<PAGE>


                                                                   Exhibit 10.52


                     FIRST AMENDMENT TO EMPLOYMENT AGREEMENT

         THIS FIRST AMENDMENT TO EMPLOYMENT AGREEMENT (the "Amendment"), dated
as of September 1, 2002, is by and between GENAISSANCE PHARMACEUTICALS, INC., a
Delaware corporation (the "Corporation") and GUALBERTO RUANO ("Executive").

         WHEREAS, the Corporation and Executive have entered into that certain
Employment Agreement, dated as of August 24, 1998 (the "Employment Agreement");
and

         WHEREAS, the Corporation and Executive wish to amend the Employment
Agreement in the manner set forth in this Amendment.

         NOW THEREFORE, in consideration of the mutual covenants and agreements
hereinafter set forth, and other good and valuable consideration, the receipt
and sufficiency of which is hereby acknowledged, the parties hereto, intending
to be legally bound, agree as follows:

         1. DEFINED TERMS. Capitalized terms used herein but not defined in this
Amendment shall have the meaning given to such terms in the Employment
Agreement.

         2. Paragraph 1 of the Employment Agreement is hereby amended to read as
follows:

                  "1. EMPLOYMENT. The Corporation hereby continues the
         employment of Executive in the capacity of Vice Chairman of the Board
         and Chief Scientific Officer (collectively, the "CSO") of the
         Corporation during the term of this Agreement, and Executive hereby
         accepts such continued employment, on the terms and conditions
         hereinafter set forth. Executive represents that his employment by the
         Corporation pursuant to this Agreement does not violate any agreement,
         covenant or obligation to which he is a party or by which he is bound."

         3. Paragraph 2 of the Employment Agreement is hereby amended to read as
follows:

                  "2. DUTIES. During the term of this Agreement, Executive shall
         perform all duties, consistent with his position as CSO, assigned or
         delegated to him by the Board of Directors of the Corporation (the
         "Board") and normally associated with the position of CSO, and he shall
         devote his full business time and best efforts to the advancement of
         the interests and business of the Corporation. With regard to
         Employee's position as Chief Scientific Officer, by way of example, and
         not by way of limitation, Employee shall, in such capacity, have
         responsibility for the scientific strategy and policy of the
         Corporation. The Corporation will use its best efforts to cause
         Executive to continue to be elected a member of the Board throughout
         the Employment Term. The Corporation shall provide and maintain an
         office located in New Haven, Connecticut, from where Executive may
         perform his duties."

<PAGE>


         4. Paragraph 4.a. of the Employment Agreement is hereby amended to read
as follows:

                  "a. BASE SALARY. The Corporation shall pay Executive a Base
         Salary, payable in equal installments at such payment intervals as are
         the usual custom of the Corporation, but not less often than monthly,
         at an annual rate of $329,600, less such deductions or amounts to be
         withheld as shall be required by applicable law (the "Base Salary").
         The Base Salary shall be reviewed annually by the Board in the third
         quarter of each fiscal year of the Corporation (commencing with the
         fiscal year ending December 31, 1999) and shall be increased (effective
         as of September 1 in such fiscal year) by such amount, if any, as the
         Board, in its sole discretion, shall determine. Neither the Corporation
         nor the Board may reduce the Base Salary as so increased."

         5. Paragraph 4.c. (v) of the Employment Agreement is hereby amended to
read as follows:

                  "(v) Throughout the Employment Term, the Corporation, at its
         expense, shall furnish an automobile to Executive (owned or leased by
         the Corporation) commensurate with his position as CSO and shall
         reimburse Executive for reasonable maintenance, operating and insurance
         expenses incurred in the use of such automobile in connection with
         business activities conducted on behalf of the Corporation."

         6. Paragraph 4.d. of the Employment Agreement is hereby amended to read
as follows:

                  "d. SEVERANCE BENEFIT. If the Employment Term expires as a
         result of the Corporation delivering a Non-Extension Notice to
         Executive, then upon the expiration of the Employment Term, the
         Corporation shall be obligated to pay Executive the applicable amounts
         specified in Section 12.a. unless such Notice is delivered by the
         Corporation within twelve (12) months following a Change of Control (as
         hereinafter defined), in which event the Corporation shall be obligated
         to pay Executive the applicable amounts specified in Section 12.b. If
         Executive delivers to the Corporation a Non-Extension Notice at least
         120 days prior to the expiration of the Initial Term, such
         Non-Extension Notice shall be considered to have been delivered by the
         Corporation prior to a Change of Control."

         7. Paragraph 11.e. of the Employment Agreement is hereby amended to
read as follows:

                  "e. Executive may, at his option, upon thirty (30) days
         written notice to the Corporation, terminate his employment hereunder,
         if the Corporation, without Executive's express written consent,
         demotes him to a position and/or assigns him duties inconsistent with
         the position and/or duties described in Sections 1 or 2. Upon any
         termination by Executive under this Section 11.e., the Corporation
         shall be obligated to pay Executive the applicable amounts specified in
         Section 12.a.; provided that if a Change of Control (as hereinafter
         defined) has occurred within the preceding 12 months, then the
         Corporation shall be obligated to pay the amounts specified in Section
         12.b. rather than the amounts specified in Section 12.a. Prior to the
         expiration of the Initial Term, Executive may, at his option, upon
         thirty (30) days written notice to the

<PAGE>


         Corporation, terminate his employment hereunder and such termination
         shall be deemed a termination by Executive pursuant to this Section
         11.e. prior to a Change of Control. In the event the Corporation
         terminates Executive's employment For Cause under Sections 11.c.(i) or
         11.c.(iii) prior to the expiration of the Initial Term, such
         termination shall be deemed to be a termination by Executive pursuant
         to this Section 11.e. prior to a Change of Control."

         8. Paragraph 11.h. of the Employment Agreement is hereby amended to
read as follows:

                  "h. For purposes of this Agreement, the term "Good Reason"
         means, during the twelve (12) month period following a Change of
         Control, without Executive's express written consent, the occurrence of
         any of the following circumstances:

                  (i) the assignment to Executive of any duties inconsistent
         (except in the nature of a promotion) with the titles and positions in
         the Corporation (including, without limitation, titles and positions as
         a Director of the Corporation) that he held immediately prior to the
         Change of Control or substantial adverse alteration in the nature or
         status of his position or responsibilities or the conditions of his
         employment from those in effect immediately prior to the Change of
         Control;

                  (ii) a reduction by the Corporation in Executive's annual Base
         Salary as in effect on the date hereof, as the same may be increased
         from time to time; or

                  (iii) the failure by the Corporation to continue in effect any
         material compensation or benefit plan in which Executive participates
         immediately prior to the Change of Control unless an equitable
         arrangement (embodied in an ongoing substitute or alternative plan) has
         been made with respect to such plan, or the failure by the Corporation
         to continue Executive's participation therein (or in such substitute or
         alternative plan) on a basis not materially less favorable, both in
         terms of the amount of benefits provided and the level of his
         participation relative to other participants, than existed immediately
         prior to the Change of Control."

         9. ENTIRE AGREEMENT. The Employment Agreement, as amended by this
Amendment, contains the entire understanding between the parties hereto with
respect to the subject matter hereof and supersedes any prior or contemporaneous
contracts, agreements, understandings and/or negotiations, whether oral or
written.

                      [THE NEXT PAGE IS THE SIGNATURE PAGE]


<PAGE>


         IN WITNESS WHEREOF, the parties hereto have made this First Amendment
effective as of the day and year first above written.



                                  CORPORATION:

                                  GENAISSANCE PHARMACEUTICALS, INC.


                                  By: /s/ Kevin L. Rakin
                                      -----------------------------------------
                                  Name: Kevin L. Rakin
                                  Its President and Chief Executive Officer


                                   EXECUTIVE:


                                   /s/ Gualberto Ruano
                                   --------------------------------------------
                                   Gualberto Ruano