FIRST AMENDMENT TO THE AGREEMENT AND PLAN OF MERGER

EXHIBIT 2.2

FIRST AMENDMENT TO THE AGREEMENT AND PLAN OF MERGER

This First Amendment (this “Amendment”) to the Agreement and Plan of Merger is entered into by and between Paradigm Genetics, Inc. (“Parent”) and TissueInformatics.Inc (the “Company”) effective as of March 10, 2004.

WITNESSETH:

WHEREAS, on January 29, 2004 (the “Signing Date”), Parent, the Company and TVM V Life Science Ventures GMBH & Co. entered into an Agreement and Plan of Merger, pursuant to which the Company will be merged with and into Parent (the “Merger Agreement”); and

WHEREAS, Capitalized terms used herein but not defined shall have the meanings ascribed to such terms in the Merger Agreement; and

WHEREAS, the Aggregate Merger Consideration to be issued to Company Stockholders and holders of Company Options and Warrants is 6,500,000 shares of Parent Common Stock, subject to adjustment in accordance with the terms of the Merger Agreement; and

WHEREAS, during the Interim Period, certain Company Options lapsed and certain shares of Company Capital Stock were repurchased from such holders; and

WHEREAS, Section 2.10 of the Merger Agreement currently provides that the Common Stock Exchange Ratio, the Series A Exchange Ratio and the Series B Exchange Ratio are all subject to adjustment to fully reflect the effect of any change in outstanding Company Capital Stock during the Interim Period, including with respect to the lapsing of any Company Options and the repurchase of any Company Capital Stock; and

WHEREAS, Parent and the Company wish to amend Section 2.10 of the Merger Agreement to provide that any change in Company Capital Stock due to the lapsing of Company Options or the repurchase of Company Capital Stock during the Interim Period will result in adjustment of the Series A Exchange Ratio only; and

WHEREAS, pursuant to Section 10.7 of the Merger Agreement, the Merger Agreement (except for Articles III and VIII which shall also require the consent of the Indemnification Representative) may be amended by written consent of Parent and the Company pursuant to action taken by their Board of Directors; and

WHEREAS, pursuant to Section 251(d) and Section 228 of the Delaware Corporation Law, this Amendment has been approved by holders of outstanding stock of the Company having not less than the minimum number of votes that would be necessary to authorize this action at a meeting at which all shares entitled to vote thereon were present and voted.

NOW, THEREFORE, Parent and the Company agree to amend the Merger Agreement as follows:

Except as modified herein, the terms and conditions of the Merger Agreement shall remain in full force and effect.

This First Amendment may be executed in one or more counterparts, and by different parties hereto on separate counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument.

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IN WITNESS WHEREOF, this First Amendment has been executed as of the date first written above.

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Schedule I

EXHIBIT D

MILESTONE EVENTS

The actual share numbers and conversion ratios used herein are subject to proportional downward adjustment if the Aggregate Merger Consideration is adjusted downward pursuant to the adjustments set forth in the definition of Aggregate Merger Consideration set forth above.

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Schedule I

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