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                                                                   EXHIBIT 10.49
                             DIRECTORSHIP AGREEMENT


        THIS DIRECTORSHIP AGREEMENT ("Agreement") is entered into as of December
15th, 1996 (the "Effective Date"), by and between Dieter Hoehn ("Director") and
IRORI, a California Corporation ("IRORI")

        Director and IRORI agree as follows:

        1. Description of Services. IRORI hereby retains Director and Director
        hereby agrees to serve as a member of IRORI's Board of Directors and to
        perform the advisory services and other duties associated with such a
        position.

        2. Compensation.

                A. Director's Fee. IRORI shall pay Director one thousand five
                hundred dollars ($1500.00) per each full business day that
                Director performs his duties as a director, payable within
                thirty (30) days. IRORI shall calculate in good faith the number
                of days worked by Director.

                B. Option Grant. IRORI shall issue to Director a non-statutory
                stock option to purchase ten thousand (10,000) shares of Common
                Stock pursuant to its 1995 Stock Option/Stock Issuance Plan upon
                the execution of this Agreement and the form of Option Agreement
                attached hereto as Exhibit A.

                C. Expenses. IRORI shall reimburse Director for reasonable
                expenses actually incurred which are incidental to the services
                performed hereunder and which are consistent with IRORI's
                standard policy for reimbursement.

                D. Invoices. Director shall provide IRORI with monthly invoices
                detailing the expenses and reimbursements which Director
                believes are due under this Agreement Invoices should specify
                the period for which compensation is claimed. Travel costs and
                other expenses claimed must be itemized. IRORI agrees to pay
                approved invoices within thirty (30) days of receipt.

        3. Independent Contractor. Director's relationship with IRORI shall be
        that of an independent contractor and nothing in this Agreement shall be
        construed to create an employer-employee relationship between IRORI and
        Director. IRORI agrees that during the time Director serves on IRORI's
        Board of Directors, Director may be employed by other persons, firms or
        corporations engaged in the same or similar business as that of IRORI,
        provided, however, that the provisions of this Agreement shall be
        strictly observed by Director with respect to such other persons, firms,
        or corporations. Since Director will not be an employee of IRORI, it is
        understood that Director will not be entitled to any of the benefits
        under IRORI's retirement or group insurance plans or any other employee
        benefits. Director is solely responsible for all taxes, withholdings,
        and other similar statutory obligations, including, but not limited to,
        Workers Compensation Insurance, Social Security, federal, state, or any
        other employee payroll taxes; and



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        Director agrees to defend, indemnify and hold IRORI harmless from any
        and all claims made by any entity on account of an alleged failure by
        Director to satisfy any such tax or withholding obligations. In the
        performance of all services hereunder, Director shall comply with all
        applicable laws and regulations.

        4. No Conflict with existing Agreements. IRORI hereby states that IRORI
        does not desire to acquire from Director any secret or confidential
        know-how or information which Director may have acquired from others.
        Accordingly, Director represents and warrants that Director is free to
        divulge to IRORI, without any obligation to, or violation of any .right
        of others, any and all information, practice or techniques which
        Director will describe, demonstrate, divulge or in any other manner make
        known to IRORI during Director's performance of services hereunder.
        Director shall exonerate, indemnify and hold harmless IRORI from and
        against any and all liability, loss, cost, expense, damage, claims or
        demands for actual or alleged violation of the rights of others in any
        trade secret know-how or other confidential information by reason of
        IRORI's receipt or use of the services or information described above,
        or otherwise in connection therewith.

        5. Non-Disclosure and Non-Use. The parties hereto acknowledge that
        during the course of Director's services to IRORI pursuant to this
        Agreement it may become necessary or desirable for IRORI to disclose to
        Director a substantial amount of IRORI Proprietary Information.
        "Proprietary Information" is information that was or will be developed,
        created, or discovered by or on behalf of IRORI, or which becomes or
        will become known by, or was or is conveyed to IRORI which has
        commercial value in IRORI's business. "Proprietary Information"
        includes, but is not limited to, information operations and maintenance,
        trade secrets, cell-lines, design, technology, ideas, know-how,
        processes, formulas, compositions, data, techniques, improvements,
        inventions (whether patentable or not), works of authorship, business
        and product development plans, customers and other information
        concerning IRORI's actual or anticipated business, research or
        development or which is received in confidence by or for IRORI from any
        other person. "Proprietary Information" does not include information
        that Director demonstrates to IRORI's satisfaction, by written evidence,
        is in the public domain by reason of prior publication not directly or
        indirectly resulting from any act or omission of Director. Director
        fully understands that the maintenance of such Proprietary Information
        in strict confidence and the confinement of its use to IRORI is of vital
        importance to IRORI. Director agrees that the Proprietary Information
        divulged to Director by IRORI or which Director acquires in connection
        with or as a result of Director's services hereunder shall be regarded
        by Director as confidential. Director shall not use, nor shall Director
        disclose, any Proprietary Information to any person either during or
        after the period of this Agreement, except to those employees of
        Director or IRORI as may be necessary in the regular course of
        Director's duties hereunder, or except as otherwise authorized in
        writing by the President of IRORI.

        6. IRORI Materials. Director recognizes that all IRORI Materials made or
        received by Director during the period of this Agreement are and shall
        be the exclusive property of IRORI, and Director shall keep the same at
        all times in Director's custody and subject to Director's control, and
        shall surrender the same to IRORI immediately upon request of IRORI.
        "IRORI Materials" are documents or other media or tangible items that
        contain



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        or embody Proprietary Information or any other information concerning
        the business, operations, or plans of IRORI, whether such documents have
        been prepared by Director or by others. "IRORI Materials" include, but
        are not limited to, blueprints, drawings, photographs, charts, graphs,
        notebooks, customer lists, computer disks, tapes or printouts, sound
        recordings and other printed, typewritten, or handwritten documents, as
        well as samples, prototypes, models, products and the like.

        7. Indemnification. Director shall exonerate, indemnify and hold
        harmless IRORI, its officers, agents and employees from and against any
        and all liability, loss, cost, damage, claims, demands or expenses of
        every kind on account of injuries (including death) to Director or loss
        of or damage to Director's property arising out of or resulting in any
        manner from or occurring in connection with Director's breach of his
        obligations hereunder unless caused by the sole negligence of IRORI or
        its servants or employees.

        8. Termination. Director agrees that this Agreement may be terminated by
        either IRORI or Director at any time for any reason, with or without
        cause, by giving written notice to the other party; termination to be
        effective upon the other party's receipt of notice. This Agreement shall
        terminate automatically in the event of Director's inability for any
        reason to perform Director's services or if Director is not elected for
        subsequent terms by the shareholders of IRORI. Upon termination of this
        Agreement, IRORI's obligation to pay any compensation, except for
        services or expenses already accrued or incurred, shall forthwith cease
        and terminate. Termination of this Agreement for any reason shall not
        affect Director's obligations under paragraphs 4, 5, 6 and 7.

        9. Remedies. Director acknowledges and agrees that a breach of this
        Agreement will result in immediate, irreparable and continuing damage to
        IRORI for which there will be no adequate remedy at law; and agrees that
        in the event of any such breach or violation or any threatened or
        intended breach or violation of this Agreement IRORI and its successors
        and assigns shall be entitled to temporary, preliminary and permanent
        injunctive relief and/or regaining orders enjoining and restraining such
        breach or violation or such threatened or intended breach or violation
        and/or other equitable relief (without needing to post any bond or other
        security) in addition to such other and further relief as may be proper.

        10. Amendments and Waivers. This Agreement may be modified, amended or
        supplemented only by a written instrument daily executed by Director and
        the President of IRORI. No term or condition or the breach thereof shall
        be deemed waived, unless it is waived in writing and signed by the party
        against whom the waiver is claimed. Any waiver or breach of any term or
        condition shall not be deemed to be a waiver of any preceding or
        succeeding breach of the same or any other term or condition. The
        failure of any party to insist upon strict performance of any term or
        condition hereunder shall not constitute a waiver of such party's right
        to demand strict compliance therewith in the future.

        11. Notices. All payments, notices, requests, demands and other
        communications required or permitted hereunder shall be in writing and
        shall be delivered personally (which shall include delivery by courier
        or overnight delivery service) or sent by first



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        class mail, postage prepaid, or sent by telecopier or other similar
        facsimile transmission to the parties at their respective address set
        forth below or at such other address as shall be given in writing by a
        party to the other parties. Items delivered personally or by telecopier
        or facsimile shall be deemed delivered on the date of actual delivery;
        items sent by first class mail shall be deemed delivered three (3) days
        after mailing.

               If to IRORI:         IRORI
                                    11025 North Torrey Pines Rd. Ste. 100
                                    La Jolla, CA 92037

               If to
               Director:            Dieter Hoehn
                                    7312 Barclery Court
                                    University Park, FL 34201
                                    (address)



        12. Governing Law; Jurisdiction and Venue. This Agreement shall be
        governed by and construed in accordance with the laws of the State of
        California, without regard to principles of conflicts of law. The
        parties agree that any dispute regarding the interpretation or validity
        of this Agreement shall be subject to the exclusive jurisdiction of the
        state and federal courts in and for the county of San Diego, California
        and each party hereby agrees to submit to the personal and exclusive
        jurisdiction and venue of such courts.

        13. Attorneys' Fees. If any action at law or in equity is necessary to
        enforce or interpret the terms of this Agreement, the prevailing party
        shall be entitled to reasonable attorneys' fees, costs and
        disbursements, in addition to any other relief to which such party may
        be en-titled.

        14. Counterparts. This Agreement may be executed in multiple copies,
        each of which shall be deemed an original and all of which shall
        constitute a single agreement binding on all parties.

        15. Entire Agreement. This Agreement (together with documents and
        agreements entered into herewith) constitutes the entire agreement
        between the parties hereto with respect to the subject matter hereof and
        supersedes all prior and contemporaneous agreements and understandings.
        Each party to this Agreement acknowledges that no representations,
        inducements, promises or agreements have been made by any party, or any
        one acting on behalf of any party, that are not embodied in this
        Agreement with respect to the subject matter hereof.

        16. Representation. By executing this Agreement Director acknowledges
        that he understands and agrees that Brobeck, Phleger & Harrison LLP
        represents the interests of IRORI solely and that he has had the
        opportunity to consult with his own attorney in connection with this
        Agreement.



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        IN WITNESS WHEREOF, the parties hereto have executed this Agreement as
of the day and year first above written.

Director                                    IRORI, a California corporation

                                            By: /s/ Michael Nova
                                               ---------------------------------
/s/ Dieter Hoehn
-----------------------------
Dieter Hoehn                                Title: Michael Nova
                                                  ------------------------------
                                            CEO




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