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                                                                 Exhibit 10.51.4

                       FIRST AMENDMENT TO CREDIT AGREEMENT

      Reference is hereby made to that certain Credit Agreement dated as of
December 28, 1998, by and between Genzyme Transgenics Corporation (the
"Borrower"), and Fleet National Bank ("Lender") (as amended, and as may be
further amended from time to time, the "Credit Agreement"). Capitalized terms
not defined herein shall have the meanings ascribed thereto in the Credit
Agreement.

      WHEREAS, the Borrower and Guarantor have requested that the Lender consent
to an increase the maximum amount of Dividends that may be paid to holders of
its Series A Convertible Preferred Stock for the redemption of such stock and
accrued Dividends thereon, and to agree to permit the payment of Dividends up to
a maximum amount for the purpose of the redemption of Series B Convertible
Preferred Stock and accrued Dividends thereon, and the Lender has agreed to such
change, subject to the terms and conditions of this First Amendment To Credit
Agreement (the "First Amendment").

      NOW, THEREFORE, for good and valuable consideration, the receipt of which
is hereby acknowledged, the parties do hereby agree as follows:

1. Dividends and Redemptions. The Credit Agreement is hereby amended as follows:

            a. Section 2.5 (Revolving Credit Loan Proceeds) of the Credit
Agreement is hereby amended by replacing the phrase "or to redeem shares of its
Series A Convertible Preferred Stock, face value $1,000 per share" with the
phrase "or to redeem shares of its Series B Convertible Preferred Stock, face
value $1,000 per share."

            b. Section 6.6 (Dividends and Redemptions) of the Credit Agreement
is hereby deleted and replaced with the following in lieu thereof:

            "6.6 Dividends and Redemptions. Pay or set aside any amount to pay
            any Dividends; provided, however, that, so long as no Default or
            Event of Default has occurred and is continuing, Borrower may pay
            Dividends to holders of its Series B Convertible Preferred Stock for
            the redemption of such stock and accrued Dividends payable in
            connection with such stock, up to a maximum amount of $15,000,000,
            in accordance with Schedule 6.6 which sets forth the payment
            schedule for the redemption of such stock."

            c. Schedule 6.6 to the Credit Agreement is hereby amended to replace
the sentence "The entire $11,500,000 could be used at any time to repurchase the
Series A Convertible Stock" as it appears therein the following sentence in lieu
thereof: "The entire $15,000,000 could be used at any time to repurchase the
Series B Convertible Stock"; and to replace the title thereof: "Series A
Convertible Stock Purchase Schedule" with the following title in lieu thereof:
"Series B Convertible Stock Purchase Schedule."

2. Consent. The Borrower and Guarantor have requested that the Lender consent to
the Borrower's payment of Dividends to holders of the Borrower's Series A
Convertible Preferred

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Stock for the redemption of such stock and accrued Dividends payable in
connection with such stock, up to a maximum amount of $12,650,000 (the "November
Redemption Transaction"). The funds to be used for such payments will consist of
the entire purchase price to be paid by the Guarantor to purchase Series B
Convertible Preferred Stock of the Borrower, up to a maximum of $12,500,000,
and, if the November Redemption Transaction requires total payments exceeding
$12,500,000, the remaining required amount of such payments will be provided by
the Borrower, up to a maximum amount of $150,000. The Lender's consent to the
payments contemplated by the November Redemption Transaction is required because
(a) prior to the effectiveness of this Amendment, Section 6.6 of the Credit
Agreement limits the total amount of such payments to $11,500,000, and the
maximum that the total aggregate payments required by the November Redemption
Transaction could be is $12,650,000, and (b) after the effectiveness of this
First Amendment, the Borrower may not make any payments of Dividends on account
of Series A Convertible Preferred Stock. The Lender hereby consents to the
Borrower's making such payments in connection with the November Redemption
Transaction.

3. Representations and Warranties. In order to induce the Lender to enter into
this First Amendment, the Borrower and Guarantor make the following
representations and warranties, all of which shall survive the execution and
delivery of this First Amendment:

      (a) Each of the Borrower and the Guarantor has all requisite corporate,
partnership or other power and authority to execute, deliver and perform its
obligations under this First Amendment and under the Credit Agreement, as
amended hereby. This First Amendment has been duly authorized, executed and
delivered by the Borrower and the Guarantor, and does not conflict with, violate
or result in a breach of or require any consent under any applicable law, rule
or regulation or any of the terms of the charter or by-laws (or equivalent
constitutional documents) of the Borrower or the Guarantor, any agreement or
instrument to which the Company, the Guarantor or any Subsidiary of either of
them is a party or to which any of them or their property is bound or to which
any of them is subject. This First Amendment and the Credit Agreement, as
amended hereby, constitute the legal, valid and binding obligation of the
Borrower and the Guarantor enforceable against each in accordance with its
terms.

      (b) On the date hereof each of the representations and warranties in the
Credit Agreement are true, accurate and complete in all material respects,
provided that, if any representation or warranty is expressly required in the
Credit Agreement to be made only as of a specific date, such representation or
warranty shall be true, accurate and complete as of such date in all material
respects.

      (c) Upon the execution and delivery of this First Amendment, and the
satisfaction of each of the conditions precedent set forth in Section 4 of this
First Amendment, no Default or Event of Default shall exist and be continuing.

4. Conditions Precedent. The agreements contained herein and the amendments
contemplated hereby shall become effective on the date (the "Effective Date")
when the Borrower, the Guarantor, and the Lender shall have executed this First
Amendment and when each of the following conditions shall have been fulfilled:

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      (a) Execution of Documents, Etc. This First Amendment and any other
agreements, documents and instruments to be executed and/or delivered in
connection herewith (collectively the "First Amendment Documents") shall have
been duly and properly authorized and executed by the Borrower, the Guarantor,
and the Lender and shall be in full force and effect on and as of the Effective
Date of this First Amendment and all representations and warranties of the
Borrower and Guarantor hereunder shall continue to be true, accurate and
complete.

      (b) Proceedings; Receipt of Documents. All requisite corporate action and
proceedings of the Borrower and Guarantor in connection with the execution and
delivery of this First Amendment and the other First Amendment Documents shall
be satisfactory in form and substance to the Lender and its counsel, and the
Lender and its counsel shall have received all information and copies of all
documents, including without limitation, records of requisite corporate action
and proceedings which the Lender or its counsel may have requested in connection
therewith, such documents where requested by the Lender or its counsel to be
certified by appropriate persons or governmental authorities.

      (c) Material Litigation. There shall be no pending or, to the best
knowledge of the Borrower, threatened litigation with respect to the Borrower or
the Guarantor before any court, arbitrator or governmental or administrative
body or agency which challenges or relates to (i) the transactions contemplated
hereby or (ii) the Loan Documents.

5. Reaffirmation and Ratification of Existing Agreements, Etc. Each of the
Borrower and the Guarantor: (i) reaffirms and ratifies all the Obligations to
the Lender, in respect of the Credit Agreement, as hereby amended, and the other
Loan Documents, (ii) certifies that there are no defenses, offsets or
counterclaims to such Obligations as of the date hereof , (iii) expressly
acknowledges its continuing liability pursuant thereto, and (iv) agrees that
each of the Credit Agreement, as amended hereby, and the other Loan Documents
shall remain in full force and effect, enforceable against the Borrower and
Guarantor in accordance with its terms.

6. Miscellaneous.

      (a) This First Amendment may be executed on separate counterparts by the
parties hereto, each of which when so executed and delivered shall be an
original, but all of which shall constitute one and the same agreement.

      (b) This First Amendment and the rights and obligations of the parties
hereunder shall be construed in accordance with and be governed by the laws of
the Commonwealth of Massachusetts (without giving effect to the conflict of law
principles thereof).

      (c) The headings of the several sections of this First Amendment are
inserted for convenience only and shall not in any way affect the meaning or
construction of any provision of this First Amendment.

      (d) This First Amendment, together with the other First Amendment
Documents, embodies the entire agreement and understanding among the parties
relating to the subject matter

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hereof and supersedes all prior proposals, negotiation, agreements and
understandings relating to such subject matter.

      (e) This First Amendment, together with the other First Amendment
Documents, shall be deemed to be Loan Documents under the Credit Agreement.

      (f) EACH OF THE BORROWER, THE GUARANTOR, AND THE LENDER HEREBY IRREVOCABLY
WAIVES, TO THE FULLEST EXTENT PERMITTED BY APPLICABLE LAW, ANY AND ALL RIGHT TO
TRIAL BY JURY IN ANY LEGAL PROCEEDING ARISING OUT OF OR RELATING TO THIS FIRST
AMENDMENT, OR THE TRANSACTIONS CONTEMPLATED HEREBY.

      (g) The Borrower shall pay on demand the reasonable costs and expenses,
including, without limitation, reasonable attorneys' fees and expenses incurred,
or which may be incurred by the Lender in connection with the negotiation,
documentation, administration and enforcement of this First Amendment.

      IN WITNESS WHEREOF, this First Amendment has been duly executed and
delivered as a sealed instrument at Boston, Massachusetts as of this 12th day of
November, 1999.

                                    THE BORROWER:

                                    GENZYME TRANSGENICS CORPORATION

                                    By: /s/ John B. Green
                                       ----------------------------
                                       Title:


                                    THE GUARANTOR:

                                    GENZYME CORPORATION

                                    By:
                                       ----------------------------
                                       Title:


                                    THE LENDER:

                                    FLEET NATIONAL BANK

                                    By:
                                       ----------------------------
                                       Title:

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hereof and supersedes all prior proposals, negotiation, agreements and
understandings relating to such subject matter.

      (e) This First Amendment, together with the other First Amendment
Documents, shall be deemed to be Loan Documents under the Credit Agreement.

      (f) EACH OF THE BORROWER, THE GUARANTOR, AND THE LENDER HEREBY IRREVOCABLY
WAIVES, TO THE FULLEST EXTENT PERMITTED BY APPLICABLE LAW, ANY AND ALL RIGHT TO
TRIAL BY JURY IN ANY LEGAL PROCEEDING ARISING OUT OF OR RELATING TO THIS FIRST
AMENDMENT, OR THE TRANSACTIONS CONTEMPLATED HEREBY.

      (g) The Borrower shall pay on demand the reasonable costs and expenses,
including, without limitation, reasonable attorneys' fees and expenses incurred,
or which may be incurred by the Lender in connection with the negotiation,
documentation, administration and enforcement of this First Amendment.

      IN WITNESS WHEREOF, this First Amendment has been duly executed and
delivered as a sealed instrument at Boston, Massachusetts as of this 12th day of
November, 1999.

                                    THE BORROWER:

                                    GENZYME TRANSGENICS CORPORATION

                                    By:
                                       ----------------------------
                                       Title:


                                    THE GUARANTOR:

                                    GENZYME CORPORATION

                                    By: /s/ Michael S. Wyzga
                                       ----------------------------
                                       Title:


                                    THE LENDER:

                                    FLEET NATIONAL BANK

                                    By:
                                       ----------------------------
                                       Title:

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hereof and supersedes all prior proposals, negotiation, agreements and
understandings relating to such subject matter.

      (e) This First Amendment, together with the other First Amendment
Documents, shall be deemed to be Loan Documents under the Credit Agreement.

      (f) EACH OF THE BORROWER, THE GUARANTOR, AND THE LENDER HEREBY IRREVOCABLY
WAIVES, TO THE FULLEST EXTENT PERMITTED BY APPLICABLE LAW, ANY AND ALL RIGHT TO
TRIAL BY JURY IN ANY LEGAL PROCEEDING ARISING OUT OF OR RELATING TO THIS FIRST
AMENDMENT, OR THE TRANSACTIONS CONTEMPLATED HEREBY.

      (g) The Borrower shall pay on demand the reasonable costs and expenses,
including, without limitation, reasonable attorneys' fees and expenses incurred,
or which may be incurred by the Lender in connection with the negotiation,
documentation, administration and enforcement of this First Amendment.

      IN WITNESS WHEREOF, this First Amendment has been duly executed and
delivered as a sealed instrument at Boston, Massachusetts as of this 12th day of
November, 1999.

                                    THE BORROWER:

                                    GENZYME TRANSGENICS CORPORATION

                                    By:
                                       ----------------------------
                                       Title:


                                    THE GUARANTOR:

                                    GENZYME CORPORATION

                                    By:
                                       ----------------------------
                                       Title:


                                    THE LENDER:

                                    FLEET NATIONAL BANK

                                    By: /s/ Kimberly Martone
                                       ----------------------------
                                       Title: SVP