D” ODN induce APC to mature and secrete IFNa and triggered NK cells to
      secrete IFNg.
      Whereas PBMC from all donors responded to at least one member of the
      “D” and “K” ODN panel, no single ODN induced an optimal response in all
      subjects. However, mixtures of ODN containing multiple CpG motifs strongly
      activated PBMC from all subjects. These mixtures also stimulated PBMC from
      non-human primates, such as chimpanzees and rhesus macaques. These mixtures
      were tested for their ability to protect rhesus monkeys from cutaneous
      leishmania infection. The severity of leishmania infection in macaques
      treated with “D” ODN 3 days before and 3 days after challenge was reduced by
      >90% (p. >
      >1. Vaccine: NEW recombinant PA (50 micrograms) + Dulbecco’s PBS + Alhydrogel (0.5 mg metallic aluminum) in a total volume of 0.5 ml, with or without formaldehyde (to be determined prior to experiment)
      >
      >2. Animals – New Zealand white rabbits, 2.5-3.5 kg and rhesus macaques, adults.
      >
      >3. Challenge – aerosol challenge with 100 – 500 LD50 of B. anthracis Ames spores.
      >
      ****************************************************************************************************************************************************************
      Immunization and challenge schedule for rabbits (10 males and 10 females per challenge group & 2 males and 2 females per control group):
      > 0 month and 1 month (4 weeks) – immunize 160 rabbits (8 groups of 20) with rPA vaccine, and immunize 8 control groups of rabbits with PBS
      > 3 months – challenge group 1 and group 1 controls
      > 6 months – challenge group 2 and group 2 controls
      > 12 months – challenge group 3 and group 3 controls
      > 12 months – immunize group 6 rabbits (with rPA vaccine) and group 6 controls (with PBS); if group 3 challenged animals have less than 80% (?) survival, challenge group 6 and group 6 control rabbits at 13 months
      > 18 months – challenge group 4 rabbits and group 4 controls
      > 18 months – immunize group 7 rabbits (with rPA vaccine) and group 7 controls (with PBS); if group 4 challenged animals have less than 80% (?) survival, challenge group 7 and group 7 control rabbits at 19 months
      > 24 months – challenge group 5 rabbits and group 5 controls
      > 24 months – immunize group 8 rabbits (with rPA vaccine) and group 8 controls (with PBS); if group 5 challenged animals have less than 80% (?) survival, challenge group 8 and group 8 control rabbits at 25 months
      >
      >5. Bleeding schedule for rabbits:
      > 1 week prior to 3 months – all rabbits
      > 4, 7, 10 and 14 days after challenge – group 1
      >>
      1 week prior to 6 months – all remaining rabbits
      > 4, 7, 10 and 14 days after challenge – group 2
      >>
      1 week prior to 12 months – all remaining rabbits
      > 4, 7, 10 and 14 days after challenge – group 3
      >>
      1 week prior to 13 months – group 6 and group 6 controls
      > 4, 7, 10 and 14 days after challenge – group 6
      >>
      1 week prior to 18 months – all remaining rabbits
      > 4, 7, 10 and 14 days after challenge – group 4
      >>
      1 week prior to 19 months – group 7 and group 7 controls
      > 4, 7, 10 and 14 days after challenge – group 7
      >>
      1 week prior to 24 months – all remaining rabbits
      > 4, 7, 10 and 14 days after challenge – group 5
      >>
      1 week prior to 25 months – group 8 and group 8 controls
      > 4, 7, 10 and 14 days after challenge – group 8
      >
      >6. Blood and sera will be assayed by ELISA, TNA, & ELISPOT.
      >*************************************************************************************************************************************************
      >7. Immunization and challenge schedule for monkeys (5 males and 5 females per challenge group & 1 male and 1 female per control group):
      >>
      0 month and 1 month (4 weeks) – immunize 77 monkeys (7 groups of 10) with rPA vaccine, and immunize 7 control groups with PBS
      > 6 months – challenge group 1 and group 1 controls
      > 12 months – challenge group 2 and group 2 controls
      > 12 months – immunize group 5 monkeys (with rPA vaccine) and group 5 controls (with PBS); if group 3 challenged animals have less than 80% (?) survival, challenge group 5 and group 5 control monkeys at 13
      months
      > 24 months – challenge group 3 rabbits and group 3 controls
      > 24 months – immunize group 6 monkeys (with rPA vaccine) and group 6 controls (with PBS); if group 5 challenged animals have less than 80% (?) survival, challenge group 6 and group 6 control monkeys at 25
      months
      > 36 months – challenge group 4 monkeys and group 4 controls
      > 36 months – immunize group 7 monkeys (with rPA vaccine) and group 7 controls (with PBS); if group 7 challenged animals have less than 80% (?) survival, challenge group 7 and group 7 control monkeys at 37
      months
      >>
      >8. Bleeding schedule for monkeys:
      >>
      1 week prior to 6 months – all monkeys
      > 4, 7, 10 and 14 days after challenge – group 1
      >>
      1 week prior to 12 months – all remaining rabbits
      > 4, 7, 10 and 14 days after challenge – group 2
      >>
      1 week prior to 13 months – group 5 and group 5 controls
      > 4, 7, 10 and 14 days after challenge – group 5
      >>
      1 week prior to 24 months – all remaining rabbits
      > 4, 7, 10 and 14 days after challenge – group 3
      >>
      1 week prior to 25 months – group 6 and group 6 controls
      > 4, 7, 10 and 14 days after challenge – group 6
      >>
      1 week prior to 36 months – all remaining rabbits
      > 4, 7, 10 and 14 days after challenge – group 4
      >>
      1 week prior to 37 months – group 7 and group 7 controls
      > 4, 7, 10 and 14 days after challenge – group 7
      >>
      >9. Blood and sera will be assayed by ELISA, TNA, & ELISPOT.
      >
      >***************************************************************************************************************************************************************************************
      >10. Surviving rabbits will be euthanized. Surviving monkeys will be “grayed out.”
      >
      >11. Rabbits will be challenged at 13, 19 or 25 months only if there is less than 80% survival at 12, 18 or 24 months.
      >
      >12. Monkeys will be challenged at 13, 25 or 37 months, only if there is less than 80% survival at 12, 24 or 36 months.
      >
      >***********************************************************************************************************************************************************************************
      >13, Points to consider:
      > a) Should part of the studies be contracted out in order to save USAMRIID animal room space? Where? SRI? Covance? SAIC?
      > b) Other points?
      (b) (6)
      (b
      )
      (6)
      From: Ivins, Bruce E Dr USAMRIID
      To:
      Subject: RE: Anthrax, mice, and CpG
      Date: Tuesday, September 11, 2001 8:47:41 AM
      It looks fine. It’s very kind of you to include me on your abstract. I have only one comment:
      1) Mice were challenged with anthrax spores via the parenteral (subcutaneous) rather than the
      aerosol (inhaled) route.
      – Bruce
      —–Original Message—–
      From:
      Sent: Tuesday, September 11, 2001 8:37 AM
      To: ‘Ivins Bruce E’
      Subject: RE: Anthrax, mice, and CpG
      Dear Bruce,
      I’ve been invited to deliver a lecture on the protective activity of CpG ODN
      in mid October. They’ve requested an abstract be submitted by the end of
      this week. Is the following OK with you?
      The ability of synthetic oligodeoxynucleotides (ODN) containing
      immunostimulatory “CpG” motifs to trigger an innate immune response capable
      of improving host survival following bacterial, viral and parasitic
      infection was investigated. Initial studies showed that normal mice treated
      with 5 – 50 ug of CpG ODN were protected for approximately 2 weeks from
      subsequent infection by >1,000 LD50 of Listeria monocytogenes or Francisella
      tularensis, or from 100 leishmania parasites. Subsequent studies
      established that higher doses of CpG ODN prolonged and/or enhanced the
      survival of mice challenged with biothreat agents such as anthrax
      and mouse-adapted Ebola virus. In each challenge model, protection was
      critically dependent on the CpG motif, being lost when the CpG dinucleotide
      was inverted or methylated.
      Two strategies were pursued to extend the protection conferred by
      CpG ODN. In the first, mice were treated with CpG ODN every two weeks for
      up to 4 months. Protection against L. monocytogenes and F. tularensis was
      induced and maintained for the duration of therapy. In the second, mice
      were injected with CpG ODN encapsulated in cationic stealth liposomes (CSL).
      CSL encapsulation significantly improved the uptake of ODN by cells of the
      immune system and increased the magnitude and persistence of the resultant
      immune response. Mice treated with encapsulated CpG ODN were protected
      from L. monocytogenes and F. tularensis for >4 weeks.
      To determine whether CpG ODN would be effective immunoprotective
      (b) (6)
      (b) (6)
      (b) (6)
      (b) (6)
      (b) (6)
      agents in humans, we examined the response of PBMC from >100 normal human
      donors to a large panel of ODN. Two distinct classes of CpG ODN were
      identified that activated human PBMC. The first (“K” type) ODN have a
      phosphorothioate backbone and multiple TCGTT and/or TCGTA. “K” ODN
      primarily stimulate B cells and monocytes to proliferate and secrete IgM,
      IL-6 and IL-10. The second (“D” type) ODN have a mixed phosphodiester/
      phosphorothioate backbone and contain a single hexameric
      purine/pyrimidine/CG/purine/pyrimidine motif flanked by self-complementary
      bases that form a stem-loop structure capped at the 3′ end by a poly G tail.
      “D” ODN induce APC to mature and secrete IFNa and triggered NK cells to
      secrete IFNg.
      Whereas PBMC from all donors responded to at least one member of the
      “D” and “K” ODN panel, no single ODN induced an optimal response in all
      subjects. However, mixtures of ODN containing multiple CpG motifs strongly
      activated PBMC from all subjects. These mixtures also stimulated PBMC from
      non-human primates, such as chimpanzees and rhesus macaques. These mixtures
      were tested for their ability to protect rhesus monkeys from cutaneous
      leishmania infection. The severity of leishmania infection in macaques
      treated with “D” ODN 3 days before and 3 days after challenge was reduced by
      >90% (p. —–Original Message—–
      > From:
      > Sent: Tuesday, September 11, 2001 8:46 AM
      > To:
      > Cc:
      > Subject: RE: rPA Rabbit serum
      >>
      I never heard anything from her after I sent her the email asking for any
      > suggestions (08/23/01). It was the rPA sera that was in the broken
      > bottles, correct?…did they supply this? We compared it side by side to
      > the normal sera, which was filterable. I was wondering if they have
      > noticed that it is so thick and how they work with it?
      >>
      We can try syringe filtering it with a 5.0 micrometer pore size (the
      > largest pore size we had been using was 0.4 micrometers) but I hate to
      > keep freezing and thawing it so I was hoping for some further direction
      (> from them before trying something else, so we could have multiple options
      > ready for the next time it is thawed. If they don’t have any ideas, we
      > can go ahead with syringe filtering it.
      >>
      >>
      —–Original Message—–
      > From:
      > Sent: Monday, September 10, 2001 5:14 PM
      > To:
      > Cc:
      > Subject: rPA Rabbit serum
      >>
      I talked to today. Did we resolve the issue with filtering
      > the broken sera? I told her we would also look at the rPA, normal, and
      > AVA sera to see if they all appear to be similar in consistency, color,
      > etc. the next time we have some thawed.
      >>

      • DXer said

        Or maybe are these the emails that Dr. Saathoff thought Dr. Ivins had purged and thus were unable to read? They were not recreated from recipients, were they? There are hundreds of emails from 2001 — to include emails far outside USAMRIID. Was Dr. Saathoff unaware of the collection of many hundreds of emails from 2001 retrieved from USAMRIID? It is the documentary evidence from 2001 that is most probative. Here, isn’t it the key October 5, 2001 email reporting on the 12 rabbit deaths relating to the 10/2 subcutaneous challenge, that when read in context of earlier emails about Covance study planning in August 2001 and September 2001, contradicts Dr. Saarthoff’s claim that Dr. Ivins time in the lab was unexplained? If he hasn’t seen these emails it would explain the discrepancies between his narrative and the documents. For example, he evidences no awareness of the time that the September 17 email was written to Mara (who he calls Technician #2), even though he discusses mailing that day. That email has not been produced pursuant to FOIA and so we don’t know the time it was sent, even though it looms large as possibly critical evidence. From: Ivins, Bruce E Dr USAMRIID To: Subject: “Old” formaldehyde experiments Date: Wednesday, September 12, 2001 9:47:56 AM Here is the information you requested on the Covance study: Five years ago we made rPA vaccine/Alhydrogel with and without formaldehyde added. We tested the vaccines after various periods of time of storage and noted (in guinea pigs) that the presence of formaldehyde appeared to boost potency of the vaccine. It was unknown whether the boost in potency was due to stabilization of the protein, or to an adjuvant effect. (Formaldehyde itself causes local inflammation which would draw APCs and other cell types to the site.) The vaccine is now 5 years old since it was formulated, and we wished to see (in the rabbit model) if there is any difference in potency between the 2 vaccines. (The rabbit model is preferred over the guinea pig model in tests of anthrax vaccine efficacy.) Twenty-four New Zealand white rabbits (12 of each gender) were immunized with 0.5-ml intramuscular doses of vaccine containing 50 micrograms rPA, Alhydrogel (0.5 mg aluminum) and PBS (with formaldehyde, 0.02%). Twenty-four New Zealand white rabbits (12 of each gender) were immunized with 0.5-ml intramuscular doses of vaccine containing 50 micrograms rPA, Alhydrogel (0.5 mg aluminum) and PBS (without formaldehyde). Four rabbits (2 of each gender) will be controls receiving Alhydrogel and PBS. Rabbits will be bled at weeks 2 and 4 for anti-PA antibody titers. They will be challenged subcutaneously with virulent anthrax spores 6 weeks after immunization and monitored for survival. This experiment will demonstrate whether the presence of formaldehyde in an rPA/Alhydrogel vaccine increases or preserves potency. – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: CRM Task Order 0086 Date: Wednesday, September 12, 2001 1:26:29 PM I approve. – Bruce Ivins >—–Original Message—– >From: >Sent: Wednesday, September 12, 2001 1:26 PM >To: Ivins, Bruce E Dr USAMRIID >Cc: >Subject: CRM Task Order 0086 > >Dr. Ivins; > >I have received invoice no. 11 for for the month of August for $5,442.33. Please email reply to all your approval. Any questions, please call. > >Thanks 9/12/01 > From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: Protocol modifications Date: Friday, September 14, 2001 10:32:09 AM – We need to wait until finishes his 2-dose study to decide what dose of rPA to use. If it turns out the dose is 10 micrograms -which is a good guess, will you have enough rPA for 2 shots, 30 rabbits of each isoform and 30 rabbits with rPA? Responses to 1. It is OK with me if we go to the larger number of rabbits. 2. OK. 3. This does not need to be a GLP study. This is still a tech-base study to tell us whether there are differences (as far as vaccinating ability) between the two isoforms. If it needs to be done GLP, then Battelle should do it. – Bruce >—–Original Message—– >From: >Sent: Tuesday, September 04, 2001 8:36 AM >To: Ivins, Bruce E Dr USAMRIID >Subject: FW: Protocol modifications > >Re: animal protocol to study the contribution of rPA isoforms to protection against a lethal anthrax infection in rabbits. suggests we do 30 rabbits per group; see below. The change would result in 94 rabbits instead of 52 ($$$?). Please advise if we wish to accept his recommendations so I can make the changes. (Bruce had originally suggested 16 per group). Thanks in advance. > <> >> —–Original Message—– >From: >Sent: Friday, August 31, 2001 3:30 PM >To: >Subject: Protocol modifications >>> The isoform protocol is suggested to undergo the following statistical revisions. There are three reasons > for the revisions: >> 1. This study is approaching the final formulation of the rPA anthrax vaccine candidate and thus must > adhere to stricter criteria. >> 2. The stricter criteria involve the concept of “equivalency” testing. This means that we seek to reject > the hypothesis that the two isoforms are NOT equivalent with respect to survival and immune response > as measured by ELISA and TNA. Rejection of the hypothesis establishes the statistical evidence that the > isoforms are equivalent. This requires larger sample sizes than a test of the hypothesis that the two > isoforms are not different (a subtle difference), which is an early developmental hypothesis. >> 3. Should this not be a strict GLP study due to the need for FDA approval of the decision that will > arise from it? We do not wish to have to repeat the study in the future under GLP standards. >> Revisions suggested: >> Page 3 replace objective with: “The hypothesis is that the two isoforms are NOT equivalent in survival rates > or immune response as measured by either ELISA and TNA. Equivalency is defined as a difference > in survival rates of no more than 20%, and a ratio of geometric mean ELISA titers and TNA titers of > no more than 4-fold respectively. The hypothesis will be tested at the 95% confidence level (2-tailed). Rejection > of the hypothesis establishes the equivalency of the survival and immune response of the two isoforms. > Failure to reject any of the hypothesis (survival or immune response) fails to establish the equivalency > of the two isoforms. Sex-specific tests will be done.” >> Page 11 replace Data Analysis with: “Sex-specific survival rates will be tested for equivalence using the method > of Farrington and Manning (ref). ELISA and TNA titers will be transformed to log10 and analyzed for > sex-specific equivalency based on the 95% confidence intervals (2-tailed) around the ratio of geometric mean titers. > Further analysis of survival correlations with sex, titers and isoform will use standard logistic regression. > Also, further analysis of titers will use multiple regression to test for sex differences and to test for > isoform differences. All tests will be at the 95% confidence level (2-tailed). All data will be automated > and verified prior to analysis. Statistical software package SAS (version 8.0 or greater) will be used > for analysis.” >> Page 11 Move the sample size justification to the page 5 and replace the statement there with: >> The test of equivalency of survival rates assumes 100% survival in both isoforms and a 20% > maximum difference resulting in a sample size of 15 of each sex per isoform. The test of > equivalency of immune response assumes a log10 standard deviation of 0.50 logs and a > maximum ratio of geometric mean titers of 4-fold (0.60 logs) resulting in a sample > size of 12 of each sex per isoform. Therefore, 30 rabbits (15 male and 15 female) must be > tested at each isoform and with the combined isoforms as a control. The unprotected controls > will be set at a nominal 4 animals (2 of each sex) due to confidence in the 100% lethality > of the challenge dose.” >> Reference: Farrington CP and Manning G. Test statistics and sample size formulae for comparative > binomial trials with null hypothesis of non-zero risk difference or non-unity relative risk. > Statistics in Medicine, vol 9, 147-1454, 1990. > > From: Ivins, Bruce E Dr USAMRIID To: ” Subject: RE: anti-rPA serum Date: Wednesday, September 19, 2001 8:13:16 AM Hi, , We will have both placebo and vaccine ready for pickup on Monday, September 24. We will make enough placebo to cover future immunizations as well, since there is no worry about antigen change or degradation. You may give my phone number or email out, but due to security precautions, they won’t be able to get on post. I will meet them at the Post office on 7th Street. They will come to Frederick via 270N, then continue on 15N. The exit they will take will be the 7th Street exit. They should bear to the right, and turn right onto 7th Street (towards Fort Detrick, not the hospital, which is towards the left.) They will go under the Route 15 overpass and take the first right into the post office parking lot. I will meet them there. If they need a map, I can send them one by FAX. – Sincerely, Bruce Ivins —–Original Message—– From: Sent: Tuesday, September 18, 2001 5:08 PM To: ‘Bruce.Ivins@DET.AMEDD.ARMY.MIL’ Subject: anti-rPA serum Bruce, It is time again to bother you. Sorry! Next booster of the 500 rPA-animals is scheduled for Tuesday, September 25 (6 micrograms in 0.5 ml doses). Our last meeting was so hectic (by the way, thanks much for all your help) that I forgot to request from you the placebo for the control group. This consists of 30 mice that will be bled in groups of ten each, three weeks after one, two or three doses of placebo (0.5 ml of same vaccine diluent containing same amount of aluminum than rPA-vaccine). Hopefully you can provide us with this latter prep this time (enough for all 30 mice; bleeding of the last group will be out of phase three weeks, but I don’t think it’s a big deal). One last thing. We are paying the contractor for picking up material; last time I delivered the vaccine myself in person, but in this instance I would prefer that Biocon picks it up directly from you. Is that possible? Please let me know, and if you don’t mind I will give them your phone to make arrangements for pick up directly. Thanks much and best regards. From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: UBMTA to sign Date: Wednesday, September 19, 2001 8:40:58 AM Thanks, – Bruce >—–Original Message—– >From: >Sent: Wednesday, September 19, 2001 8:40 AM >To: Ivins, Bruce E Dr USAMRIID >Subject: UBMTA to sign > >Hi Bruce, >I received the signed UBMTAs from Whenever you get a chance can you please come by and sign & date the agreements. I’ll be at a meeting this morning. I’ll leave them on my chair. Before even receiving them, I started the routing initials (as you know it takes awhile). Once I get okay, we’re good to go. > (b) (6) From: Ivins, Bruce E Dr USAMRIID To: Subject: SPores Date: Thursday, September 20, 2001 9:41:06 AM If you think it would be helpful, I would be willing to come up to Battelle to offer advice or suggestions with respect to spore production, purification, storage, etc. When we first started working on it years ago, it took us quite awhile to learn the “art” and techniques involved in getting spores which were, stable, pure, unclumped, etc. Honestly, in 1 day to no more than a week, I might be able to save more than several weeks to several months worth of work on your part. Although spore production and purification sounds, on the surface, very easy and cookbook, there are some little nuances in the methodology which are important, yet hard to write down. Seriously, please let me know if you’d like me to come, and if so, when. At a time like this, I think we all need to come together in single directed purpose, and if that includes my coming there for one or a few days, I’d be happy to do it. – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: Research Progress report Date: Thursday, September 20, 2001 9:52:09 AM Attachments: I have enclosed my research progress report, with changes made as required by the Anthrax Steering Committee. – Bruce (b) (6) From: Ivins, Bruce E Dr USAMRIID To: Subject: FW: SPores Date: Thursday, September 20, 2001 10:12:05 AM I just sent this to and I thought I’d send it to you. If you think it might be helpful for me to make a trip to Battelle for advice, suggestions, etc. on spore purification, harvest, storage, etc., I’d be happy to come. It’s as much an art as a science, and I could be there for whatever parts of the process you’d like. The purification on gradients is especially tricky. – Bruce >—–Original Message—– >From: Ivins, Bruce E Dr USAMRIID >Sent: Thursday, September 20, 2001 9:41 AM >To: >Subject: SPores > , > If you think it would be helpful, I would be willing to come up to Battelle to offer advice or suggestions with respect to spore production, purification, storage, etc. When we first started working on it years ago, it took us quite awhile to learn the “art” and techniques involved in getting spores which were, stable, pure, unclumped, etc. Honestly, in 1 day to no more than a week, I might be able to save more than several weeks to several months worth of work on your part. Although spore production and purification sounds, on the surface, very easy and cookbook, there are some little nuances in the methodology which are important, yet hard to write down. >> Seriously, please let me know if you’d like me to come, and if so, when. At a time like this, I think we all need to come together in single directed purpose, and if that includes my coming there for one or a few days, I’d be happy to do it. >> – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: Contract Mod Date: Thursday, September 20, 2001 10:20:26 AM Thanks, I also think that a parenteral challenge will be the best in this situation, having been involved in both parenteral and aerosol challenges. – Bruce —–Original Message—– From: Sent: Thursday, September 20, 2001 10:18 AM To: ‘ Cc: Ivins, Bruce E Dr USAMRIID; Subject: RE: Contract Mod We are completing the protocols and I plan to send them to you by tomorrow. They will not be in SOP form but instead in rougher form, as you call “study specific methods.” I want to preview for you the following changes not mentioned in the SOW: 1. Two methods for desorption of rPA will be used as follows. Sodium carbonate for protein to be assayed by SDS-PAGE, Western, and RP-HPLC. Sodium Phosphate for assay by native PAGE (Phast Gel). These procedures are identical except for the solution as indicated. The rationale is that while sodium carbonate will desorb much of the rPA its biophysical form is altered as seen by native PAGE but not by the other assays. Sodium phosphate will elute rPA that is identical to unadsorbed rPA, but the yield is only about 50%. So, we will look at the bulk of the adjuvanted protein with assays that are not sensitive to slight changes in charge, and look at a smaller portion of the adjuvanted protein using an assay that will distinguish between charge forms. 2. The tech base committee recommended injection rather than aerosol for exposure due to much greater precision in delivery of spores and subsequent confidence in statistical analysis of results. However, I am still awaiting a “go” from our prime systems contractor. I know this would change the costing and planning, so I will get back to you as soon as I get a final word from those in higher authority. —–Original Message—– From: Sent: Monday, September 17, 2001 1:20 PM To: ‘ Cc: Subject: Contract Mod Hi On Friday we received the contract mod from the USAMRMC Contracting Officer to start your stability project. We have started to write the animal use protocol and we ordered the PhastSystem today. Any idea when you can provide us with all the SOPs and Methods that we need to have in place (in our format) before we can start the work? We also need to schedule the first teleconference – perhaps a better use of everybody’s time if we schedule it after you have sent us the SOPs and we have had a couple of days to review them so that we can ask relevant questions. Thanks From: Ivins, Bruce E Dr USAMRIID To: Cc: Subject: rPA Date: Thursday, September 20, 2001 2:41:41 PM , Thank you for the 30 vials of rPA, lot 100506, 1.18 mg/ml, that you gave me this morning for tech-base studies in support of the development of a new human anthrax vaccine. It will be put to use immediately. – Bruce Ivins From: Ivins, Bruce E Dr USAMRIID To: Cc: Subject: B98-03 rabbit bacteremia data Date: Tuesday, September 25, 2001 9:13:34 AM Attachments: Here are the B98-03 rabbit bacteremia data in an EXCEL file. – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: Money for long-term rabbit study Date: Tuesday, September 25, 2001 11:22:04 AM This is the money I come up with for the long-term rabbit study. What is needed for the long-term monkey study and the strain study will be forthcoming. The figures are for supplies, animals, etc. necessary to do the study. Personnel money (salaries, travel, etc.) is not included. Costs: 192 rabbits…………………………………………………$21,120 Aerosolization costs………………………………………$1,920 Supplies costs (Tyveks, gloves, booties, head covers, syringes, needles, tubes…………………$10,000 ELISA and TNA costs…………………………………….$3,400 Husbandry costs (daily rabbit care)…………………$296,640 __________ Total………………………………………………………..$330,080 ********************************************************************************************************************************************************************** as just given me her costs for the diverse strain study: Costs: 200 rabbits………………………………………………..$22,000 Animal husbandry (100 days)…………………………$60,000 Aerosolization costs………………………………………$2,000 Supplies……………………………………………………$10,000 ELISA and TNA assays………………………………….$1,000 _______ Total………………………………………………………..$95,000 I’ll get the monkey study info to you as soon as possible. – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: Money for long-term rabbit study Date: Tuesday, September 25, 2001 11:22:04 AM This is the money I come up with for the long-term rabbit study. What is needed for the long-term monkey study and the strain study will be forthcoming. The figures are for supplies, animals, etc. necessary to do the study. Personnel money (salaries, travel, etc.) is not included. Costs: 192 rabbits…………………………………………………$21,120 Aerosolization costs………………………………………$1,920 Supplies costs (Tyveks, gloves, booties, head covers, syringes, needles, tubes…………………$10,000 ELISA and TNA costs…………………………………….$3,400 Husbandry costs (daily rabbit care)…………………$296,640 __________ Total………………………………………………………..$330,080 ********************************************************************************************************************************************************************** as just given me her costs for the diverse strain study: Costs: 200 rabbits………………………………………………..$22,000 Animal husbandry (100 days)…………………………$60,000 Aerosolization costs………………………………………$2,000 Supplies……………………………………………………$10,000 ELISA and TNA assays………………………………….$1,000 _______ Total………………………………………………………..$95,000 I’ll get the monkey study info to you as soon as possible. – Bruce From: Ivins, Bruce E Dr USAMRIID To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Money for long-term rabbit study Date: Tuesday, September 25, 2001 4:07:00 PM Monkey long-term efficacy study money requirements. Please keep in mind that the costs are for 3 years. We plan to use 10 monkeys + 2 controls per time point (3 months, 6 months, 12 months, 24 months, 25 months (if 24 month survival is less than 80%), 36 months, and 37 months (if 36 month survival is less than 80%). Cost: 72 monkeys….($3,000 per monkey)………………………….$216,000 Aerosolization costs…………………………………………………$1,000 Supplies………………………………………………………………$10,000 ELISA and TNA costs……………………………………………….$2,000 Husband costs ($6.00 per day per animal)…………………..$822,240 __________ Total………………………………………………………………..$1,051,240 If the costs are deemed too high, then we can lower the number of timepoints, thus lowering the total number of monkeys. – Bruce >—–Original Message—– >From: Ivins, Bruce E Dr USAMRIID >Sent: Tuesday, September 25, 2001 11:22 AM >To: Ivins, Bruce E Dr USAMRIID; >Subject: Money for long-term rabbit study > This is the money I come up with for the long-term rabbit study. What is needed for the long-term monkey study and the strain study will be forthcoming. The figures are for supplies, animals, etc. necessary to do the study. Personnel money (salaries, travel, etc.) is not included. > >Costs: > >192 rabbits…………………………………………………$21,120 >Aerosolization costs………………………………………$1,920 >Supplies costs (Tyveks, gloves, booties, head > covers, syringes, needles, tubes…………………$10,000 >ELISA and TNA costs…………………………………….$3,400 >Husbandry costs (daily rabbit care)…………………$296,640 > __________ >Total………………………………………………………..$330,080 >> >********************************************************************************************************************************************************************** has just given me her costs for the diverse strain study: > >Costs: > >200 rabbits………………………………………………..$22,000 >Animal husbandry (100 days)…………………………$60,000 >Aerosolization costs………………………………………$2,000 >Supplies……………………………………………………$10,000 >ELISA and TNA assays………………………………….$1,000 > _______ >Total………………………………………………………..$95,000 >>> >I’ll get the monkey study info to you as soon as possible. >- Bruce (b) (6) (b) (6) (b) (6) ( b From: Ivins, Bruce E Dr USAMRIID To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Money for long-term rabbit study Date: Tuesday, September 25, 2001 4:07:00 PM Monkey long-term efficacy study money requirements. Please keep in mind that the costs are for 3 years. We plan to use 10 monkeys + 2 controls per time point (3 months, 6 months, 12 months, 24 months, 25 months (if 24 month survival is less than 80%), 36 months, and 37 months (if 36 month survival is less than 80%). Cost: 72 monkeys….($3,000 per monkey)………………………….$216,000 Aerosolization costs…………………………………………………$1,000 Supplies………………………………………………………………$10,000 ELISA and TNA costs……………………………………………….$2,000 Husband costs ($6.00 per day per animal)…………………..$822,240 __________ Total………………………………………………………………..$1,051,240 If the costs are deemed too high, then we can lower the number of timepoints, thus lowering the total number of monkeys. – Bruce >—–Original Message—– >From: Ivins, Bruce E Dr USAMRIID >Sent: Tuesday, September 25, 2001 11:22 AM >To: Ivins, Bruce E Dr USAMRIID; >Subject: Money for long-term rabbit study > > This is the money I come up with for the long-term rabbit study. What is needed for the long-term monkey study and the strain study will be forthcoming. The figures are for supplies, animals, etc. necessary to do the study. Personnel money (salaries, travel, etc.) is not included. > >Costs: > >192 rabbits…………………………………………………$21,120 >Aerosolization costs………………………………………$1,920 >Supplies costs (Tyveks, gloves, booties, head > covers, syringes, needles, tubes…………………$10,000 >ELISA and TNA costs…………………………………….$3,400 >Husbandry costs (daily rabbit care)…………………$296,640 > __________ >Total………………………………………………………..$330,080 >> >********************************************************************************************************************************************************************** has just given me her costs for the diverse strain study: > >Costs: > >200 rabbits………………………………………………..$22,000 >Animal husbandry (100 days)…………………………$60,000 >Aerosolization costs………………………………………$2,000 >Supplies……………………………………………………$10,000 >ELISA and TNA assays………………………………….$1,000 > _______ >Total………………………………………………………..$95,000 >>> >I’ll get the monkey study info to you as soon as possible. >- Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: Strains Date: Monday, October 01, 2001 2:41:38 PM Hi, Thanks for your phone call earlier today. and I both gave some thought as to the B. anthracis strains of interest with respect to sequencing. Am I correct that the Ames strain has been sequenced? It certainly would be a fine candidate for a “type strain.” The other strains would be 1) Vollum 1B 2) The Australia strain that you and sent (It killed all 16 immunized guinea pigs.) 3) The Kruger A isolate 4) The Kruger B isolate I think that if you do one of the Kruger isolates, you should do the other. The Vollum 1B strain is of interest because it has been so extensively used, and because it is demonstrably less virulent than the Ames strain in certain animal models. The Australia strain is of interest because of its exceptional virulence in the immunized guinea pig. Hope this is helpful. If you’d like to talk about these any more, I’d be happy to do so. Have a great fall! – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: Florida case(?) Date: Thursday, October 04, 2001 9:57:19 PM Hi, I just heard this evening (and read over internet news) that a case of pulmonary anthrax may have been identified in Florida. Is this true, or is this just hysteria? The only Florida strain of B. anthracis that I am familiar with is V770, which is the parent of V770-NP1-R, the strain used in production of the human anthrax vaccine. (I believe that V770 was originally isolated from a cow in Florida in the early 1950s.) The article said that this person was an “Outdoorsman,” and had drunk water from a creek in North Carolina. If he really does have anthrax, could he have gotten it this way, or did he get it by tromping around some dusty field area. (Has North Carolina been dry this summer?) I know that in the wild in Africa, animals are supposed to be able to get it from water holes by stirring up spores and presumably ingesting and possibly inhaling them as an aerosol. Could this have happened? What if an animal had died upstream and the stream was contaminated? (Drinking from a stream or creek without boiling or purifying the water first is an invitation to intestinal disease or parasites, but have any other human anthrax cases been documented from people drinking contaminated water?) You called me several times in the recent past with regards to another anthrax issue. If there’s anything I can help with here (if you or coworkers are involved) please let me know. I don’t know if there’s anything I can do, but I’m certainly willing to provide whatever informational assistance I can. (I would have been less surprised if the Florida man had been hunting deer in Texas, where there is identifiable anthrax. I don’t recall North Carolina as having ideal soil for preservation of anthrax spores or for anthrax cycling of spore-vegetative cell-spore-vegetative cell etc., but I suppose there could be areas of higher soil calcium and alkalinity.) Anyway, please don’t hesitate to give me a call if there’s anything I can do. We are currently testing the virulence (in immunized and unimmunized guinea pigs) of B. anthracis strains from all over the world, including China, and we’ve come up with some very interesting differences in virulence among the strains. Take care of yourself, – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: Stabilizer in a new rPA vaccine Date: Friday, October 05, 2001 10:52:45 AM The data we are getting from our with formaldehyde/without formaldehyde experiment in rabbits is giving us VERY strong evidence that we should incorporate a stabilizer in with rPA and Alhydrogel. weren’t some FDA-acceptable stabilizers going to be identified? If there some out there, maybe we should start thinking about them now. Basically what we have as far as the experiment: 1) Five years ago rPA/Alhydrogel/PBS vaccine was made with or without 0.02% formaldehyde (the level that’s in AVA) and stored at 4C. With these vaccines we immunized groups of rabbits as follows (0.5 ml per intramuscular dose): Group A – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/0.02% formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. Group B – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/No formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. Group C – 4 rabbits (2 males, 2 females) get PBS/Alhydrogel (0.5 mg) at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. 2) Results so far, 3 days after challenge: Group Survived/Total A – Vaccine plus formaldehyde 24/24 (no deaths) B – Vaccine minus formaldehyde 16/24 (8 deaths) C – Controls 0/4 (4 deaths) Note: We originally studied the effect of formaldehyde on rPA vaccine potency/stability in guinea pigs. The cumulative data indicated that stability/potency was enhanced by the presence of formaldehyde. – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: Stabilizer in a new rPA vaccine Date: Friday, October 05, 2001 11:04:56 AM No, just survival data. – Bruce —–Original Message—– From: Sent: Friday, October 05, 2001 10:56 AM To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Stabilizer in a new rPA vaccine Bruce, Do you have any data yet on the protein composition (i.e. is it degraded) in the with or without formaldehyde? —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Friday, October 05, 2001 10:53 AM To: Subject: Stabilizer in a new rPA vaccine The data we are getting from our with formaldehyde/without formaldehyde experiment in rabbits is giving us VERY strong evidence that we should incorporate a stabilizer in with rPA and Alhydrogel. weren’t some FDA-acceptable stabilizers going to be identified? If there some out there, maybe we should start thinking about them now. Basically what we have as far as the experiment: 1) Five years ago rPA/Alhydrogel/PBS vaccine was made with or without 0.02% formaldehyde (the level that’s in AVA) and stored at 4C. With these vaccines we immunized groups of rabbits as follows (0.5 ml per intramuscular dose): Group A – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/0.02% formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. Group B – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/No formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. Group C – 4 rabbits (2 males, 2 females) get PBS/Alhydrogel (0.5 mg) at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. 2) Results so far, 3 days after challenge: Group Survived/Total A – Vaccine plus formaldehyde 24/24 (no deaths) B – Vaccine minus formaldehyde 16/24 (8 deaths) C – Controls 0/4 (4 deaths) Note: We originally studied the effect of formaldehyde on rPA vaccine potency/stability in guinea pigs. The cumulative data indicated that stability/potency was enhanced by the presence of formaldehyde. – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: Stabilizer in a new rPA vaccine Date: Friday, October 05, 2001 11:04:56 AM No, just survival data. – Bruce —–Original Message—– From: Sent: Friday, October 05, 2001 10:56 AM To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Stabilizer in a new rPA vaccine Bruce, Do you have any data yet on the protein composition (i.e. is it degraded) in the with or without formaldehyde? —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Friday, October 05, 2001 10:53 AM To: Subject: Stabilizer in a new rPA vaccine The data we are getting from our with formaldehyde/without formaldehyde experiment in rabbits is giving us VERY strong evidence that we should incorporate a stabilizer in with rPA and Alhydrogel. and .weren’t some FDA-acceptable stabilizers going to be identified? If there some out there, maybe we should start thinking about them now. Basically what we have as far as the experiment: 1) Five years ago rPA/Alhydrogel/PBS vaccine was made with or without 0.02% formaldehyde (the level that’s in AVA) and stored at 4C. With these vaccines we immunized groups of rabbits as follows (0.5 ml per intramuscular dose): Group A – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/0.02% formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. Group B – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/No formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. Group C – 4 rabbits (2 males, 2 females) get PBS/Alhydrogel (0.5 mg) at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. 2) Results so far, 3 days after challenge: Group Survived/Total A – Vaccine plus formaldehyde 24/24 (no deaths) B – Vaccine minus formaldehyde 16/24 (8 deaths) C – Controls 0/4 (4 deaths) Note: We originally studied the effect of formaldehyde on rPA vaccine potency/stability in guinea pigs. The cumulative data indicated that stability/potency was enhanced by the presence of formaldehyde. – Bruce From: Ivins, Bruce E Dr USAMRIID To: Ivins, Bruce E Dr USAMRIID; Subject: FW: Stabilizer in a new rPA vaccine Date: Friday, October 05, 2001 11:07:04 AM It’s up to everyone else. It does strongly appear as though we will need a stabilizer, however. – Bruce >—–Original Message—– >From: >Sent: Friday, October 05, 2001 11:05 AM >To: Ivins, Bruce E Dr USAMRIID >Subject: RE: Stabilizer in a new rPA vaccine > >Bruce, >This could figure into the upcoming stability/efficacy study, for which I specifically asked about an concurrent set with an excipient but DVC considered this too early. Should we meet? >> —–Original Message—– >From: Ivins, Bruce E Dr USAMRIID >Sent: Friday, October 05, 2001 10:53 AM >To: >Subject: Stabilizer in a new rPA vaccine >> The data we are getting from our with formaldehyde/without formaldehyde experiment in rabbits is giving us VERY strong evidence that we should incorporate a stabilizer in with rPA and Alhydrogel. weren’t some FDA-acceptable stabilizers going to be identified? If there some out there, maybe we should start thinking about them now. >> Basically what we have as far as the experiment: >> 1) Five years ago rPA/Alhydrogel/PBS vaccine was made with or without 0.02% formaldehyde (the level that’s in AVA) and stored at 4C. With these vaccines we immunized groups of rabbits as follows (0.5 ml per intramuscular dose): > Group A – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/0.02% formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group B – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/No formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group C – 4 rabbits (2 males, 2 females) get PBS/Alhydrogel (0.5 mg) at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. >> 2) Results so far, 3 days after challenge: >>> Group Survived/Total >> A – Vaccine plus formaldehyde 24/24 (no deaths) >> B – Vaccine minus formaldehyde 16/24 (8 deaths) >> C – Controls 0/4 (4 deaths) >>> Note: We originally studied the effect of formaldehyde on rPA vaccine potency/stability in guinea pigs. The cumulative data indicated that stability/potency was enhanced by the presence of formaldehyde. >> – Bruce > From: Ivins, Bruce E Dr USAMRIID To: Ivins, Bruce E Dr USAMRIID; Subject: FW: Stabilizer in a new rPA vaccine Date: Friday, October 05, 2001 11:07:04 AM It’s up to everyone else. It does strongly appear as though we will need a stabilizer, however. – Bruce >—–Original Message—– >From: >Sent: Friday, October 05, 2001 11:05 AM >To: Ivins, Bruce E Dr USAMRIID >Subject: RE: Stabilizer in a new rPA vaccine > >Bruce, >This could figure into the upcoming stability/efficacy study, for which I specifically asked about an concurrent set with an excipient but DVC considered this too early. Should we meet? >> —–Original Message—– >From: Ivins, Bruce E Dr USAMRIID >Sent: Friday, October 05, 2001 10:53 AM >To: >Subject: Stabilizer in a new rPA vaccine >> The data we are getting from our with formaldehyde/without formaldehyde experiment in rabbits is giving us VERY strong evidence that we should incorporate a stabilizer in with rPA and Alhydrogel. weren’t some FDA-acceptable stabilizers going to be identified? If there some out there, maybe we should start thinking about them now. >> Basically what we have as far as the experiment: >> 1) Five years ago rPA/Alhydrogel/PBS vaccine was made with or without 0.02% formaldehyde (the level that’s in AVA) and stored at 4C. With these vaccines we immunized groups of rabbits as follows (0.5 ml per intramuscular dose): > Group A – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/0.02% formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group B – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/No formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group C – 4 rabbits (2 males, 2 females) get PBS/Alhydrogel (0.5 mg) at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. >> 2) Results so far, 3 days after challenge: >>> Group Survived/Total >> A – Vaccine plus formaldehyde 24/24 (no deaths) >> B – Vaccine minus formaldehyde 16/24 (8 deaths) >> C – Controls 0/4 (4 deaths) Note: We originally studied the effect of formaldehyde on rPA vaccine potency/stability in guinea pigs. The cumulative data indicated that stability/potency was enhanced by the presence of formaldehyde. >> – Bruce > From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: Stabilizer in a new rPA vaccine Date: Friday, October 05, 2001 11:10:17 AM I don’t have an earlier time point in rabbits, just guinea pigs. – Bruce >—–Original Message—– >From: >Sent: Friday, October 05, 2001 11:10 AM >To: Ivins, Bruce E Dr USAMRIID >Subject: RE: Stabilizer in a new rPA vaccine > >Do you have an earlier time point? Is this the same batch of protein that showed to be more degraded with formaldehyde than without? >> —–Original Message—– > From: Ivins, Bruce E Dr USAMRIID > Sent: Friday, October 05, 2001 11:07 AM > To: Ivins, Bruce E Dr USAMRIID; > Subject: FW: Stabilizer in a new rPA vaccine >> It’s up to everyone else. It does strongly appear as though we will need a stabilizer, however. > – Bruce > —–Original Message—– > From: > Sent: Friday, October 05, 2001 11:05 AM > To: Ivins, Bruce E Dr USAMRIID > Subject: RE: Stabilizer in a new rPA vaccine >> Bruce, > This could figure into the upcoming stability/efficacy study, for which I specifically asked about an concurrent set with an excipient but DVC considered this too early. Should we meet? > >> —–Original Message—– > From: Ivins, Bruce E Dr USAMRIID > Sent: Friday, October 05, 2001 10:53 AM > To: > Subject: Stabilizer in a new rPA vaccine >> The data we are getting from our with formaldehyde/without formaldehyde experiment in rabbits is giving us VERY strong evidence that we should incorporate a stabilizer in with rPA and Alhydrogel. weren’t some FDA-acceptable stabilizers going to be identified? If there some out there, maybe we should start thinking about them now. >> Basically what we have as far as the experiment: >> 1) Five years ago rPA/Alhydrogel/PBS vaccine was made with or without 0.02% formaldehyde (the level that’s in AVA) and stored at 4C. With these vaccines we immunized groups of rabbits as follows (0.5 ml per intramuscular dose): > Group A – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/0.02% formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group B – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/No formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group C – 4 rabbits (2 males, 2 females) get PBS/Alhydrogel (0.5 mg) at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. >> 2) Results so far, 3 days after challenge: >>> Group Survived/Total >> A – Vaccine plus formaldehyde 24/24 (no deaths) >> B – Vaccine minus formaldehyde 16/24 (8 deaths) >> C – Controls 0/4 (4 deaths) >>> Note: We originally studied the effect of formaldehyde on rPA vaccine potency/stability in guinea pigs. The cumulative data indicated that stability/potency was enhanced by the presence of formaldehyde. >> – Bruce > From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: Stabilizer in a new rPA vaccine Date: Friday, October 05, 2001 11:21:42 AM That is domain. – Bruce —–Original Message—– From: Sent: Friday, October 05, 2001 11:02 AM To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Stabilizer in a new rPA vaccine You will still need the protein data to confirm that it is a stability problem and not an adjuventing affect. (yeah, I know, I always have to play devil’s advocate). —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Friday, October 05, 2001 11:07 AM To: Ivins, Bruce E Dr USAMRIID; Subject: FW: Stabilizer in a new rPA vaccine It’s up to everyone else. It does strongly appear as though we will need a stabilizer, however. – Bruce > —–Original Message—– > From: > Sent: Friday, October 05, 2001 11:05 AM > To: Ivins, Bruce E Dr USAMRIID > Subject: RE: Stabilizer in a new rPA vaccine >> Bruce, > This could figure into the upcoming stability/efficacy study, for which I specifically asked about an concurrent set with an excipient but DVC considered this too early. Should we meet? > >> —–Original Message—– > From: Ivins, Bruce E Dr USAMRIID > Sent: Friday, October 05, 2001 10:53 AM > To: > Subject: Stabilizer in a new rPA vaccine >> The data we are getting from our with formaldehyde/without formaldehyde experiment in rabbits is giving us VERY strong evidence that we should incorporate a stabilizer in with rPA and Alhydrogel. and .weren’t some FDA-acceptable stabilizers going to be identified? If there some out there, maybe we should start thinking about them now. >> Basically what we have as far as the experiment: >> 1) Five years ago rPA/Alhydrogel/PBS vaccine was made with or without 0.02% formaldehyde (the level that’s in AVA) and stored at 4C. With these vaccines we immunized groups of rabbits as follows (0.5 ml per intramuscular dose): > Group A – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/0.02% formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group B – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/No formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group C – 4 rabbits (2 males, 2 females) get PBS/Alhydrogel (0.5 mg) at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. >> 2) Results so far, 3 days after challenge: >>> Group Survived/Total >> A – Vaccine plus formaldehyde 24/24 (no deaths) >> B – Vaccine minus formaldehyde 16/24 (8 deaths) >> C – Controls 0/4 (4 deaths) >>> Note: We originally studied the effect of formaldehyde on rPA vaccine potency/stability in guinea pigs. The cumulative data indicated that stability/potency was enhanced by the presence of formaldehyde. > > – Bruce > From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: Stabilizer in a new rPA vaccine Date: Friday, October 05, 2001 11:21:42 AM That is domain. – Bruce —–Original Message—– Sent: Friday, October 05, 2001 11:02 AM To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Stabilizer in a new rPA vaccine You will still need the protein data to confirm that it is a stability problem and not an adjuventing affect. (yeah, I know, I always have to play devil’s advocate). —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Friday, October 05, 2001 11:07 AM To: Ivins, Bruce E Dr USAMRIID; Subject: FW: Stabilizer in a new rPA vaccine It’s up to everyone else. It does strongly appear as though we will need a stabilizer, however. – Bruce > —–Original Message—– > From: > Sent: Friday, October 05, 2001 11:05 AM > To: Ivins, Bruce E Dr USAMRIID > Subject: RE: Stabilizer in a new rPA vaccine >> Bruce, > This could figure into the upcoming stability/efficacy study, for which I specifically asked about an concurrent set with an excipient but DVC considered this too early. Should we meet? >> —–Original Message—– > From: Ivins, Bruce E Dr USAMRIID > Sent: Friday, October 05, 2001 10:53 AM > To: > Subject: Stabilizer in a new rPA vaccine >> The data we are getting from our with formaldehyde/without formaldehyde experiment in rabbits is giving us VERY strong evidence that we should incorporate a stabilizer in with rPA and Alhydrogel. and ..weren’t some FDA-acceptable stabilizers going to be identified? If there some out there, maybe we should start thinking about them now. >> Basically what we have as far as the experiment: >> 1) Five years ago rPA/Alhydrogel/PBS vaccine was made with or without 0.02% formaldehyde (the level that’s in AVA) and stored at 4C. With these vaccines we immunized groups of rabbits as follows (0.5 ml per intramuscular dose): > Group A – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/0.02% formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group B – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/No formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group C – 4 rabbits (2 males, 2 females) get PBS/Alhydrogel (0.5 mg) at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. >> 2) Results so far, 3 days after challenge: >>> Group Survived/Total >> A – Vaccine plus formaldehyde 24/24 (no deaths) >> B – Vaccine minus formaldehyde 16/24 (8 deaths) >> C – Controls 0/4 (4 deaths) >>> Note: We originally studied the effect of formaldehyde on rPA vaccine potency/stability in guinea pigs. The cumulative data indicated that stability/potency was enhanced by the presence of formaldehyde. > > – Bruce > From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: Stabilizer in a new rPA vaccine Date: Friday, October 05, 2001 11:31:44 AM The only data we have on this is the guinea pig data. Perhaps the question can be addressed by the stability study at Battelle. .your thoughts??? – Bruce —–Original Message—– From: Sent: Friday, October 05, 2001 11:21 AM To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Stabilizer in a new rPA vaccine If all or most of the rabbits die in the without formaldehyde group, then this would more strongly suggest that you need a stabilizer. Still, the vaccine is 5 years old; and if the rPA did degrade, we don’t know anything about the rate of degradation or how this correlates to efficacy. For the licensed vaccine, the ORD says it needs to be stable for 2 years. —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Friday, October 05, 2001 11:22 AM To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Stabilizer in a new rPA vaccine That is domain. – Bruce —–Original Message—– From: Sent: Friday, October 05, 2001 11:02 AM To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Stabilizer in a new rPA vaccine You will still need the protein data to confirm that it is a stability problem and not an adjuventing affect. (yeah, I know, I always have to play devil’s advocate). —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Friday, October 05, 2001 11:07 AM To: Ivins, Bruce E Dr USAMRIID; Subject: FW: Stabilizer in a new rPA vaccine It’s up to everyone else. It does strongly appear as though we will need a stabilizer, however. – Bruce > —–Original Message—– > From: > Sent: Friday, October 05, 2001 11:05 AM > To: Ivins, Bruce E Dr USAMRIID > Subject: RE: Stabilizer in a new rPA vaccine >> Bruce, > This could figure into the upcoming stability/efficacy study, for which I specifically asked about an concurrent set with an excipient but DVC considered this too early. Should we meet? >>> —–Original Message—– > From: Ivins, Bruce E Dr USAMRIID > Sent: Friday, October 05, 2001 10:53 AM > To: > Subject: Stabilizer in a new rPA vaccine >> The data we are getting from our with formaldehyde/without formaldehyde experiment in rabbits is giving us VERY strong evidence that we should incorporate a stabilizer in with rPA and Alhydrogel. and weren’t some FDA-acceptable stabilizers going to be identified? If there some out there, maybe we should start thinking about them now. >> Basically what we have as far as the experiment: >> 1) Five years ago rPA/Alhydrogel/PBS vaccine was made with or without 0.02% formaldehyde (the level that’s in AVA) and stored at 4C. With these vaccines we immunized groups of rabbits as follows (0.5 ml per intramuscular dose): > Group A – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/0.02% formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group B – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/No formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group C – 4 rabbits (2 males, 2 females) get PBS/Alhydrogel (0.5 mg) at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. >> 2) Results so far, 3 days after challenge: >>> Group Survived/Total >> A – Vaccine plus formaldehyde 24/24 (no deaths) >> B – Vaccine minus formaldehyde 16/24 (8 deaths) >> C – Controls 0/4 (4 deaths) >>> Note: We originally studied the effect of formaldehyde on rPA vaccine potency/stability in guinea pigs. The cumulative data indicated that stability/potency was enhanced by the presence of formaldehyde. >> – Bruce > From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: Stabilizer in a new rPA vaccine Date: Friday, October 05, 2001 11:31:44 AM The only data we have on this is the guinea pig data. Perhaps the question can be addressed by the stability study at Battelle. …your thoughts??? – Bruce —–Original Message—– From: Sent: Friday, October 05, 2001 11:21 AM To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Stabilizer in a new rPA vaccine If all or most of the rabbits die in the without formaldehyde group, then this would more strongly suggest that you need a stabilizer. Still, the vaccine is 5 years old; and if the rPA did degrade, we don’t know anything about the rate of degradation or how this correlates to efficacy. For the licensed vaccine, the ORD says it needs to be stable for 2 years. —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Friday, October 05, 2001 11:22 AM To: Subject: RE: Stabilizer in a new rPA vaccine That is domain. – Bruce —–Original Message—– From: Sent: Friday, October 05, 2001 11:02 AM To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Stabilizer in a new rPA vaccine You will still need the protein data to confirm that it is a stability problem and not an adjuventing affect. (yeah, I know, I always have to play devil’s advocate). —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Friday, October 05, 2001 11:07 AM To: Ivins, Bruce E Dr USAMRIID; Subject: FW: Stabilizer in a new rPA vaccine It’s up to everyone else. It does strongly appear as though we will need a stabilizer, however. – Bruce > —–Original Message—– > From: > Sent: Friday, October 05, 2001 11:05 AM > To: Ivins, Bruce E Dr USAMRIID > Subject: RE: Stabilizer in a new rPA vaccine >> Bruce, > This could figure into the upcoming stability/efficacy study, for which I specifically asked about an concurrent set with an excipient but DVC considered this too early. Should we meet? >>> —–Original Message—– > From: Ivins, Bruce E Dr USAMRIID > Sent: Friday, October 05, 2001 10:53 AM > To: > Subject: Stabilizer in a new rPA vaccine >> The data we are getting from our with formaldehyde/without formaldehyde experiment in rabbits is giving us VERY strong evidence that we should incorporate a stabilizer in with rPA and Alhydrogel. and .weren’t some FDA-acceptable stabilizers going to be identified? If there some out there, maybe we should start thinking about them now. >> Basically what we have as far as the experiment: >> 1) Five years ago rPA/Alhydrogel/PBS vaccine was made with or without 0.02% formaldehyde (the level that’s in AVA) and stored at 4C. With these vaccines we immunized groups of rabbits as follows (0.5 ml per intramuscular dose): > Group A – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/0.02% formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group B – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/No formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group C – 4 rabbits (2 males, 2 females) get PBS/Alhydrogel (0.5 mg) at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. >> 2) Results so far, 3 days after challenge: >>> Group Survived/Total >> A – Vaccine plus formaldehyde 24/24 (no deaths) >> B – Vaccine minus formaldehyde 16/24 (8 deaths) >> C – Controls 0/4 (4 deaths) >>> Note: We originally studied the effect of formaldehyde on rPA vaccine potency/stability in guinea pigs. The cumulative data indicated that stability/potency was enhanced by the presence of formaldehyde. >> – Bruce > From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: Stabilizer in a new rPA vaccine Date: Friday, October 05, 2001 2:29:40 PM All – After the final data are in, shall we plan a meeting to discuss where we (tech base/advanced development) go from here with respect to incorporating a stabilizer in the vaccine? Possible questions to address: 1) What if any studies are necessary to follow up these data? 2) What stabilizers are acceptable to the FDA? 3) What path should we take as far as incorporating a particular stabilizer into a new anthrax vaccine? 4) Others(???) – Bruce —–Original Message—– From Sent: Friday, October 05, 2001 12:17 PM To: Subject: RE: Stabilizer in a new rPA vaccine In my opinion, this shows that half of the rPA had spontaneously desorbed from the Alhydrogel after 5 years, and remained undegraded in the presence of formaldehyde (lane 9), or completely degraded in the absence of formaldehyde (lane 8). Protein that remained on the Alhydrogel multimerized in the presence of formaldehyde (lane 4) or remained largely intact in the absence of formaldehyde, while at the same time having a larger number of breakdown products of small concentration (lane 5). Both of the latter samples contain the familiar charge isoforms of full-length rPA protein. —–Original Message—– From: Sent: Friday, October 05, 2001 11:51 AM To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Stabilizer in a new rPA vaccine Here is the gel on rPA desorbed from 5 year old vaccine. —–Original Message—– From: Ivins, Bruce E Dr USAMRIID Sent: Friday, October 05, 2001 11:22 AM To: Subject: RE: Stabilizer in a new rPA vaccine That is domain. – Bruce —–Original Message—– From: Sent: Friday, October 05, 2001 11:02 AM To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Stabilizer in a new rPA vaccine You will still need the protein data to confirm that it is a stability problem and not an adjuventing affect. (yeah, I know, I always have to play devil’s advocate). —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Friday, October 05, 2001 11:07 AM To: Ivins, Bruce E Dr USAMRIID; Subject: FW: Stabilizer in a new rPA vaccine It’s up to everyone else. It does strongly appear as though we will need a stabilizer, however. – Bruce > —–Original Message—– > From: > Sent: Friday, October 05, 2001 11:05 AM > To: Ivins, Bruce E Dr USAMRIID > Subject: RE: Stabilizer in a new rPA vaccine ( >> Bruce, > This could figure into the upcoming stability/efficacy study, for which I specifically asked about an concurrent set with an excipient but DVC considered this too early. Should we meet? >> —–Original Message—– > From: Ivins, Bruce E Dr USAMRIID > Sent: Friday, October 05, 2001 10:53 AM > To: > Subject: Stabilizer in a new rPA vaccine >> The data we are getting from our with formaldehyde/without formaldehyde experiment in rabbits is giving us VERY strong evidence that we should incorporate a stabilizer in with rPA and Alhydrogel. ..weren’t some FDA-acceptable stabilizers going to be identified? If there some out there, maybe we should start thinking about them now. >> Basically what we have as far as the experiment: >> 1) Five years ago rPA/Alhydrogel/PBS vaccine was made with or without 0.02% formaldehyde (the level that’s in AVA) and stored at 4C. With these vaccines we immunized groups of rabbits as follows (0.5 ml per intramuscular dose): > Group A – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/0.02% formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group B – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/No formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group C – 4 rabbits (2 males, 2 females) get PBS/Alhydrogel (0.5 mg) at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. >> 2) Results so far, 3 days after challenge: >>> Group Survived/Total >> A – Vaccine plus formaldehyde 24/24 (no deaths) >> B – Vaccine minus formaldehyde 16/24 (8 deaths) >> C – Controls 0/4 (4 deaths) >>> Note: We originally studied the effect of formaldehyde on rPA vaccine potency/stability in guinea pigs. The cumulative data indicated that stability/potency was enhanced by the presence of formaldehyde. >> – Bruce >
        • DXer said

          Or maybe the emails from 2001 that Dr. Saathoff mistakenly thought had been deleted were these? How could the 9 folks picked by Dr. Saathoff all not know of the 100s of emails from 2001 available to anyone to read? Isn’t that body of emails a hugely important documentary source to draw on in profiling his state of mind in September and October 2001? I realize that they relied on the Amerithrax Investigative Summary extensively. But that Summary conflicts in critical aspects with the documentary record. From: Ivins, Bruce E Dr USAMRIID To: Subject: Florida Date: Monday, October 08, 2001 2:02:26 PM Hi, again, I just heard some more news this morning concerning anthrax in Florida. If B. anthracis was found in a building or on/in other individuals in a building, is it possible that someone brought into work an article of clothing (sweater, vest, suit, socks, etc.) made out of infected sheep wool or alpaca/llama hair? This might have special likelihood if someone had bought or received as a gift some imported article(s) of clothing. One of the women that works in my lab said she heard on the radio that the individual who contracted anthrax had been around sheep recently. If this is true, then this could also be a possibility. Finally, what about the possibility that someone inadvertently brought back some B. anthracis recently while out of the country? We’re quite busy here still with our work both on AVA as well as on a possible new vaccine. Have a good fall! – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: Anthrax, mice, and CpG Date: Thursday, October 11, 2001 11:30:21 AM Hi, Thanks for your letter. I think that the titer data will be extremely important. However, All the monkeys involved are likely to be protected from challenge, regardless whether they received CpG oligos, so challenging them probably wouldn’t provide us with a great deal of information. I think that the evidence of increased ELISA/TNA titers should be sufficient to push the CpG to a front burner as far as both possibly incorporating with the current vaccine and including with the new rPA vaccine. Being a “tech-base” scientist, I’m not sure where to start, but I can get the information to people higher up on the chain. They will hopefully put the CpG work into the product development/clinical trial track, and get it out of the tech-base work. Let’s first see how the titers go, then proceed from there. The use of CpG in non-human primates as a non-antigen-specific protector against anthrax and other possible BW threat agents would be a good area to probe. Perhaps it could be explored as a DARPA grant with collaboration between you and us. Please let me know when you will send the serum. Thanks!! – Bruce —–Original Message—– From: Sent: Thursday, October 11, 2001 11:17 AM To: ‘Ivins Bruce E’ Subject: RE: Anthrax, mice, and CpG Dear Bruce, Hope you are well. I’m just back from the major CpG ODN meeting (held once every 2 years). It is clear that the anti-pathogen role of CpG ODN has been recognized by other groups. DARPA has agreed to support studies of CpG ODN against anthrax (first in mice, then monkeys) by one of my competitors. If you and I are to succeed in establishing the activity of the “D” ODN against anthrax, we need to get moving. I’d like to send you the sera from the monkeys in which our ODN were used as adjuvants immediately for you to test titers. If the titers are significantly elevated, would it be possible to use the animals in an aerosol challenge test? Given what’s happened in Florida, I believe evidence of protection in a primate model would be most relevant. Finally, if we see that the ODN act as adjuvants, I’d like to have you test them alone as protective agents (given before or immediately after exposure). I’d be happy to meet with whoever in the chain of command needs to be persuaded to move forward with these studies. Given the evidence of a clear and present danger, we should start immediately. As an aside, several dozen subjects have now been treated with CpG ODN without major side effects. —–Original Message—– (b) (6) (b) (6) (b) (6) (b) (6) From: Ivins Bruce E [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Thursday, October 07, 1999 8:40 AM To: ‘ Subject: Anthrax, mice, and CpG Hi, , As you remember, in our first experiment with the mice, we got some time-to-death extension with CpG for mice challenged with virulent B. anthracis spores. In the second experiment, we demonstrated not only time-to-death extension, but also protection from death with the CpG. In this last experiment which we just concluded, we strangely got no protection at all, in terms of either survival or increased time-to-death. I believe that the main problem is that the mouse is such a generally poor and unpredictable model for anthrax. The guinea pig is a MUCH better model for anthrax infection/protection, and our guinea pig protocol for CpG has been approved, so I think the next step should be (when we get the funds released) to go into the guinea pigs. We’ll be able to look at specific as well as non-specific protection, and if we get some promising results, we can head into non-human primates. Hopefully we’ll get some money released within a few weeks and we can get started then. I’ll let you know. I’m sure that mice are an excellent animal model for a number of diseases, but anthrax isn’t one of them. – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: Anthrax, mice, and CpG Date: Thursday, October 11, 2001 11:31:26 AM —–Original Message—– From: Ivins, Bruce E Dr USAMRIID Sent: Thursday, October 11, 2001 11:30 AM To: Subject: RE: Anthrax, mice, and CpG Hi, Thanks for your letter. I think that the titer data will be extremely important. However, All the monkeys involved are likely to be protected from challenge, regardless whether they received CpG oligos, so challenging them probably wouldn’t provide us with a great deal of information. I think that the evidence of increased ELISA/TNA titers should be sufficient to push the CpG to a front burner as far as both possibly incorporating with the current vaccine and including with the new rPA vaccine. Being a “tech-base” scientist, I’m not sure where to start, but I can get the information to people higher up on the chain. They will hopefully put the CpG work into the product development/clinical trial track, and get it out of the tech-base work. Let’s first see how the titers go, then proceed from there. The use of CpG in non-human primates as a non-antigen-specific protector against anthrax and other possible BW threat agents would be a good area to probe. Perhaps it could be explored as a DARPA grant with collaboration between you and us. Please let me know when you will send the serum. Thanks!! – Bruce —–Original Message—– From: Sent: Thursday, October 11, 2001 11:17 AM To: ‘Ivins Bruce E’ Subject: RE: Anthrax, mice, and CpG Dear Bruce, Hope you are well. I’m just back from the major CpG ODN meeting (held once every 2 years). It is clear that the anti-pathogen role of CpG ODN has been recognized by other groups. DARPA has agreed to support studies of CpG ODN against anthrax (first in mice, then monkeys) by one of my competitors. If you and I are to succeed in establishing the activity of the “D” ODN against anthrax, we need to get moving. I’d like to send you the sera from the monkeys in which our ODN were used as adjuvants immediately for you to test titers. If the titers are significantly elevated, would it be possible to use the animals in an aerosol challenge test? Given what’s happened in Florida, I believe evidence of protection in a primate model would be most relevant. Finally, if we see that the ODN act as adjuvants, I’d like to have you test them alone as protective agents (given before or immediately after exposure). I’d be happy to meet with whoever in the chain of command needs to be persuaded to move forward with these studies. Given the evidence of a clear and present danger, we should start immediately. As an aside, several dozen subjects have now been treated with CpG ODN without major side effects. —–Original Message—– From: Ivins Bruce E [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Thursday, October 07, 1999 8:40 AM To: Subject: Anthrax, mice, and CpG Hi, , As you remember, in our first experiment with the mice, we got some time-to-death extension with CpG for mice challenged with virulent B. anthracis spores. In the second experiment, we demonstrated not only time-to-death extension, but also protection from death with the CpG. In this last experiment which we just concluded, we strangely got no protection at all, in terms of either survival or increased time-to-death. I believe that the main problem is that the mouse is such a generally poor and unpredictable model for anthrax. The guinea pig is a MUCH better model for anthrax infection/protection, and our guinea pig protocol for CpG has been approved, so I think the next step should be (when we get the funds released) to go into the guinea pigs. We’ll be able to look at specific as well as non-specific protection, and if we get some promising results, we can head into non-human primates. Hopefully we’ll get some money released within a few weeks and we can get started then. I’ll let you know. I’m sure that mice are an excellent animal model for a number of diseases, but anthrax isn’t one of them. – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: FW: Information on “Ames” strain of B. Anthracis Date: Thursday, October 11, 2001 12:40:42 PM This was the information on the “Ames” strain sent to – Bruce >—–Original Message—– >From: Ivins, Bruce E Dr USAMRIID >Sent: Thursday, October 11, 2001 12:30 PM >To: >Subject: Information on “Ames” strain of B. Anthracis > > Here is information on the Ames strain of B. anthracis: >> In December of 1980 USAMRIID Bacteriology Division, received a strain of Bacillus anthracis (originally from a dead cow) from the After receipt of this strain, it was immediately transferred to the B3 biocontainment suite. Access to this and other biocontainment suites was (and still is) strictly controlled and limited to those individuals authorized to work with B. anthracis strains. The strain was found to have both pXO1 and pXO2 plasmids, produce edema toxin, lethal toxin and capsule, and have a median lethal dose (LD50) in mice of 7 spores, and in guinea pigs, 100 spores. This strain has been termed the “Ames” strain ever since its arrival at USAMRIID. >> – Bruce Ivins From: Ivins, Bruce E Dr USAMRIID To: ” Subject: RE: MPL Investigations Date: Friday, October 12, 2001 7:50:23 AM Hi, Yes, we are incredibly busy here. Our work with anthrax vaccine development is continuing at a rapid pace, as are experiments on other vaccines. At this point, it appears that the very next anthrax vaccine (scheduled soon for Phase I human clinical testing) will contain protective antigen and aluminum hydroxide, but not any other adjuvants. The reason that this decision was made – not by me – as I understand it, was that MPL and other adjuvants were not yet part of any fully FDA approved vaccines, although they have certainly been in humans with very promising results. I do want to tell you that we will be still working on improving the anthrax vaccine even more after the new vaccine comes out – it’s just that there was an incredible push to turn out a new vaccine as quickly as possible. A new plague vaccine may contain MPL (or other adjuvant) in an aerosol formulation to stimulate lung mucosal immunity. We are still very interested in adjuvant formulations for human-use vaccines, especially ones that have been into humans. Please keep us informed of these formulations. If you send to me packets of information, I will see that they get to the right people. I can think of 4 or five researchers here who would be interested in the material. If you would like their names and email addresses, I’d be happy to send them to you. If you would like to talk on the phone, my number is I hope that you are doing well, and if you ever hear from please send him by best regards. – Bruce —–Original Message—– From: Sent: Thursday, October 11, 2001 5:46 PM To: ‘bruce.ivins@AMEDD.ARMY.MIL’ Subject: MPL Investigations Dear Bruce: Hello and I hope this message finds you doing well. It’s been quite awhile since we last corresponded and, with all the news lately about anthrax, I thought I should contact you regarding your work with MPL. When we talked last year, you were still working with MPL in both anthrax and plague vaccines. Are you still involved in these projects? As you may or may not be aware, Corixa has a several new adjuvant formulations, including synthetic compounds, which are being studied in many disease indications. I would like to chat with you further when you have a few minutes. Please let me know when would be a convenient time to call. Thanks in advance. Best regards, From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: Dangerous Pathogens 2002 Date: Saturday, October 13, 2001 10:34:23 PM Hi, We are all quite busy here, as you may have guessed. is probably the most qualified individual here to talk about the aerosol route of infection, since We’re doing some more work with various isolates of B. anthracis, and we’re also looking into CpG oligonucleotides as specific and non-specific enhancers of protection against anthrax. Please keep those of us “across the pond” in mind when you send out information on the conference. By the way…do you think (as I have my suspicions) that our old friend Saddam may have something to do with the anthrax “problems” currently occurring in the US? It would certainly be a sneaky sort of “payback” for the Gulf War. – Best regards! (I can almost taste the Guiness now!) – Bruce —–Original Message—– From: Sent: Wednesday, October 10, 2001 1:03 PM To: Bruce.Ivins@DET.AMEDD.ARMY.MIL Subject: RE: Dangerous Pathogens 2002 Bruce I have decided to organise another conference in the UK to be held near Porton Down next September (2002). I am look to identify speakers who call talk about the aerosol route of infection and of course thought of you guys. Would you be able to recommend someone or perhaps talk yourself ? We would of course cover their costs and given that I am organising the event their will be a lot of beer. regards Keep the cartoons coming >From: “Ivins, Bruce E Dr USAMRIID” >To: >Subject: RE: Session Six >Date: Wed, 14 Mar 2001 08:46:46 -0500 > >Hi, > Do you have any comments on the suggestions below? and I think >that in the time space allowed, it gives a reasonable chance for overview, >substance, and specific subject flexibility. Hope to hear from you soon! >- Bruce > > —–Original Message—– > > From: Ivins, Bruce E Dr USAMRIID > > Sent: Thursday, March 08, 2001 2:51 PM > > To: > > Subject: Session Six > > > > Hi, I talked, and this is our idea for session 6: > > > > 1) 45 Minutes – presents a summary of USAMRIID > > research. > > 2) 45 Minutes – if you want to have > > present her microencapsulation work during this 45-minute segment, you can > > do so, or you can summarize it yourself if you would rather do that. > > 3) 15 Minute Break > > 4) 45 Minutes – if she wishes to have > > present some of the spore vaccination work in this 45-minute segment, she > > may do so. > > 5) 15 Minutes – presents his correlate of protective > > immunity work. > > 6) 15 Minutes – presents her work on engineering anitbody > > therapeutics. > > > > This gives you, some flexibility. > > > > What do you think? > > > > – Bruce ________________________________ Get your FREE download of MSN Explorer at http://explorer.msn.com (b) (6) (b) (6) From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: Dangerous Pathogens 2002 Date: Monday, October 15, 2001 7:39:34 AM Sure, Have a fine day! – Bruce —–Original Message—– From: Sent: Monday, October 15, 2001 7:37 AM To: Bruce.Ivins@DET.AMEDD.ARMY.MIL Subject: RE: Dangerous Pathogens 2002 Bruce Could you send me e mail address. Thanks >From: “Ivins, Bruce E Dr USAMRIID” >To: ‘ >Subject: RE: Dangerous Pathogens 2002 >Date: Sat, 13 Oct 2001 22:34:23 -0400 > >Hi, > We are all quite busy here, as you may have guessed. s >probably the most qualified individual here to talk about the aerosol route >of infection, since she is the head of the Aerobiology Department. We’re >doing some more work with various isolates of B. anthracis, and we’re also >looking into CpG oligonucleotides as specific and non-specific enhancers of >protection against anthrax. Please keep those of us “across the pond” in >mind when you send out information on the conference. By the way…do you >think (as I have my suspicions) that our old friend Saddam may have >something to do with the anthrax “problems” currently occurring in the US? >It would certainly be a sneaky sort of “payback” for the Gulf War. >> – Best regards! (I can almost taste the Guiness now!) >> – Bruce >> —–Original Message—– >From: >Sent: Wednesday, October 10, 2001 1:03 PM >To: Bruce.Ivins@DET.AMEDD.ARMY.MIL >Subject: RE: Dangerous Pathogens 2002 >>> >Bruce > >I have decided to organise another conference in the UK to be held near >Porton Down next September (2002). I am look to identify speakers who call >talk about the aerosol route of infection and of course thought of you >guys. Would you be able to recommend someone or perhaps talk yourself ? We >would of course cover their costs and given that I am organising the event >their will be a lot of beer. > >regards > > >Keep the cartoons coming >>>>>>>> >From: “Ivins, Bruce E Dr USAMRIID” > >To: ‘ > > > >Subject: RE: Session Six > >Date: Wed, 14 Mar 2001 08:46:46 -0500 > > > >Hi, > > Do you have any comments on the suggestions below? and I think > >that in the time space allowed, it gives a reasonable chance for >overview, > >substance, and specific subject flexibility. Hope to hear from you soon! > >- Bruce > > > > > —–Original Message—– > > > From: Ivins, Bruce E Dr USAMRIID > > > Sent: Thursday, March 08, 2001 2:51 PM > > > To: ‘ > > > Subject: Session Six > > > > > > Hi, > > > and I talked, and this is our idea for session 6: > > > > > > 1) 45 Minutes – presents a summary of USAMRIID > > > research. > > > 2) 45 Minutes – if you want to have > > > present her microencapsulation work during this 45-minute segment, you >can > > > do so, or you can summarize it yourself if you would rather do that. > > > 3) 15 Minute Break > > > 4) 45 Minutes – if she wishes to have > > > present some of the spore vaccination work in this 45-minute segment, >she > > > may do so. > > > 5) 15 Minutes – presents his correlate of protective > > > immunity work. > > > 6) 15 Minutes – presents her work on engineering anitbody > > > therapeutics. > > > > > > This gives you, and some flexibility. > > > > > > What do you think? > > > > > > – Bruce (6) >> _____ > >Get your FREE download of MSN Explorer at http://explorer.msn.com > >> _________________________________________________________________ Get your FREE download of MSN Explorer at http://explorer.msn.com/intl.asp From: Ivins, Bruce E Dr USAMRIID To: Subject: FW: Ames Strain Date: Monday, October 15, 2001 8:05:40 AM >—–Original Message—– >From: Ivins, Bruce E Dr USAMRIID >Sent: Saturday, October 13, 2001 9:29 PM >To: >Subject: RE: Ames Strain >> >Good little serf that I am, I send to you all, late on Saturday, the following requested information: > Strains: > Ames – has pXO1 and pXO2, fully virulent, produces lethal toxin, edema toxin and capsule > ANR – has pXO1 only, attenuated, produces lethal toxin and edema toxin > Delta Ames – has pXO2 only, attenuated, produces capsule >>>> >>> Other points to make again: > 1) Ames and Ames derivative strains were probably also sent out by . > 2) We keep a record of how much material (X ml at Y concentration) of our B. anthracis strains we have on hand, and how much we use. > 3) The ANR strain can be rendered into a fully virulent strain by transfer of pXO2 into it. Thus one can have ANR and Delta Ames and come up with Ames. > 4) The primary questions as to what laboratories possess this “Ames” strain does not rest with us, but with the Department of Agriculture. I hope that the individual requesting this information realizes this. >> – Bruce >> —–Original Message—– >From: >Sent: Friday, October 12, 2001 10:29 PM >To: >Subject: RE: Ames Strain > I think you should indicate in the list to exactly what strain was sent to each of the individuals you identified. That is, who got Ames, delta Ames (pX01-, pX02+) etc. This more specific information should be put in the tasker. > > ———- > From: Ivins, Bruce E Dr USAMRIID > Sent: Friday, October 12, 2001 9:02 AM > To: > Subject: FW: Ames Strain >>>> —–Original Message—– > From: Ivins, Bruce E Dr USAMRIID > Sent: Friday, October 12, 2001 1:00 PM > To: > Subject: RE: Ames Strain >> > I can tell you to whom I have sent this so-called “Ames” strain. Please keep in mind that a) it is apparently 50 years old; b) that USAMRIID received this strain 20 years ago; c) that it is a USDA strain, not a USAMRIID strain, U. S. Army strain, or Department of Defense strain; d) the individuals primarily responsible for determining the location of the strain are located in Ames, Iowa, not in Frederick, Maryland; e) that of any U.S. labs having human pathogenic strains (including B. anthracis), none have higher security than USAMRIID; f) that if we are the only recipients of this “tasker,” it is transparently evident that we are being harassed by our regular detractors simply because we are DOD researchers. It is not within the purview of USAMRIID researchers to ascertain where the USDA has sent its strains of Bacillus anthracis or any other organism. > I, and people in my lab, have sent the so-called “Ames” strain (either original parent or subcultured derivative) of B. anthracis to the following. (By subcultured derivative, I am referring to strains such as Delta-Ames and ANR, which can be converted to full virulence using existing molecular biology methods, and which would be identified as the “Ames” strain.) >> – Bruce Ivins >>>>> —–Original Message—– > From: > Sent: Friday, October 12, 2001 8:26 AM > To: Ivins, Bruce E Dr USAMRIID > Cc: > Subject: Ames Strain >> Bruce: >> We have a tasker to report to whom we may have sent the Ames strain in the past several years. Do you, or someone else in BACT, have any records relating to such information? If so, could you please provide me with that information? >> We are checking our MTA’s as well, but I want to make sure we haven’t overlooked anything. >> Thanks for your help! >>>>> (b) (6) From: Ivins, Bruce E Dr USAMRIID To: Subject: FW: MPL Investigations Date: Tuesday, October 16, 2001 9:41:10 PM FYI, everyone….On MPL as a human-use adjuvant. —–Original Message—– From: Sent: Tuesday, October 16, 2001 6:33 PM To: ‘Ivins, Bruce E Dr USAMRIID’ Subject: RE: MPL Investigations Bruce… Thanks for the response. I can certainly provide Product Data Sheets outlining our clinical adjuvant development to your interested colleagues. Please let me know their names and addresses and I will mail the information directly to them. If it would be beneficial, a couple of Corixa scientists would be willing to visit USAMRIDD and give a presentation on the status of our adjuvant programs. As you are probably aware, MPL is approved in Canada as part of Detox, the adjuvant in Melacine, a therapeutic vaccine for melanoma. MPL is also commercially available in some European countries as a part of a named-patient allergy immunotherapeutic treatment regimen. Through our partnerships with GlaxoSmithKline and Wyeth-Lederle, as well as others, MPL has been safely administered to over ten thousand patients. Corixa maintains Drug Master Files with the FDA for MPL and it’s various formulations, as well as our new synthetic compound, RC-529, which is presently in a Phase 3 clinical study of a preventive hepatitis B vaccine. Let me know your thoughts on a visit and I will discuss with the folks here. I see from time-to-time and will give him your regards. As you can imagine, he is missed around here. He always thought very highly of you and enjoyed your collaborative efforts. Thanks again and I look forward to hearing from you. From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: MPL Investigations Date: Wednesday, October 17, 2001 9:28:47 AM Sounds good to me! I’ll get back in touch with at Corixa. – Bruce —–Original Message—– From: Sent: Wednesday, October 17, 2001 8:32 AM To: Subject: RE: MPL Investigations Bruce, Lets get them here What do you think?? —–Original Message—– From: Ivins, Bruce E Dr USAMRIID Sent: Tuesday, October 16, 2001 9:41 PM To: Subject: FW: MPL Investigations FYI, everyone….On MPL as a human-use adjuvant. —–Original Message—– From: Sent: Tuesday, October 16, 2001 6:33 PM To: ‘Ivins, Bruce E Dr USAMRIID’ Subject: RE: MPL Investigations Bruce… Thanks for the response. I can certainly provide Product Data Sheets outlining our clinical adjuvant development to your interested colleagues. Please let me know their names and addresses and I will mail the information directly to them. If it would be beneficial, a couple of Corixa scientists would be willing to visit USAMRIDD and give a presentation on the status of our adjuvant programs. As you are probably aware, MPL is approved in Canada as part of Detox, the adjuvant in Melacine, a therapeutic vaccine for melanoma. MPL is also commercially available in some European countries as a part of a named-patient allergy immunotherapeutic treatment regimen. Through our partnerships with GlaxoSmithKline and Wyeth-Lederle, as well as others, MPL has been safely administered to over ten thousand patients. Corixa maintains Drug Master Files with the FDA for MPL and it’s various formulations, as well as our new synthetic compound, RC-529, which is presently in a Phase 3 clinical study of a preventive hepatitis B vaccine. Let me know your thoughts on a visit and I will discuss with the folks here. I see from time-to-time and will give him your regards. As you can imagine, he is missed around here. He always thought very highly of you and enjoyed your collaborative efforts. Thanks again and I look forward to hearing from you. From: Ivins, Bruce E Dr USAMRIID To: Subject: FW: A simple question Date: Thursday, October 18, 2001 8:21:17 PM Could you please take care of this? (You may have already.) The “Ames” strain of Bacillus anthracis was sent to us in the late 1980-early 1981 time frame from the United States Department of Agriculture, Animal & Plant Health Inspection Services, National Veterinary Services Laboratories, Ames, Iowa. We were told it came from a dead cow. We were not told the specifics of the strain, specifically where it was isolated, or when it was isolated. Basically, we were told it was Bacillus anthracis that had been isolated from a clinical veterinary case. I’ve read that the strain was originally isolated in the 1950s at Iowa State University, but we were not given that information when we got the strain. I have also read that the strain is very common in veterinary labs, clinical labs, university bacteriology labs and research institutes all over the country, and that doesn’t surprise me. From the literature, it seems that many places have the “Ames” strain or its derivatives. The proper place to find out the details of the strain is the USDA, not us. They sent it to us. It’s their strain, and it’s their responsibility to know the details about it. Thanks! – Bruce —–Original Message—– From: Sent: Thursday, October 18, 2001 7:22 PM To: bruce.ivins@amedd.army.mil Subject: A simple question Dear Dr. Ivins, I’m a staff writer at the New Yorker magazine. I have a simple question about the “Ames strain” of anthrax. Why is it called Ames (yes, I know that it was supposedly isolated at a lab there in the 1950s, etc etc etc, but you’d be stunned by the degree to which govt officials in Ames have gone dumb on the subject; or, maybe you wouldn’t be stunned)? I guess I’m wondering about the “fact,” passingly mentioned in dozens of news stories (and in professional literature) that “a laboratory in Ames, Iowa” (variously a USDA lab, an Iowa State lab, etc) isolated this strain in the 1950s, grew it for “biomedical research” and distributed it to labs around the world. ‘Zat so? Gratefully, From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: MPL Investigations Date: Friday, October 19, 2001 2:35:25 PM Hi, We would be interested in having some Corixa Scientists visit and give us some updated information on MPL. Things are quite busy at the moment, but perhaps in a month or two they could come. I’m hoping things will eventually settle down sometime in the near future, but who knows? Shall we tentatively plan for sometime in the November – January timeframe? I can’t commit to a particular time yet, but that should provide a ballpark timeframe. Thanks again, and hope you have a fine fall. – Bruce —–Original Message—– From: Sent: Tuesday, October 16, 2001 6:33 PM To: ‘Ivins, Bruce E Dr USAMRIID’ Cc: Subject: RE: MPL Investigations Bruce… Thanks for the response. I can certainly provide Product Data Sheets outlining our clinical adjuvant development to your interested colleagues. Please let me know their names and addresses and I will mail the information directly to them. If it would be beneficial, a couple of Corixa scientists would be willing to visit USAMRIDD and give a presentation on the status of our adjuvant programs. It is unfortunate that the decision was made to proceed into a Phase 1 trial without MPL or another Corixa adjuvant. I realize the decision was made without your input, however, it seems like having an alum/MPL arm would have made more sense. As you are probably aware, MPL is approved in Canada as part of Detox, the adjuvant in Melacine, a therapeutic vaccine for melanoma. MPL is also commercially available in some European countries as a part of a named-patient allergy immunotherapeutic treatment regimen. Through our partnerships with GlaxoSmithKline and Wyeth-Lederle, as well as others, MPL has been safely administered to over ten thousand patients. Corixa maintains Drug Master Files with the FDA for MPL and it’s various formulations, as well as our new synthetic compound, RC-529, which is presently in a Phase 3 clinical study of a preventive hepatitis B vaccine. Let me know your thoughts on a visit and I will discuss with the folks here. I see from time-to-time and will give him your regards. As you can imagine, he is missed around here. He always thought very highly of you and enjoyed your collaborative efforts. Thanks again and I look forward to hearing from you. —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Friday, October 12, 2001 5:50 AM To: ‘ Subject: RE: MPL Investigations (b) (6) Hi, Yes, we are incredibly busy here. Our work with anthrax vaccine development is continuing at a rapid pace, as are experiments on other vaccines. At this point, it appears that the very next anthrax vaccine (scheduled soon for Phase I human clinical testing) will contain protective antigen and aluminum hydroxide, but not any other adjuvants. The reason that this decision was made – not by me – as I understand it, was that MPL and other adjuvants were not yet part of any fully FDA approved vaccines, although they have certainly been in humans with very promising results. I do want to tell you that we will be still working on improving the anthrax vaccine even more after the new vaccine comes out – it’s just that there was an incredible push to turn out a new vaccine as quickly as possible. A new plague vaccine may contain MPL (or other adjuvant) in an aerosol formulation to stimulate lung mucosal immunity. We are still very interested in adjuvant formulations for human-use vaccines, especially ones that have been into humans. Please keep us informed of these formulations. If you send to me packets of information, I will see that they get to the right people. I can think of 4 or five researchers here who would be interested in the material. If you would like their names and email addresses, I’d be happy to send them to you. If you would like to talk on the phone, my number is I hope that you are doing well, and if you ever hear from , please send him by best regards. – Bruce —–Original Message—– From: Sent: Thursday, October 11, 2001 5:46 PM To: ‘bruce.ivins@AMEDD.ARMY.MIL’ Subject: MPL Investigations Dear Bruce: Hello and I hope this message finds you doing well. It’s been quite awhile since we last corresponded and, with all the news lately about anthrax, I thought I should contact you regarding your work with MPL. When we talked last year, you were still working with MPL in both anthrax and plague vaccines. Are you still involved in these projects? As you may or may not be aware, Corixa has a several new adjuvant formulations, including synthetic compounds, which are being studied in many disease indications. I would like to chat with you further when you have a few minutes. Please let me know when would be a convenient time to call. Thanks in advance. Best regards, From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: PDT Charter Date: Monday, October 22, 2001 8:34:11 AM Attachments: Here are some comments. – Bruce >—–Original Message—– >From: >Sent: Monday, October 22, 2001 6:04 AM >To: Ivins, Bruce E Dr USAMRIID; >Subject: PDT Charter >> >Please make changes and/or corrections and send back to me. TNX! >> <> -G >>>>>>> From: Ivins, Bruce E Dr USAMRIID To: Subject: FW: Anthrax, mice, and CpG Date: Monday, October 22, 2001 2:51:43 PM Hi, I sent you a reply, but something must have gone wrong in the process. Here it is again. Sorry it didn’t reach you when I sent it on the 11th. – Bruce —–Original Message—– From: Ivins, Bruce E Dr USAMRIID Sent: Thursday, October 11, 2001 11:31 AM To: Subject: RE: Anthrax, mice, and CpG —–Original Message—– From: Ivins, Bruce E Dr USAMRIID Sent: Thursday, October 11, 2001 11:30 AM To: ‘ Subject: RE: Anthrax, mice, and CpG Hi, Thanks for your letter. I think that the titer data will be extremely important. However, All the monkeys involved are likely to be protected from challenge, regardless whether they received CpG oligos, so challenging them probably wouldn’t provide us with a great deal of information. I think that the evidence of increased ELISA/TNA titers should be sufficient to push the CpG to a front burner as far as both possibly incorporating with the current vaccine and including with the new rPA vaccine. Being a “tech-base” scientist, I’m not sure where to start, but I can get the information to people higher up on the chain. They will hopefully put the CpG work into the product development/clinical trial track, and get it out of the tech-base work. Let’s first see how the titers go, then proceed from there. The use of CpG in non-human primates as a non-antigen-specific protector against anthrax and other possible BW threat agents would be a good area to probe. Perhaps it could be explored as a DARPA grant with collaboration between you and us. Please let me know when you will send the serum. Thanks!! – Bruce —–Original Message—– From: Sent: Thursday, October 11, 2001 11:17 AM To: ‘Ivins Bruce E’ Subject: RE: Anthrax, mice, and CpG Dear Bruce, Hope you are well. I’m just back from the major CpG ODN meeting (held once every 2 years). It is clear that the anti-pathogen role of CpG ODN has been recognized by other groups. DARPA has agreed to support studies of CpG ODN against anthrax (first in mice, then monkeys) by one of my competitors. If you and I are to succeed in establishing the activity of the “D” ODN against anthrax, we need to get moving. I’d like to send you the sera from the monkeys in which our ODN were used as adjuvants immediately for you to test titers. If the titers are significantly elevated, would it be possible to use the animals in an aerosol challenge test? Given what’s happened in Florida, I believe evidence of protection in a primate model would be most relevant. Finally, if we see that the ODN act as adjuvants, I’d like to have you test them alone as protective agents (given before or immediately after exposure). I’d be happy to meet with whoever in the chain of command needs to be persuaded to move forward with these studies. Given the evidence of a clear and present danger, we should start immediately. As an aside, several dozen subjects have now been treated with CpG ODN without major side effects. —–Original Message—– From: Ivins Bruce E [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Thursday, October 07, 1999 8:40 AM To: Subject: Anthrax, mice, and CpG Hi, As you remember, in our first experiment with the mice, we got some time-to-death extension with CpG for mice challenged with virulent B. anthracis spores. In the second experiment, we demonstrated not only time-to-death extension, but also protection from death with the CpG. In this last experiment which we just concluded, we strangely got no protection at all, in terms of either survival or increased time-to-death. I believe that the main problem is that the mouse is such a generally poor and unpredictable model for anthrax. The guinea pig is a MUCH better model for anthrax infection/protection, and our guinea pig protocol for CpG has been approved, so I think the next step should be (when we get the funds released) to go into the guinea pigs. We’ll be able to look at specific as well as non-specific protection, and if we get some promising results, we can head into non-human primates. Hopefully we’ll get some money released within a few weeks and we can get started then. I’ll let you know. I’m sure that mice are an excellent animal model for a number of diseases, but anthrax isn’t one of them. – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: CpG and guinea pigs Date: Monday, October 22, 2001 2:53:33 PM I sent you a reply, but it keeps coming back as “undeliverable.” I’m not sure what the problem is. I’m looking into it. – Bruce —–Original Message—– From: Sent: Monday, October 22, 2001 1:28 PM To: ‘Ivins Bruce E USAMRIID’ Subject: RE: CpG and guinea pigs Dear Bruce, I didn’t receive a reply from my last E mail. I suspect your being kept quite busy. However, when you can spare the time, I’d very much appreciate a chance to discuss how to proceed with the anthrax studies. All the best, —–Original Message—– From: Ivins Bruce E USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Tuesday, December 14, 1999 4:01 PM To: ‘ Subject: CpG and guinea pigs Hi, Good news – we just received funding in our supply line. We will now order the guinea pigs – it takes about one month for the order to be processed and the animals to get here, so we can start immunizing and injecting CpG in January. Would it be convenient to come pick up the oligos, both CpG and non-CpG, about the first week in January (5th through the 7th)? If not, please let me know what would be a good time. What I figure I will need are: 1) Non-CpG oligonucleotides, 1.2 ml at 100 micrograms per ml. (Please let me know the sequence.) 2) CpG oligonucleotides, 12 ml at 100 micrograms per ml. (Again, please let me know the sequence, so I can enter into my lab notebook.) I’m quite excited about the experiment. This model should be a better anthrax model than the mouse. Happy Holidays! – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: FW: Anthrax, mice, and CpG Date: Monday, October 22, 2001 2:56:36 PM —–Original Message—– From: Ivins, Bruce E Dr USAMRIID Sent: Monday, October 22, 2001 2:52 PM To: Subject: FW: Anthrax, mice, and CpG Hi, , I sent you a reply, but something must have gone wrong in the process. Here it is again. Sorry it didn’t reach you when I sent it on the 11th. – Bruce —–Original Message—– From: Ivins, Bruce E Dr USAMRIID Sent: Thursday, October 11, 2001 11:31 AM To: Subject: RE: Anthrax, mice, and CpG —–Original Message—– From: Ivins, Bruce E Dr USAMRIID Sent: Thursday, October 11, 2001 11:30 AM To: ‘ Subject: RE: Anthrax, mice, and CpG Hi, Thanks for your letter. I think that the titer data will be extremely important. However, All the monkeys involved are likely to be protected from challenge, regardless whether they received CpG oligos, so challenging them probably wouldn’t provide us with a great deal of information. I think that the evidence of increased ELISA/TNA titers should be sufficient to push the CpG to a front burner as far as both possibly incorporating with the current vaccine and including with the new rPA vaccine. Being a “tech-base” scientist, I’m not sure where to start, but I can get the information to people higher up on the chain. They will hopefully put the CpG work into the product development/clinical trial track, and get it out of the tech-base work. Let’s first see how the titers go, then proceed from there. The use of CpG in non-human primates as a non-antigen-specific protector against anthrax and other possible BW threat agents would be a good area to probe. Perhaps it could be explored as a DARPA grant with collaboration between you and us. Please let me know when you will send the serum. Thanks!! – Bruce —–Original Message—– From: Sent: Thursday, October 11, 2001 11:17 AM To: ‘Ivins Bruce E’ Subject: RE: Anthrax, mice, and CpG Dear Bruce, Hope you are well. I’m just back from the major CpG ODN meeting (held once every 2 years). It is clear that the anti-pathogen role of CpG ODN has been recognized by other groups. DARPA has agreed to support studies of CpG ODN against anthrax (first in mice, then monkeys) by one of my competitors. If you and I are to succeed in establishing the activity of the “D” ODN against anthrax, we need to get moving. I’d like to send you the sera from the monkeys in which our ODN were used as adjuvants immediately for you to test titers. If the titers are significantly elevated, would it be possible to use the animals in an aerosol challenge test? Given what’s happened in Florida, I believe evidence of protection in a primate model would be most relevant. Finally, if we see that the ODN act as adjuvants, I’d like to have you test them alone as protective agents (given before or immediately after exposure). I’d be happy to meet with whoever in the chain of command needs to be persuaded to move forward with these studies. Given the evidence of a clear and present danger, we should start immediately. As an aside, several dozen subjects have now been treated with CpG ODN without major side effects. —–Original Message—– From: Ivins Bruce E [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Thursday, October 07, 1999 8:40 AM To: Subject: Anthrax, mice, and CpG Hi, As you remember, in our first experiment with the mice, we got some time-to-death extension with CpG for mice challenged with virulent B. anthracis spores. In the second experiment, we demonstrated not only time-to-death extension, but also protection from death with the CpG. In this last experiment which we just concluded, we strangely got no protection at all, in terms of either survival or increased time-to-death. I believe that the main problem is that the mouse is such a generally poor and unpredictable model for anthrax. The guinea pig is a MUCH better model for anthrax infection/protection, and our guinea pig protocol for CpG has been approved, so I think the next step should be (when we get the funds released) to go into the guinea pigs. We’ll be able to look at specific as well as non-specific protection, and if we get some promising results, we can head into non-human primates. Hopefully we’ll get some money released within a few weeks and we can get started then. I’ll let you know. I’m sure that mice are an excellent animal model for a number of diseases, but anthrax isn’t one of them. – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: CpG and guinea pigs Date: Monday, October 22, 2001 3:01:29 PM Please send me your phone number. I keep sending you messages, and they all keep coming back. I DID reply to your email, but it didn’t go through. I have your email address as Is that correct? Thanks for your phone number! – Bruce —–Original Message—– From: ] Sent: Monday, October 22, 2001 1:28 PM To: ‘Ivins Bruce E USAMRIID’ Subject: RE: CpG and guinea pigs Dear Bruce, I didn’t receive a reply from my last E mail. I suspect your being kept quite busy. However, when you can spare the time, I’d very much appreciate a chance to discuss how to proceed with the anthrax studies. All the best, —–Original Message—– From: Ivins Bruce E USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Tuesday, December 14, 1999 4:01 PM To: Subject: CpG and guinea pigs Hi, Good news – we just received funding in our supply line. We will now order the guinea pigs – it takes about one month for the order to be processed and the animals to get here, so we can start immunizing and injecting CpG in January. Would it be convenient to come pick up the oligos, both CpG and non-CpG, about the first week in January (5th through the 7th)? If not, please let me know what would be a good time. What I figure I will need are: 1) Non-CpG oligonucleotides, 1.2 ml at 100 micrograms per ml. (Please let me know the sequence.) 2) CpG oligonucleotides, 12 ml at 100 micrograms per ml. (Again, please let me know the sequence, so I can enter into my lab notebook.) I’m quite excited about the experiment. This model should be a better anthrax model than the mouse. Happy Holidays! – Bruce From: Ivins, Bruce E Dr USAMRIID To: Ivins, Bruce E Dr USAMRIID Subject: FW: Stabilizer in a new rPA vaccine Date: Monday, October 22, 2001 3:31:43 PM Attachments: —–Original Message—– From: Sent: Friday, October 05, 2001 11:51 AM To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Stabilizer in a new rPA vaccine Here is the gel on rPA desorbed from 5 year old vaccine. —–Original Message—– From: Ivins, Bruce E Dr USAMRIID Sent: Friday, October 05, 2001 11:22 AM To: Subject: RE: Stabilizer in a new rPA vaccine That is domain. – Bruce —–Original Message—– From: Sent: Friday, October 05, 2001 11:02 AM To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Stabilizer in a new rPA vaccine You will still need the protein data to confirm that it is a stability problem and not an adjuventing affect. (yeah, I know, I always have to play devil’s advocate). —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Friday, October 05, 2001 11:07 AM To: Ivins, Bruce E Dr USAMRIID; Subject: FW: Stabilizer in a new rPA vaccine It’s up to everyone else. It does strongly appear as though we will need a stabilizer, however. – Bruce > —–Original Message—– > From: > Sent: Friday, October 05, 2001 11:05 AM > To: Ivins, Bruce E Dr USAMRIID > Subject: RE: Stabilizer in a new rPA vaccine >> Bruce, > This could figure into the upcoming stability/efficacy study, for which I specifically asked about an concurrent set with an excipient but DVC considered this too early. Should we meet? >> —–Original Message—– > From: Ivins, Bruce E Dr USAMRIID > Sent: Friday, October 05, 2001 10:53 AM > To: > Subject: Stabilizer in a new rPA vaccine >> The data we are getting from our with formaldehyde/without formaldehyde experiment in rabbits is giving us VERY strong evidence that we should incorporate a stabilizer in with rPA and Alhydrogel. weren’t some FDA-acceptable stabilizers going to be identified? If there some out there, maybe we should start thinking about them now. >> Basically what we have as far as the experiment: >> 1) Five years ago rPA/Alhydrogel/PBS vaccine was made with or without 0.02% formaldehyde (the level that’s in AVA) and stored at 4C. With these vaccines we immunized groups of rabbits as follows (0.5 ml per intramuscular dose): > Group A – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/0.02% formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group B – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/No formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group C – 4 rabbits (2 males, 2 females) get PBS/Alhydrogel (0.5 mg) at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. >> 2) Results so far, 3 days after challenge: >>> Group Survived/Total >> A – Vaccine plus formaldehyde 24/24 (no deaths) >> B – Vaccine minus formaldehyde 16/24 (8 deaths) >> C – Controls 0/4 (4 deaths) >>> Note: We originally studied the effect of formaldehyde on rPA vaccine potency/stability in guinea pigs. The cumulative data indicated that stability/potency was enhanced by the presence of formaldehyde. >> – Bruce > From: Ivins, Bruce E Dr USAMRIID To: Ivins, Bruce E Dr USAMRIID Subject: FW: Stabilizer in a new rPA vaccine Date: Monday, October 22, 2001 3:31:43 PM Attachments: —–Original Message—– From: Sent: Friday, October 05, 2001 11:51 AM To: Ivins, Bruce E Dr USAMRIID; Subject: RE: Stabilizer in a new rPA vaccine Here is the gel on rPA desorbed from 5 year old vaccine. —–Original Message—– From: Ivins, Bruce E Dr USAMRIID Sent: Friday, October 05, 2001 11:22 AM To: in a new rPA vaccine That is domain. – Bruce —–Original Message—– From: Sent: Friday, October 05, 2001 11:02 AM To: Ivins, Bruce E Dr USAMRIID; vaccine You will still need the protein data to confirm that it is a stability problem and not an adjuventing affect. (yeah, I know, I always have to play devil’s advocate). —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Friday, October 05, 2001 11:07 AM To: Ivins, Bruce E Dr USAMRIID; Subject: FW: Stabilizer in a new rPA vaccine It’s up to everyone else. It does strongly appear as though we will need a stabilizer, however. – Bruce > —–Original Message—– > From: > Sent: Friday, October 05, 2001 11:05 AM > To: Ivins, Bruce E Dr USAMRIID > Subject: RE: Stabilizer in a new rPA vaccine >> Bruce, > This could figure into the upcoming stability/efficacy study, for which I specifically asked about an concurrent set with an excipient but DVC considered this too early. Should we meet? >> —–Original Message—– > From: Ivins, Bruce E Dr USAMRIID > Sent: Friday, October 05, 2001 10:53 AM > To: > Subject: Stabilizer in a new rPA vaccine >> The data we are getting from our with formaldehyde/without formaldehyde experiment in rabbits is giving us VERY strong evidence that we should incorporate a stabilizer in with rPA and Alhydrogel. weren’t some FDA-acceptable stabilizers going to be identified? If there some out there, maybe we should start thinking about them now. >> Basically what we have as far as the experiment: >> 1) Five years ago rPA/Alhydrogel/PBS vaccine was made with or without 0.02% formaldehyde (the level that’s in AVA) and stored at 4C. With these vaccines we immunized groups of rabbits as follows (0.5 ml per intramuscular dose): > Group A – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/0.02% formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group B – 24 rabbits (12 males, 12 females) get PA (50 ug)/Alhydrogel (0.5 mg)/PBS/No formaldehyde at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. > Group C – 4 rabbits (2 males, 2 females) get PBS/Alhydrogel (0.5 mg) at 0 weeks. Challenge (subcutaneous) at 6 weeks with about 100 LD50 Ames spores. >> 2) Results so far, 3 days after challenge: >>> Group Survived/Total >> A – Vaccine plus formaldehyde 24/24 (no deaths) >> B – Vaccine minus formaldehyde 16/24 (8 deaths) >> C – Controls 0/4 (4 deaths) >>> Note: We originally studied the effect of formaldehyde on rPA vaccine potency/stability in guinea pigs. The cumulative data indicated that stability/potency was enhanced by the presence of formaldehyde. >> – Bruce > From: Ivins, Bruce E Dr USAMRIID To: Ivins, Bruce E Dr USAMRIID Subject: FW: ELISA DATA RABBITS Date: Monday, October 22, 2001 3:33:26 PM Attachments: >—–Original Message—– >From: >Sent: Wednesday, October 10, 2001 5:11 PM >To: Ivins, Bruce E Dr USAMRIID >Subject: ELISA DATA RABBITS >> > (b) (6) From: Ivins, Bruce E Dr USAMRIID To: Ivins, Bruce E Dr USAMRIID Subject: FW: ELISA DATA RABBITS Date: Monday, October 22, 2001 3:33:26 PM Attachments: >—–Original Message—– >From: >Sent: Wednesday, October 10, 2001 5:11 PM >To: Ivins, Bruce E Dr USAMRIID >Subject: ELISA DATA RABBITS >> > (b) (6) From: Ivins, Bruce E Dr USAMRIID To: Subject: Read Ahead info Date: Tuesday, October 23, 2001 9:39:13 AM Attachments: Here is the read-ahead info. – Bruce From: Ivins, Bruce E Dr USAMRIID To: Subject: FW: rPA vaccine preparation Date: Tuesday, October 23, 2001 12:23:46 PM Hi, asked me to send this to you. – Bruce >—–Original Message—– >From: Ivins, Bruce E Dr USAMRIID >Sent: Wednesday, August 15, 2001 9:00 AM >To: >Subject: rPA vaccine preparation >>> >rPA vaccine per 0.5-ml dose: > >50 micrograms rPA >0.047 ml of Alhydrogel (2% aluminum oxide) containing 0.5 mg of metallic aluminum >Dulbeccos PBS (pH 7.4) without calcium or magnesium, qs to 0.5 ml > >First add PBS then Alhydrogel. Mix. Then add rPA and mix. Allow to adsorb for 1 hour (or longer). >> – Bruce >> ( From: Ivins, Bruce E Dr USAMRIID To: Subject: RE: rPA vaccine preparation Date: Tuesday, October 23, 2001 12:43:31 PM Yes, We dropped the aluminum level down because we were told that the FDA prefers lower levels of the metal in adjuvants, and newer vaccines are using 0.5 mg of aluminum. I can’t quote an official source, however. – Bruce —–Original Message—– From: Sent: Tuesday, October 23, 2001 12:42 PM To: Ivins, Bruce E Dr USAMRIID Subject: RE: rPA vaccine preparation Thanks for sending this to me, is the procedure for 0.725 mg aluminum the same just with more Alhydrogel? —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Tuesday, October 23, 2001 12:24 PM To: Subject: FW: rPA vaccine preparation Hi, asked me to send this to you. – Bruce > —–Original Message—– > From: Ivins, Bruce E Dr USAMRIID > Sent: Wednesday, August 15, 2001 9:00 AM > To: > Subject: rPA vaccine preparation > > > > rPA vaccine per 0.5-ml dose: > > 50 micrograms rPA > 0.047 ml of Alhydrogel (2% aluminum oxide) containing 0.5 mg of metallic aluminum > Dulbeccos PBS (pH 7.4) without calcium or magnesium, qs to 0.5 ml > > First add PBS then Alhydrogel. Mix. Then add rPA and mix. Allow to adsorb for 1 hour (or longer). > > – Bruce > > From: Ivins, Bruce E Dr USAMRIID To: Ivins, Bruce E Dr USAMRIID Cc: Subject: RE: rPA vaccine preparation Date: Wednesday, October 24, 2001 8:30:39 AM OK, – Bruce —–Original Message—– From: Sent: Tuesday, October 23, 2001 1:08 PM To: Ivins, Bruce E Dr USAMRIID Cc: Subject: RE: rPA vaccine preparation We were talking about using 0.5 mg, but for the phase I trials we are presenting to the FDA the plan to use 0.725 mg because most of the supporting animal studies were conducted with that concentration of aluminum. Right now, it is open for debate until the FDA reviews the pre-IND material. —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Tuesday, October 23, 2001 12:44 PM To: Subject: RE: rPA vaccine preparation Yes, We dropped the aluminum level down because we were told that the FDA prefers lower levels of the metal in adjuvants, and newer vaccines are using 0.5 mg of aluminum. I can’t quote an official source, however. – Bruce —–Original Message—– From: Sent: Tuesday, October 23, 2001 12:42 PM To: Ivins, Bruce E Dr USAMRIID Subject: RE: rPA vaccine preparation Thanks for sending this to me, is the procedure for 0.725 mg aluminum the same just with more Alhydrogel? (b) (6) (b) (6) —–Original Message—– From: Ivins, Bruce E Dr USAMRIID [ mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL ] Sent: Tuesday, October 23, 2001 12:24 PM To: Subject: FW: rPA vaccine preparation Hi, asked me to send this to you. – Bruce > —–Original Message—– > From: Ivins, Bruce E Dr USAMRIID > Sent: Wednesday, August 15, 2001 9:00 AM > To: > Subject: rPA vaccine preparation > > > > rPA vaccine per 0.5-ml dose: > > 50 micrograms rPA > 0.047 ml of Alhydrogel (2% aluminum oxide) containing 0.5 mg of metallic aluminum > Dulbeccos PBS (pH 7.4) without calcium or magnesium, qs to 0.5 ml > > First add PBS then Alhydrogel. Mix. Then add rPA and mix. Allow to adsorb for 1 hour (or longer). > > – Bruce > > (b) (6) From: Ivins, Bruce E Dr USAMRIID To: Ivins, Bruce E Dr USAMRIID; Subject: FW: Anthrax, mice, and CpG Date: Wednesday, October 24, 2001 11:19:45 AM Let’s try again…. —–Original Message—– From: Ivins, Bruce E Dr USAMRIID Sent: Thursday, October 11, 2001 11:30 AM To: ‘ Subject: RE: Anthrax, mice, and CpG Hi, Thanks for your letter. I think that the titer data will be extremely important. However, All the monkeys involved are likely to be protected from challenge, regardless whether they received CpG oligos, so challenging them probably wouldn’t provide us with a great deal of information. I think that the evidence of increased ELISA/TNA titers should be sufficient to push the CpG to a front burner as far as both possibly incorporating with the current vaccine and including with the new rPA vaccine. Being a “tech-base” scientist, I’m not sure where to start, but I can get the information to people higher up on the chain. They will hopefully put the CpG work into the product development/clinical trial track, and get it out of the tech-base work. Let’s first see how the titers go, then proceed from there. The use of CpG in non-human primates as a non-antigen-specific protector against anthrax and other possible BW threat agents would be a good area to probe. Perhaps it could be explored as a DARPA grant with collaboration between you and us. Please let me know when you will send the serum. Thanks!! – Bruce —–Original Message—– From: Sent: Thursday, October 11, 2001 11:17 AM To: ‘Ivins Bruce E’ Subject: RE: Anthrax, mice, and CpG Dear Bruce, Hope you are well. I’m just back from the major CpG ODN meeting (held once every 2 years). It is clear that the anti-pathogen role of CpG ODN has been recognized by other groups. DARPA has agreed to support studies of CpG ODN against anthrax (first in mice, then monkeys) by one of my competitors. If you and I are to succeed in establishing the activity of the “D” ODN against anthrax, we need to get moving. I’d like to send you the sera from the monkeys in which our ODN were used as adjuvants immediately for you to test titers. If the titers are significantly elevated, would it be possible to use the animals in an aerosol challenge test? Given what’s happened in Florida, I believe evidence of protection in a primate model would be most relevant. Finally, if we see that the ODN act as adjuvants, I’d like to have you test them alone as protective agents (given before or immediately after exposure). I’d be happy to meet with whoever in the chain of command needs to be persuaded to move forward with these studies. Given the evidence of a clear and present danger, we should start immediately. As an aside, several dozen subjects have now been treated with CpG ODN without major side effects. —–Original Message—– From: Ivins Bruce E [mailto:Bruce.Ivins@DET.AMEDD.ARMY.MIL] Sent: Thursday, October 07, 1999 8:40 AM To: ‘ Subject: Anthrax, mice, and CpG As you remember, in our first experiment with the mice, we got some time-to-death extension with CpG for mice challenged with virulent B. anthracis spores. In the second experiment, we demonstrated not only time-to-death extension, but also protection from death with the CpG. In this last experiment which we just concluded, we strangely got no protection at all, in terms of either survival or increased time-to-death. I believe that the main problem is that the mouse is such a generally poor and unpredictable model for anthrax. The guinea pig is a MUCH better model for anthrax infection/protection, and our guinea pig protocol for CpG has been approved, so I think the next step should be (when we get the funds released) to go into the guinea pigs. We’ll be able to look at specific as well as non-specific protection, and if we get some promising results, we can head into non-human primates. Hopefully we’ll get some money released within a few weeks and we can get started then. I’ll let you know. I’m sure that mice are an excellent animal model for a number of diseases, but anthrax isn’t one of them. – Bruce (b) (6) (b) (6) (b) (6) From: Ivins, Bruce E Dr USAMRIID To: Subject: Hope this goes through! Date: Wednesday, October 24, 2001 11:30:56 AM I’m still having severe problems with email. My phone number is I am retyping the letter I unsuccessfully sent you on October 11. I hope this makes it to you. Thanks for your letter. I think that the titer data will be extremely important. However, all the immunized monkeys (regardless of whether they received CpG oligos) are likely to be protected from challenge, so challenging them probably wouldn’t provide us with a great deal of information. I think that the evidence of increased ELISA/TNA titers should be sufficient to push the CpG to a front burner as far as a) possibly incorporating it into the current vaccine or b) including it with the new rPA vaccine. Being a “techbase” scientist, I’m not sure where to start, but I can get the information to people higher up on the chain. They will hopefully put the CpG work into the product development/clinical trial track, and get it out of the tech-base work. Lets first see how the titers go, then proceed from there. The use of CpG in non-human primates as a non-antigen-specific protector against anthrax and other possible BW threat agents would be a good area to probe. Perhaps it could be explored as a DARPA grant with collaboration between you and us. Please let me know when you will send the serum. Thanks!!! – Bruce ******************************************************************************************8 —–Original Message—– From: Sent: Monday, October 22, 2001 3:09 PM To: ‘Ivins, Bruce E Dr USAMRIID’ Subject: RE: CpG and guinea pigs Bruce – both E mails got through. Just keep h
  4. DXer said

    What?! Is that Dr. Saathoff really hasn’t seen Dr. Ivins’ 2001 emails!? Uploaded at the USAMRIID website? Not provided by recipients but by USAMRIID pursuant to the normal retrieval of emails? If Dr. Saathoff needs confirmation of the point, the email for the FOIA person is sandra Ms CIV USA MEDCOM USAMRMC Rogers

    She has someone standing by to answer all questions about the email database.

    By all means, if the FBI is now representing that all of Dr. Ivins’ September and October 2001 emails have not been provided, speak clearly to the issue. (And at the same time they should provide the September 17, 2001 email to Mara).

    “Although he had purged his own 2001 emails, his recipients kept many of theirs, and shared them
    with investigators.”

    • Old Atlantic said

      Maybe that part of the report was published before the USAMRIID emails were made public? But then of course, if they had all this access, why didn’t they get them?

  5. DXer said

    It is just not true that this report is merely a parroting of Ken and Rachel’s investigative summary.

    Forget that Ayman Zawahiri’s and Atef used “Green Team” to describe the group led by Saif Adel for moment.

    Forget that Ayman in a June 2001 letter to all his supporters used ‘school’ as code to describe the Egyptian Islamic Jihad.

    Grab yourself a doobie and go with the flow as you follow Dr. Saathoff’s explanation for the return address.

    Feel the brilliance of these psychiatrists and Red Cross officials who don’t need to know any of the relevant stuff about Ayman’s plan to use anthrax against the United States.

    There is some real original thinking here.

    Dr. Saathoff writes:

    “As we have already seen in the Narrative section of this report,
    “4th Grade, Greendale School” was most likely a reference to a
    story in a magazine Dr. Ivins read relating to a civil liberties case.
    Franklin Park is a real town in New Jersey, not far from Princeton.
    Why he chose it is unknown; we have no information to shed light on
    that question. But Franklin Park’s ZIP code is in fact not 08852. That
    ZIP code belongs to a place called Monmouth Junction, N.J. About that
    name, we have a great deal of information.

    On his father’s side, as we’ve noted, and as Dr. Ivins knew, the Ivins
    family came from Monmouth, N.J. (Note: Monmouth County, N.J. does
    not contain a municipality by that name; whether the Ivins family
    records that Dr. Ivins kept refer to the county or a farm community is
    unclear; regardless, they refer to “Monmouth, N.J.”) KKG, as also
    discussed, was founded at Monmouth College in Monmouth, Ill.

    Dr. Ivins did not use the ZIP code of either of these places, however,
    because doing so would not have demonstrated the link between
    them. Code lover that he was, he appears to have come up with
    something much richer.

    Dr. Ivins felt that his own identity, aspirations and resentments,
    were entwined in KKG. His decades of obsession demonstrated
    that entanglement.

    By using the ZIP code of Monmouth Junction, Dr. Ivins may have been
    portraying in code the connection between KKG and his own identity.
    Monmouth Junction may have represented the union of father
    (Monmouth, N.J.) and mother (Monmouth College, KKG), i.e., himself.
    And it also represented his entanglement, his obsession with KKG.
    In other words, in two inter-related ways, the Monmouth Junction may
    have represented Dr. Ivins himself. With the return address on his
    Senatorial letters, he appears to have revealed the identity — at the
    deepest level — of the mailer. Dr. Ivins, in short, signed his letters.”

  6. DXer said

    As evidence of the use of the mails for nefarious purposes, Dr. Saathoff writes:

    “He had sent the KKG ritual book back to West Virginia University through the mail.”

    Yikes. Your tough. Anyone else would give him some credit for returning the book.

  7. DXer said

    “Understanding Dr. Ivins’ motives may also help explain why he sent
    two sets of letters. After the fi rst set was sent, on either September 17
    or 18, nothing happened publicly until October 4, when it was fi rst
    reported that Robert Stevens had become ill in Florida with anthrax.
    Mr. Stevens’ death was reported the next day. But there were no
    reports of a letter having been received in connection with this death,
    and in fact the letter that infected Mr. Stevens was never found. Thus
    the mailer likely felt, even after Mr. Stevens died, that he was not
    achieving his purpose. Without public exposure of his letters, his effort
    to stir panic by linking the anthrax with the Islamic terrorists who had
    just attacked the United States was in jeopardy. And without that
    panic, he was less likely to induce Technician #2 to return to the lab,
    impress KKG Sister #2, or redeem the anthrax vaccine program.
    Without publicity for his letters, he was also being denied the
    satisfaction of knowing that the letters had reached their targets
    — that he had achieved direct, personal revenge. In short, the letters
    themselves — not only the anthrax they contained — were essential to
    the achievement of his motives. So he prepared and mailed a new set,
    to Senators Daschle and Leahy. Eventually, both sets of mailings were
    discovered and publicized.”

    Comment:

    But Dr. Saatoff, don’t you think that the rabbits had been subcutaneously
    challenged on October 2, and 12 died on October 3 , 4 and 5, the thing
    that explained Bruce’s time in the lab? See 10/5 email and related emails
    about covance study involving shipment of immunized animals from Covance
    to USAMRIID for challenge by injection. It took him 1 1/2 – 2 hours to
    autoclave a dead animal. Can you ask the FBI to produce those documents?
    Why do you say his time in the lab was unexplained? Just because that’s what
    the prosecutors said?

    His lawyer was prevented from interviewing his co-workers by the
    FBI agents and prosecutors that you were advising.

    DOJ: Comply with FOIA please and provide Dr. Ivins contemporaneous lab notes
    for 9/28 – 10/2 and then the documents relating to the 12 dead rabbits.
    The autoclave should have had a log.

  8. DXer said

    If all the other theories as to motivation fails, Dr. S ventures that he sent the anthrax to get the girl:

    “Technician #2’s [Mara Lisncott’s] departure from Dr. Ivins’ laboratory in 1999 to go
    to medical school in New York State represented a serious personal
    blow. In the poem he wrote to mark her departure, he had
    expressed the thinly veiled wish that she would return and that “[we
    will] miss you lots — more than you’ll ever know.” After she left, his
    emails described his sense of loss and even depression. By early
    2000, he was again seeking psychiatric treatment for symptoms
    related to depression and anxiety, for the fi rst time in 20 years.
    Launching the anthrax attacks was in part an effort to infl ate his
    importance with Technician #2 and potentially induce her return to
    the laboratory. Technician #2 had been inoculated against anthrax
    and had the skills to work with it. In the aftermath of the attacks,
    people like her were in demand. “I just heard tonight that Bin Laden
    terrorists for sure have anthrax and sarin gas,” he wrote her on
    September 26, 2001, after the fi rst letters were mailed but before
    they were reported. “You should feel good about having received
    anthrax shots.” In the aftermath of the attacks, physicians with
    research backgrounds in anthrax were in demand. Technician #2
    conceivably could have returned to the laboratory — embraced by
    her peers as an authority and with only Dr. Ivins, her mentor,
    to thank.”

  9. Old Atlantic said

    Are billing records for the BSL-3 and autoclaving part of why the first team of FBI agents cleared
    Ivins? Because the autoclave and BSL-3 billing showed Ivins time in August, September, and October
    2001 in the evenings was all billed?

    Was the autoclave billed by the hour?

    At what rate? Autoclave billing code?

    To what departments, agencies, projects?

    Did projects have billing id’s?

    Is billing mentioned in any Ivins emails?

    In any of the documents being withheld? Is this one of the reasons they can’t release any of the lab notebook records or some of the other records being requested? Because they indicate some sort of billing information for Ivins’ lab time or the autoclaving?

  10. Old Atlantic said

    http://glennsacks.com/blog/?p=4703

    “But the actual monetary cost, I’ve never considered, until now. Watson, with the help of Mike McCormick, estimates the number of TROs to be issued this year at somewhere between 2 and 3 million at a cost of $2,000 apiece. That would be $4 – 6 billion for TROs alone. Now, I don’t know where those figures come from, and they look inflated to me, but they do give an idea of just what we’re spending on TROs.”

    No Temporary Restraining Order (TR0) was ever asked for or issued on Bruce Ivins?

  11. DXer said

    “When KKG Sister #1 rejected Dr. Ivins’ request for a date during his
    undergraduate years, the rejection cut Dr. Ivins to the core, perhaps
    because it seemed to confi rm his experience of childhood isolation and
    validate what at some level he feared the most — that his parents had
    been right to reject him. Moreover, given his fragile sense of self, he
    would have presumed that she shared word of her rejection with her
    sorority sisters and friends — and thus once again, he would have
    been publicly humiliated.”

    This is highly speculative. KKG Sister #1 does even remember the request for a date.

    “When, in his view, KKG Sister #2 [Nancy Haigwood] initially
    showed him some measure of kindness, he may have seen her as the
    mother he had never had and a fi gure that could validate his worth.”

    I can’t wait to watch “Bones” so I can hear Sweets say stuff like this.

    It’s not the type of evidence that would ever substitute for evidence in court.

    • DXer said

      Page 117:

      “In seeking revenge, as we have seen, Dr. Ivins targeted not only
      KKG Sister #2 but KKG the institution. His burglaries of KKG houses
      took place when women were absent. They were not the object of his
      obsession — rather, it was KKG as the symbol of authority that
      engaged and enraged him. From what we now know about his
      statements and actions, KKG appears to have represented a symbol
      of female authority. His decades-long war with KKG, the “fatwa” he
      described in 2007, was a continuation of the self-described “payback”
      to his long-deceased mother.”

  12. DXer said

    “His blindfolding of Technician #2 may relate to these childhood
    experiences And any or all of these experiences may help
    account for his lifelong pattern of sexual arousal by women’s
    undergarments, as well as his self-reported cross-dressing.”

    So if Dr Saathoff knew Dr. Ivins was troubled and suicidal, and his cross-dressing
    was self-reported, why did they want to test his panties for semen in July 2008?

    Was Dr. S. consulted prior to that decision?

  13. Old Atlantic said

    FOIA requests are billed by the agency? They have billing codes for this? It is part of their billing system? Along with billing outside the installation to other parts of the government and internally to projects, experiments, departments, etc?

  14. Old Atlantic said

    Heavy metals found at Ft. Detrick landfill


    4.17.1.9 Area B-6 Landfill (FTD 69)
    This 3.7-acre landfill is currently undeveloped grassland located in the southwest corner of Area
    B. From 1948 to 1960, this area received metal, wood, general debris from laboratory remodeling and building demolition, possibly including decontaminated (sterilized) materials from Fort Detrick laboratories dismantled in the early 1950s and autoclaved carcasses of animals ranging from mice to horses.”

    page 74 search on autoclave

    Click to access FORT_DETRICK_AREA_B_EA_24DEC2010.pdf

    Search

    autoclave site:detrick.army.mil
    “These animals had been used in special operations with live biological agents and were reportedly autoclaved prior to leaving the laboratory. Investigations found metals above background concentrations, VOCs, explosives, and Aroclors 1254 and 1260 in soil samples. In April 2008, the RI/FS for the site was finalized. The RI focused only on the waste and soil. COPCs and their associated maximum concentrations were: arsenic (17 mg/kg), chromium (80.57 mg/kg), iron (88,000 mg/kg), vanadium (260 mg/kg), 2-methylnaphthalene (10,000 microgram/kilogram [μg/kg]), 3,3’-dichlorobenzidine (41 μg/kg), benzo(a)pyrene (10,000 μg/kg), chloroform (12 μg/kg), naphthalene (30,000 μg/kg), PCE (17 μg/kg), and TCE (500 μg/kg) in soil.”

  15. Old Atlantic said

    Search in Google

    Ft. Detrick internal billings

    Ft. Detrick internal billing

    internal billing site:detrick.army.mil

    billing site:detrick.army.mil

    accounting site:detrick.army.mil

    “billing code” site:detrick.army.mil

    auditor site:detrick.army.mil

    billing 1425 site:detrick.army.mil

    billing BSL-3 site:detrick.army.mil


    [PDF]
    Environmental Assessment
    File Format: PDF/Adobe Acrobat
    BSL-3, and BSL-4), laboratory space for animal research, …… developed by summing laboratory billing data for FY 2009 for each utility or waste, …

    GAO should know all about this type of tracking and audit of a military research installation.

    • Old Atlantic said

      BSL-3 billing hit:

      Click to access AreasACMPEA18MAR2010.pdf

    • Old Atlantic said

      “Transient offensive odors may result from autoclave and incineration processes; however, these are typically localized and rapidly dispersed in the ambient atmosphere. Steam sterilization processes at the NCI-Frederick Animal Production Area (Buildings 1021 through 1039 and Buildings 1044 through 1049), the existing USAMRIID laboratories (Buildings 1412 and 1425), and the existing SSP (Building 375) have resulted in odorous emissions. In 1989, an investigation into the likely cause of odors emanating from these facilities determined that the odors resulted from the degradation of protein-containing substances, such as animal feed materials (NCI-Frederick Animal Production Area), microorganisms (USAMRIID), and effluent discharges (SSP) (DA, 1991).”

      Page 153 of above doc link.

      Now how do odors get out of the autoclave? Is that like it is not airtight?

      Ft. Detrick personnel keep telling us that if spores were dried in volume in the BSL-3 they would spread around the lab.

      Here we have confirmation that odors from the autoclave did spread around the lab. This indicates that air currents from the autoclave could spread. Those same currents could carry spores?

  16. DXer said

    The FBI consultant writes:

    “Dr. Ivins also made a practice of attempting to be humorous by writing
    notes while purporting to be someone else. He expected others to
    know he was the author — as in this note to Technician #2 [Mara], written
    sometime between the summer of 1997 and summer of 1999, in which
    he joked about anthrax and Islam:

    To the Future [Researcher in Microbiology]

    “Many congratulations to you. Allah smiles on all of your
    accomplishments. After your degree please come to my
    country and talk to us about your work at Fort Detrick.
    Please bring your anthrax strains with you when you come.

    Most sincerely,
    Saddam”

    What was the date of this note? Shouldn’t it be produced under FOIA?

    Given that Mara and Bruce worked alongside in the BL-3 with a former Zawahiri associate
    (with the 16 pages relating to that research first being obtained by the FBI in February 2005),
    the timing of the note would be something interesting to know. Mara and Bruce, according to
    the 302s, worked in the BL-3 in the Spring of 1998.

    Numerous documents are referenced in the report that have not been produced under FOIA.

    • DXer said

      It’s really not probative of the crime that Bruce liked Mara. There’s no reason to doubt that she is very likable.

      “As was his custom when someone departed USAMRIID, Dr. Ivins wrote
      a poem he recited at Technician #2’s going away party in July of 1999.
      Then and on subsequent occasions, he expressed the hope that she
      would consider returning to USAMRIID after her medical training.
      The 1999 poem included the following lines:
      She worked with nasty anthrax strains.
      Yes, there were quite a few.
      She was super in the lab, and super outside, too.
      Her work made us feel better ‘bout that vaccine in our arm.
      It keeps us safe from anthrax and from bioterrorist harm.
      —Soon you’ll leave these diehards, rooting for the O’s.
      Since you’re a Yankee fan forever, you can thumb your nose.
      Med school now awaits you. We’re sure that you’ll do great.
      Then you’ll be a doctor- bet you can hardly wait.
      Want to work back here again? There won’t be any fuss—
      We’ll take up a collection to bring you back to us.
      The poem went on to say that the lab will “miss you lots — more than
      you’ll ever know.”

  17. DXer said

    What Dr. Ivins did with respect to Dr. Haigwood was despicable.

    Dr. Ivins had first written this woman in 1982, after she had become
    known as an outspoken critic of hazing and had been interviewed by
    Tom Brokaw on the “Today Show.” (Brokaw, it is worth adding, noted
    in that interview that his co-host Jane Pauley was a KKG alumna.) On
    May 29, 1983, Dr. Ivins provided this woman with a clipping of his
    fraudulently signed letter. The woman gave the letter to the author of
    several books on hazing, who then referred to KKG Sister #2 by name
    in a book he was writing. The book also quoted a KKG official as saying
    that KKG Sister #2 “does not speak for the organization and never
    has” and that “it is a ‘most isolated’ occurrence to have a sorority
    woman come out in favor of hazing, which is ‘strictly prohibited’ by
    the national [KKG organization].”

    • DXer said

      “The statements Dr. Ivins fabricated in KKG Sister #2’s name have
      continued to be referenced and attributed to her in scholarly works,
      such as the 2004 thesis, “Defi nitions of Hazing: Differences Among
      Selected Student Organizations.” In fact, the letter triggered a libelous
      cascade of publications that led to a personal repudiation of KKG Sister
      #2 by the sorority’s leadership and continuing damage to her
      reputation. Interviewed in 2008, Dr. Ivins admitted to the FBI that he
      had written the letter to the newspaper and had provided the clipping
      to the grieving mother. He said he could not explain why.”

  18. DXer said

    More from the FBI consultant on the reason that the alleged anthrax mailer targeted Tom Brokaw:

    “On March 24, 1987, he sent a letter addressed to Brandon Tartikoff,
    NBC Television, 30 Rockefeller Plaza, New York, NY 10112 —
    the same address used for the anthrax mailing to Tom Brokaw —
    concerning a proposal to develop a mini-series about the
    Challenger Space Shuttle. He also contacted CBS and ABC about
    this idea. Writing back from the same 30 Rockefeller Plaza address,
    a representative of NBC’s law department informed him, in what
    appeared to be a pro-forma rejection, that his unsolicited program
    submission “has not been read by anyone at NBC.”

    • DXer said

      “30 Rock,” of course, is justifiedly one of the most famous addresses in the world — the TV show by that name is great!

    • DXer said

      I don’t care how much he appreciated Christa McAuliffe. I just don’t think it flies as a reason to target Tom Brokaw. (He kept all his correspondence and so the fact he kept that seems immaterial.)

      “In 1986, the death of Christa McAuliffe, the teacher who died in the
      Challenger Space Shuttle explosion, apparently affected him deeply.
      He wrote two personal letters of condolence to her husband, Steven:
      on January 31, three days after the explosion, and again less than two
      weeks later, on February 11. He wrote about the accident to members
      of Congress, and he even wrote a song in her honor, which he tried to
      promote to the music industry. Those efforts failed; the letters of
      rejection were found in a file he kept at home. As noted above, his
      attempts to develop a television series based on the life of Christa
      McAuliffe were also rebuffed. Those letters of rejection also went in
      the fi le. Eventually, he gave the song to the late astronaut’s family.”

  19. DXer said

    The FBI Quantico partner/consultant writes:

    “Dr. Ivins’ obsession with KKG Sister #2 was significant enough that
    he also burglarized the KKG house in Chapel Hill while they were both
    living there — Talking to investigators 30 years later, in February of 2008,
    he could still recall one of the breakins
    in vivid detail. According to investigators’ notes of that interview,

    Dr. Ivins: entered the house at night through a first floor bathroom
    window which was located behind a shrub. Although there were
    several lights on inside, [I] knew nobody was there as those
    lights were always left on. Using a small pen light to help [me]
    see, [I] went upstairs and looked for anything which was locked
    and may contain secretive sorority documents or materials.
    There was a hallway closet which was locked, so [I] used a coat
    hanger or some similar object to open the door. Inside the closet
    [I] found the “Cipher” and some documents regarding KKG
    rituals. The Cipher was a document encased in glass, and it
    referred to a book of ritual which [I] also looked for but did not
    fi nd. In an unlocked closet directly across from that which
    contained the Cipher were some blindfolds made from torn bed
    sheets. [I] assumed the blindfolds were used for the KKG
    initiation, but did not take them.” Dr. Ivins said he “left after
    spending about an hour in the house, taking with [me] the
    Cipher and ritual materials.”

    Comment: Let me describe my experience in 1981.
    Dressed in a dark blue sweatsuit, I climbed up the fire
    escape of the fraternity knowing that the brothers were
    being entertained by a stripper at a party in the downstairs
    living room.

    I carefully slid the window open and positioned myself behind a door
    leading to hallway. As prearranged with an initiate, the initiate called up my
    target “You’re killer is on the telephone!” (It was a game
    called Killer, involving water pistols.) My prey came up to
    get the phone in the booth in the fraternity hall, mistaking
    what end of the telephone I was on. (The initiate “set up”
    his brother to get back at him for hazing).

    I leapt out and fired a lone shot, in front of the required
    one and only witness.

    Not probative of a damn thing except that I had a great time
    in college. What? Only the fraternity brothers and sisters
    can have fun?

  20. Old Atlantic said

    Was all of Ivins time at night in the BSL3 billed to some project, department, or agency? As overtime? Was a bill created for each of the nights in August, September and October 2001 for Ivins time?

    Was each animal that was autoclaved separately billed for and listed in a bill to some project, department or agency?

    Don’t computer departments at government agencies routinely bill for use of the computer? They bill per hour of computer time and for other things? Wasn’t this type of billing set up before the 1970’s in many government departments that had central computers?

    Didn’t this type of billing persist for this type of common resource in a Ft. Detrick type situation?

    Wouldn’t the BSL3, autoclave, and specialist time like Ivins be billed for and accounted for down to the minute and animal autoclaved on this basis?

    • Old Atlantic said

      In fact, in the old days of central computers, this type of billing was standard in corporate America as well? Each department was billed for each minute that it used the mainframe? Every company did it that way almost?

      Ft. Detrick likely had a central mainframe computer decades ago with that type of billing system. That likely applied to all service departments. BSL3 and the autoclave were service departments that billed projects, other departments, outside agencies etc? It was just like Battelle?

  21. Old Atlantic said

    Excellent graphic. They need to provide all documents on all 3 topics and all of Ivins’ emails not already disclosed, i.e. including ones from private email.

    All the records on autoclaving of the animals for the year 2001 should be released for comparison purposes, but definitely all autoclaves in August, September, and October 2001. In addition, all lab notebooks for checks and records of calendars, assignments, etc. for this work.

    Also, don’t the family still own that? Ivins’ email from his home computer on his personal email account? Can’t they get a copy of the emails?

    • Old Atlantic said

      Also receipts. Are these projects billed internally somehow? Is each animal autoclaved billed to some department?

      The autoclave has its own book keeping account? It bills other departments at Ft. Detrick for using the autoclave?

      Does BSL3 bill other departments?

      Was the time of Ivins and others in his lab billed to other departments? To outside entities?
      To Battelle?

      Was Covance being billed for this experiment? Drug companies?

    • Old Atlantic said

      DOJ made a big deal out of Battelle billing for all its time. Therefore, no one could have done it because all time was billed for. Billed to whom? Parts of the government?

      Did Ft. Detrick do the same thing internally? Did it also bill the same government agencies as did Battelle for the same work? With the same codes and similar rates?

      • Old Atlantic said

        Did Battelle and Ft. Detrick bill each other? Then turn around and bill that to other government agencies?

        How does the accounting system work? Is it audited internally? Do those audit records exist?

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