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                                                                   EXHIBIT 10.52

                                                                    CONFIDENTIAL
                                                                  EXECUTION COPY

                                 THIRD AMENDMENT
                                       TO
                  COLLABORATION RESEARCH AND LICENSE AGREEMENT

This Third Amendment ("Third Amendment") is entered into by and between ELI
LILLY AND COMPANY, an Indiana corporation, having offices at Lilly Corporate
Center, Indianapolis, Indiana 46285 ("Lilly"), and between AURORA BIOSCIENCES
CORPORATION, a Delaware corporation having offices at 11010 Torreyana Road, San
Diego, California 92121 ("Aurora") and is effective as of the last date that
this Third Amendment is executed below.

WHEREAS, effective December 18, 1996, Lilly and Aurora entered into a
Collaborative Research and License Agreement, a First Amendment thereto on July
2, 1997, and a Second Amendment thereto on December 12, 1997 (the "Agreement");
and

WHEREAS, Lilly and Aurora are obligated to develop in collaboration with one
another the LILLYUHTSS under the Agreement;

WHEREAS, Lilly and Aurora desire to amend their obligations and rights under the
Agreement with respect to the LILLYUHTSS;

WHEREAS, Lilly desires to license certain intellectual property rights
Controlled by Aurora; and

NOW, THEREFORE, in consideration of the foregoing premises and of faithful
performance of the covenants herein contained, the parties hereto agree as
follows:

1.      All definitions not specifically defined herein are defined in the
        Agreement.

2.      Within *** days of the effective date of this Third Amendment, Lilly
        will pay to Aurora a *** payment of *** Dollars ($***), for designing,
        developing and manufacturing Module ***.

3.      Lilly shall have no obligation to make further payments of any kind to
        Aurora with respect to the LILLYUHTSS or any portion thereof, except as
        provided in Section 2 of this Third Amendment. Lilly *** under Section
        5.1.1 (iii) of the Agreement to use *** and *** the LILLYUHTSS for ***
        and ***.

4.      Aurora shall have no further obligations whatsoever related to design,
        development, manufacture, support, validation or completion related to
        *** or any portion thereof. Aurora shall not have any obligations under
        Section *** of the Agreement to pay any payment related to the
        completion of the LILLYUHTSS. Aurora's obligations under Section *** of
        the Agreement are abrogated as of the effective date of this Third
        Amendment.

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5.      Lilly and Aurora may elect, by specific written agreement by both
        parties, to re-initiate the LILLYUHTSS development and delivery on
        conditions, terms and scheduling to be agreed upon at such time, in
        writing.

6.      Sections 2.1 (including 2.1.1 (Project Management), 2.1.2 (Development
        and Delivery), 2.1.3 (Validation and Completion), 2.1.5 (Penalty), 2.1.4
        (Payments), and 2.1.6 (Most Favored Nations and Syndicate Limitations),
        2.1.7 (Supply of Aurora Reporters), 2.1.8 (terms for Aurora Reporters),
        4.1 (Service and Support), 11.3 (Termination Without Cause by Lilly),
        11.4 (Partial Performance) and Exhibits 1.1 and 4.1 of the Agreement are
        hereby removed and shall have no force or effect.

7.      Aurora will deliver to Lilly the VIPR in accordance with the terms set
        forth in Aurora invoice number ***, attached hereto as Exhibit ***.

8.      Lilly will pay Aurora the following payments in consideration of the use
        of Aurora Reporter System Technology and Aurora Reporter System Patent
        Rights from December 18, *** through December 17, ***:

               a) *** Dollars ($***) payable by ***;

               b) *** Dollars ($***) payable as follows *** (i) *** or (ii) ***
               of *** ($***) *** to be paid by *** and ***; and

               c) *** Dollars ($***) payable as follows *** (i) *** or (ii) ***
               of *** Dollars ($***) *** to be paid by *** and ***.

        Lilly may elect to renew the licenses to Aurora Reporter System
        Technology and Aurora Reporter System Patent Rights on an annual basis
        beyond December 17, 2002 by providing Aurora with at least *** written
        notice of Lilly's election to renew its *** for ***, and by payment of
        *** payment of *** Dollars ($***) to *** as a *** payment of *** Dollars
        ($***) and a *** payment of *** Dollars ($***).


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9.      So long as Lilly has made payments in accordance with Section 8 of this
        Third Amendment hereof, then, at Lilly's request, Aurora will use ***
        supply Aurora Reporters *** days after receipt of a written purchase
        order therefor, *** pertaining to the Aurora Reporter Systems as Lilly
        may require in order to use the Aurora Reporter Systems *** Lilly. Lilly
        will be charged for all supplies so delivered ***. Lilly will pay for
        all supplies so ordered within *** days after delivery to Lilly.

10.     So long as Lilly satisfies its payment obligations under Section 8 of
        this Third Amendment for Aurora Reporters, Aurora *** Lilly to use ***
        Exhibit 1.2 of the Agreement and developed by Aurora, for *** comparable
        to those *** by ***.

11.     Exhibit 1.2 of the Agreement is replaced with the new Exhibit 1.2
        attached *** and ***.

12.     Exhibit 5.1 of the Agreement is replaced with new Exhibit 5.1 attached,
        ***.

13.     Each party hereby voluntarily and knowingly releases and forever
        discharges the other party, its Affiliates and their respective
        shareholders, officers, directors, employees, agents, successors and
        assigns, from any and all actions, causes of action, debts, sums of
        money, damages, judgments, obligations, claims and demands whatsoever,
        whether or not presently known, and whether or not presently capable of
        being known, which have been, could have been, or may in the future be,
        asserted against any of the released parties involving, arising from or
        under, or related to a party's performance (or lack thereof) under
        Sections 2.1 (first paragraph only), 2.1.1, 2.1.2, 2.1.3, 2.1.4, 2.1.5,
        2.1.6 and 4.1 and Exhibit 4.1 of the Agreement.

14.     The parties and each of them represent, warrant and agree that they have
        been fully advised by their respective attorneys regarding the contents
        of Section 1542 of the Civil Code of the State of California. Such
        Section 1542 reads as follows: "A general release does not extend to
        claims which the creditor does not know or suspect to exist in his favor
        at the time of executing the release, which if known by him must have
        materially effected his settlement with the debtor." The parties
        expressly waive and relinquish all rights and benefits under such
        Section 1542 and any similar law or common law principle of similar
        effect of any state or territory of the United States with respect to
        any claim released herein.



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15.     Lilly and its Affiliates and Aurora and its Affiliates shall *** to
        ensure that their respective officers, directors, consultants and
        employees *** any *** Third Party *** party including, but not limited
        to, the *** other party.

16.     Lilly and Aurora shall make reasonable efforts to agree promptly to the
        text of an Aurora Press Release (together with a "Q&A" document)
        announcing the substance of this amendment, subject to the terms in
        Section 8 of the Agreement.

17.     The obligations of Lilly and Aurora set forth in Section *** of the
        Agreement shall no longer apply with respect to Aurora UHTSS Technology,
        Aurora UHTSS Patent Rights, Lilly UHTSS Technology, and Lilly UHTSS
        Patent Rights, but shall continue in all other respects.

18.     The obligations of Lilly set forth in Section *** of the Agreement shall
        no longer apply with respect to Aurora UHTSS and Aurora UHTSS Patent
        Rights, but shall continue in all other respects.

19.     The last sentence of Section 11.7.1 shall be deleted in its entirety and
        replaced with the following: "Except as otherwise expressly provided in
        this Agreement, the rights and obligations of the parties under Sections
        *** and *** shall *** further *** or *** upon *** except that the
        licenses granted under *** and *** of the LILLYUHTSS for *** deemed
        ***."

20.     Except as hereby amended, the parties confirm and ratify that the terms
        and conditions of the Agreement remain in full force and effect.

IN WITNESS WHEREOF, the parties, by duly authorized representatives, execute
this Third Amendment to the Agreement

ELI LILLY AND COMPANY                       AURORA BIOSCIENCES CORPORATION



By:  /s/  August M. Watanabe                By:    /s/  Stuart Collinson
     -------------------------------           ---------------------------------

Title:  Executive Vice President            Title: CEO & President
     -------------------------------              ------------------------------

Date:   November 22, 1999                   Date:  11-17-99
     -------------------------------             -------------------------------


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                                   EXHIBIT 1.2

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                                   EXHIBIT 5.1


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                                  EXHIBIT TA-7


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