<PAGE>
                                                                    EXHIBIT 99.2

                                 FIRST AMENDMENT
                         TO CERTAIN OPERATIVE AGREEMENTS

                          Dated as of September 17, 2001

                                      among

                         LEXICON GENETICS INCORPORATED,
                  as the Construction Agent and as the Lessee,

                WELLS FARGO BANK NORTHWEST, NATIONAL ASSOCIATION
              (formerly First Security Bank, National Association)
    not individually, except as expressly stated in the Operative Agreements,
          but solely as the Owner Trustee under the Lexi Trust 2000-1,

                THE VARIOUS BANKS AND OTHER LENDING INSTITUTIONS
       WHICH ARE PARTIES TO THE PARTICIPATION AGREEMENT AND CERTAIN OTHER
                     OPERATIVE AGREEMENTS FROM TIME TO TIME,
                                 as the Holders,

                THE VARIOUS BANKS AND OTHER LENDING INSTITUTIONS
              WHICH ARE PARTIES TO THE PARTICIPATION AGREEMENT AND
              CERTAIN OTHER OPERATIVE AGREEMENTS FROM TIME TO TIME,
                                 as the Lenders,

                                       and

                             BANK OF AMERICA, N.A.,
                        as the Agent for the Lenders and,
                       respecting the Security Documents,
                      as the Agent for the Secured Parties

<PAGE>

                                 FIRST AMENDMENT
                        TO CERTAIN OPERATIVE AGREEMENTS

         This FIRST AMENDMENT TO CERTAIN OPERATIVE AGREEMENTS (this "Amendment")
dated as of September 17,2001, to by and among LEXICON GENETICS INCORPORATED, a
Delaware corporation (the "Lessee" or the "Construction Agent"); WELLS FARGO
BANK NORTHWEST, NATIONAL ASSOCIATION (formerly First Security Bank, National
Association), a national banking association, not individually but solely as
the Owner Trustee under the Lexi Trust 2000-1 (the "Owner Trustee" or the
"Lessor"); the various banks and other lending institutions listed on the
signature pages hereto (subject to the definition of Lender in Appendix A to
the Participation Agreement referenced below, individually, a "Lenders" and
collectively, the "Lenders"); the various banks and other lending institutions
listed on the signature pages hereto as holders of certificates issued with
respect to the Lexi Trust 2000-1 (subject to the definition of Holders in
Appendix A to the Participation Agreement referenced below, individually, a
"Holder") and collectively, the "Holders"); and BANK OF AMERICA, N.A. a
national banking association, as the agent for the Lenders and, respecting the
Security Documents, as the agent for the Lenders and the Holders, to the extent
of their interests (in such capacity, the "Agent"). Capitalized terms used in
this Amendment but not otherwise defined herein shall have the meanings set
forth in Appendix A to the Participation Agreement (hereinafter defined).

                              W I T N E S S E T H

         WHEREAS, the parties to this Amendment are parties to that certain
Participation Agreement dated as of October 19, 2000 (the "Participation
Agreement"), certain of the parties to this Amendment are parties to that
certain Credit Agreement dated as of October 19, 2000 (the "Credit Agreement"),
certain of the parties to this Amendment are parties to that certain Trust
Agreement dated as of October 19, 2000 (the "Trust Agreement"), and certain of
the parties to this Amendment are parties to the other Operative Agreements
relating to a $45 million lease facility (the "Facility") that has been
established in favor of the Lessee;

         WHEREAS, the Lessee has requested certain modifications to the
Participation Agreement, the Credit Agreement, the Trust Agreement and the other
Operative Agreements to, among other things, increase the size of the Facility
from $45 million to $50 million for the construction of a central plant at the
Lessee's Montgomery County, Texas site and purchases of equipment related
thereto;

         WHEREAS, the Financing Parties have agreed to the requested
modifications on the terms and conditions set forth herein;

         NOW, THEREFORE, IN CONSIDERATION of the premises and other good and
valuable consideration, the receipt and sufficiency of which is hereby
acknowledged, the parties agree as follows:

<PAGE>

                             PARTICIPATION AGREEMENT

         1.       Section 5.10(b) of the Participation Agreement is amended and
restated in its entirety to read as follows:

                  (b)      Maintenance of Borrowing Base. At all times, the
         Lessee shall maintain Class A Collateral represented by U.S. dollar
         denominated certificates of deposit of Bank of America, N.A. in
         accordance with the standard described in subsection (ii) below and
         shall furnish to the Agent an Officer's Certificate in the form of
         Exhibit L no later than the date that the Lessee is obligated to
         deliver the financial statements referenced in Sections 8.3A(a)(i) and
         8.3A(a)(ii): (i) setting forth (A) the Lessee's calculation, in
         reasonable detail, of the Borrowing Base as of such date and (B) the
         Class A Collateral Percentage as of such date and (ii) confirming that,
         at all times, (A) prior to the Construction Period Termination Date,
         the amount of Class A Collateral represented by U.S. dollar denominated
         certificates of deposit of Bank of America, N.A. is not in excess of
         the Property Cost of all the Properties for which the Rent Commencement
         Date has occurred at such time and (B) after the Construction Period
         Termination Date, the amount of Class A Collateral represented by U.S.
         dollar denominated certificates of deposit of Bank of America, N.A. is
         greater than or equal to $5,000,000.

         2.       Section 5.12 of the Participation Agreement is deleted in its
entirety and replaced with the words "[Intentionally Omitted]".

         3.       Section 5.16 of the Participation Agreement is amended and
restated in its entirety to read as follows:

         5.16     LIMITATION ON CERTIFICATE OF DEPOSIT COLLATERAL.

         At any time prior to the Construction Period Termination Date, the
Lessee shall not permit the aggregate amount of Class A Collateral represented
by U.S. dollar denominated certificates of deposit of Bank of America, N.A. to
be in excess of the Property Cost of all the Properties for which the Rent
Commencement Date has occurred at such time.

         4.       Each of the following sections of the Participation Agreement
is amended to delete the following references therefrom:

                  (a)      "but subject to Section 5.12," in Section 5.2(f) of
         the Participation Agreement;

                  (b)      "(subject to Section 5.12)" in Sections 5.3(hh) and
         5.4(n) of the Participation Agreement; and

                  (c)      "subject to Section 5.12," in Section 5.4(g) of the
         Participation Agreement.

                                       2

<PAGE>

         5.       A new Section 5.17 is added to the Participation Agreement to
read as follows:

                  5.17     CONSOLIDATION OF EURODOLLAR LOANS AND EURODOLLAR
HOLDER ADVANCES.

                  At no time after the end of the Consolidation Period shall
more than a total of twelve (12) Eurodollar Loans and Eurodollar Holder Advances
be outstanding at any one time. Notwithstanding anything to the contrary in any
Operative Agreement, the parties hereto agree that, during the Consolidation
Period, the Agent, in consultation with the Lessee, may, with respect to any
Eurodollar Loan or Eurodollar Holder Advance maturing prior to the Completion of
all Properties, cause the subsequent Interest Period for such Eurodollar Loan or
Eurodollar Holder Advance to consist of such number of days as is necessary to
consolidate such Eurodollar Loans and Eurodollar Holder Advances in order to
comply with the preceding sentence; provided that (a) no such Interest Period
may be less than thirty (30) days or more than ninety (90) days and (b) during
the Consolidation Period, interest on each such Eurodollar Loan and Holder Yield
on each such Eurodollar Holder Advance, as applicable, shall accrue at (i) an
overseas interbank offered rate for Dollar deposits determined by the Agent from
a recognized service or interbank quotation plus (ii) the Applicable Percentage.

         6.       Section 6.2 of the Participation Agreement is amended to add a
new subsection (aa) at the end thereof, to read as follows:

                  (aa) (i) Each service contract with respect to the Planned
Central Plant has a term of less than twenty-four months and (ii) the Planned
Central Plant, and each item of Equipment in connection therewith, is of such a
general nature and design that it can be built, installed, managed, repaired,
improved and otherwise operated by any trained professional in the business of
constructing and operating central plant facilities.

         7.       A new Section 8.2(i) is added to the Participation Agreement
to read as follows:

                  (i) The Lessor authorizes the Agent at the expense of the
Lessor to file fixture filings and/or financing statements with respect to any
collateral under or pursuant to any Operative Agreement without the signature of
the Lessor, in such form and in such filling offices as the Agent reasonably
determines necessary or appropriate to perfect the security interests of the
Agent under the applicable Operative Agreement.

         8.       A new Section 8.3(v) is added to the Participation Agreement
to read as follows:

                  (v) The Lessee authorizes the Agent at the expense of the
Lessee to file fixture fillings and/or financing statements with respect to any
collateral under or pursuant to any Operative Agreement without the signature of
the Lessee, in such form and in such filing offices as the Agent reasonably
determines necessary or appropriate to perfect the security interests of the
Agent under the applicable Operative Agreement.

         9.       Appendix A to the Participation Agreement is amended as
follows:

                                        3

<PAGE>

         (a)      The definition of "Class A Collateral Percentage" is amended
and restated in its entirety to read as follows:

                  "Class A Collateral Percentage" shall mean, at any time on and
         after June 29, 2001, the ratio (expressed as a percentage) of (a) the
         market value of Class A Collateral to (b) the sum of then current
         outstanding Loans plus the then current outstanding Holder Amounts.

         (b)      A new definition of "Consolidation Period" is added to read as
follows:

                  "Consolidation Period" shall mean the period from September
         21, 2001 to the later to occur of (x) the maturity of all Construction
         Advances made prior to the Completion of all Properties and (y) 90 days
         after the Completion of all Properties.

         (c)      The definition of "Equipment" is amended and restated in its
entirety to read as follows:

                  "Equipment" shall mean equipment, apparatus, furnishings,
         fittings and personal property of every kind and nature whatsoever
         purchased, leased or otherwise acquired using the proceeds of the Loans
         or the Holder Advances by the Construction Agent, the Lessee or the
         Lessor and all improvements and modifications thereto and replacements
         thereof, whether or not now owned or hereafter acquired or now or
         subsequently attached to, contained in or used or usable in any way in
         connection with any operation of any Improvements, including but
         without limiting the generality of the foregoing, (a) all equipment
         described on Schedule 1 to the Participation Agreement and (b) all
         equipment described in any Appraisal including without limitation all
         heating, electrical, and mechanical equipment (including without
         limitation generators and other central plant equipment), lighting,
         switchboards, plumbing, ventilation, air conditioning and air-cooling
         apparatus, refrigerating, and incinerating equipment, escalators,
         elevators, loading and unloading equipment and systems, cleaning
         systems (including without limitation window cleaning apparatus),
         telephones, communication systems (including without limitation
         satellite dishes and antennae), televisions, computers, sprinkler
         systems and other fire prevention and extinguishing apparatus and
         materials, security systems, motors, engines, machinery, pipes, pumps,
         tanks, conduits, appliances, fittings and fixtures of every kind and
         description.

         (d)      The definition of "Non-Integral Equipment" is amended to add a
proviso before the period at the end thereof, to read as follows:

         ; provided that no item of Equipment listed on Schedule 1 to the
         Participation Agreement shall at any time be deemed Non-Integral
         Equipment.

                                        4

<PAGE>

                  (e)      The definition of "Permitted Facility" is amended to
         add the words", central plant associated therewith" immediately
         following the words "parking facility associated therewith" therein.

                  (f)      The definition of "Structure" is amended to add the
         words", the Planned Central Plant" immediately following the words
         "the Planned Vivarium" therein.

                  (g)      A new definition of "Planned Central Plant" is added
         to read as follows:

                  "Planned Central Plant" shall mean the central plant
                  contemplated to be constructed by the Construction Agent on
                  the real property identified in Lease Supplement No. 1
                  pursuant to the Operative Agreements.

         10.      A new Schedule 1 is added to the Participation Agreement in
the form of Exhibit A to this Amendment.

                                CREDIT AGREEMENT

         1.       Schedule 2.1 of the Credit Agreement is hereby deemed amended
and restated in its entirety to read as Schedule 2.1 attached hereto as EXHIBIT
B.

                                TRUST AGREEMENT

         1.       Schedule I of the Trust Agreement is hereby deemed amended and
restated in its entirety to read as Schedule I attached hereto as EXHIBIT C.

                                LEASE AGREEMENT

         1.       Subclause (x) of the second sentence of Section 11.2 of the
Lease is amended to add the words "and are not a part or a component of the
Planned Central Plant" immediately following the words "Section 11.1(a)".

                              COLLATERAL AGREEMENT

         1.       The first paragraph of Section 3.2 of the Collateral Agreement
is amended to add the words "from time to time" immediately following the words
"the Uniform Commercial Code as in effect" therein.

                                  MISCELLANEOUS

         1.       This Amendment shall be effective upon satisfaction of the
following conditions (with regard to delivery of any documents, agreements,
instruments, UCC Amendments,

                                       5

<PAGE>

certificates, budgets or other items, each of the foregoing shall be in form and
substance reasonably satisfactory to the Agent):

                  (a)      (i) execution and delivery of this Amendment by the
         parties hereto and (ii) such other documents, agreements or instruments
         reasonably deemed necessary or advisable by the Agent;

                  (b)      receipt by the Agent of an officer's certificate of
         the Lessee and the Construction Agent, dated as of the date hereof and
         in form and in substance reasonably satisfactory to the Agent,
         certifying that (i) each and every representation and warranty of the
         Lessee contained in the Operative Agreements to which is a party is
         true and correct on and as of the date hereof; (ii) no Default or Event
         of Default has occurred and is continuing under any Operative
         Agreement; (iii) each Operative Agreement to which the Lessee is a
         party in full force and effect with respect to it; and (iv) the Lessee
         has duly performed and complied with all covenants, agreements and
         conditions contained in any Operative Agreement required to be
         performed or complied with by it on or prior to the date hereof;

                  (c)      receipt by the Agent of a secretary's certificate of
         the Lessee certifying (i) resolutions duly adopted by the Board of
         Directors of Lessee approving and authorizing the execution, delivery,
         and performance of this Amendment and (ii) the incumbency of the
         officer of the Lessee executing this Amendment;

                  (d)      receipt by the Agent, for the ratable benefit of each
         Lender and each Holder, of an amendment fee equal to $50,000;

                  (e)      receipt by the Agent of a duly completed and executed
         Requisition, together with supporting invoices, with respect to
         Advances, if any, to be funded on the closing date of this Amendment;

                  (f)      receipt by the Agent of good standing certificates
         for the Lessee from the States of Texas and Delaware;

                  (g)      receipt by the Agent of a good standing certificate
         for the Lessor from the Office of the Comptroller of the Currency;

                  (h)      confirmation by the Agent of the appropriate funding
         of the Collateral Account as required in accordance with the Operative
         Agreements;

                  (i)      payment by the Lessee of all reasonable costs and
         expenses of the Agent in connection with the preparation, execution and
         delivery of this Amendment, including without limitation the reasonable
         fees and expenses of Moore & Van Allen PLLC;

                  (j)      receipt by the Agent of the following outstanding
         items with respect to each Property for which Completion has not
         occurred prior to the Property Closing Date therefore, to the extent
         not heretofore delivered by the Construction Agent to the Agent:

                                       6
<PAGE>

                           (i)      a preliminary Construction Budget for such
                  Property in accordance with Section 5.3(r) of the
                  Participation Agreement;

                           (ii)     the Construction Contract with respect to
                  such Property in accordance with Section 5.3(hh) of the
                  Participation Agreement; and

                           (iii)    a comprehensive Construction Budget for all
                  such Properties.

         2.       Except as modified hereby, all of the terms and provisions of
the Operative Agreements (including all Schedules and Exhibits thereto) shall
remain unmodified and in full force and effect.

         3.       This Amendment may be executed in any number of counterparts,
each of which when so executed and delivered shall deemed an original and it
shall not be necessary in making proof of this Amendment to produce or account
for more than one such counterpart.

         4.       This Amendment shall be deemed to be a contract made under,
and for all purposes shall be construed in accordance with, the laws of the
State of North Carolina other than amendments of the Trust Agreement and the
Collateral Agreement. With respect to the application of this Amendment to the
Trust Agreement, this Amendment shall be deemed to be a contract made under, and
for all purposes shall be construed in accordance with, the laws of the State of
Utah. With respect to the application of this Amendment to the Collateral
Agreement, this Amendment shall be deemed to be a contract made under, and for
all purposes shall be construed in accordance with, the laws of the State of
Taxas.

         [The remainder of this page has been left blank intentionally.]

                                       7

<PAGE>

         IN WITNESS WHEREOF, each of the parties hereto has caused counterpart
of this Amendment to be duly executed and delivered as of the date first above
written.

                                      LEXICON GENETICS INCORPORATED, as
                                      the Construction Agent and as the Lessee

                                      By: /s/ JULIA P. GREGORY
                                         ---------------------------------------
                                      Name: Julia P. Gregory
                                      Title: Executive Vice President and CFO

                                      WELLS FARGO BANK NORTHWEST,
                                      NATIONAL ASSOCIATION (formerly First
                                      Security Bank, National Association), not
                                      individually, except as expressly stated
                                      herein, but solely as the Owner Trustee
                                      under the Lexi Trust 2000-1

                                      By: /s/ VAL T. ORTON
                                         ---------------------------------------
                                      Name: Val T. Orton
                                           -------------------------------------
                                      Title: Vice President
                                            ------------------------------------

                                      BANK OF AMERICA, N.A., as a Holder, as a
                                      Lender and as the Agent

                                      By: /s/ CURTIS L. ANDERSON
                                         ---------------------------------------
                                      Name: Curtis L. Anderson
                                           -------------------------------------
                                      Title: Senior Vice President
                                            ------------------------------------
<PAGE>

                                    EXHIBIT A

                      Schedule 1 to Participation Agreement

                                    Equipment

<TABLE>
<CAPTION>
    ITEM         MANUFACTURER              MODEL                SERIAL NOS.    QUANTITY
    ----         ------------              -----                -----------    --------
<S>              <C>              <C>                           <C>            <C>
Chiller          York             YKGBFDH7-CWE0, CWE00                            3
Coding Tower     Marley           NC8311-G                                        3
Pumps            Armstrong        4300-8x8x13                                     3
Pumps            Armstrong        4300-10x10x13                                   3
Pumps            Armstrong        4300-10x10x15                                   3
Generator        Mustang/Cat      3512B TA W/1500KW                               2
HV Switchgear    Russelectric     Series RPCS,                                    1
                                  5 Compartments
LV Switchgear    Cutler Hammer    Series DS Magnum,                               1
                                  5 Compartments
Transformers     ABB              MTR-2500                                        1
Transformers     ABB              MTR-1500                                        1
Transformers     ABB              MTR-750                                         1
</TABLE>
<PAGE>

                                    EXHIBIT B

                        Schedule 2.1 to Credit Agreement

<TABLE>
<CAPTION>
                                           Tranche A Commitment         Tranche B Commitment
                                       ---------------------------   --------------------------
    Name and Address of Lenders            Amount       Percentage       Amount      Percentage
    ---------------------------        --------------   ----------   -------------   ----------
<S>                                    <C>              <C>          <C>             <C>
Bank of America, N.A.                  $43,155,000.00      100%      $4,595,000.00      100%
555 California Street, 12th Floor
Mail Code: CA5-705-12-08
San Francisco, CA 94104-1502
Attention: Jouni Korhonen
Telephone: (415) 622-7293
Telecopy: (415) 622-4057

TOTAL                                  $43,155,000.00      100%      $4,595,000.00      100%
</TABLE>

<PAGE>

                                    EXHIBIT C

                          SCHEDULE I TO TRUST AGREEMENT

                               HOLDER COMMITMENTS

<TABLE>
<CAPTION>
                                                             HOLDER COMMITMENT
                                                             -----------------
           NAME OF HOLDER                          AMOUNT                       PERCENTAGE
           --------------                          ------                       ----------
<S>                                             <C>                             <C>
Bank of America, N.A.                           $2,250,000.00                       100%
555 California Street, 12th Floor
Mail Code: CA5-705-12-08
San Francisco, CA. 94104-1502
Attention: Jouni Korhonen
Telephone: (415) 622-7293
Telecopy: (415) 622-4057

TOTAL                                           $2,250,000.00                       100%
</TABLE>
<PAGE>
                                SECOND AMENDMENT
                         TO CERTAIN OPERATIVE AGREEMENTS

                          Dated as of February 17, 2002

                                      among

                         LEXICON GENETICS INCORPORATED,
                  as the Construction Agent and as the Lessee,

                WELLS FARGO BANK NORTHWEST, NATIONAL ASSOCIATION
              (formerly First Security Bank, National Association)
    not individually, except as expressly stated in the Operative Agreements,
          but solely as the Owner Trustee under the Lexi Trust 2000-1,

                THE VARIOUS BANKS AND OTHER LENDING INSTITUTIONS
       WHICH ARE PARTIES TO THE PARTICIPATION AGREEMENT AND CERTAIN OTHER
                     OPERATIVE AGREEMENTS FROM TIME TO TIME,
                                 as the Holders,

                THE VARIOUS BANKS AND OTHER LENDING INSTITUTIONS
              WHICH ARE PARTIES TO THE PARTICIPATION AGREEMENT AND
              CERTAIN OTHER OPERATIVE AGREEMENTS FROM TIME TO TIME,
                                 as the Lenders,

                                       and

                             BANK OF AMERICA, N.A.,
                        as the Agent for the Lenders and,
                       respecting the Security Documents,
                      as the Agent for the Secured Parties
<PAGE>
                                SECOND AMENDMENT
                         TO CERTAIN OPERATIVE AGREEMENTS

      This SECOND AMENDMENT TO CERTAIN OPERATIVE AGREEMENTS (this "Amendment")
dated as of February 17, 2002, is by and among LEXICON GENETICS INCORPORATED, a
Delaware corporation (the "Lessee" or the "Construction Agent"); WELLS FARGO
BANK NORTHWEST, NATIONAL ASSOCIATION (formerly First Security Bank, National
Association), a national banking association, not individually but solely as the
Owner Trustee under the Lexi Trust 2000-1 (the "Owner Trustee" or the "Lessor");
the various banks and other lending institutions listed on the signature pages
hereto (subject to the definition of Lenders in Appendix A to the Participation
Agreement referenced below, individually, a "Lender" and collectively, the
"Lenders"); the various banks and other lending institutions listed on the
signature pages hereto as holders of certificates issued with respect to the
Lexi Trust 2000-1 (subject to the definition of Holders in Appendix A to the
Participation Agreement referenced below, individually, a "Holder" and
collectively, the "Holders"); and BANK OF AMERICA, N.A., a national banking
association, as the agent for the Lenders and, respecting the Security
Documents, as the agent for the Lenders and the Holders, to the extent of their
interests (in such capacity, the "Agent"). Capitalized terms used in this
Amendment but not otherwise defined herein shall have the meanings set forth in
Appendix A to the Participation Agreement (hereinafter defined) and the Rules of
Usage set forth in Appendix A to the Participation Agreement shall apply herein.

                                   WITNESSETH

      WHEREAS, the parties to this Amendment are parties to that certain
Participation Agreement dated as of October 19, 2000 as amended by the First
Amendment to Certain Operative Agreements dated as of September 17, 2001 among
the parties hereto (as amended, modified, extended, supplemented, restated
and/or replaced from time to time in accordance with the terms thereof, the
"Participation Agreement"), certain of the parties to this Amendment are parties
to that certain Credit Agreement dated as of October 19, 2000, certain of the
parties to this Amendment are parties to that certain Trust Agreement dated as
of October 19, 2000, and certain of the parties to this Amendment are parties to
the other Operative Agreements relating to a $50 million lease facility (the
"Facility") that has been established in favor of the Lessee;

      WHEREAS, the Lessee has requested certain modifications to the Credit
Agreement and the Trust Agreement to, among other things, increase the size of
the Facility from $50 million to $55 million for the construction and completion
of the Properties;

      WHEREAS, the Financing Parties have agreed to the requested modifications
on the terms and conditions set forth herein;

      NOW, THEREFORE, IN CONSIDERATION of the premises and other good and
valuable consideration, the receipt and sufficiency of which is hereby
acknowledged, the parties agree as follows:
<PAGE>
                            PARTICIPATION AGREEMENT

      1. Section 5.11 of the Participation Agreement is hereby amended and
restated in its entirety to read as follows:

            "5.11 FUNDING OF ESCROW ACCOUNT FOR PUNCH LIST ITEMS, RETAINAGE AND
      OTHER AMOUNTS NECESSARY FOR FINAL COMPLETION.

                  Prior to the submission by the Construction Agent of the
            Officer's Certificate referenced in Section 5.5(a) regarding
            Completion of a given Property, the Construction Agent shall submit
            a Requisition for a Construction Advance to cover all anticipated
            punch list items, retainage and other amounts necessary for Final
            Completion of the applicable Property. To the extent the conditions
            precedent set forth in Section 5.4 are satisfied or waived and prior
            to the termination of the Lender Commitments and the Holder
            Commitments for the applicable Property, the above-described
            Construction Advance shall be funded in accordance with the terms of
            the Operative Agreements into an escrow account in the name of and
            under the control of the Agent. Neither the Lessor, the Construction
            Agent nor the Lessee shall have any interest in the escrow account,
            its contents or any proceeds therefrom.

                  Thereafter, the Construction Agent shall request funding for
            punch list items, retainage or other amounts necessary for Final
            Completion regarding the applicable Property pursuant to
            Requisitions describing such punch list items, retainage or other
            amounts necessary for Final Completion and the amounts payable
            therefor. The Agent shall advance amounts from the escrow account
            regarding such funding requests to the extent the conditions
            precedent set forth in Section 5.4 are satisfied or waived at that
            time.

                  All amounts deposited in the escrow account from time to time
            shall constitute Advances for purposes of determining the Property
            Cost of the applicable Property (the "Prior Property") identified in
            the relevant Requisition from the date of such Advance by the
            Lenders and the Holders for deposit into the escrow account;
            provided, amounts deposited in the escrow account may be thereafter
            counted as Property Cost of another Property if (a) the Prior
            Property reaches Final Completion in accordance with the terms of
            the Operative Agreements, (b) there remains a positive balance in
            the escrow account regarding the Prior Property and (c) prior to the
            occurrence and continuation of any Default or Event of Default, the
            Construction Agent notifies the Agent in writing to re-allocate such
            positive balance in the escrow account from the Prior Property to a
            different Property which has not reached Completion at such time.

                  Upon the Payment Date immediately following the termination or
            expiration of the Lender Commitments, the remaining balance in the
            escrow account shall be allocated by the Agent in accordance with
            Section 8.7(b)(iv) and returned to the Lenders and the Holders in
            accordance with Section 2.6(c) of the


                                       2
<PAGE>
            Credit Agreement and Section 3.3 of the Trust Agreement,
            respectively, and the amounts so returned shall reduce, in each case
            regarding the last Property to reach Final Completion, the Property
            Cost, the outstanding balance of Loans and the outstanding balance
            of Holder Amounts."

      2. Section 6.1 of the Participation Agreement is hereby amended by adding
the following provision as Section 6.1(n) thereof:

                  "(n) The Operative Agreements (including without limitation
            all Schedules and Exhibits thereto) represent the entire agreement
            among the Owner Trustee and the other parties thereto with respect
            to the subject matter thereof, and there are no other oral or side
            agreements with respect to such subject matter."

      3. Section 6 of the Participation Agreement is hereby amended to include
the following provision as Section 6.3 thereof:

            "6.3 REPRESENTATIONS AND WARRANTIES OF THE HOLDERS. As of February
      17, 2002, each Holder hereby represents and warrants to each of the other
      parties hereto as follows:

                  (a) Such Holder does not own ten percent (10%) or more of the
            common stock of the Lessee.

                  (b) Such Holder has not obtained any residual insurance policy
            with respect to the value of the Properties or, except as provided
            in the Operative Agreements, received from any party any guarantee
            of the residual value of the Properties.

                  (c) Such Holder has not pledged its ownership interest in the
            Trust to secure non-recourse financing, either to finance the Holder
            Advances at the time they were made or subsequently through such
            date.

                  (d) The Operative Agreements (including without limitation all
            Schedules and Exhibits thereto) represent all of the agreements
            among the parties thereto relating to the subject matter thereof.
            There are no other agreements or understandings to which such Holder
            is party or of which such Holder has actual knowledge which, in any
            way, modify, change or limit the Operative Agreements."

      4. Section 8.3(q) of the Participation Agreement is hereby amended and
restated in its entirety to read as follows:

            "(q) If any credit facility, loan agreement or other financing
      arrangement in favor of the Lessee or any Affiliate of the Lessee, other
      than pursuant to Permitted Liens or the Operative Agreements, is ever
      secured by any collateral, the Secured Parties shall share on a pari-passu
      basis (based on the



                                       3
<PAGE>
      respective amounts outstanding under the Operative Agreements relative to
      the amounts outstanding under any such credit facility, loan agreement or
      other financing arrangement) in all such collateral."

      5. Section 8 of the Participation Agreement is hereby amended to include
the following provision as Section 8.9 and Section 8.10 thereof:

            "8.9 ADDITIONAL COVENANT OF THE HOLDERS. Only on a one time basis
      and only upon no less than ten (10) Business Days prior written request
      from the Lessee, each Holder hereby covenants and agrees on or prior to
      March 21, 2002 to deliver to the Lessee a certificate substantially in the
      form attached hereto as EXHIBIT O and made a part hereof for all
      purposes."

      6. The definition of "Permitted Liens" set forth in Appendix A of the
Participation Agreement is hereby amended to delete item (h) thereof in its
entirety and the following item (h) shall be substituted in its place:

            "(h) Liens securing purchase money and sale/leaseback Indebtedness
      (including Capitalized Leases) to the extent permitted under Section
      8.3B(a)(vi) of the Participation Agreement, provided that any such Lien
      attaches only to the Subject Property (but not to any Property) financed
      or leased and such Lien attaches thereto concurrently with or within 90
      days after the acquisition thereof in connection with the purchase money
      transactions and within 30 days after the closing of any sale/leaseback
      transaction;"

      7. The Participation Agreement is hereby amended to include EXHIBIT A
attached hereto as EXHIBIT O to the Participation Agreement as if it were
initially attached to the Participation Agreement.

                                CREDIT AGREEMENT

      1. Schedule 2.1 of the Credit Agreement is hereby amended and restated in
its entirety to read as Schedule 2.1 attached hereto as EXHIBIT B.

                                 TRUST AGREEMENT

      1. Schedule I of the Trust Agreement is hereby amended and restated in its
entirety to read as Schedule I attached hereto as EXHIBIT C.

                                  MISCELLANEOUS

      1. This Amendment shall be effective upon satisfaction of the following
conditions (with regard to delivery of any documents, agreements, instruments,
UCC Amendments,


                                       4
<PAGE>
certificates, budgets or other items, each of the forgoing shall be in form and
substance reasonably satisfactory to the Agent):

            (a) (i) execution and delivery of this Amendment by the parties
      hereto and (ii) such other documents, agreements or instruments reasonably
      deemed necessary or advisable by the Agent;

            (b) receipt by the Agent of an officer's certificate of the Lessee
      and the Construction Agent, dated as of the date hereof and in form and in
      substance reasonably satisfactory to the Agent, certifying that (i) each
      and every representation and warranty of the Lessee contained in the
      Operative Agreements to which it is a party is true and correct on and as
      of the date hereof; (ii) no Default or Event of Default has occurred and
      is continuing under any Operative Agreement; (iii) each Operative
      Agreement to which the Lessee is a party is in full force and effect with
      respect to it; and (iv) the Lessee has duly performed and complied with
      all covenants, agreements and conditions contained in any Operative
      Agreement required to be performed or complied with by it on or prior to
      the date hereof;

            (c) receipt by the Agent of a secretary's certificate of the Lessee
      certifying (i) the continued effectiveness of the resolutions duly adopted
      by the Board of Directors of the Lessee approving and authorizing the
      execution, delivery, and performance of amendments to the Operative
      Agreements, (ii) the continued effectiveness of the Certificate of
      Incorporation and Bylaws of the Lessee, and (iii) the incumbency or
      continued incumbency of the officer of the Lessee executing this
      Amendment;

            (d) receipt by the Agent, for the ratable benefit of each Lender and
      each Holder, of an amendment fee equal to $50,000;

            (e) deposit by the Lessee of the appropriate amount (if any) into
      the Collateral Account in accordance with Sections 5.4(m) and 5.10 of the
      Participation Agreement and confirmation by the Agent of the appropriate
      funding (if any) of the Collateral Account as required in accordance with
      such Sections 5.4(m) and 5.10; and

            (f) payment by the Lessee of all reasonable costs and expenses of
      the Agent in connection with the preparation, execution and delivery of
      this Amendment, including without limitation the reasonable fees and
      expenses of Moore & Van Allen PLLC.

      2. The notice address for the Agent, the Lender and the Holder for all
Operative Agreements (including without limitation Section 12.2 of the
Participation Agreement, Schedule I of the Trust Agreement, Schedule 2.1 of the
Credit Agreement and Section 10 of the Security Agreement) shall be modified to
read as follows:


                                       5
<PAGE>
                         Bank of America, N.A.
                         TX1-492-67-01
                         901 Main Street
                         Dallas, TX 75202-3714
                         Attention:   Dan Penkar
                                      Senior Vice President
                         Telephone:  (214) 209-1178
                         Telecopy:  (214) 209-3140

      3. By its execution hereof, except as set forth in Schedule 1 to this
Amendment, each of the Construction Agent and the Lessee represents, warrants
and certifies to each Financing Party that as of the date hereof (a) a
Construction Budget and Plans and Specifications with respect to each Property
have been delivered to the Agent and such documents are true and accurate and no
changes have been made or could reasonably be expected to be made which would
affect the accuracy of such documents, (b) all Construction Contracts have been
previously delivered to the Agent and have not been amended or modified, or such
amendments or modifications have been previously provided to the Agent, (c) the
Property Cost of each Property is within the applicable Construction Budget for
such Property, (d) each Property is on schedule for Completion on the date set
forth in the Plans and Specifications of such Property, but in all cases prior
to the Construction Period Termination Date, (e) there are sufficient Available
Commitments and Available Holder Commitments to cause the Completion of each
Property as a Permitted Facility and otherwise in accordance with the terms and
conditions of the Operative Agreements, and (f) all construction and Work with
respect to each Property has been and is being done in a workmanlike manner.

      4. Except as modified hereby, all of the terms and provisions of the
Operative Agreements (including all Schedules and Exhibits thereto) shall remain
unmodified and in full force and effect. Except as modified hereby, the
Operative Agreements (including all Schedules and Exhibits thereto) represent
the entire agreement between the parties hereto with respect to the subject
matter thereof and there are no other oral or side agreements with respect to
such subject matter.

      5. This Amendment may be executed in any number of counterparts, each of
which when so executed and delivered shall be deemed an original and it shall
not be necessary in making proof of this Amendment to produce or account for
more than one such counterpart.

      6. This Amendment shall be deemed to be a contract made under, and for all
purposes shall be construed in accordance with, the laws of the State of North
Carolina other than amendments of the Trust Agreement and the Collateral
Agreement. With respect to the application of this Amendment to the Trust
Agreement, this Amendment shall be deemed to be a contract made under, and for
all purposes shall be construed in accordance with, the laws of the State of
Utah. With respect to the application of this Amendment to the Collateral
Agreement, this Amendment shall be deemed to be a contract made under, and for
all purposes shall be construed in accordance with, the laws of the State of
Texas.


                                       6
<PAGE>
      IN WITNESS WHEREOF, each of the parties hereto has caused a counterpart of
this Amendment to be duly executed and delivered as of the date first above
written.

                                      LEXICON GENETICS INCORPORATED, as the
                                      Construction Agent and as the Lessee

                                      By: /s/ JULIA P. GREGORY
                                         ---------------------------------------
                                      Name: Julia P. Gregory
                                           -------------------------------------
                                      Title: Executive Vice President and CFO
                                            ------------------------------------


                                      WELLS FARGO BANK NORTHWEST,
                                      NATIONAL ASSOCIATION

                                      (formerly First Security Bank, National
                                      Association), not individually, except
                                      as expressly stated herein, but solely
                                      as the Owner Trustee under the Lexi
                                      Trust 2000-1

                                      By: /s/ VAL T. ORTON
                                         ---------------------------------------
                                      Name: Val T. Orton
                                           -------------------------------------
                                      Title: Vice President
                                            ------------------------------------


                                      BANK OF AMERICA, N.A., as a Holder, as a
                                      Lender and as the Agent

                                      By: /s/ DANIEL H. PENKAR
                                         ---------------------------------------
                                      Name: Daniel H. Penkar
                                           -------------------------------------
                                      Title: Senior Vice President
                                            ------------------------------------
<PAGE>

                                   SCHEDULE 1

                             [Construction Matters]

                                     None.
<PAGE>
                                    EXHIBIT A

                      EXHIBIT O TO PARTICIPATION AGREEMENT

        FORM OF CONFIRMATION LETTER TO BE EXECUTED BY EACH OF THE HOLDERS




March    , 2002

Bank of America, N.A.
901 Main Street
Dallas, Texas 75202-3714
Attention: Daniel Penkar
           Senior Vice President

Dear Dan:

Arthur Andersen LLP ("Andersen") is now engaged in an audit of our financial
statements. Your company, Bank of America, N.A. ("Bank of America"), made Holder
Advances to the Lexi Trust 2000-1 (the "Trust"), of which Wells Fargo Bank
Northwest, National Association (formerly First Security Bank, National
Association), serves as Owner Trustee (the "Owner Trustee"), in connection with
the transactions contemplated by (i) the Participation Agreement dated as of
October 19, 2000 (the "Original Participation Agreement"), by and among Lexicon
Genetics Incorporated ("Lexicon"), the Owner Trustee, the various banks and
other lending institutions which are parties thereto, as lenders (the
"Lenders"), the various banks and other lending institutions which are parties
thereto, as holders (the "Holders") and Bank of America, as the agent for the
Lenders and respecting the Security Documents, as the agent for the Secured
Parties, and (ii) the Operative Agreements referred to therein (the "Original
Operative Agreements"), in each case as amended by that certain First Amendment
to Certain Operative Agreements dated as of September 17, 2001 (the "First
Amendment") by and among the parties to the Original Participation Agreement and
as further amended by that certain Second Amendment to Certain Operative
Agreements dated as of February 17, 2002 (the "Second Amendment") by and among
the parties to the Original Participation Agreement. The Original Participation
Agreement, as amended by the First Amendment and the Second Amendment, is
referred to herein as the "Participation Agreement." The Original Operative
Agreements, as amended by First Amendment and the Second Amendment, are referred
to herein as the "Operative Agreements." Capitalized terms used without
definition herein shall have the meanings given to such terms in the
Participation Agreement.
<PAGE>
In connection with the foregoing, please confirm the following information:

-     Bank of America has made Holder Advances to the Trust in the aggregate
      amount of $          as of December 31, 2001.

-     Bank of America, in its capacity as Holder, has not obtained any residual
      insurance policy with respect to the value of the Properties or, except as
      provided in the Operative Agreements, received from any party any
      guarantee of the residual value of the Properties, except as described
      below.

      --------------------------------------------------------------------------
      --------------------------------------------------------------------------
      --------------------------------------------------------------------------

-     Bank of America has not pledged its ownership interest in the Trust to
      secure non-recourse financing, either to finance the Holder Advances at
      the time they were made or subsequently through the date of this letter,
      except as described below:

      --------------------------------------------------------------------------
      --------------------------------------------------------------------------
      --------------------------------------------------------------------------

-     Payments to Bank of America and/or its Affiliates from or on behalf of the
      Trust, from the inception of the Trust (October 19, 2000) through December
      31, 2001 are as follows (if none, please indicate below):

<TABLE>
<CAPTION>
      Date of Payment        Nature of Payment          Amount of Payment
      ---------------        -----------------          -----------------
<S>                          <C>                        <C>

</TABLE>
<PAGE>
-     The Operative Agreements contain all of the agreements among the parties
      thereto relating to the subject matter thereof. There are no other
      agreements or understandings to which Bank of America is party or of which
      Bank of America has actual knowledge which, in any way, modify, change or
      limit the Operative Agreements.

-     If Bank of America has sold, transferred, or assigned part or all of its
      interest in the Trust, please provide such information below (if none,
      please indicate below).

<TABLE>
<CAPTION>
      Amount         Date        Name of buyer(s), transferee(s), or assignee(s)
      ------         ----        -----------------------------------------------
<S>                  <C>         <C>
      ------         ----        -----------------------------------------------
      ------         ----        -----------------------------------------------
      ------         ----        -----------------------------------------------
</TABLE>

Please state in the space below whether or not the above statements and
information, including the amounts and terms, are in agreement with your
records. If not, please furnish any information you may have that will assist in
reconciling any differences.

Please return this confirmation directly to Andersen. A stamped, addressed
envelope is enclosed for your convenience.

                                             Very truly yours,

                                             Lexicon Genetics Incorporated

                                             By:
                                                  ------------------------------
                                                    Julia P. Gregory
                                                    Executive Vice President and
                                                    Chief Financial Officer
<PAGE>
To:  Arthur Andersen LLP:

The above statements and information, including the amounts and terms, are in
agreement with our records, with the following exceptions (If above information
is correct, please confirm. If your understanding of anything described above
differs in any respect, please explain):


--------------------------------------------------------------------------------
--------------------------------------------------------------------------------
--------------------------------------------------------------------------------
By:                                           Date:
    ---------------------------------              -----------------------------
    Daniel Penkar
    Senior Vice President
<PAGE>
                                    EXHIBIT B

                        Schedule 2.1 to Credit Agreement

<TABLE>
<CAPTION>
                                                       Tranche A Commitment                    Tranche B Commitment
                                                 --------------------------------         -------------------------------
Name and Address of Lenders                        Amount            Percentage            Amount            Percentage
---------------------------                        ------            ----------            ------            ----------
<S>                                              <C>                 <C>                  <C>                <C>
Bank of America, N.A.                            $47,470,500.00           100%            $5,054,500.00           100%
TX1-492-67-01
901 Main Street
Dallas, TX 75202-3714
Attention:  Dan Penkar
            Senior Vice President
Telephone:  (214) 209-1178
Telecopy:   (214) 209-3140


TOTAL                                            $47,470,500.00           100%            $5,054,500.00           100%
</TABLE>
<PAGE>
                                    EXHIBIT C

                          SCHEDULE I TO TRUST AGREEMENT

                               HOLDER COMMITMENTS

<TABLE>
<CAPTION>
                                                              Holder Commitment
                                                  ----------------------------------------
Name of Holder                                        Amount                    Percentage
<S>                                               <C>                           <C>
Bank of America, N.A.                             $2,475,000.00                    100%
TX1-492-67-01
901 Main Street
Dallas, TX 75202-3714
Attention:  Dan Penkar
            Senior Vice President
Telephone:  (214) 209-1178
Telecopy:   (214) 209-3140
TOTAL                                             $2,475,000.00                    100%
</TABLE>






<PAGE>

                                 THIRD AMENDMENT
                         TO CERTAIN OPERATIVE AGREEMENTS

                           Dated as of August 7, 2002

                                      among

                        LEXICON GENETICS INCORPORATED,
                 as the Construction Agent and as the Lessee,

                WELLS FARGO BANK NORTHWEST, NATIONAL ASSOCIATION
              (formerly First Security Bank, National Association)
    not individually, except as expressly stated in the Operative Agreements,
          but solely as the Owner Trustee under the Lexi Trust 2000-1,

                THE VARIOUS BANKS AND OTHER LENDING INSTITUTIONS
              WHICH ARE PARTIES TO THE PARTICIPATION AGREEMENT AND
             CERTAIN OTHER OPERATIVE AGREEMENTS FROM TIME TO TIME,
                                 as the Holders,

                THE VARIOUS BANKS AND OTHER LENDING INSTITUTIONS
              WHICH ARE PARTIES TO THE PARTICIPATION AGREEMENT AND
              CERTAIN OTHER OPERATIVE AGREEMENTS FROM TIME TO TIME,
                                 as the Lenders,

                                       and

                             BANK OF AMERICA, N.A.,
                        as the Agent for the Lenders and,
                       respecting the Security Documents,
                      as the Agent for the Secured Parties
<PAGE>
                                 THIRD AMENDMENT
                         TO CERTAIN OPERATIVE AGREEMENTS

      This THIRD AMENDMENT TO CERTAIN OPERATIVE AGREEMENTS (this "Amendment")
dated as of August 7, 2002, is by and among LEXICON GENETICS INCORPORATED, a
Delaware corporation (the "Lessee" or the "Construction Agent"); WELLS FARGO
BANK NORTHWEST, NATIONAL ASSOCIATION (formerly First Security Bank, National
Association), a national banking association, not individually but solely as the
Owner Trustee under the Lexi Trust 2000-1 (the "Owner Trustee" or the "Lessor");
the various banks and other lending institutions listed on the signature pages
hereto (subject to the definition of Lenders in Appendix A to the Participation
Agreement referenced below, individually, a "Lender" and collectively, the
"Lenders"); the various banks and other lending institutions listed on the
signature pages hereto as holders of certificates issued with respect to the
Lexi Trust 2000-1 (subject to the definition of Holders in Appendix A to the
Participation Agreement referenced below, individually, a "Holder" and
collectively, the "Holders"); and BANK OF AMERICA, N.A., a national banking
association, as the agent for the Lenders and, respecting the Security
Documents, as the agent for the Lenders and the Holders, to the extent of their
interests (in such capacity, the "Agent"). Capitalized terms used in this
Amendment but not otherwise defined herein shall have the meanings set forth in
Appendix A to the Participation Agreement (hereinafter defined) and the Rules of
Usage set forth in Appendix A to the Participation Agreement shall apply herein.

                               W I T N E S S E T H

      WHEREAS, the parties to this Amendment are parties to that certain
Participation Agreement dated as of October 19, 2000 as amended by the First
Amendment to Certain Operative Agreements dated as of September 17, 2001 among
the parties hereto and the Second Amendment to Certain Operative Agreements
dated as of February 17, 2002 among the parties hereto (as amended, modified,
extended, supplemented, restated and/or replaced from time to time in accordance
with the terms thereof, the "Participation Agreement"), certain of the parties
to this Amendment are parties to that certain Credit Agreement dated as of
October 19, 2000 as amended by the First Amendment to Certain Operative
Agreements dated as of September 17, 2001 among the parties hereto and the
Second Amendment to Certain Operative Agreements dated as of February 17, 2002
among the parties hereto, certain of the parties to this Amendment are parties
to that certain Trust Agreement dated as of October 19, 2000 as amended by the
First Amendment to Certain Operative Agreements dated as of September 17, 2001
among the parties hereto and the Second Amendment to Certain Operative
Agreements dated as of February 17, 2002 among the parties hereto, and certain
of the parties to this Amendment are parties to the other Operative Agreements
relating to a $55 million lease facility (the "Facility") that has been
established in favor of the Lessee;

      WHEREAS, the Lessee has requested certain modifications to the
Participation Agreement to, among other things, amend the liquidity requirements
of the Facility;
<PAGE>
      WHEREAS, the Financing Parties have agreed to the requested
modifications on the terms and conditions set forth herein;

      NOW, THEREFORE, IN CONSIDERATION of the premises and other good and
valuable consideration, the receipt and sufficiency of which is hereby
acknowledged, the parties agree as follows:

                             PARTICIPATION AGREEMENT

      1.    Section 8.3A(f) of the Participation Agreement is hereby amended
and restated in its entirety to read as follows:

                  "(f) Financial Covenant. The Consolidated Group shall at all
            times maintain Liquidity in an amount greater than or equal to (a)
            from the Initial Closing Date to the Final Completion Date,
            $45,000,000 and (b) on and after the Final Completion Date,
            $30,000,000. The Consolidated Group shall not permit any amount
            necessary to satisfy the Liquidity requirements of the previous
            sentence to be subject to any Lien or used as security or as a
            pledge for any obligation."

      2.    Appendix A-7 of the Participation Agreement is amended as follows:

            (a)   The definition of "Cash Equivalents" is hereby amended and
            restated in its entirety to read as follows:

                  "`Cash Equivalents' shall mean (a) securities issued or
            directly and fully guaranteed or insured by the United States or any
            agency or instrumentality thereof (provided that the full faith and
            credit of the United States is pledged in support thereof) having
            maturities of (i) not more than twelve months from the date of
            acquisition, or (ii) more than twelve months from the date of
            acquisition, but in such case under this subsection (ii) shall be
            valued at the market price thereof (which shall not in any event
            exceed $10,000,000 in the aggregate and shall be marked to market on
            the last Business Day of each calendar month), (b) Dollar
            denominated certificates of deposit of (i) any Lender or the Holder,
            or (ii) any domestic commercial bank of recognized standing (y)
            having capital and surplus in excess of $750,000,000 and (z) whose
            short-term commercial paper rating from S&P is at least A-1 or the
            equivalent thereof or from Moody's is at least P-1 or the equivalent
            thereof (any such bank being an "Approved Bank"), in each case with
            maturities of not more than twelve months from the date of
            acquisition, (c) commercial paper and variable or fixed rate notes
            issued by any Approved Bank (or by the parent company thereof) or
            any variable rate notes issued by, or guaranteed by, any domestic
            corporation rated A-1 (or the equivalent thereof) or better by S&P
            or P-1 (or the equivalent thereof) or better by Moody's and maturing
            within twelve months from the date of acquisition, (d) the common or
            preferred Capital Stock of any Person listed on a national
            securities exchange, (e) the commercial paper or notes (including
            medium term notes) or bonds of any Person having an unexpired
            remaining term and duration to maturity from each


                                       2
<PAGE>
            point of calculation not to exceed twelve months from the date of
            its inclusion as Cash Equivalents (i) whose short-term credit rating
            from S&P is at least A-1 or the equivalent thereof or from Moody's
            is at least P-1 or the equivalent thereof or from Fitch is at least
            F-1 or the equivalent thereof, or (ii) whose long-term credit rating
            from S&P is at least A or the equivalent thereof or from Moody's is
            at least A-2 or the equivalent thereof or from Fitch is at least A
            or the equivalent thereof, (f) the municipal bonds and/or notes of
            any Person having an unexpired remaining term and duration to
            maturity from each point of calculation not to exceed twelve months
            from the date of its inclusion as Cash Equivalents whose rating from
            S&P is at least AA- or the equivalent thereof or from Moody's is at
            least Aa3 or the equivalent thereof, (g) asset-backed securities of
            any Person having an unexpired remaining term and duration to
            maturity from each point of calculation not to exceed twelve months
            from the date of its inclusion as Cash Equivalents whose rating is
            at least AAA or the equivalent thereof by two of three rating
            agencies and (h) AAA-rated money market mutual funds; provided that
            all Cash Equivalents shall be of a type eligible to be held with a
            Federal Reserve Bank or the Depository Trust Company."

                                  MISCELLANEOUS

      1. This Amendment shall be effective upon satisfaction of the following
conditions (with regard to delivery of any documents, agreements, instruments,
UCC Amendments, certificates, budgets or other items, each of the forgoing shall
be in form and substance reasonably satisfactory to the Agent):

            (a)   (i) execution and delivery of this Amendment by the parties
      hereto and (ii) such other documents, agreements or instruments reasonably
      deemed necessary or advisable by the Agent;

            (b)   receipt by the Agent of an officer's certificate of the Lessee
      and the Construction Agent, dated as of the date hereof and in form and in
      substance reasonably satisfactory to the Agent, certifying that (i) each
      and every representation and warranty of the Lessee contained in the
      Operative Agreements to which it is a party is true and correct on and as
      of the date hereof; (ii) no Default or Event of Default has occurred and
      is continuing under any Operative Agreement; (iii) each Operative
      Agreement to which the Lessee is a party is in full force and effect with
      respect to it; and (iv) the Lessee has duly performed and complied with
      all covenants, agreements and conditions contained in any Operative
      Agreement required to be performed or complied with by it on or prior to
      the date hereof;

            (c)   receipt by the Agent of a secretary's certificate of the
      Lessee certifying (i) the continued effectiveness of the resolutions duly
      adopted by the Board of Directors of the Lessee approving and authorizing
      the execution, delivery and performance of amendments to the Operative
      Agreements, (ii) the continued effectiveness of the


                                       3
<PAGE>
      Certificate of Incorporation and Bylaws of the Lessee, and (iii) the
      incumbency or continued incumbency of the officer of the Lessee executing
      this Amendment;

            (d)   deposit by the Lessee of the appropriate amount (if any) into
      the Collateral Account in accordance with Sections 5.4(m) and 5.10 of the
      Participation Agreement and confirmation by the Agent of the appropriate
      funding (if any) of the Collateral Account as required in accordance with
      such Sections 5.4(m) and 5.10; and

            (e)   payment by the Lessee of all reasonable costs and expenses of
      the Agent in connection with the preparation, execution and delivery of
      this Amendment, including without limitation the reasonable fees and
      expenses of Moore & Van Allen PLLC.

      2.    By its execution hereof, each of the Construction Agent and the
Lessee represents, warrants and certifies to each Financing Party that as of the
date hereof (a) a Construction Budget and Plans and Specifications with respect
to each Property have been delivered to the Agent and such documents are true
and accurate and no changes have been made or could reasonably be expected to be
made which would affect the accuracy of such documents, (b) all Construction
Contracts have been previously delivered to the Agent and have not been amended
or modified, or such amendments or modifications have been previously provided
to the Agent, (c) the Property Cost of each Property is within the applicable
Construction Budget for such Property, (d) each Property is on schedule for
Completion on the date set forth in the Plans and Specifications of such
Property, but in all cases prior to the Construction Period Termination Date,
(e) there are sufficient Available Commitments and Available Holder Commitments
to cause the Completion of each Property as a Permitted Facility and otherwise
in accordance with the terms and conditions of the Operative Agreements, and (f)
all construction and Work with respect to each Property has been and is being
done in a workmanlike manner.

      3.    Except as modified hereby, all of the terms and provisions of the
Operative Agreements (including all Schedules and Exhibits thereto) shall remain
unmodified and in full force and effect. Except as modified hereby, the
Operative Agreements (including all Schedules and Exhibits thereto) represent
the entire agreement between the parties hereto with respect to the subject
matter thereof and there are no other oral or side agreements with respect to
such subject matter.

      4.    This Amendment may be executed in any number of counterparts, each
of which when so executed and delivered shall be deemed an original and it shall
not be necessary in making proof of this Amendment to produce or account for
more than one such counterpart.

      5.    This Amendment shall be deemed to be a contract made under, and for
all purposes shall be construed in accordance with, the laws of the State of
North Carolina other than amendments of the Trust Agreement and the Collateral
Agreement. With respect to the application of this Amendment to the Trust
Agreement, this Amendment shall be deemed to be a contract made under, and for
all purposes shall be construed in accordance with, the laws of the State of
Utah. With respect to the application of this Amendment to the Collateral
Agreement, this Amendment shall be deemed to be a contract made under, and for
all purposes shall be construed in accordance with, the laws of the State of
Texas.


                                       4
<PAGE>
      IN WITNESS WHEREOF, each of the parties hereto has caused a counterpart of
this Amendment to be duly executed and delivered as of the date first above
written.

                                    LEXICON GENETICS INCORPORATED, as the
                                    Construction Agent and as the Lessee

                                    By: /S/ JULIA P. GREGORY
                                       -------------------------------------
                                    Name:   Julia P. Gregory
                                         -----------------------------------
                                    Title:  Executive Vice President and CFO
                                          ----------------------------------

                                    WELLS FARGO BANK NORTHWEST, NATIONAL
                                    ASSOCIATION (formerly First Security Bank,
                                    National Association), not individually,
                                    except as expressly stated herein, but
                                    solely as the Owner Trustee under the Lexi
                                    Trust 2000-1

                                    By: /s/ VAL T. ORTON
                                       -------------------------------------
                                    Name:   Val T. Orton
                                         -----------------------------------
                                    Title:  Vice President
                                          ----------------------------------

                                    BANK OF AMERICA, N.A., as a Holder, as a
                                    Lender and as the Agent

                                    By: /s/ DANIEL H. PENKAR
                                       -------------------------------------
                                    Name:   Daniel H. Penkar
                                         -----------------------------------
                                    Title:  Senior Vice President
                                          ----------------------------------
<PAGE>

                                FOURTH AMENDMENT
                         TO CERTAIN OPERATIVE AGREEMENTS

                          Dated as of December 20, 2002

                                      among

                         LEXICON GENETICS INCORPORATED,
                  as the Construction Agent and as the Lessee,

                WELLS FARGO BANK NORTHWEST, NATIONAL ASSOCIATION
              (formerly First Security Bank, National Association)
    not individually, except as expressly stated in the Operative Agreements,
          but solely as the Owner Trustee under the Lexi Trust 2000-1,

                THE VARIOUS BANKS AND OTHER LENDING INSTITUTIONS
       WHICH ARE PARTIES TO THE PARTICIPATION AGREEMENT AND CERTAIN OTHER
                    OPERATIVE AGREEMENTS FROM TIME TO TIME,
                                 as the Holders,

                THE VARIOUS BANKS AND OTHER LENDING INSTITUTIONS
              WHICH ARE PARTIES TO THE PARTICIPATION AGREEMENT AND
              CERTAIN OTHER OPERATIVE AGREEMENTS FROM TIME TO TIME,
                                 as the Lenders,

                                       and

                             BANK OF AMERICA, N.A.,
                        as the Agent for the Lenders and,
                       respecting the Security Documents,
                      as the Agent for the Secured Parties
<PAGE>
                                FOURTH AMENDMENT
                         TO CERTAIN OPERATIVE AGREEMENTS

      This FOURTH AMENDMENT TO CERTAIN OPERATIVE AGREEMENTS (this "Amendment")
dated as of December 20, 2002, is by and among LEXICON GENETICS INCORPORATED, a
Delaware corporation (the "Lessee" or the "Construction Agent"); WELLS FARGO
BANK NORTHWEST, NATIONAL ASSOCIATION (formerly First Security Bank, National
Association), a national banking association, not individually but solely as the
Owner Trustee under the Lexi Trust 2000-1 (the "Owner Trustee" or the "Lessor");
the various banks and other lending institutions listed on the signature pages
hereto (subject to the definition of Lenders in Appendix A to the Participation
Agreement referenced below, individually, a "Lender" and collectively, the
"Lenders"); the various banks and other lending institutions listed on the
signature pages hereto as holders of certificates issued with respect to the
Lexi Trust 2000-1 (subject to the definition of Holders in Appendix A to the
Participation Agreement referenced below, individually, a "Holder" and
collectively, the "Holders"); and BANK OF AMERICA, N.A., a national banking
association, as the agent for the Lenders and, respecting the Security
Documents, as the agent for the Lenders and the Holders, to the extent of their
interests (in such capacity, the "Agent"). Capitalized terms used in this
Amendment but not otherwise defined herein shall have the meanings set forth in
Appendix A to the Participation Agreement (hereinafter defined) and the Rules of
Usage set forth in Appendix A to the Participation Agreement shall apply herein.

                               W I T N E S S E T H

      WHEREAS, the parties to this Amendment are parties to that certain
Participation Agreement dated as of October 19, 2000, as amended by the First
Amendment to Certain Operative Agreements dated as of September 17, 2001 (the
"First Amendment") among the parties hereto, the Second Amendment to Certain
Operative Agreements dated as of February 17, 2002 (the "Second Amendment")
among the parties hereto and the Third Amendment to Certain Operative Agreements
dated as of August 7, 2002 (the "Third Amendment") among the parties hereto (as
amended, modified, extended, supplemented, restated and/or replaced from time to
time in accordance with the terms thereof, the "Participation Agreement"),
certain of the parties to this Amendment are parties to that certain Credit
Agreement dated as of October 19, 2000, as amended by the First Amendment, the
Second Amendment and the Third Amendment, certain of the parties to this
Amendment are parties to that certain Trust Agreement dated as of October 19,
2000, as amended by the First Amendment, the Second Amendment and the Third
Amendment and certain of the parties to this Amendment are parties to the other
Operative Agreements relating to a $55 million lease facility (the "Facility")
that has been established in favor of the Lessee;

      WHEREAS, the Lessee has requested certain modifications to the
Participation Agreement to, among other things, amend the liquidity requirements
of the Facility;
<PAGE>
      WHEREAS, the minimum liquidity requirements required as of the Final
Completion Date as specified in Section 8.3A(f)(b) of the Participation
Agreement were modified from $35,000,000 to $30,000,000 pursuant to the Third
Amendment and are being further modified from $30,000,000 to $12,000,000
pursuant to this Amendment;

      WHEREAS, the Financing Parties have agreed to the requested
modifications on the terms and conditions set forth herein;

      NOW, THEREFORE, IN CONSIDERATION of the premises and other good and
valuable consideration, the receipt and sufficiency of which is hereby
acknowledged, the parties agree as follows:

                             PARTICIPATION AGREEMENT

      1.    Section 8.3A(f) of the Participation Agreement is hereby amended
and restated in its entirety to read as follows:

                  "(f) Financial Covenant. The Consolidated Group shall at all
            times maintain Liquidity in an amount greater than or equal to (a)
            from the Initial Closing Date to the Final Completion Date,
            $45,000,000 and (b) on and after the Final Completion Date,
            $12,000,000. The Consolidated Group shall not permit any amount
            necessary to satisfy the Liquidity requirements of the previous
            sentence to be subject to any Lien or used as security or as a
            pledge for any obligation. At the Initial Closing Date, the
            requirement regarding Liquidity on and after the Final Completion
            Date (as referenced in this Section 8.3A(f)(b)) was $35,000,000.
            Pursuant to the Third Amendment to Certain Operative Agreements
            dated as of August 7, 2002 among the parties to this Agreement, the
            requirement regarding Liquidity on and after the Final Completion
            Date (as referenced in this Section 8.3A(f)(b)) was reduced to
            $30,000,000. The requirement regarding Liquidity on and after the
            Final Completion Date (as referenced in this Section 8.3A(f)(b)) is
            now $12,000,000, as such is referenced in the first sentence of this
            paragraph."

      2.    Appendix A-4 and A-5 of the Participation Agreement are amended
as follows:

            (a) The definition of "Applicable Percentage" is hereby amended and
            restated in its entirety to read as follows:

                  ""Applicable Percentage" shall mean for each Eurodollar Loan
            and each Eurodollar Holder Advance, the rate per annum set forth
            below opposite the corresponding Class A Collateral Percentage
            determined as of the most recent Calculation Date:


                                       2
<PAGE>
<TABLE>
<CAPTION>
===============================================================================================
                                                         APPLICABLE
                                      APPLICABLE       PERCENTAGE FOR
                                      PERCENTAGE         EURODOLLAR            APPLICABLE
                                         FOR                HOLDER           PERCENTAGE FOR
 CLASS A COLLATERAL PERCENTAGE     EURODOLLAR LOANS        ADVANCES            UNUSED FEES
-----------------------------------------------------------------------------------------------
<S>                               <C>                  <C>                   <C>
       > or = 75%                     .20%                  .95%                   .20%
-----------------------------------------------------------------------------------------------
   > or = 50% BUT < 75%               .25%                 1.00%                   .2375%
-----------------------------------------------------------------------------------------------
   > or = 25% BUT < 50%               .30%                 1.05%                   .2375%
-----------------------------------------------------------------------------------------------
        < 25%                         .35%                 1.10%                   .2375%
===============================================================================================
</TABLE>

                  The Applicable Percentage for Eurodollar Loans and Eurodollar
            Holder Advances shall be determined and adjusted quarterly on the
            date (the "Calculation Date") by which the Officer's Certificate is
            required to be delivered to the Agent in accordance with the
            provisions of Section 5.10(b) of the Participation Agreement;
            provided, however, that (x) the Applicable Percentage for each
            Eurodollar Loan and Eurodollar Holder Advance from the Initial
            Closing Date until the next occurring Calculation Date shall be
            determined based on the Class A Collateral Percentage determined as
            of the date of such Advance, (y) if the Lessee fails to provide the
            Officer's Certificate referenced in Section 5.10(b) of the
            Participation Agreement to the Agent on or before any Calculation
            Date, the Applicable Percentage for Eurodollar Loans shall be .35%,
            the Applicable Percentage for Eurodollar Holder Advances shall be
            1.10% from such Calculation Date until such time that the Officer's
            Certificate referenced in Section 5.10(b) and the Applicable
            Percentage for Unused Fees shall be .2375% of the Participation
            Agreement is provided to the Agent, whereupon the Applicable
            Percentage shall be determined as specified above. Each Applicable
            Percentage shall be effective from one Calculation Date until the
            next Calculation Date. Any adjustment in the Applicable Percentage
            shall be applicable to all existing Eurodollar Loans and Eurodollar
            Holder Advances, as well as to any new Eurodollar Loans and
            Eurodollar Holder Advances made or issued."

                                  MISCELLANEOUS

      1. This Amendment shall be effective upon satisfaction of the following
conditions (with regard to delivery of any documents, agreements, instruments,
UCC Amendments, certificates, budgets or other items, each of the forgoing shall
be in form and substance reasonably satisfactory to the Agent):

            (a) (i) execution and delivery of this Amendment by the parties
      hereto and (ii) such other documents, agreements or instruments reasonably
      deemed necessary or advisable by the Agent;

            (b) receipt by the Agent of an officer's certificate of the Lessee
      and the Construction Agent, dated as of the date hereof and in form and in
      substance reasonably satisfactory to the Agent, certifying that (i) each
      and every representation and warranty of


                                       3
<PAGE>
      the Lessee contained in the Operative Agreements to which it is a party is
      true and correct on and as of the date hereof; (ii) no Default or Event of
      Default has occurred and is continuing under any Operative Agreement;
      (iii) each Operative Agreement to which the Lessee is a party is in full
      force and effect with respect to it; and (iv) the Lessee has duly
      performed and complied with all covenants, agreements and conditions
      contained in any Operative Agreement required to be performed or complied
      with by it on or prior to the date hereof;

            (c) receipt by the Agent of a secretary's certificate of the Lessee
      certifying (i) the continued effectiveness of the resolutions duly adopted
      by the Board of Directors of the Lessee approving and authorizing the
      execution, delivery and performance of amendments to the Operative
      Agreements, (ii) the continued effectiveness of the Certificate of
      Incorporation and Bylaws of the Lessee, and (iii) the incumbency or
      continued incumbency of the officer of the Lessee executing this
      Amendment;

            (d) deposit by the Lessee of the appropriate amount (if any) into
      the Collateral Account in accordance with Sections 5.4(m) and 5.10 of the
      Participation Agreement and confirmation by the Agent of the appropriate
      funding (if any) of the Collateral Account as required in accordance with
      such Sections 5.4(m) and 5.10; and

            (e) payment by the Lessee of all reasonable costs and expenses of
      the Agent in connection with the preparation, execution and delivery of
      this Amendment, including without limitation the reasonable fees and
      expenses of Moore & Van Allen PLLC.

      2. Except as modified hereby, all of the terms and provisions of the
Operative Agreements (including all Schedules and Exhibits thereto) shall remain
unmodified and in full force and effect. Except as modified hereby, the
Operative Agreements (including all Schedules and Exhibits thereto) represent
the entire agreement between the parties hereto with respect to the subject
matter thereof and there are no other oral or side agreements with respect to
such subject matter.

      3. This Amendment may be executed in any number of counterparts, each of
which when so executed and delivered shall be deemed an original and it shall
not be necessary in making proof of this Amendment to produce or account for
more than one such counterpart.

      4. This Amendment shall be deemed to be a contract made under, and for all
purposes shall be construed in accordance with, the laws of the State of North
Carolina other than amendments of the Trust Agreement and the Collateral
Agreement. With respect to the application of this Amendment to the Trust
Agreement, this Amendment shall be deemed to be a contract made under, and for
all purposes shall be construed in accordance with, the laws of the State of
Utah. With respect to the application of this Amendment to the Collateral
Agreement, this Amendment shall be deemed to be a contract made under, and for
all purposes shall be construed in accordance with, the laws of the State of
Texas.


                                       4
<PAGE>
      IN WITNESS WHEREOF, each of the parties hereto has caused a counterpart of
this Amendment to be duly executed and delivered as of the date first above
written.

                                    LEXICON GENETICS INCORPORATED, as the
                                    Construction Agent and as the Lessee

                                    By: /S/ JULIA P. GREGORY
                                       -------------------------------------
                                    Name:   Julia P. Gregory
                                         -----------------------------------
                                    Title:  Executive Vice President and CFO
                                          ----------------------------------

                                    WELLS FARGO BANK NORTHWEST, NATIONAL
                                    ASSOCIATION (formerly First Security Bank,
                                    National Association), not individually,
                                    except as expressly stated herein, but
                                    solely as the Owner Trustee under the Lexi
                                    Trust 2000-1

                                    By: /s/ VAL T. ORTON
                                       -------------------------------------
                                    Name:   Val T. Orton
                                         -----------------------------------
                                    Title:  Vice President
                                          ----------------------------------

                                    BANK OF AMERICA, N.A., as a Holder, as a
                                    Lender and as the Agent

                                    By: /s/ DANIEL H. PENKAR
                                       -------------------------------------
                                    Name:   Daniel H. Penkar
                                         -----------------------------------
                                    Title:  Senior Vice President
                                          ----------------------------------


