EXHIBIT 10.8

        Cooperative Research and Development Agreement dated December 18, 1995,
        by and between the Registrant and the National Cancer Institute




                         PUBLIC HEALTH SERVICE
                                    
            COOPERATIVE  RESEARCH AND DEVELOPMENT AGREEMENT
                                   


This Cooperative Research and Development Agreement, hereinafter
referred to as the "CRADA," consists of this Cover Page, an attached
Agreement, and various Appendices referenced in the Agreement.  This
Cover Page serves to identify the Parties to this CRADA:


          (1)  the following Bureau(s), Institute(s), Center(s) or
Division(s) of the National Institutes of Health ("NIH"), the Food and
Drug Administration ("FDA"), and the Centers for Disease Control and
Prevention ("CDC"):

               The Laboratory of Tumor Cell Biology
               Division of Basic Science
               National Cancer Institute

hereinafter singly or collectively referred to as the Public Health
Service ("PHS"); and

          (2) Paracelsian, Inc. 
                                                                        
                    
which has offices at

               222 Languir Laboratories
               95 Brown Road
               Cornell Tecvhnology Park
               Ithaca, NY USA 14850
                                                                        
                                
 hereinafter referred to as the "Collaborator."






             COOPERATIVE  RESEARCH AND DEVELOPMENT AGREEMENT


Article 1.    Introduction

This Cooperative Research and Development Agreement (CRADA) between PHS
and the Collaborator will be effective when signed by all Parties.  The
research and development activities which will be undertaken by each of
the Parties in the course of this CRADA are detailed in the Research
Plan (RP) which is attached as Appendix A.  The funding and staffing
commitments of the Parties are set forth in Appendix B.  Any exceptions
or changes to the CRADA are set forth in Appendix C.

Article 2.    Definitions

As used in this CRADA, the following terms shall have the indicated
meanings:

2.1  "Affiliate" means any corporation or other business entity
     controlled by, controlling, or under common control with
     Collaborator.  For this purpose, "control" means direct or indirect
     beneficial ownership of at least fifty (50) percent of the voting
     stock or at least fifty (50) percent interest in the income of
     such corporation or other  business.

2.2  "Cooperative Research and Development Agreement" or "CRADA" means
     this Agreement, entered into by PHS pursuant to the Federal
     Technology Transfer Act of 1986, as amended, 15 U.S.C. 3710a et
     seq. and Executive Order 12591 of October 10, 1987.

2.3  "Government" means the Government of the United States as
     represented through the PHS agency that is a Party to this
     agreement.

2.4  "IP" means intellectual property.

2.5  "Invention" means any invention or discovery which is or may be
     patentable or otherwise protected under title 35, United States
     Code, or any novel variety or plant which is or may be protectable
     under the Plant Variety Protection Act (7 U.S.C. 2321 et seq.).

2.6  "Principal Investigator(s)" or "PIs"  means the persons designated
     respectively by the Parties to this CRADA who will be responsible
     for the scientific and technical conduct of the RP.

2.7  "Proprietary/Confidential Information" means confidential
     scientific, business, or financial information provided that such
     information does not include:

     2.7.1     information that is publicly known or available from
               other sources who are not under a confidentiality
               obligation to the source of the information;

     2.7.2     information which has been made available by its owners
               to others without a confidentiality obligation; 

     2.7.3     information which is already known by or available to
               the receiving Party without a confidentiality
               obligation; or

     2.7.4     information which relates to potential hazards or
               cautionary warnings associated with the production,
               handling or use of the subject matter of the Research
               Plan of this CRADA.

2.8  "Research Materials" means all tangible materials other than
     Subject Data first produced in the performance of this CRADA.

2.9  "Research Plan" or "RP" means the statement in Appendix A of the
     respective research and development commitments of the Parties to
     this CRADA.

2.10 "Subject Invention" means any Invention of the Parties, conceived
     or first actually reduced to practice in the performance of the
     Research Plan of this CRADA.  

2.11 "Subject Data" means all recorded information first produced in
     the performance of this CRADA by the Parties.

Article 3.    Cooperative Research

3.1  Principal Investigators.  PHS research work under this CRADA will
     be performed by the PHS laboratory identified in the RP, and the
     PHS Principal Investigator (PI) designated in the RP will be
     responsible for the scientific and technical conduct of this
     project on behalf of PHS.  Also designated in the RP is the
     Collaborator PI who will be responsible for the scientific and
     technical conduct of this project on behalf of the Collaborator.

3.2  Research Plan Change.  The RP may be modified by mutual written
     consent of the Principal Investigators.  Substantial changes in
     the scope of the RP will be treated as amendments under Article
     13.6.

Article 4.    Reports

4.1  Interim Reports.  The Parties shall exchange formal written
     interim progress reports on a schedule agreed to by the PIs, but
     at least within twelve (12) months after this CRADA becomes
     effective and at least within every twelve (12) months thereafter. 
     Such reports shall set forth the technical progress made,
     identifying such problems as may have been encountered and
     establishing goals and objectives requiring further effort, any
     modifications to the Research Plan pursuant to Article 3.2, and
     all CRADA-related patent applications filed.

4.2  Final Reports.  The Parties shall exchange final reports of their
     results within four (4) months after completing the projects
     described in the RP or after the expiration or termination of this
     CRADA.

Article 5.   Financial and Staffing Obligations

5.1  PHS and Collaborator Contributions.  The contributions of the
     Parties, including payment schedules, if applicable, are set forth
     in Appendix B.  PHS shall not be obligated to perform any of the
     research specified herein or to take any other action required by
     this CRADA if the funding is not provided as set forth in
     Appendix B.  PHS shall return excess funds to the Collaborator
     when it sends its final fiscal report pursuant to Article 5.2,
     except for staffing support pursuant to Article 10.3. 
     Collaborator acknowledges that the U.S. Government will have the
     authority to retain and expend any excess funds for up to one (1)
     year subsequent to the expiration or termination of the CRADA to
     cover any costs incurred during the term of the CRADA in
     undertaking the work set forth in the RP.  

5.2  Accounting Records.  PHS shall maintain separate and distinct
     current accounts, records, and other evidence supporting all its
     obligations under this CRADA, and shall provide the Collaborator a
     final fiscal report pursuant to Article 4.2.

5.3  Capital Equipment.  Equipment purchased by PHS with funds provided
     by the Collaborator shall be the property of PHS.  All capital
     equipment provided under this CRADA by one party for the use of
     another Party remains the property of the providing Party unless
     other disposition is mutually agreed upon by in writing by the
     Parties.  If title to this equipment remains with the providing
     Party, that Party is responsible for maintenance of the equipment
     and the costs of its transportation to and from the site where it
     will be used.

Article 6.  Intellectual Property Rights and Patent Applications

6.1  Reporting.  The Parties shall promptly report to each other in
     writing each Subject Invention resulting from the research
     conducted under this CRADA that is reported to them by their
     respective employees.  Each Party shall report all Subject
     Inventions to the other Party in sufficient detail to determine 
     inventorship.  Such reports shall be treated as
     Proprietary/Confidential Information in accordance with Article
     8.4.

6.2  Collaborator Employee Inventions.  If the Collaborator does not
     elect to retain its IP rights, the Collaborator shall offer to
     assign these IP rights to the Subject Invention to PHS pursuant to
     Article 6.5.  If PHS declines such assignment, the Collaborator
     may release its IP rights as it may determine.

6.3  PHS Employee Inventions.  PHS on behalf of the U.S. Government may
     elect to retain IP rights to each Subject Invention made solely by
     PHS employees.  If PHS does not elect to retain IP rights, PHS
     shall offer to assign these IP rights to such Subject Invention to
     the Collaborator pursuant to Article 6.5.  If the Collaborator
     declines such assignment, PHS may release IP rights in such
     Subject Invention to its employee inventors pursuant to Article
     6.6.

6.4  Joint Inventions.  Each Subject Invention made jointly by PHS and
     Collaborator employees shall be jointly owned by PHS and the
     Collaborator.  The Collaborator may elect to file the joint patent
     or other IP application(s) thereon and shall notify PHS promptly
     upon making this election.  If the Collaborator decides to file
     such applications, it shall do so in a timely manner and at its
     own expense.  If the Collaborator does not elect to file such
     application(s), PHS on behalf of the U.S. Government shall have
     the right to file the joint application(s) in a timely manner and
     at its own expense.  If either Party decides not to retain its IP
     rights to a jointly owned Subject Invention, it shall offer to
     assign such rights to the other Party pursuant to Article 6.5.  If
     the other Party declines such assignment, the offering Party may
     release its IP rights as provided in Articles 6.2, 6.3, and 6.6.

6.5  Filing of Patent Applications.  With respect to Subject Inventions
     made by the Collaborator as described in Article 6.2, or by PHS as
     described in Article 6.3, a Party exercising its right to elect to
     retain IP rights to a Subject Invention agrees to file patent or
     other IP applications in a timely manner and at its own expense
     and after consultation with the other Party.  The Party shall
     notify the other Party of its decision regarding filing in
     countries other than the United States in a timely manner.  The
     Party may elect not to file a patent or other IP application
     thereon in any particular country or countries provided it so
     advises the other Party ninety (90) days prior to the expiration
     of any applicable filing deadline, priority period or statutory
     bar date, and hereby agrees to assign its IP right, title and
     interest in such country or countries to the Subject Invention to
     the other Party and to cooperate in the preparation and filing of
     a patent or other IP applications.  In any countries in which
     title to patent or other IP rights is transferred to the
     Collaborator, the Collaborator agrees that PHS inventors will
     share in any royalty distribution that the Collaborator pays to
     its own inventors.

6.6  Release to Inventors.  In the event neither of the Parties to this
     CRADA elects to file a patent or other IP application on a Subject
     Invention, either or both (if a joint invention) may retain or
     release their IP rights in accordance with their respective
     policies and procedures.  However, the Government shall retain a
     nonexclusive, non-transferrable, irrevocable, royalty-free license
     to practice any such Subject Invention or have it practiced
     throughout the world.

6.7  Patent Expenses.  The expenses attendant to the filing of patent
     or other IP applications generally shall be paid by the Party
     filing such application.  If an exclusive license to any Subject
     Invention is granted to the Collaborator, the Collaborator shall
     be responsible for all past and future out-of-pocket expenses in
     connection with the preparation, filing,  prosecution and
     maintenance of any applications claiming such exclusively-licensed
     inventions and any patents or other IP grants that may issue on
     such applications.  The Collaborator may waive its exclusive
     license rights on any application, patent or other IP grant at any
     time, and incur no subsequent compensation obligation for that
     application, patent or IP grant.

6.8  Prosecution of Intellectual Property Applications.  Within one
     month of receipt or filing,  each Party shall provide the other
     Party with copies of the applications and all documents received
     from or filed with the relevant patent or other IP office in
     connection with the prosecution of such applications.  Each Party
     shall also provide the other Party with the power to inspect and
     make copies of all documents retained in the patent or other IP
     application files by the applicable patent or other IP office. 
     Where licensing is contemplated by Collaborator, the Parties agree
     to consult with each other with respect to the prosecution of
     applications for PHS Subject Inventions described in Article 6.3
     and joint Subject Inventions described in Article 6.4.  If the
     Collaborator elects to file and prosecute IP applications on joint
     Subject Inventions pursuant to Article 6.4,  PHS will be granted
     an associate power of attorney (or its equivalent) on such IP
     applications.

Article 7.    Licensing

7.1  Option for Commercialization License.  With respect to Government
     IP rights to any Subject Invention not made solely by the
     Collaborator's employees for which a patent or other IP
     application is filed, PHS hereby grants to the Collaborator an
     option to elect an exclusive or nonexclusive commercialization
     license, which is substantially in the form of the appropriate
     model PHS license agreement.  This option does not apply to
     Subject Inventions conceived prior to the effective date of this
     CRADA that are reduced to practice under this CRADA, if prior to
     that reduction to practice, PHS has filed a patent application on
     the invention and has licensed it or offered to license it to a
     third party.  The terms of the license will fairly reflect the
     nature of the invention, the relative contributions of the Parties
     to the invention and the CRADA, the risks incurred by the
     Collaborator and the costs of subsequent research and development
     needed to bring the invention to the marketplace.  The field of
     use of the license will be commensurate with the scope of the RP.  

7.2  Exercise of License Option.  The option of Article 7.1 must be
     exercised by written notice mailed within three (3) months after
     either (i) Collaborator receives written notice from PHS that the
     patent or other IP application has been filed; or (ii) the date
     Collaborator files such IP application; whichever comes first. 
     Exercise of this option by the Collaborator initiates a
     negotiation period that expires nine (9) months after the exercise
     of the option.  If the last proposal by the Collaborator has not
     been responded to in writing by PHS within this nine (9) month
     period, the negotiation period shall be extended to expire one (1)
     month after PHS so responds, during which month the Collaborator
     may accept in writing the final license proposal of PHS.  In the
     absence of such acceptance, PHS will be free to license such IP
     rights to others.  In the event that the Collaborator elects the
     option for an exclusive license, but no such license is executed
     during the negotiation period, PHS agrees not to make an offer for
     an exclusive license on more favorable terms to a third party for
     a period of six (6) months without first offering Collaborator
     those more favorable terms.

7.3  License for PHS Employee Inventions and Joint Inventions. 
     Pursuant to 15 U.S.C. 3710a(b)(1)(A), for inventions made by PHS
     employees or jointly with a Collaborator under this CRADA,
     pursuant to Articles 6.3 and 6.4, the Collaborator grants to PHS a
     nonexclusive, nontransferable, irrevocable, paid-up license to
     practice the invention or have the invention practiced throughout
     the world by or on behalf of the Government.  In the exercise of
     such license, the Government shall not publicly disclose trade
     secrets or commercial or financial information that is privileged
     or confidential within the meaning of 5 U.S.C. 552(b)(4) or which
     would be considered as such if it had been obtained from a non-Federal
     party.

7.4  License in Collaborator Inventions.  Pursuant to 15 U.S.C.
     3710a(b)(2), for inventions made solely by Collaborator employees
     under this CRADA, pursuant to Article 6.2, the Collaborator grants
     to PHS a nonexclusive, nontransferable, irrevocable, paid-up
     license to practice the invention or have the invention practiced
     throughout the world by or on behalf of the Government for
     research or other Government purposes.
7.5  Third Party License.  Pursuant to 15 U.S.C. 3710a(1)(B), if PHS
     grants an exclusive license to a Subject Invention made wholly by
     PHS employees or jointly with a Collaborator under this CRADA,
     pursuant to Articles 6.3 and 6.4, the Government shall retain the
     right to require the Collaborator to grant to a responsible
     applicant a nonexclusive, partially exclusive, or exclusive
     sublicense to use the invention in Collaborator's licensed field
     of use on terms that are reasonable under the circumstances; or if
     the Collaborator fails to grant such a license, to grant the
     license itself.  The exercise of such rights by the Government
     shall only be in exceptional circumstances and only if the
     Government determines (i) the action is necessary to meet health
     or safety needs that are not reasonably satisfied by Collaborator,
     (ii) the action is necessary to meet requirements for public use
     specified by Federal regulations, and such requirements are not
     reasonably satisfied by the Collaborator; or (iii) the
     Collaborator has failed to comply with an agreement containing
     provisions described in 15 U.S.C. 3710a(c)(4)(B).  The
     determination made by the Government under this Article is subject
     to administrative appeal and judicial review under 35 U.S.C.
     203(2).

7.6  Joint Inventions Not Exclusively Licensed.  In the event that the
     Collaborator does not acquire an exclusive commercialization
     license to IP rights in all fields in joint Subject Inventions
     described in Article 6.4, then each Party shall have the right to
     use the joint Subject Invention and to license its use to others
     in all fields not exclusively licensed to Collaborator.  The
     Parties may agree to a joint licensing approach for such IP
     rights.

Article 8.    Proprietary Rights and Publication

8.1  Right of Access.  PHS and the Collaborator agree to exchange all
     Subject Data produced in the course of research under this CRADA,
     whether developed solely by PHS or jointly with the Collaborator. 
     Research Materials will be shared equally by the Parties to the
     CRADA unless other disposition is agreed to by the Parties.  All
     Parties to this CRADA will be free to utilize Subject Data and
     Research Materials for their own purposes, consistent with their
     obligations under this CRADA.

8.2  Ownership of Subject Data and Research Materials.  Subject to the
     sharing requirements of Paragraph 8.1 and the regulatory filing
     requirements of Paragraph 8.3, the producing Party will retain
     ownership of and title to all Subject Inventions, all Subject Data
     and all Research Materials produced solely by their investigators. 
     Jointly developed Subject Inventions, Subject Data and Research
     Materials will be jointly owned.  

8.3  Dissemination of Subject Data and Research Materials.  To the
     extent allowed under law, the Collaborator and PHS agree to use
     reasonable efforts to keep Subject Data and Research Materials
     confidential until published or until corresponding patent
     applications are filed.  Any information that would identify human
     subjects of research or patients will always be maintained
     confidentially.    Collaborator shall have the exclusive right to
     use any and all CRADA Subject Data in and for any regulatory
     filing by or on behalf of Collaborator, except that PHS shall have
     the exclusive right to use Subject Data for that purpose, and
     authorize others to do so, if the CRADA is terminated or if
     Collaborator abandons its commercialization efforts.

8.4  Proprietary/Confidential Information.  Each Party agrees to limit
     its disclosure of Proprietary/Confidential Information to the
     amount necessary to carry out the Research Plan of this CRADA, and
     shall place a confidentiality notice on all such information. 
     Confidential oral communications shall be reduced to writing
     within 30 days by the disclosing Party.  Each Party receiving
     Proprietary/Confidential Information agrees that any information
     so designated shall be used by it only for the purposes described
     in the attached Research Plan.  Any Party may object to the
     designation of information as Proprietary/Confidential Information
     by another Party.  Subject Data and Research Materials developed
     solely by the Collaborator may be designated as
     Proprietary/Confidential Information when they are wholly
     separable from the Subject Data and Research Materials developed
     jointly with PHS investigators, and advance designation of such
     data and material categories is set forth in the RP.  The exchange
     of other confidential information, e.g.,  patient-identifying
     data, should be similarly limited and treated.  Jointly developed
     Subject Data and Research Material derived from the Research Plan
     may be disclosed by Collaborator to a third party under a
     confidentiality agreement for the purpose of possible sublicensing
     pursuant to the Licensing Agreement and subject to Article 8.7.

8.5  Protection of Proprietary/Confidential Information. 
     Proprietary/Confidential Information shall not be disclosed,
     copied, reproduced or otherwise made available to any other person
     or entity without the consent of the owning Party except as
     required under court order or the Freedom of Information Act (5
     U.S.C. Sect. 552).  Each Party agrees to use its best efforts to
     maintain the confidentiality of Proprietary/Confidential
     Information.  Each Party agrees that the other Party is not liable
     for the disclosure of Proprietary/Confidential Information which,
     after notice to and consultation with the concerned Party, the
     other Party in possession of the Proprietary/Confidential
     Information determines may not be lawfully withheld, provided the
     concerned Party has been given an opportunity to obtain a court
     order to enjoin disclosure.

8.6  Duration of Confidentiality Obligation.  The obligation to
     maintain the confidentiality of Proprietary/Confidential
     Information shall expire at the earlier of the date when the
     information is no longer Proprietary Information as defined in
     Article 2.5 or three (3) years after the expiration or termination
     date of this CRADA.  The Collaborator may request an extension to
     this term when necessary to protect Proprietary/Confidential
     Information relating to products not yet commercialized.

8.7  Publication.  The Parties are encouraged to make publicly
     available the results of their research.  Before either Party
     submits a paper or abstract for publication or otherwise intends
     to publicly disclose information about a Subject Invention,
     Subject Data or Research Materials, the other Party shall be
     provided thirty (30) days to review the proposed publication or
     disclosure to assure that Proprietary/Confidential Information is
     protected.  The publication or other disclosure shall be delayed
     for up to thirty (30) additional days upon written request by any
     Party as necessary to preserve U.S. or foreign patent or other IP
     rights.

Article 9.    Representations and Warranties

9.1  Representations and Warranties of PHS.  PHS hereby represents and
     warrants to the Collaborator that the official signing this CRADA
     has authority to do so.

9.2  Representations and Warranties of the Collaborator.  

     (a)  The Collaborator hereby represents and warrants to PHS that
     the Collaborator has the requisite power and authority to enter
     into this CRADA and to perform according to its terms, and that
     the Collaborator's official signing this CRADA has authority to do
     so.  The Collaborator further represents that it is financially
     able to satisfy any funding commitments made in Appendix B.

     (b)  The Collaborator certifies that the statements herein
     are true, complete, and accurate to the best of its
     knowledge.  The Collaborator is aware that any false,
     fictitious, or fraudulent statements or claims may subject it
     to criminal, civil, or administrative penalties.

Article 10.    Termination

10.1 Termination By Mutual Consent.  PHS and the Collaborator may
     terminate this CRADA, or portions thereof, at any time by mutual
     written consent.  In such event the Parties shall specify the
     disposition of all property, inventions, patent or other IP
     applications and other results of work accomplished or in
     progress, arising from or performed under this CRADA, all in
     accordance with the rights granted to the Parties under the terms
     of this Agreement.

10.2 Unilateral Termination.  Either PHS or the Collaborator may
     unilaterally terminate this entire CRADA at any time by giving
     written notice at least thirty (30) days prior to the desired
     termination date, and any rights accrued in property, patents or
     other IP rights shall be disposed of as provided in paragraph
     10.1.

10.3 Staffing.  If this CRADA is mutually or unilaterally terminated
     prior to its expiration, funds will nevertheless remain available
     to PHS for continuing any staffing commitment made by the
     Collaborator pursuant to Article 5.1 above and Appendix B, if
     applicable, for a period of six (6) months after such termination. 
     If there are insufficient funds to cover this expense, the
     Collaborator agrees to pay the difference.

10.4 New Commitments.  No Party shall make new commitments related to
     this CRADA after a mutual termination or notice of a unilateral
     termination and shall, to the extent feasible, cancel all
     outstanding commitments and contracts by the termination date. 

10.5 Termination Costs.  Concurrently with the exchange of final
     reports pursuant to Articles 4.2 and 5.2, PHS shall submit to the
     Collaborator for payment a statement of all costs incurred prior
     to the date of termination and for all reasonable termination
     costs including the cost of returning Collaborator property or
     removal of abandoned property, for which Collaborator shall be
     responsible.

Article 11.    Disputes

11.1 Settlement.  Any dispute arising under this CRADA which is not
     disposed of by agreement of the Principal Investigators shall be
     submitted jointly to the signatories of this CRADA.  If the
     signatories are unable to jointly resolve the dispute within
     thirty (30) days after notification thereof, the Assistant
     Secretary for Health (or his/her designee or successor) shall
     propose a resolution.  Nothing in this Article shall prevent any
     Party from pursuing any additional administrative remedies that
     may be available and, after exhaustion of such administrative
     remedies, pursuing all available judicial remedies.
 
11.2 Continuation of Work.  Pending the resolution of any dispute or
     claim pursuant to this Article, the Parties agree that performance
     of all obligations shall be pursued diligently in accordance with
     the direction of the PHS signatory. 

Article 12.    Liability

12.1 Property.  The U.S. Government shall not be responsible for
     damages to any Collaborator property  provided to PHS, where
     Collaborator retains title to the property, or any property
     acquired by Collaborator for its own use pursuant to this CRADA. 

12.2 NO WARRANTIES.  EXCEPT AS SPECIFICALLY STATED IN ARTICLE 9, THE
     PARTIES MAKE NO EXPRESS OR IMPLIED WARRANTY AS TO ANY MATTER
     WHATSOEVER, INCLUDING THE CONDITIONS OF THE RESEARCH OR ANY
     INVENTION OR PRODUCT, WHETHER TANGIBLE OR INTANGIBLE, MADE, OR
     DEVELOPED UNDER THIS CRADA, OR THE OWNERSHIP, MERCHANTABILITY, OR
     FITNESS FOR A PARTICULAR PURPOSE OF THE RESEARCH OR ANY INVENTION
     OR PRODUCT.

12.3 Indemnification.  The Collaborator agrees to hold the U.S.
     Government harmless and to indemnify the Government for all
     liabilities, demands, damages, expenses and losses arising out of
     the use by the Collaborator for any purpose of the Subject Data,
     Research Materials and/or Subject Inventions produced in whole or
     part by PHS employees under this CRADA, unless due to the
     negligence or willful misconduct of PHS, its employees, or agents. 
     The Collaborator shall be liable for any claims or damages it
     incurs in connection with this CRADA.  PHS has no authority to
     indemnify the Collaborator. 

12.4 Force Majeure.  Neither Party shall be liable for any
     unforeseeable event beyond its reasonable control not caused by
     the fault or negligence of such Party, which causes such Party to
     be unable to perform its obligations under this CRADA, and which
     it has been unable to overcome by the exercise of due diligence. 
     In the event of the occurrence of such a force majeure event, the
     Party unable to perform shall promptly notify the other Party.  It
     shall further use its best efforts to resume performance as
     quickly as possible and shall suspend performance only for such
     period of time as is necessary as a result of the force majeure
     event.

Article 13.    Miscellaneous

13.1 Governing Law.  The construction, validity,  performance and
     effect of this CRADA shall be governed by Federal law, as applied
     by the Federal Courts in the District of Columbia.  Federal law
     and regulations will preempt any conflicting or inconsistent
     provisions in this CRADA.

13.2 Entire Agreement.  This CRADA constitutes the entire agreement
     between the Parties concerning the subject matter of this CRADA
     and supersedes any prior understanding or written or oral
     agreement. 

13.3 Headings.  Titles and headings of the articles and subarticles of
     this CRADA are for convenient reference only, do not form a part
     of this CRADA, and shall in no way affect its interpretation. 

13.4 Waivers.  None of the provisions of this CRADA shall be considered
     waived by any Party unless such waiver is given in writing to the
     other Party.  The failure of a Party to insist upon strict
     performance of any of the terms and conditions hereof, or failure
     or delay to exercise any rights provided herein or by law, shall
     not be deemed a waiver of any rights of any Party.

13.5 Severability.  The illegality or invalidity of any provisions of
     this CRADA shall not impair, affect, or invalidate the other
     provisions of this CRADA.

13.6 Amendments.  If either Party desires a modification to this CRADA,
     the Parties shall, upon reasonable notice of the proposed
     modification or extension by the Party desiring the change, confer
     in good faith to determine the desirability of such modification
     or extension.  Such modification shall not be effective until a
     written amendment is signed by the signatories to this CRADA or by
     their representatives duly authorized to execute such amendment. 

13.7 Assignment.  Neither this CRADA nor any rights or obligations of
     any Party hereunder shall be assigned or otherwise transferred by
     either Party without the prior written consent of the other Party.

13.8 Notices.  All notices pertaining to or required by this CRADA
     shall be in writing and shall be signed by an authorized
     representative and shall be delivered by hand or sent by certified
     mail, return receipt requested, with postage prepaid, to the
     addresses indicated on the signature page for each Party.  Notices
     regarding the exercise of license options shall be made pursuant
     to Article 7.2.  Any Party may change such address by notice given
     to the other Party in the manner set forth above.

13.9 Independent Contractors.  The relationship of the Parties to this
     CRADA is that of independent contractors and not agents of each
     other or joint venturers or partners.  Each Party shall maintain
     sole and exclusive control over its personnel and operations. 
     Collaborator employees who will be working at PHS facilities may
     be asked to sign a Guest Researcher or Special Volunteer Agreement
     appropriately modified in view of the terms of this CRADA.
 
13.10     Use of Name or Endorsements.  By entering into this CRADA,
          PHS does not directly or indirectly endorse any product or
          service provided, or to be provided, whether directly or
          indirectly related to either this CRADA or to any patent or
          other IP license or agreement which implements this CRADA by
          its successors, assignees, or licensees.  The Collaborator
          shall not in any way state or imply that this CRADA is an
          endorsement of any such product or service by the U.S.
          Government or any of its organizational units or employees. 
          Collaborator issued press releases that reference or rely
          upon the work of PHS under this CRADA shall be made available
          to PHS at least 7 days prior to publication for review and
          comment.

13.11     Exceptions to this CRADA.  Any exceptions or modifications to
          this CRADA that are agreed to by the Parties prior to their
          execution of this CRADA are set forth in Appendix C.

13.12     Reasonable Consent.  Whenever a Party's consent or permission
          is required under this CRADA, such consent or permission
          shall not be unreasonably withheld.

Article 14.    Duration of Agreement

14.1 Duration.  It is mutually recognized that the duration of this
     project cannot be rigidly defined in advance, and that the
     contemplated time periods for various phases of the RP are only
     good faith guidelines subject to adjustment by mutual agreement to
     fit circumstances as the RP proceeds.  In no case will the term of
     this CRADA extend beyond the term indicated in the RP unless it is
     revised in accordance with Article 13.6.

14.2 Survivability.  The provisions of Articles 4.2,  5-8, 10.3-10.5, 
     11.1,  12.2-12.4,  13.1,  13.10  and 14.2 shall survive the
     termination of this CRADA.
                                   
<PAGE>                                   
                                   
                                   
                         APPENDIX A: RESEARCH PLAN
                             Title of CRADA

 Role of certain signal transduction pathways in malignant cell growth
                          and in cell death 
                                   
                      NCI  PRINCIPAL INVESTIGATOR
                        Dr. Genoveffa Franchini
      Laboratory of Tumor Cell Biology/Division of Basic Sciences
                                   
                          NCI CO-INVESTIGATOR
                          Dr. David I. Cohen
      Laboratory of Tumor Cell Biology/Division of Basic Sciences
                                   
                  COLLABORATOR PRINCIPAL INVESTIGATOR
                            Dr. John Babish
                            Paracelsian, Inc.
                                   
                             Term of CRADA
        Two (2) years from the date of execution of the CRADA.
                                   
    Work on this project has commenced pursuant to letter of intent
executed between Paracelsian, Inc. and NCI on December 20, 1995

Conflict of Interest Information
See attached Conflict of Interest and Fair Access Survey form.


GOALS OF THIS CRADA

The principal goals of this CRADA are:

1. To screen for unique pharmacological agents from a library of
traditional Chinese medicines (TCMs) for their capability of modulating
a cell signaling pathway induced by the cell lines HIVenv(2-2) and
HIVenv(2-8) expressing HIV-1 envelope proteins gp160, gp120 and/or
gp41. This pathway is triggered coincident with a GP120/41-dependent
cell interaction with CD4+ T lymphocytes ("fusion"), eventually leading
to depletion of the CD4+ T cells.

2. To screen for unique pharmacological agents from a library of
traditional Chinese medicines (TCMs) for their capability of modulating
a cell signaling pathway within various cancer cell lines to promote
cell death during the course of tumorigenesis.  This signaling pathway
will have components which are in common with the pathway discussed in
#1 and limited to the following cell lines: human pancreatic tumor cell
lines ASPC-1, PANC1-60, and M776T; human Kaposi's sarcoma cell line
KSY-1 and related cells; human breast cancer cell lines HTB 20, HTB 22,
HTB 121, HTB 122, and HTB 126.

3. To develop an understanding of the molecular interactions of the
various screen-positive TCMs with the cell signaling pathways in the
cell.  A detailed knowledge of these interactions will be useful for
potential future molecular modeling and design of improved
therapeutics.

Scientific Background

Dramatic changes in cellular growth and viability are controlled by
protein phosphorylation/dephosphorylation, and protein kinases have
frequently been transduced as oncogenes into the genome of acutely
transforming retroviruses.   Protein phosphorylation physiologically
occurs in response to specific extracellular, and intracellular,
stimuli, but viral infections can also aberrantly trigger protein
phosphorylation.  In both cases, these phosphorylation events are
mediated by cellular protein kinases.  Several protein kinases have
been shown to interact like links in a chain to pass signals from one
compartment of the cell to another.  Upsetting these normal signaling
pathways within a cell, such as occurs during tumorigenesis or viral
infection, can lead to dramatic effects on cell growth and on cell
viability.

CD4+ T cell death associated with HIV-1 infections has been mapped to
the envelope glycoprotein, gp120/41 of the virus.  HIV-1 isolates
infect cells by a process of membrane fusion through the utilization of
specific cellular receptors.  In the case of HIV-1, the primary
receptor is CD4, while the main co-receptors involved in membrane
fusion are the chemokine receptors CC-CKR5, for macrophage infection,
and CXC-4 (LESTR, FUSIN), for T cell infection.  Co-receptor
utilization is also a property of the HIV envelope glycoproteins. 
During HIV-1 infection, CD4+ T cells are rapidly lost .  This
depletion of CD4+ T cells is the major contributing factor that
cripples the immune system and leads to the eventual death of AIDS
patients.

A helper T-cell line, stably expressing the HIV-1 envelope surface
glycoproteins gp160, gp120, and gp41 (HIVenv), tat and rev proteins,
but not surface CD4, has been established [(HIVenv(2-8)]  as a model
for the HIV cell death process.  Studies with either HIV-1 infected
peripheral blood mononuclear cells (PBMCs), or with HIVenv(2-8),  show
that the HIVenv glycoproteins are expressed on the surface of the cell
after infection with HIV-1.  HIVenv then interacts with a CD4 molecule
and chemokine co-receptor(s) on the surface of another CD4+ T cell to
induce membrane fusion and cell death.  During this process, protein
kinases are activated, and inhibition of kinase triggering strongly
reduces cell death.    Some of the protein kinases identified within
this pathway are c-mos , and the p34cdc2/cyclin B complex .  It is
hoped that further delineation of the kinases and the overall
mechanisms involved in this pathway will help in explaining how
depletion of CD4+ T cells occurs.   Using this HIV-1/T-cell model
system, pharmaceuticals can be identified which modulate this cellular
kinase death pathway, possibly leading to improved therapeutics for
AIDS. 

The cell signaling pathway, inducing cell death in HIV infected cells,
shares in common kinases known to aberrantly trigger cell growth during
tumorigenesis (oncogenes).  As examples, Fyn and Lck are two protein
tyrosine kinases (PTKs) activated during HIV-cell death, that are also
oncogenes.  Therefore, the HIVenv model system can lead to better
understanding of the different outcomes (cell death versus unregulated
cell division) that can follow activation of the same kinase(s).  This
knowledge may be used to tip the balance of a kinase pathway in favor
of the desired outcome, such as cell death in the case of cancer. 
Using the model system, pharmaceuticals may be identified which enhance
or accelerate HIV-induced cell death, which might be predicted to
induce cell death in the context of unregulated proliferation
(malignancy).  Alternatively, synthetic modifications to cell death
inhibitory compounds might produce the opposite outcome, and trigger
cell death.

Androvir (andrographolide)(PN355) is a proprietary compound of 
Paracelsian, Inc.  Paracelsian has purified Androvir from a panel of
traditional Chinese medicines (TCMs), and has demonstrated that it
inhibits several kinases, including the c-src PTK and the mitotic
cyclin-dependent kinase, cdc2.  Androvir is also proposed to inhibit in
vitro HIV-1 replication.   Androvir is a compound with unique cell
cycle effects, in so far as it first reduces the percentage of cells in
S phase at lowest doses (<1 mg/ml), arrests cells in G1 phase at
somewhat higher doses (1-5 mg/ml), and at the highest doses begins to
trigger cell death and apoptosis.  No other compound with a similar
effect has been described.  The mode of action of Androvir in cell
cycle, and its specific target of activity, are at this time unknown
and are one of the goals of this CRADA.

In short term trials of one to three months conducted by Paracelsian,
Inc., under compassionate-use protocols, humans with endstage cancer
have been administered oral doses of Androvir corresponding to a peak
serum concentration of 10-:g/ml, without serious side effect.  These
studies were performed in Aberdeen, TX, between January and March,
1996.  Rats administered similar doses for 60 days become infertile,
but suffered no other deleterious effects, suggesting that a part of
the meiotic cell cycle is most sensitive to andrographolide.


                          Introduction
                                
Dr. Genoveffa Franchini and Dr. David Cohen, who will undertake this
project collaboratively within the NCI, have extensive experience in
the areas of gene expression systems and protein interactions designed
to mimic given aspects of HIV-1 and HTLV-1 infection in cell culture,
  the development of recombinant vectors, the identification,
characterization and cloning of HIV-1 genes, the design of assays to
measure kinase levels and their activation state within cells, and
testing these observations in animal models. In addition, NCI has
designed and synthesized bacterial expression vectors to produce large
quantities of the human kinase c-mos. The NCI collaborators have worked
extensively on the characterization of other serine-threonine kinases,
including the cyclin-dependent kinases and the MAP kinases, and PTKs,
including Fyn and Lck kinases, which are candidate targets of action
                         for Androvir.
                                
Paracelsian, Inc. has extensive experience in the design, development,
and marketing of products that detect cancerous tissues and identify
toxic chemicals. The company has developed kits based on the ELISA
system as well as diagnostics for the detection of cancer in animals. 
These products rely heavily on their knowledge and experience in the
field of intracellular signaling processes.  A recent merger between
Paracelsian and Pacific Liaisons has afforded the company access to a
collection of over 2,000 traditional Chinese medicines (TCMs) and the
ability to collect an additional 5,000 to 10,000 extracts.  This places
Paracelsian in a position of holding the world's largest databases of
TCM.  Paracelsian has the capabilities of producing recombinant protein
     in large quantities for future crystallographic work.
                                
The subject of this CRADA, including any in vitro and in vivo testing
conducted by Drs. David Cohen and Genoveffa Franchini in conjunction
with this CRADA Research Plan, is strictly limited to investigation of
  the mechanism(s), definition of novel compounds derived from
Paracelsian's library of TCMs, and development and use of assays
related to components of the cell signaling pathways involved in
 HIVenv-dependent cytotoxicity or increased cell growth during
tumorigenesis.  The pathways are defined in terms of all of their
components, that may be modulated from the cell surface through the
nucleus.  Additionally, these studies may involve other TCMs that may
be collected by the company.  The addition of vectors, genes, cell
types, antigens, cytokines or other medicinal compounds to this
Research Plan shall be added by amendment in accordance with paragraph
                      13.6 of the CRADA. 
                                
Although HIV-associated Kaposi's sarcoma and pancreatic malignancy are
viewed as possible future targets of this research, no clinical trials
will be conducted under this Research Plan.  Any future clinical
studies will be added either by amendment in accordance with paragraph
    13.6 of this CRADA or under a new CRADA as appropriate.
                                
To date experimental protocols have been performed under the Letter of
Intent between the National Cancer Institute and Paracelsian, Inc.
signed on 12/20/95.  However, the original collaborative research
effort dates to a meeting between Drs. David Cohen and Genoveffa
Franchini (representing the NCI) and Keith Rhodes, President and CEO of
 Paracelsian, and Dr. John Babish (Vice President of Science of
Paracelsian) on September 7, 1995 conducted in Bldg. 37, National
Cancer Institute, National Institutes of Health, Bethesda, MD.  A
confidentiality agreement was signed and exchanged between the Parties
on August 25, 1995, in preparation for this meeting.  Thus far, these
studies have involved the use of Androvir with cell lines HIVenv(2-8),
SupT1, PANC1-60, M776T, and ASPC-1; and kinases c-src, cdc2, cdk2, and
                             c-mos.
                                
                                
             WORK SCOPE OF PROPOSED CRADA BETWEEN 
                   NCI AND PARACELSIAN, INC.
                                

It is proposed that the objectives of this CRADA will be divided into
five parts:

Part I:        
NIH will supply Paracelsian, Inc. with stabile transfected Jurkat T
cell lines expressing the HIVenv protein combinations of  gp160 or
gp160, gp120, and gp41 having been assigned the names HIVenv(2-2) and
HIVenv(2-8) respectively.  (See summary of Material Transfer Agreement
and Biological Materials License under "Description of Other Agreements"
below.) These cell lines will be used to test compounds that have an
inhibitory role in the HIV-1env induced cytotoxicity.  Compounds to be
tested shall be limited to those found in the TCM database supplied by
Paracelsian, Inc.  The compounds for future work will be limited to
those having an effect on the HIVenv-dependent cytotoxicity.  NCI may
also supply other selected cell lines as agreed upon in writing by both
Parties.  It is anticipated that the assay for novel compounds will
continue throughout the two years of this agreement, and the completion
of these studies is not dependent upon other aspects of this research
plan.  Inhibitory compounds will be tested at NCI for the ability to
limit HIV-1 and SIV infection of PBMCs in vitro.  Compounds
demonstrating anti-SIV activity in vitro will be tested in monkeys
infected with SIVmac251 or with SIVpbj simian immunodeficiency viruses.
 
Part II:  
NCI will develop vectors for the production of bacterially expressed
c-mos protein and any mutants of c-mos as agreed upon by both Parties. 
Paracelsian will use these vectors to express and purify mg quantities
of the c-mos protein for use in  x-ray crystallography to determine the
three dimensional structure of the protein.  In addition, the purified
enzyme will be used to examine the potential molecular interactions of
said enzyme with compounds identified in Part I.  These studies may
assist in the rational design of future drugs with activity in the
signaling pathway, which will be performed at Paracelsian.  Additional
protein expression vectors and scale-up production thereof may be
needed to investigate other kinases identified within the signaling
pathway .  The c-mos expression vectors, and 1 ml of affinity-purified
rabbit anti-human c-mos antibody, will be provided by NCI to
Paracelsian immediately upon the execution of this agreement.  The
antibody will be employed in Part V of these objectives.  It is
anticipated that these studies will be ongoing throughout the two years
of the initial agreement, and may aide, but are not required for the
completion of Part V of these objectives.  

Part III:

NCI and Paracelsian, Inc. will carry out experiments to test compounds
for their affect on the uncontrolled cell growth of several tumor cell
lines.  Paracelsian will select for anti-signaling compounds according
to their cdc2 inhibition assay or according to the joint HIVenv
cytotoxicity assay.  These selected compounds will be further tested on
the human pancreatic tumor cell lines ASPC-1, PANC1-60, and M776T;
human Kaposi's sarcoma cell line KSY-1 and related cells; human breast
cancer cell lines HTB 20, HTB 22, HTB 121, HTB 122, and HTB 126; human
infected HTLV-1 cell lines, CR45-8166, C91-PL, ESS, 1186, and I-94. 
The cell lines will be used to test compounds that have an inhibitory
role in the uncontrolled growth of said cell lines.  Compounds to be
tested shall be limited to those found in the TCM database supplied by
Paracelsian, Inc.  The compounds for future work will be limited to
those having an effect on reducing or inhibiting cell growth from the
above tests.  NCI may also supply other selected cell lines as agreed
upon in writing by both Parties.  NCI anticipates testing compounds
displaying anti-tumor activity in small animal models relevant to the
tumor under study, by amendment to the research plan in accordance with
paragraph 13.6 of the CRADA. These tests will depend upon the rate of
discovery of novel compounds at Paracelsian.  Several such novel
compounds will be identified by Paracelsian and provided to NIH at the
time of execution of this CRADA.  This part of the work will extend
throughout the two years of this agreement. 


 Part IV. 

Those compounds showing a reduction in cell growth from Part III will
be examined for their ability to interact with given kinases.  The
study shall be limited to kinases which have been previously identified
to be altered in some manner as a result of their particular types of
cancer, and/or are kinases that are part of the signal pathway altered
during HIVenv-dependent cytotoxicity.   Kinases involved may be
commercially available or obtained through a<PAGE>
 collaboration between NCI and
Paracelsian as outlined in Part II above.  Studies to determine the rational
design of future drugs based on this information will be conducted at
Paracelsian in accordance with Part II, and will be ongoing throughout this
CRADA.   Kinase studies employing defined compounds should be completed within
the first year of this CRADA.

Part V:   

The activities and mechanisms of action of Androvir in terms of
inhibition of and/or activation of protein kinases that function in
cell cycle regulation, or that function by directly triggering
programmed cell death in sensitive cells will be jointly investigated. 
To do this, the activity and phosphorylation state of the cyclin-dependent
kinases cdk1, cdk2, and cdk4 will be examined.  Additionally,
c-mos, MAPK, JNK, and p38 kinases, recently implicated in multiple
forms of programmed cell death, will be assessed.  These studies will
employ several types of human cell lines such as: pancreatic, breast,
HTLV-1 transformed, Kaposi's sarcoma,  and HIVenv(2-1) and HIVenv(2-8). 
A therapeutic window in which cancer cells lines may be killed more
readily by Androvir than normal cells will be determined.  These
studies can be completed within the first year of this CRADA, and are
not linked to other studies.  




DESCRIPTION OF CONTRIBUTIONS AND RESPONSIBILITIES OF THE PARTIES 


             Laboratory of Tumor Cell Biology, NCI

-    Provide cell lines HIVenv(2-2) and HIVenv(2-8) and protocols for
cell lysis of CD4+  lymphocytes.  (See summary of Material Transfer
                    Agreement and Biological Materials License under
                    "Description of Other Agreements" below.)

-    Test Androvir and other kinase inhibitory compounds identified by
     Paracelsian for the ability to inhibit SIV-1 infection in vitro. 
     Test compounds with clearly defined in vitro activity (greater than
     one logarithmic reduction of viral growth in the absence of
     significant cellular toxicity), for therapeutic benefit in SIV-1
     infected monkeys.

-    Obtain and/or clone genes encoding specific kinases involved in the
     cell signaling pathway leading to HIVenv-dependent cell death, and
     modify genes as necessary for expression in DNA plasmid constructs.

-    Collaborate in the analysis and design of protein expression from
     vectors containing these genes for their use in X-ray
     crystallography, molecular interactions with TCMs.

-    Provide plasmids to be used for subsequent scale-up into research
     grade reagents.

-    Provide polyclonal antibodies with specificity and affinity to
     proteins used as    immunogen.  Produce rabbit polyclonal antibodies
     to human c-mos kinase.

-    Design and synthesize DNA vectors producing c-mos peptides and
recombinant    protein substrates.

-    Test anti-signaling compounds identified by Paracelsian according to
     their cdc2 inhibition assay, or according to the joint HIVenv
     cytotoxicity assay, for activity against  human pancreatic tumor cell
     lines ASPC-1, PANC1-60, and M776T; human Kaposi's sarcoma cell line
     KSY-1 and related cells; human breast cancer cell lines; HTB 20, HTB
     22, HTB 121, HTB 122, and HTB 126; human infected HTLV-1 cell lines,
     CR45-8166, C91-PL, ESS, 1186, and I-94.


                       Paracelsian, Inc.


-    Paracelsian will test Androvir and the remaining TCMs for their
     effects on cdc2 inhibition or on the HIVenv-dependent
     cytotoxicity of CD4+ T cells.

-    Using expression vectors designed in LTCB, Paracelsian will express
and purify c-mos    protein in sufficient quantities for X-ray
crystallography (mg quantities) from bacteria.

-    Test Androvir and the remaining TCMs for their affects on
reducing or inhibiting cell   growth of selected tumor cell lines.

-    Paracelsian will provide input as to the design of future expression
     vectors.

-    Purify c-mos protein and peptide substrates produced from DNA vectors
synthesized    by  LTCB.

-    Paracelsian will perform X-ray crystallographic studies to determine
the three dimensional structure of human c-mos, and other
compounds discovered in the course of these studies.  These
investigations will form the basis for rational drug design performed
at Paracelsian. 


Paracelsian, Inc. and Laboratory of Tumor Cell Biology, NCI


-    Design of in vitro assays to assess the molecular interactions taking
place between  Androvir and other screen-positive TCMs with cell
cycle regulators and kinases  found to play a role in either HIVenv-dependent
cell death or tumorigenesis.

-    Test antibodies to kinases, such as c-mos, for ability to prevent
interaction of the  kinases with screen positive TCMs in the above
mentioned in vitro assays.

-    Develop other reagents necessary to determine the molecular
interaction of additional     TCMs, favorably screened by Paracelsian,
Inc,. for activity on the cell signaling     pathway.

     DESCRIPTION OF OTHER AGREEMENTS AND INTELLECTUAL PROPERTY OF THE
                            PARTIES


OTHER CRADAs BETWEEN PARACELSIAN AND NIH:    none

RELATED PATENTS/PATENT APPLICATIONS of PARACELSIAN: 

     "Use of Androgapholide Compounds to Treat or Prevent Pathogenicity of
      Diseases" 
     Inventor: John G. Babish
     US applications: 08/349,989 filed December 6, 1994 08/551,418 filed
     Nov 1, 1995
     WO 96/17605 published June 13, 1996 and filed December 6, 1995.
     
     "Products for Measuring Cell Growth and Propensity and Methods for
     Their Use"
     Inventors: John G. Babish, Xinfang Ma, Joseph A. Rininger and Brian
     E. Johnson
     US applications 08/007,636 filed January 21, 1993; 08/075,744 filed
     June 11, 1993
     WO 9417413 (published August 4, 1994; filed January 21, 1994

RELATED PATENTS/PATENT APPLICATIONS OF NIH

     None identified

MATERIAL TRANSFER AGREEMENT:

     1-06222-96
     Provider: NCI; Recipient: Paracelsian
     Material:  Transfected Human T cell lines stably expressing the HIV-1
     envelope, tat, and rev proteins."
     Project: Pharmacologic methods, including agents derived from
     Traditional Chinese Medicines for reducing HIV-1 cytopathicity as
     specified in CRADA LOI # 344
     MTA Executed: April 10, 1996

CONFIDENTIAL DISCLOSURE AGREEMENTS:
     
     Subject: Andrographolide and a proprietary screening technology
     Effective Date: August 25, 1995

     Subject: Kinases and therapeutic inhibitors of cellular kinases
     involved in Human Immunodeficiency Virus growth.
     Effective Date: September 4, 1995

     Subject: Role of certain signal transduction pathways in malignant
     cell growth and in cell death"
     Effective Date:  July 2, 1996

LICENSES:

     Paracelsian is currently negotiating the terms of a Biological
     Material License with the Office of Technology Transfer, NIH, for the
     use of cell lines HIVenv(2-8) and (2-2) developed by Dr. Cohen while
     working for NIAID.  These cell lines were created prior to the
     effective date of the CRADA, and as such are not a Subject Invention
     under the CRADA.
                                

 Abstract FOR PUBLIC RELEASE of the Research Plan of the CRADA

The principal goals of this proposed CRADA involve the screening of a
library of traditional Chinese medicines (TCMs) for their affects on
reducing  HIV induced cytotoxicity and /or their ability to inhibit
cell growth in various tumor cell lines.  It is hoped that this CRADA
will lead to new drug designs for future anti-HIV and anti-cancer
therapy.

Thus, the specific objectives of this CRADA will be:

1. To screen for unique pharmacological agents from a library of TCMs
for their capability of modulating a cell signaling pathway induced in
the cell lines HIVenv(2-2) and HIVenv(2-8) expressing HIV-1 envelope
proteins gp160, gp120 and/or gp41. This pathway is triggered coincident
with a GP120/41-dependent cell interaction with CD4+ T lymphocytes,
leading to depletion of the CD4+ T cells.

2. To screen for unique pharmacological agents from a library of TCMs
for their ability to modulate a cell signaling pathway within various
cancer cell lines, to promote cell death of the tumors.  This signaling
pathway will have components which are in common with the pathway
discussed in #1 and limited to the following cell lines:  human
pancreatic tumor cell lines ASPC-1, PANC1-60, and M776T; human Kaposi's
sarcoma cell line KSY-1 and related cells; human breast cancer cell
lines HTB 20, HTB 22, HTB 121, HTB 122, and HTB 126.  

3. To develop an understanding of the molecular interactions of the
various screen-positive TCMs with the cell signaling pathways in the
cell.  A detailed knowledge of these interactions will be useful for
potential future molecular modeling and design of improved
therapeutics.

References

1.  Mordret, G. Biol. Cell (1993) 79, 193-207.

2.  Gougeon, M-L and Montagnier, L. Science (1993) 260, 1269-1270.

3.  Tani, Y., Tian, H., Lane, H. C. and Cohen, D.I., J. of Immunol. (1993)
    151, 7337-7348.

4.  Cohen, D.I., Wahl, L., Sharpe, S and Blatner, G. XI International
    Conference on AIDS, Vancouver Cananda, July 7-11, 1996.

5.  Kolesnitchenko, V. Wahl, L. M., Tian, H., et al., Proc.Natl Acad. Sci.
    (USA), (1995) 92, 11889-11893.





                               APPENDIX B:  CACR-0344

               FINANCIAL AND STAFFING CONTRIBUTIONS OF THE PARTIES

 The Laboratory of Tumor Cell Biology (LTCB),NCI

 The LTCB will provide scientific staff and other support as necessary to
 conduct the research outlined in Appendix A, Research Plan.  Present
 estimates are that Dr. Franchini will devote approximately 10% of her time,
 and Dr. Cohen approximately 10% of his time.

 Paracelsian, Inc.

 Paracelsian will provide scientific staff and other support as necessary
 to its research responsibilities outlined in Appendix A, Research Plan.
 Present estimates are that Dr. Babish will devote approximately 10% of
 his time.  Other scientific and technical staff will contribute the balance
 of the approximately two Paracelsian person years to be committed to this
 CRADA research.

 In addition, Paracelsian will provide financial support for personnel,
 reagents and supplies, animal studies, equipment and travel to be
 deposited to an NCI CAN account established for the administration of
 this CRADA.  No full-time tenured NCI employees will be supported under
 this CRADA by Paracelsian.

 A check in the amount of $73,400 will be provided to NCI by Paracelsian
 upon execution of the CRADA.  Three additional payments of $50,000 will
 be made quarterly during the first year.  A payment of $100,000 is due
 on the one year anniversary of the execution of the CRADA, with three
 additional payments of $50,000 made quarterly, during the second year.
 (Total funds for Year 1 are $223,400; and for Year 2 are $250,000.)

 Following the execution of the Letter of Intent, Paracelsian has been
 paying the salaries of staff working at the Laboratory of Tumor Cell
 Biology under Special Volunteer Agreements.  It is the intention of LTCB,NCI
 to assume responsibility for the salaries of these staff upon execution of
 the CRADA using funds provided to the CRADA CAN.  Should it be mutually
 agreed that Paracelsian continue to fund these positions beyond December 1,
 1996, the above payment schedule will be adjusted by amendment in accordance
 with Paragraph 13.6 of the CRADA to offset these salary payments.  The total
 financial support provided by Paracelsian in funds provided to NCI as set
 forth above, and for funds paid to staff working at LTCB,NCI shall not
 exceed $500,000.

 <PAGE>


                               APPENDIX C

                EXCEPTIONS OR MODIFICATIONS TO THIS CRADA
 


          There are no exceptions or modifications to this CRADA.              
<PAGE>