Bliley PM
RE: Summary CTR Research Conducted by Bio-Research
Abstract
Provides overview of the relationship between Bio-Research and CTR (Council for Tobacco Research). Discusses the historical relationship between CTR and Dr. Freddy Homburger. Details studies done by Dr. Homburger for CTR and others. Recounts the deterioration of the relationship between Homburger and CTR.
Fields
- Notes
Includes PM internal Bates numbers
- Company
- Philip Morris Cos., Inc.
- Type
- Memorandum
- Author
- Barnett, Orville L (PM; BW Attorney, Shook, Hardy & Bacon)
- Smith, T.R.
- Recipient (Organization)
- Philip Morris Research Document Reviewers
- Named Person
- Bernfeld, P.
- Braunstein, H.
- Charles, J.
- Dontenwill
- Fagab
- Gardner, Dr.
- Graves, J.
- Hamperl
- Hockett, Robert Casad, Ph.D. (CTR Scientific Director)Scientific Director of the Council for Tobacco Research from 1972-1974 (WSJ 2/11/93; Allman complaint). Bio-Research Institute BRI conducted a study for the CTR. When Syrian hamsters were exposed to smoke twice a day for 59 to 80 weeks, 40% of those of a cancer-susceptible strain and 4% of a resistant strain developed malignant tumors (WSJ 2/11/93). Before publishing the study in 1974, BRI's founder, Frederic Homberger, sent a manuscript to Robert Hockett, then scientific director of the CTR. Dr. Homberger says he had to do so because halfway through his study, the CTR had changed it from a grant to a contract so they could control publication. They were quite open about that (WSJ 2/11/94. Soon thereafter, Hockett and CTR lawyer Edwin Jacob went to Dr. Homburger's summer house in Maine. Hockett and Jacob did not want BRI to call anything cancer, they wanted it to be "pseudo-epitheliomatous hyperplasis," a euphemism for lesions preceding cancer (WSJ 2/11/93). Dr. Homberger said no, this is not right, it is cancer. Jacob told Dr. Homberger that BRI would never get a penny more if the paper was published without the changes. At the last minute, Dr. Homberger changed the final proofs to read "microinvasive" cancer, a microscopic malignancy. Nevertheless, BRI was never funded by the CTR again (WSJ 2/11/96) Hochett made a statement, as scientific director of the CTR circa February 1972 that neither tobacco and health research in general, nor that of the Council for Tobacco Research has established that tobacco use or cigarette smoking in particular is a major health hazard (Allman complaint, pp. 41-42). Robert C. Hockett was Scientific Director, Vice President and Research Director of CTR. See Bio-Research Institute, TTLA Almanac - Names. (N.M.'s CTR Who's Who)
- Holtzman, Alexander (PM Asst General Counsel. 1975-85.)
- Homburger, Freddy, M.D. (Claims CTR tried to prevent him from publishing his research)Plaintiff
- Hoyt, Willson Thomas (W. Thomas) (CTR, President, Executive Director 1954-1984)Previously with Hill & Knowlton
- Huebner, Gilbert Dolan (Medical Director for the Tobacco Institute)Gilbert Dolan Huebner was the Medical Director for the Tobacco Institute. (PMI's Introduction to Privilege Log and Glossary of Names, Estate of Burl Butler v. PMI, et al, April 19, 1996)
- Kreisher, Dr.
- Kuschner
- LaBelle
- Leuchtenberger
- Little, Arthur D. (Arthur Little died in the 1930s. References to Arthur D. Lit)Defense
- Nettesheim, P.
- Ramm, H.H.
- Rosenkranz, Dr.
- Sommers, Sheldon Charles, M.D. (CTR Scientific Director c.1979, Industry Consultant)Dr. Sheldon C. Sommers was an Industry Consultant, CTR Scientific Director and served on the CTR Scientific Advisory Board. (PMI's Introduction to Privilege Log and Glossary of Names, Estate of Burl Butler v. PMI, et al, April 19, 1996)
- Wakeman
- Wynder, Ernst L., M.D. (Epidemiologist, Sloan Kettering, Anti-Tobacco Expert)1993 First scientist to report in 1950 on the carginocencity of cigarettes in rats painted with tar. Assistant at Sloan-Kettering Institute for Cancer Research Directed the American Health Foundation (AHF) from 1984 to his death in 1998.
- Zahn, L.S.
- Named Organization
- Bio-Research Consultants, Inc.
- Bio-Research Institute (Conducted studies for CTR)Conducted study for Council for Tobacco Research on hamsters exposed to tobacco smoke, finding that it produced malignant tumors.
- *Council for Tobacco Research-- U.S.A. Inc. CTR (Formerly Tobacco Industry Research Committee (TIRC))Created and funded by the tobacco industry to award grants to study of the link between smoking and disease. Part of a four decade effort to cast doubt on the links between smoking and disease.
- AMA-ERF
- ASEP
- Federation of American Societies for Experimental Biology
- Richmond Times Dispatch
- ORNL
- *Scientific Advisory Board (SAB) (Only use SAB with name of specific org.)
- Additive
- Benzo[rst]pentaphene
- d-limonene
- DBP
- Diacetate
- Dibenzoate
- Quinone
- Terpenes
- Keyword
- CTR redbook
- Tumorigenicity
- Anti-tumorigenic
- World Conference on Smoking and Health
- Thesaurus Term
- industry sponsored research
- tobacco industry internal policy
- tobacco industry scientist
Document Images
M E:M O R A N D,U M
TO,:
FROM:
DATE:
RE::
PHI:LIP MORRIS RESEARCH DOCUMENT REVIEWERS
ORVILLE L. BARNETT,~ X-C2:~8
THERESA R. SMITH, X-C206
JANUARY ii, 1988
SUMMARY CTR RESEARCH CONDU~CTED BY BIO-RESEARCH
Overvilew
Bio-Research received its first CTR.grant in 1955. They
continued to receive grants from CTR until 1970. In ~970 they
entered into. a contra~ct relationship with CTR.. This continued
until the end of 1973. In March 197'3, the SAB! elected to close
out the Bio-Research contracts. Prior to this CTR and Bio-
Research, appeared to have a very good working relationship. Dr.
Hockett and Freddy H,omburger, most of awl, seemed to have mutual
respect and admiration four one another. Durfng the 1960:'s CTR
relied a, great deal on Homburger for his opinions and research.
It was. not until the late 1960's andi early 1970's that criticism
of Homburger became preva~lent among the SAB and CTR staff. After
th.e cancellation of h
of: CTR.
In gelneral, CTRs' criticisms w,ere related to Homburger' s
techniques and interpretations, not of Homburger himself. On the
other hand, Homburger attacked CTR on a, persona~ level. He accused
them of trying to suppress results and hide important information
from the: pub~ic. Except for Zahn's involvemen~ in. the cancellation
of Homburger"s ~r~s conference~~-R ac~~~~ ~--~--~f~--~u',,,~
manner.
Cost.
Bio-Research was comprisedl o:f two separate: entities,~
Bio-Research Consultants, Inc. and B~o-Research Institute, Inc.
Bio-Research In,st:itute was a non-profit entity while Bio-Research
COnsultants was for profit. CTRuti~ized both~ organizations.
Over a period of m~e~en ~.~. ~ ,. ;~i~-w~march received
o_v.er ~i. 5 ~[ll~ion from C~. [See Atta,chment A]
Memorandum to: Philip Morris
Re:search Document Reviewers
January ~i, ~988
Page 2
Historical V~ew of CTR and Homburger's Rielationship
196i0-~969~- Building a Relationship
Hockett's respect for Homburger's work wa~s very ev~d,ent
in th,e early 1960"s. For instance, the Leuchtenberger's research
had been, yieldingi some important results, but they did not have the
capabilities to~ follow up on some of the results. Hockett suggested
to Dr. Little that Homburger's laboratolry follow-up some o~f the
Leuchtenberger'~slea~dS ~LT00~04147/4~48, Ex-list]i. In 1963, Hockett
sent Peter Hamil~copies of H,omburger's~paper, "Mouse-Skin, Painting
with CondensatesofPipe, Cigarand CigaretteSmoke~s,~[PM10!05!~012807.,.
Ex-list].
The~ midl to late 19610's were marked by mixed asse~ssments
of Homburger. In a memo. from ~akeham to~ Osdeme it wa~s. stated that
the SAB was c~nherned about H,omburgelr's capability of performing
his grant program. The SAB decide!d that Dr. Sommers and Dr..
Kreisher should visit Homburg,er's! ~aboratory andl ~nspect his
facility [PMI00003!7173!,~ produced]. Apparently, Hockett had a
different a:ssessment of Homburgers.' abil~t~es. In 19~69, Hockett
wantedl to follow up some of LaBelle's ~ork with~ "~ong term
experiments with Kotin, Homburg!er,. Mascon, Leuchtenberger or some
other chronic inhalation 'expert'~''~ [!HK00~!5015/51016, taken].
Dr. Sommers respected! Homburqer"s work enough to ask
Homburgerto supply Dr. Herb~ertBraunstein (Un~v.ersity of Kentu,cky)
with histologic slides.~ The slid,es demonstrated squamous cell
carcinomasproducedbytobacco smoke cond~insates[HK0:861605, taken]i.
Homburger apparently, complied becau~se Dr. Braunstein toldl Sommers
that Homburger ~ad been very helpful [HK018660~60,. taken]. Dr.
Braunstein also mentioned! in the letter that he and! Homburger both,
found the current commercial c~garettes to. be "poorly carcinogenic
for mousse skin~." Dr. Sommers re~spondied to this ~etter and statedl
if Braunstein and Homburger were correct "the 'safer c~qarette' is
already that b~ng soldl commercially" ~HK086606~,~ taken~].
By ~ate 1969 there w,ere indications that H,omburger's~
ability was a,ga~n being~qu,estionedl by CTR. Another site visit was!
made to Bio-Research. On. th~s occasio~n Dr. Huebner made thereport.
Dr. Huebn,er'~s as~sessment of Homburg,er's laboratory wa~s that it
was best suited for studies o~f in vivo. carcinogenesis. He saidl
"the weak link in. Hombur~er's 0Pera~ion is the lack o~~ v~~d!
tissue culture competence an~ ~tron~: an~ knowledgeable
&~ien~ific personnel" ~nK0:8660136-6037, taken].
Memo~randum to Philip Morri.s
Research Document Reviewers
Janu~ary 11, 19188
Page 3!
1970-19~74 - H, ombu'rqer' s Demise
~n May 1970 Homburger aD~D!ie~
~ The title of his application w~s. "'Inhalation Carc!in~s!
andViruses in Syrian Hamsters.,,~ Dr.. Kotin"~recommended diisapproval
because the omnibus nature and confused text o~f the application~
preclude evaluation of! the indiv.~d~a~ components." Dr. Kuschner
"thought the project was trivial and costly," and recommended
rej'e,ction. The a~Dlication w~s d~ed bi~ ~'~e ~m~tee [Macensk~ ~:
Exhibit 4,~ Ex-~Iist]~ At this same time Homburger began his contract
~or determining the usefulness of the Syrian hamster for inhalation
studies with CTR. It is interesting that Homburg,er wou~d apply to
both the AMA,ERF and CTR to do ba~sica~ly the: same research.
Regardless of the criticisms about his research, CTR
found Homburger helpful outside of the: laboratory. In N,ovember
1972, Homburger was invited! to attend a workshop on "Endpoints in
TObacco Smoke ~nhalation Studies" spons~ored by O}~NL. Homburger
informed Hockett o~fthis wo~kshopand Hockett d!iscussedthe workshop
with ~r. Paul Nettesheim.. Dr. Neltteshe~m explained the conference
to Hockett but was not "receptive to. the addition of another
ob:serv.er or commentator for the Council." Hockett said Homburger
wa,s g~ven permi.ss~on to attend, as we~l a~s. Dr. Bernfeldi and Dr.
Rosenkranz (MRI) [ZN15722-57~23!,. taken~]. Dr. Homburger submitted
a report of this meeting to Dr. H,ockett ~ZN15!724-57.27, taken].
~n 197'3 H,omburger's relationsh~ip with CTRI came to an
explosiv.e conclusion,. At a CTR annu~al meeting, in January 1973, the
re!sults o~ Homburger's ~nha,lation research w~th Syrian hamsters
was f~rst repolrted. According to Zahn's noltes of the meeting,
Homburgelr reported info~mally toSommersthat, he found larynx cancer
in hamsters, exposed to smoke. The notes went on to say "but
[laryngeal] changes ~real] mild. But not sev.ere [andl] is. not
[can~cer] not even clo:se ~and] can't be called, precancerous. Only
mild dysplasia" [Z~497-499, taken]l.
Ironically,. these results occurred a.t. the same time
Dontenwi~l"s_ manuscript on nls hamster studies was comlng ou~.
c'x~ an~u~nce~ a~ ~ne Janua~y'l~ ~ee~ng ~na~ ~ney Were ~rying to
ha~e someolne look at Dontenwill'.s slides. That someone turned out
to be Professor. H~. Hamper1. Dir. Sommers wrote to hiim and. explain~ed
that Dontenwill reported squamous cell carcinomas of the la~nx ~n
smoke-exposedl hamsters.. Sommers sa~id "having been stung so often
with dysplasia cl!a~med to be carcinoma, we wonder if he really has
invasive squamous cell carcinomas, and ii~ so how many." Dir. Somme~rs
sa~i!d CTR~wouldpay~rofesso~rHamperl,~s expenses if h~ewo~d!arrange
tol look at Donte~will's slide~ [HKI008!3041,. taken]. Professor
Hamperl agreed and told! Dr.. Sommers that he asked Donte~.~ll~ to
Memorandum to. Philip Morris
Research. DocumentReviewers
Jlanuary ii, 19:88
Page 4
send! him sectio~ns from the lesions! o~f the larynx. "For different
not very convincing reasons he would not comply with my request
and invited me instead! to come to his laboratory and see for
myself" [HK0~083!O40, taken]. I have located no further
correspondence onthismatter. It ~s obvious that CTRwa~sco~ncerned
that both Homburger and Diontenwill came up with the~ same results.
It was not surprising that by March 19173!, Homburger,s
laboratory wa~s. being categolrized by CTR as "dirty" and "loaded
w.ith~ ~nfections." In notes of the meeting it was said that the
CTR staff ~ould holt consider it for an, inhalat~o~n study folr this
rea~son. Again, a discussion was held about Homburger's cla!~ms
that laryngeal tumors had developed in his hamsters.. Dr. Sommers
said Homburger was "'a reliable pathologist but Freddie tendis to a
liberal interpretation, [PMI000256~I0-.6113, produced]. ~pparently
other SAB members felt differently and votedl that the Bio-Research
contracts should! be c~osed out [[SM02OO24-0032, Rev andi Ex-list.]..
In September 19~3 Peter Bernfeld a,sked CTR for renewal
of Bio-Relsearch"s contract "The Determination o~f the Usefulness
of the Syrian Golden Hamster a,s Model Animal for Inhalation
S!tudies" [i0102.638095-810~,. produced]. This application ~as denied
and Homburger became very disgruntled. He reacted by writing a
letter to many of the research d~rectors of the tobacco companies.
H,e felt they should, be aware of CTR's. a,ctions [LORI 0119~574,
producedi]. Attachedi to this: letter was a letter h~e wrote to Dr.
Gardner outlining his! intense d~sapprova~ o~ CTR'~s actions. [PM
i000~8~!971-39178, ~x-list]. This letter gave a. chronology of events
lea,ding up to the cancellation~ of this contract.. The chronology
i.nclud~dI accusations that CTR believed Homburger"s hamsters were
infectediwith, a virus. A,ccordingtoHomburgerthishadibeen checked
and proven to have no scientific bases. In the letter he requested
that CTR recolnsid.er their decision.
~r. Gardner respondedl to H,omburger by s~aying "no useful
purpose wou~d be served by detailed reference to thee mistakes and
distortions contained! in them[Homburger's!letterand chronology]."'
Gardner went on to say that CTR did wish to expedite publication
olf the results. H.e said CTR' could not agree, however, to
"~fragmentaryorimprec!ise publicatiolns, which maybe misinterpreted.
Therefore, we must insist on your observing your contract
.obligations not to. publish without our approval"' [RJR 51036549017-
4.909., Ex-list].
Homburger demandedi an apology from Gardner four implying
that he might publish something "fragmentary"' or "imprecise."'
H,omburger said CTR's decision was"indefensible~ and w.asteful from
the point of v~ew of the gelneral public. It couldl be inferredi that
Memorandum to Philip Morris
Research Document Reviewers
January ll,~ 19:88
Page 5
you wish to. suppress, rather than to~ encourage, scientific
investigation"' ~RJR510365490!5-4~9061, Ex-~ist]!. Homburger was
upset that CTR wanted photographs o~f the ~esions. He said that Dr.
Sommers had a chance tlo. examine in detail several o~f the original
microscopic slides.
19174~-1975- Presentation, of the Results. to the Public
In April 1974~, H,omburger submitted!his manuscript "Strain
Differences In, Thee, Respolnse Of ~nbre~ Svri~ w~m~ ~n ~arett~i
~moke" to CTR. T~e.-~anus6ript acknowledged CTR's support, but
'said--~it]he views expressed in this paper are those of the a~thors!
and do not reflect the opinion of t'he ~ouncil for. Tobacco ~esearch,,~
[ZN19~62!6-9670, taken]. H,omburger presented this. at a mee~ingl in
~tlantic City. ~n a mem6Uto, n~ ~mm an~ T. Hoyt, Zahn~ descriDed~
h~w he ~epr Homburger from holding a press, conference at th~is'
meeting. Mr. Zahn had engaged! the help o~ Judy Graves, who said!
some of the AS~P people consid,ered Homburg!er an "operator"
[ZN19,604-9605, Ex-list].
Zahn's notes of th~is Atlantic ~ity meeting attribute
some very unfortunate statements to. Homburger. Kccording to his
notes, Homburger said "Good friend - Research Director of CTR-
has asked me to withdraw paper pub in abstract form [and] since I
wanted to give d~ta, I put together someth~ing they've approved."
The rest o~ the notes reflect the details o~ Homburger's
presentation [ZN191617-96~O, taken].
The t~ed notes, of this meeting of the Federation of
American Societies for Experimenta~ Biology are more damaging~:
Since my good friend, the Research~ Director o~f
The Council for Tobacco Research., has asked me
to withdraw the paper that has been published
in abstract form andl since I do not wish~ to
violate my contractual obligations, at the
same time ~i do not wish to d!isappoint this
audence [!sic]. I have p~t to~ether some:things
that have been previously published with the
permission of The ~oun~cil fo~Tobacco Research
which u~til a very short time ago supported
these stu,dies [ZN~i5~5-3528., taken]i.
In June 1974 Homburger wrote a very c~rdia~ letter to
Dr. H,ocket~. He than~ed"D~. ~,~,~ f...~ d~'m-~,,~ re~!~w of
~is paper. "Cigarette Smoke Inhalation Studies in~ Inbred syr~a~
~ams~ers~" n~u.~e~ saidl ~e pa~er had been
publlication i~ the proceedinqs ~f the .S~at~]~, S~vmDosium
Memo~randum to: Philip Mo~rris
Research Document Reviewers
Janu~ary ~i, ~9:88
Page 6
Experimental Respiratory Carcinogenesis.. He asked if CTR wouldl pay
folr his and Bernfeld's expen,ses to attend the meeting [ZN19612,
Ex-list]. It is not c~ear whether CTR paid four his expen,ses, but
Homburger d~d attend the meeting andi presented his. paper.
In a memo to Holtzman, Wakeham relayed Fa,gan's analysis
of the CTR-H,omburger controversy [PMI004'864285-428i6., not produced].
PM found Homburger and his organization to be very respectful of
PM suggestions on~ how project work was conducted. PM felt that if
there were deficiencies su,ch as those claimed by CTR, they could
have been solved with proper communication~ and coordination.
In October 1974, J~im Charles (IPM) visited Bio-Research.
Peter Bernfeldi toldl him that "'in the CTR study' w~th hamster
inhalation ....... a viral screen was performed~ at CTR"s request.
Peter insisted' on blind cod!ing and he stated Huebner wa~s. ~urious.
Results of vir.al stud!ies apparently showed no relation to~ inhalation
results," [ 1003114289-429:2, produced].
1975-1.981 - The Aftermath
In Zahn's typed notes, for presentation at the ~975 CTR
annual meeting,~ the ~omburger press conference was mentioned again:.
The dliscussion of Homburger was crossed out so this may indicate
he did not actually present this at the meeting. The notes say:
Homburger -- unique in my 2'0 years with industry
(today). A grantee who ha~dl project turnedl into,
contract, scheduled press conference::
censorship of this findings, etc.. Got press
conference killed, without his knowingi why or
how. Did not try to get his release on, his
sch,eduledi talk out of press room, but arr.anged
to g!et him out when he appeared next day. No.
press mention of this report [ZN474-477, Ex-
i i st ] .
an article appeared in the Richmond Times
19~78
Dispatch,. It detailed Homburger ' s results and subsequent
cancellation, of ~is. CT~ contra~t [ZN196~5., taken]i. CTR prepared
press releases to rebut the accusations made in the article.
[ZN19609, 19610 Ex-list]. There was no indication whether these
were ever run.
Zahn addressed the press conference fiasco agBin at the
1981 Tobacco Co~loquium. Zahn explained in his presentation that
if one grantee complained publicly that CTR had tried to. influence
t~e research or the results it wou~d d~stroy its credibility.
Memorandum to, Philip Morris
Re,search Document Reviewers
January II, 19,88
Page 7
Therefore, he said one hadi to believe that grant recipients we!re
independent and free to do their work and disclose~their~ findings.
At this point~h~edescribed a case that he said related to this area.
The man, I learned, wa~s to tell the press that
CTR. allegedly had tried to influence him. to
chang!ehis findings andha~dlrefu,sed tocontinue
its support of his work. I won't go into
detai~, but the grantee had d~ne a poor
of research, was really trying to: bla~ckmail
the Council,. and was upset that anoth,er
scientist had recently published findings
similar to his. I so informed th,e public
information representative and officers of the
o~rgianization andl said! I was prepared to issue
a statement to that effect.
The result of! th~is was cancellation of the press conference. It
~ould appear that Zahn tried! to ju~stify his actions by categorizing.
H,omburger"s actions as "blackmail" [T0~64,~21~/41.29, taken].
Bio-ResearchProjects Eun~edl by CT~
~ It was very difficult to ana~yzeth~e B~o-Research research
funded by CTR. The primary problem being the correlation of
researchgrant or contract with the completed report. Perhaps not
a~ll the d~ta was containedl in the PM fi~es or perhaps Bio-Riesearch
was! negligent in preparing~ formal reports. If it ~as the latter,
this could have been an underlying factor in the breakdown o~f
relations between the two. institutions. An example of this problem
was th,e Homburger report on, his CTR Contract 4. The purpose of
this work conducted in th~eearly ~970'~s was to determine the effect
of exposing mousse skin to fresh whole smoke. A. complete report on
this work. w.as not found in th~e:PM files. Evid.ently in 1982, someone
at PM was interested! in seeing, the data,, Homburger sent PM a copy
of a summary of the data with an~ acknowledgement r~ceipt from CTRI
which had a 1973 date. This exchange couldi mean that CTR staff
personnel were of! the opinfoln that Homburger never submitted a
report.
Regardless of problems ~n reporting~, h,is! research didl
have some important a~spects. I~his 1.96!7 grant application he said!
~arcin~genicity and co-carcinogenici~y ~ad ~eclin~~ in mouse~s.ki.n!
~a~inting~stu,dies since 1960d~e to. chan~esinci@arette composition.
The title o~ the grant was "Bioassay of Tobacco. Smoke Condensates.
and Relatedl Problems" [PMI0035468!24-'68~32:, Ex-list]!. His 196!7
manuscript, presented at the Worlld Conference o:n Smoking and Health,
Memo~randum to. Philip Morris
Re,search Document Reviewers
January ii, 19~88
Page 8
stated: "w,e are, not co~cern~ h~ ..... ~ ~ ...... ~- ..,~~ ~h~,
[gkin palntinq carc~0qen~cityl bears any relat~io~shiD: ~Q ]inng -.
can~er-~ ,'" The manuscript was titled "Experimental Studies
On The ~nhibition Off Carcinogenesis ByCigarette Smoke COndensates
And Carcinogen-Related Substances" [PMI0050500:88-010~5, Rev-list].
Notes by Wa~eham. (.PM)I on CTR redbook sheet for th~s contract said
the philosophy behind the study, was "that if the jlet is! different
from th,e skin painting there may be ju~stification for discrediting
and/olr abandoning~ skin painting as a'relevant' bioassay technique"
[PM100Q22189~68!, produced]. In 197'11 Homburger began a contract
titled, "An Expanded Study o~f Mouse Skin Exposure to Whole Fresh
Smoke Compared to Skin Pa~inting:."
Sgecific:Project Summaries
Bio-Riesearch conducted! a mouse skin painting experiment
for CTR which compared pipe, cigar and cigarette tobacco. In th~s
trial all of th,e tolbacco u~sed to col~ect condensate was smoked, in,
the same maunder as c~garettes. The combu~stion, temperature o~f the
cigarette-like materials was very similar to cigarettes. The m~ce.
receiv.ed 62 to: 6,4 mg of condensate per week for up to 1.14 w, eeks..
~sedlon,.~iina~ t,,~i~i~__~c_!@~ ~h~ ~qt~qnificant d~ffereDces
b~etweenthe:.condensiates[!PM10,05134i551-45i86, taken]. This!repo~°c~as~
a~ ~D~.isne~.__
Bio-Research conducted a projlect fund,ed by CTR. to compare
the tumorigenicity of conventional, smoke condensate with: smoke
condensate obtained by impingement. (Contract4)i Aftertwo years
of convention:al skin pa.int~ng85.5%! of the miceexhibited!papi~lomas
as opposed! to papi.l~omas; on 18.7 to: 310.2% of the mice exposed to
fresh, smoke. The investigations! concluded that the lower
tumorigenicity of instant over precondensed smoke condensate was
due to d~fferences in. the level of ca,rcinogens in the two types of
condensate. A complete repo:rt of this work wa:s not found in the
PM f~les ~PM10i021970101-011, taken]i.
Bernfel~ and Hombur~r published the: data obtained from
the CTR Gr~:~ ~. The titl!e of this publ:ication was! "strain!
~l~erence:s in tb~ ~cn~z ~: ±~.~r~, ~y~.~a~ ~.amsters t~'"Ciq~r~
Smoke ~nhallation." ~n~ this work they found over 90% of the: smok:e
....... __ .... ~tlc or.
neo~las~ic
~n~anse!s in the laryn~x. However, microin_v_91s~Me cancer was nearly 5
~ ~ /=eq~e~ in q ~.t~ii'n ~n ~, ~h~ ~th,er [PMI00480i0440-
6~, ±ui~2967531~7.5~I~ holt produced, publi.she~]i.
B~o-Nesearch played! an a,cti~v.e role in the development of
smoking machines. Through CTR funding andl the con~sultant services
Memorandum to Philip Morris
Research Document Reviewers
January ii,. 19188!
Page 9
oil R. Walton, a, smoking machine was developed. This machine was
criticized by many researchers, because the cigarettes! were smoked
in a, vertical po:sition and air wa~spu~sh,ed through the cigarette by
creating positiv.e pressure on the c~al end of the cigarette. This
machine wa~s used in the acute inhalation o~f smoke to mice
experiments conducted for PM!.
CTR fun~ded the Bio-Research work on the effect of tobacco
condensate injections on the incidience of lung tumors in mice.
The results indicated that the tumor growth was. inhibited but the
number of tumors! present was not effectedi. Bio-Research felt that
the smoke condensate inhibitedl tumor growth, by either competing~
with, the carcinogen for available sites of metabolic activity,
effecting tumor growth or havinga chemotherapeutic effect. This
work a~iso demonstrated that the g.rowth rate of! subcutaneously
induced sarcomas wasinhibitedbythe injiectionof smoke condensate.
Bio-Research, also condu,cted research, on the inhibition,
of' tumors by injections of derivatives of benzo[irst]pentaphene
(iDibenzpyrene). The derivatives evaluated were the diacetate,
dibenzoate andl quinone. Lung~ tumors were developed in the mice by
injections with dibenzpyrene and then the derivativ.es of the
carcinogen, were injected into the~ mice. All three of the:
d,eriv~atives of DBP reduced! the carcinogenicity potency o~f DBP.
Additional workwas conductedi on transplanting subcutaneous tumors
induced in, mice to additional mice. The quinone d,erivative o~f ~BP
resulted in inhibitioln of growth of transplanted tumors while the
diacetate and benzoate: had no, significant effect. Bio-Research
did not fee~ that the quinone derivative o~f DBP would be: usefu~ as
an addiitive to cigarettes because of its low volatility. They
felt that mo~re volatile anti-tumorig!enic compounds should! be
investigated as! cigarette a,dditives. They a!iso, plo~nte~ ~,~ that
these additives may or may not have any re~ationshi~ to safety_to
~an..~he. reason b~ing that the researcher was focused on the
-- carclnogenlc: effect of smoke condensate~ to mouse skin not on the
carcinogenic effect on man [I010505008!7-0105,. Ex-lis!t].
Bio-Research conductedl research funded by CTR~ on the
anti-carcinogenic properties of natural terpenes.(citrus oils), d-
~im~nene and the oxidation products of' d-~imonene.. T.h~is: work
demonstrated that the ~njection of orange oils! and d,limonene
reduced! the growth rate oil inducedl subcutaneou~s tumors. Limonene
injections reducedthe number ofspontaneousand inducedi~ung tumors
in mice [i003113!23!~'3251,. not produced].
No formal report was found on the MSP work conducted! by
Bio-Research, for CTR, on/2~decline in tumorigenicity of smoke
colnd,en!sate. ~owever, in ~tter to Holtzman of PM, Homburger
Memorandum to Philip Morris
R~search Document Reviewers
January Ii, 1988
Page i0.
reported that he had determined that the tumoriq,eni, city of WSC ha~i
decllnedl du~i~g the past decad,e. His. r~sults co~firmed th~e:re~ul~ts
Drl Wynde~ [PMI~O!50,50,010-0i011, not produ,ced].
The results of work on a~ccelerated~ carcinogen testi~ng I/
was presented by H,omburge~r at the s~econd re~sea~rch co~nference on
tobacco and h, ea~th for AMA-ERF grantees (.1970). The objective for
the project was to shorten the time required for the d~tectio'n of
ca.rcin~ogenic activity. The data presentedl indicated that
transformed malignant cells, exist in carcinogen injection sites
four weeks after the injectioln~ of the carcfnogen. [:PMiOi0003689!9-
699.7,~ produced, taken,].
~mm\,mOOO~9\KRS\OLB
