content: <PAGE>   1
      As filed with the Securities and Exchange Commission on January 16, 1997
  
                                                             REGISTRATION NO. 333-
  ================================================================================
  --------------------------------------------------------------------------------
  
                         SECURITIES AND EXCHANGE COMMISSION
                               Washington, D. C. 20549
  
                             ---------------------------
  
  
                                      FORM S-8
  
                            REGISTRATION STATEMENT UNDER
                             THE SECURITIES ACT OF 1933
  
                             ---------------------------
  
  
                            TRANSKARYOTIC THERAPIES, INC.
               (Exact name of registrant as specified in its charter)
  
           DELAWARE                                               04-3027191
  (State or other jurisdiction                                 (I.R.S. Employer 
       of incorporation)                                      Identification No.)
  
   195 ALBANY STREET, CAMBRIDGE, MASSACHUSETTS                     02139 
    (Address of Principal Executive Offices)                     (Zip Code)
  
                             ---------------------------
  
  
  
                            1993 LONG-TERM INCENTIVE PLAN
                              (Full Title of the Plan)
  
                                  RICHARD F SELDEN
                        PRESIDENT AND CHIEF EXECUTIVE OFFICER
                            Transkaryotic Therapies, Inc.
                                  195 Albany Street
                                 Cambridge, MA 02139
                       (Name and Address of Agent For Service)
  
                                   (617) 349-0200
                       (Telephone Number, Including Area Code
                                of Agent For Service)
  
  
  
                             ---------------------------
  
  
  <TABLE>
                                                  CALCULATION OF REGISTRATION FEE
  <CAPTION>
  -------------------------------------------------------------------------------------------------------------------------------
      Title Of Securities To Be            Amount To Be              Proposed             Proposed Maximum          Amount Of
              Registered                    Registered           Maximum Offering        Aggregate Offering      Registration Fee
                                                                Price Per Share(1)            Price(1)
  -------------------------------------------------------------------------------------------------------------------------------
  <S>                                       <C>                     <C>                      <C>                    <C>          
  Common Stock, $0.01 par value             2,242,052               $18.625                  $41,758,218            $12,654
  -------------------------------------------------------------------------------------------------------------------------------
  <FN>
  (1)  Estimated solely for the purpose of determining the registration fee and computed pursuant to Rule 457(h) based upon the
       average of the high and low sale prices on January 10, 1997 as reported by the Nasdaq National Market System.
  </TABLE>
  ================================================================================
  
                                    Page 1 of 10
                           Exhibit Index appears at Page 8
  
  <PAGE>   2
  
                                       PART I
                INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS
  
       The information required by Part I is included in the documents sent or
  given to participants in the 1993 Long-Term Incentive Plan of Transkaryotic
  Therapies, Inc. (the "Registrant") pursuant to Rule 428(b)(1) of the Securities
  Act of 1933, as amended (the "Securities Act").
  
                                       PART II
                 INFORMATION REQUIRED IN THE REGISTRATION STATEMENT
  
  Item 3. Incorporation of Documents by Reference.
  ------------------------------------------------
  
       The Registrant is subject to the informational and reporting requirements
  of Sections 13(a), 14 and 15(d) of the Securities Exchange Act of 1934, as
  amended (the "Exchange Act"), and in accordance therewith files reports, proxy
  statements and other information with the Securities and Exchange Commission
  (the "Commission"). The following documents filed with the Commission are
  incorporated herein by reference:
  
       (a) The Registrant's latest annual report filed pursuant to Section 13(a)
  or 15(d) of the Exchange Act, or the latest prospectus filed pursuant to Rule
  424(b), or otherwise, under the Securities Act that contains, either directly or
  by incorporation by reference, audited financial statements for the Registrant's
  latest fiscal year for which such statements have been filed.
  
       (b) All reports filed by the Registrant pursuant to Section 13(a) or 15(d)
  of the Exchange Act since the end of the fiscal year covered by the annual
  report or prospectus referred to in (a) above.
  
       (c) The description of the common stock of the Registrant, par value $.01
  per share, (the "Common Stock"), contained in a registration statement filed
  under the Exchange Act, including any amendment or report filed for the purpose
  of updating such description.
  
       (d) The Registrant's definitive proxy statement or information statement,
  if any, filed pursuant to Section 14 of the Exchange Act in connection with the
  latest annual meeting of its stockholders, and any definitive proxy or
  information statements so filed in connection with any subsequent special
  meetings of its stockholders.
  
       (e) Information as to stock options, including the amount outstanding,
  exercises, prices and expiration dates, included in the Registrant's definitive
  proxy statement, described in (d) above and which will be included in the future
  either in the Registrant's proxy statements, annual reports or appendices to the
  prospectus.
  
       All documents filed after the date of this Registration Statement by the
  Registrant pursuant to Section 13(a), 13(d), 14 and 15(d) of the Exchange Act
  and prior to the filing of a post-effective amendment that indicates that all
  shares of Common Stock offered hereunder have been sold or which deregisters all
  shares of Common Stock remaining unsold shall be deemed to be incorporated by
  reference herein and to be a part hereof from the date of the filing of such
  reports and documents.
  
  
  Item 4. Description of Securities.
  ----------------------------------
  
       Not Applicable.
  
                                    Page 2 of 10
  
  <PAGE>   3
  
  Item 5. Interests of Named Experts and Counsel.
  -----------------------------------------------
  
       Not Applicable.
  
  Item 6. Indemnification of Directors and Officers.
  --------------------------------------------------
  
       Section 145 of the Delaware General Corporation Law permits the Registrant
  to indemnify directors, officers, employees and agents of the Registrant against
  actual and reasonable expenses (including attorneys' fees) incurred by them in
  connection with any action, suit or proceeding brought against them by reason of
  their status or service as a director, officer, employee or agent by or on
  behalf of the Registrant, and against expenses (including attorneys' fees),
  judgments, fines and settlements actually and reasonably incurred by him in
  connection with any such action, suit or proceeding, if (i) he acted in good
  faith and in a manner he reasonably believed to be in or not opposed to the best
  interests of the Registrant, and (ii) in the case of a criminal proceeding, he
  had no reasonable cause to believe his conduct was unlawful. Except as ordered
  by a court, no indemnification shall be made in connection with any proceeding
  brought by or in the right of the corporation where the person involved is
  adjudged to be liable to the Registrant.
  
       Article VII of the Registrant's Restated Certificate of Incorporation
  provides that a director shall not be personally liable to the Registrant or its
  stockholders for monetary damages for breach of fiduciary duty as a director,
  except to the extent that elimination or limitation of liability is not
  permitted under the Delaware General Corporation Law as in effect when such
  liability is determined.
  
       Article VIII of the Registrant's Restated Certificate of Incorporation
  provides that the Registrant shall, to the fullest extent permitted by the
  General Corporation Law of the State of Delaware, as amended from time to time,
  indemnify each person who was or is a party or is threatened to be made a party
  to any threatened, pending or completed action, suit or proceeding whether
  civil, criminal, administrative or investigative, by reason of the fact that he
  is or was, or has agreed to become a director or officer of the Registrant, or
  is or was serving, or has agreed to serve at the request of the Registrant as a
  director, officer or trustee of, or in a similar capacity with, another
  corporation, partnership, joint venture, trust or other enterprise. The
  indemnification provided for in Article VIII is expressly not exclusive of any
  other rights to which those seeking indemnification may be entitled under any
  law, agreement or vote of stockholders or disinterested directors or otherwise,
  and shall inure to the benefit of the heirs, executors and administrators of
  such persons. Article VIII further permits the Board of Directors to authorize
  the grant of indemnification rights to other employees and agents of the
  Registrant and such rights may be equivalent to, or greater or less than, those
  set forth in Article VIII.
  
       Article VIII of the Registrant's Restated Certificate of Incorporation also
  provides that the Registrant shall have the power to purchase and maintain
  insurance on behalf of any person who is or was a director, officer, employee or
  agent of the Registrant, or is or was serving at the request of the Registrant
  as a director, officer, employee or agent of another corporation, partnership,
  joint venture, trust or other enterprise against any liability asserted against
  such person and incurred by such person in any such capacity or arising out of
  such person's status as such. The Registrant maintains insurance for directors
  and officers.
  
       Article VIII, Section 8 of the Registrant's By-Laws provides that the
  Registrant shall indemnify any and all of its directors or officers, who serve
  as an officer or director of the Registrant or of any other corporation at the
  request of the Registrant, to the fullest extent permitted under and in
  accordance with the laws of the state of Delaware.
  
                                    Page 3 of 10
  
  <PAGE>   4
  
  Item 7. Exemption from Registration Claimed.
  --------------------------------------------
  
       Not Applicable.
  
  
  Item 8. Exhibits.
  -----------------
  
       The Exhibit Index immediately preceding the exhibits is incorporated herein
  by reference.
  
  
  Item 9. Undertakings.
  ---------------------
  
       (a) The undersigned Registrant hereby undertakes:
  
           (1) To file, during any period in which offers or sales are being
  made, a post-effective amendment to this registration statement:
  
               (i)   To include any prospectus required by Section 10(a)(3) of
  the Securities Act of 1933;
  
               (ii)  To reflect in the prospectus any facts or events arising
  after the effective date of this Registration Statement (or the most recent
  post-effective amendment thereof) which, individually or in the aggregate,
  represents a fundamental change in the information set forth in this
  Registration Statement;
  
               (iii) To include any material information with respect to the
  plan of distribution not previously disclosed in this Registration Statement or
  any material change to such information in this Registration Statement;
  
  PROVIDED, HOWEVER, that paragraphs (a)(1)(i) and (a)(1)(ii) do not apply if the
  information required to be included in a post-effective amendment by those
  paragraphs is contained in periodic reports filed by the Registrant pursuant to
  Section 13 or Section 15(d) of the Securities Exchange Act of 1934 that are
  incorporated by reference in this Registration Statement.
  
           (2) That, for the purpose of determining any liability under the
  Securities Act of 1933, each such post-effective amendment shall be deemed to be
  a new registration statement relating to the securities offered therein, and the
  offering of such securities at that time shall be deemed to be the initial bona
  fide offering thereof.
  
           (3) To remove from registration by means of a post-effective amendment
  any of the securities being registered which remain unsold at the termination of
  the offering.
  
       (b) The undersigned Registrant hereby undertakes that, for purposes of
  determining any liability under the Securities Act of 1933, each filing of the
  Registrant's annual report pursuant to Section 13(a) or Section 15(d) of the
  Securities Exchange Act of 1934 that is incorporated by reference in this
  Registration Statement shall be deemed to be a new registration statement
  relating to the securities offered therein, and the offering of such securities
  at that time shall be deemed to be the initial bona fide offering thereof.
  
                                    Page 4 of 10
  <PAGE>   5
  
       (c) Insofar as indemnification for liabilities arising under the Securities
  Act of 1933 may be permitted to directors, officers and controlling persons of
  the Registrant pursuant to the provisions referred to in Item 6 hereof, or
  otherwise, the Registrant has been advised that in the opinion of the Securities
  and Exchange Commission such indemnification is against public policy as
  expressed in the Act and is, therefore, unenforceable. In the event that a claim
  for indemnification against such liabilities (other than the payment by the
  Registrant of expenses incurred or paid by a director, officer or controlling
  person of the registrant in the successful defense of any action, suit or
  proceeding) is asserted by such director, officer or controlling person in
  connection with the securities being registered, the Registrant will, unless in
  the opinion of its counsel the matter has been settled by controlling precedent,
  submit to a court of appropriate jurisdiction the question whether such
  indemnification by it is against public policy as expressed in the Act and will
  be governed by the final adjudication of such issue.
  
                                    Page 5 of 10
  <PAGE>   6
  
                                     SIGNATURES
  
       Pursuant to the requirements of the Securities Act of 1933, the Registrant
  certifies that it has reasonable grounds to believe that it meets all of the
  requirements for filing on Form S-8 and has duly caused this Registration
  Statement to be signed on its behalf by the undersigned, thereunto duly
  authorized, in the City of Cambridge, Massachusetts, on this 16th day of
  January, 1997.
  
                                         TRANSKARYOTIC THERAPIES, INC.
  
  
                                         By: /s/ Richard F Selden
                                             --------------------------------
                                             Richard F Selden
                                             President and Chief Executive Officer
  
  
                                    Page 6 of 10
  
  <PAGE>   7
  
                                  POWER OF ATTORNEY
  
  
       We, the undersigned officers and directors of Transkaryotic Therapies, Inc.
  hereby severally constitute and appoint Richard F Selden and Michael Lytton, and
  each of them singly, our true and lawful attorneys-in-fact, with full power to
  them in any and all capacities, to sign any and all amendments to this
  Registration Statement on Form S-8 including any post-effective amendments
  thereto, and to file the same, with exhibits thereto and other documents in
  connection therewith, with the Securities and Exchange Commission, hereby
  ratifying and confirming all that each of said attorneys-in-fact may do or cause
  to be done by virtue hereof.
  
  <TABLE>
       Pursuant to the requirements of the Securities Act of 1933, this
  Registration Statement has been signed below by the following persons in the
  capacities and on the dates indicated:
  <CAPTION>
           SIGNATURE                      TITLE                              DATE
           ---------                      -----                              ----
  <S>                             <C>                                 <C>
   /s/ Richard F Selden           President, Chief Executive          January 16, 1997
  ----------------------------    Officer and Director
  Richard F Selden                (Principal Executive
                                  Officer)
  
  
   /s/ Anthony R. Hall            Vice President, Finance and         January 16, 1997
  ----------------------------    Administration; Chief Financial
  Anthony R. Hall                 Officer (Principal Financial and
                                  Accounting Officer)
  
  
   /s/ William R. Miller          Director                            January 16, 1997
  ----------------------------
  William R. Miller
  
  
  
   /s/ Rodman W. Moorhead, III    Director                            January 16, 1997
  ----------------------------
  Rodman W. Moorhead, III
  
  
   /s/ James E. Thomas            Director                            January 16, 1997
  ---------------------------
  James E. Thomas
  </TABLE>
  
                                    Page 7 of 10
  
  <PAGE>   8
                                 EXHIBIT INDEX
                                 -------------
  
  Exhibit Number                     Description                       Page Number
  --------------                     -----------                       -----------
  
       4.1       Restated Certificate of Incorporation of the
                 Registrant.                                               (1)
  
       4.2       Amended and Restated By-laws of the Registrant.           (1)
  
       4.3       Specimen certificate for shares of Common Stock,
                 $.01 par value per share of the Registrant.               (2)
  
       5.1       Opinion of Palmer & Dodge LLP as to the legality
                 of the securities registered hereunder.                    9
  
       23.1      Consent of Ernst & Young LLP, independent
                 auditors.                                                 10
  
       23.2      Consent of Palmer & Dodge LLP (contained in
                 Opinion of Palmer & Dodge LLP, filed as Exhibit
                 5.1).
  
       24.1      Power of Attorney (set forth on the signature page
                 to this Registration Statement).
  
  ------------------------------------
  (1)  Filed as an exhibit to the Registrant's Quarterly Report on Form 10-Q for
       the quarter ended September 30, 1996 (File No. 0-21481) on November 26,
       1996 and incorporated herein by reference.
  
  (2)  Filed as an exhibit to the Registrant's Registration Statement on Form S-1
       (File No. 333-10845) declared effective on October 16, 1996 and
       incorporated herein by reference.
  
  
                                    Page 8 of 10
metadata_documents: [{"type": "S-8", "sequence": "1", "description": "TRANSKARYOTIC THERAPIES, INC. INCENTIVE PLAN", "secsgml_size_bytes": 19178}]
metadata_filer: {"company-data": {"conformed-name": "TRANSKARYOTIC THERAPIES INC", "cik": "0000885259", "assigned-sic": "2836", "irs-number": "043027191", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-19915", "film-number": "97507058"}, "business-address": {"street1": "195 ALBANY STREET", "city": "CAMBRIDGE", "state": "MA", "zip": "02138", "phone": "6173490200"}}
text: 1
      As filed with the Securities and Exchange Commission on January 16, 1997
  
                                                             REGISTRATION NO. 333-
  ================================================================================
  --------------------------------------------------------------------------------
  
                         SECURITIES AND EXCHANGE COMMISSION
                               Washington, D. C. 20549
  
                             ---------------------------
  
                                      FORM S-8
  
                            REGISTRATION STATEMENT UNDER
                             THE SECURITIES ACT OF 1933
  
                             ---------------------------
  
                            TRANSKARYOTIC THERAPIES, INC.
               (Exact name of registrant as specified in its charter)
  
           DELAWARE                                               04-3027191
  (State or other jurisdiction                                 (I.R.S. Employer 
       of incorporation)                                      Identification No.)
  
   195 ALBANY STREET, CAMBRIDGE, MASSACHUSETTS                     02139 
    (Address of Principal Executive Offices)                     (Zip Code)
  
                             ---------------------------
  
                            1993 LONG-TERM INCENTIVE PLAN
                              (Full Title of the Plan)
  
                                  RICHARD F SELDEN
                        PRESIDENT AND CHIEF EXECUTIVE OFFICER
                            Transkaryotic Therapies, Inc.
                                  195 Albany Street
                                 Cambridge, MA 02139
                       (Name and Address of Agent For Service)
  
                                   (617) 349-0200
                       (Telephone Number, Including Area Code
                                of Agent For Service)
  
                             ---------------------------
  
                                                  CALCULATION OF REGISTRATION FEE
  -------------------------------------------------------------------------------------------------------------------------------
      Title Of Securities To Be            Amount To Be              Proposed             Proposed Maximum          Amount Of
              Registered                    Registered           Maximum Offering        Aggregate Offering      Registration Fee
                                                                Price Per Share(1)            Price(1)
  -------------------------------------------------------------------------------------------------------------------------------
  Common Stock, $0.01 par value             2,242,052               $18.625                  $41,758,218            $12,654
  -------------------------------------------------------------------------------------------------------------------------------
  (1)  Estimated solely for the purpose of determining the registration fee and computed pursuant to Rule 457(h) based upon the
       average of the high and low sale prices on January 10, 1997 as reported by the Nasdaq National Market System.
  ================================================================================
  
                                    Page 1 of 10
                           Exhibit Index appears at Page 8
  2
  
                                       PART I
                INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS
  
       The information required by Part I is included in the documents sent or
  given to participants in the 1993 Long-Term Incentive Plan of Transkaryotic
  Therapies, Inc. (the "Registrant") pursuant to Rule 428(b)(1) of the Securities
  Act of 1933, as amended (the "Securities Act").
  
                                       PART II
                 INFORMATION REQUIRED IN THE REGISTRATION STATEMENT
  
  Item 3. Incorporation of Documents by Reference.
  ------------------------------------------------
  
       The Registrant is subject to the informational and reporting requirements
  of Sections 13(a), 14 and 15(d) of the Securities Exchange Act of 1934, as
  amended (the "Exchange Act"), and in accordance therewith files reports, proxy
  statements and other information with the Securities and Exchange Commission
  (the "Commission"). The following documents filed with the Commission are
  incorporated herein by reference:
  
       (a) The Registrant's latest annual report filed pursuant to Section 13(a)
  or 15(d) of the Exchange Act, or the latest prospectus filed pursuant to Rule
  424(b), or otherwise, under the Securities Act that contains, either directly or
  by incorporation by reference, audited financial statements for the Registrant's
  latest fiscal year for which such statements have been filed.
  
       (b) All reports filed by the Registrant pursuant to Section 13(a) or 15(d)
  of the Exchange Act since the end of the fiscal year covered by the annual
  report or prospectus referred to in (a) above.
  
       (c) The description of the common stock of the Registrant, par value $.01
  per share, (the "Common Stock"), contained in a registration statement filed
  under the Exchange Act, including any amendment or report filed for the purpose
  of updating such description.
  
       (d) The Registrant's definitive proxy statement or information statement,
  if any, filed pursuant to Section 14 of the Exchange Act in connection with the
  latest annual meeting of its stockholders, and any definitive proxy or
  information statements so filed in connection with any subsequent special
  meetings of its stockholders.
  
       (e) Information as to stock options, including the amount outstanding,
  exercises, prices and expiration dates, included in the Registrant's definitive
  proxy statement, described in (d) above and which will be included in the future
  either in the Registrant's proxy statements, annual reports or appendices to the
  prospectus.
  
       All documents filed after the date of this Registration Statement by the
  Registrant pursuant to Section 13(a), 13(d), 14 and 15(d) of the Exchange Act
  and prior to the filing of a post-effective amendment that indicates that all
  shares of Common Stock offered hereunder have been sold or which deregisters all
  shares of Common Stock remaining unsold shall be deemed to be incorporated by
  reference herein and to be a part hereof from the date of the filing of such
  reports and documents.
  
  Item 4. Description of Securities.
  ----------------------------------
  
       Not Applicable.
  
                                    Page 2 of 10
  3
  
  Item 5. Interests of Named Experts and Counsel.
  -----------------------------------------------
  
       Not Applicable.
  
  Item 6. Indemnification of Directors and Officers.
  --------------------------------------------------
  
       Section 145 of the Delaware General Corporation Law permits the Registrant
  to indemnify directors, officers, employees and agents of the Registrant against
  actual and reasonable expenses (including attorneys' fees) incurred by them in
  connection with any action, suit or proceeding brought against them by reason of
  their status or service as a director, officer, employee or agent by or on
  behalf of the Registrant, and against expenses (including attorneys' fees),
  judgments, fines and settlements actually and reasonably incurred by him in
  connection with any such action, suit or proceeding, if (i) he acted in good
  faith and in a manner he reasonably believed to be in or not opposed to the best
  interests of the Registrant, and (ii) in the case of a criminal proceeding, he
  had no reasonable cause to believe his conduct was unlawful. Except as ordered
  by a court, no indemnification shall be made in connection with any proceeding
  brought by or in the right of the corporation where the person involved is
  adjudged to be liable to the Registrant.
  
       Article VII of the Registrant's Restated Certificate of Incorporation
  provides that a director shall not be personally liable to the Registrant or its
  stockholders for monetary damages for breach of fiduciary duty as a director,
  except to the extent that elimination or limitation of liability is not
  permitted under the Delaware General Corporation Law as in effect when such
  liability is determined.
  
       Article VIII of the Registrant's Restated Certificate of Incorporation
  provides that the Registrant shall, to the fullest extent permitted by the
  General Corporation Law of the State of Delaware, as amended from time to time,
  indemnify each person who was or is a party or is threatened to be made a party
  to any threatened, pending or completed action, suit or proceeding whether
  civil, criminal, administrative or investigative, by reason of the fact that he
  is or was, or has agreed to become a director or officer of the Registrant, or
  is or was serving, or has agreed to serve at the request of the Registrant as a
  director, officer or trustee of, or in a similar capacity with, another
  corporation, partnership, joint venture, trust or other enterprise. The
  indemnification provided for in Article VIII is expressly not exclusive of any
  other rights to which those seeking indemnification may be entitled under any
  law, agreement or vote of stockholders or disinterested directors or otherwise,
  and shall inure to the benefit of the heirs, executors and administrators of
  such persons. Article VIII further permits the Board of Directors to authorize
  the grant of indemnification rights to other employees and agents of the
  Registrant and such rights may be equivalent to, or greater or less than, those
  set forth in Article VIII.
  
       Article VIII of the Registrant's Restated Certificate of Incorporation also
  provides that the Registrant shall have the power to purchase and maintain
  insurance on behalf of any person who is or was a director, officer, employee or
  agent of the Registrant, or is or was serving at the request of the Registrant
  as a director, officer, employee or agent of another corporation, partnership,
  joint venture, trust or other enterprise against any liability asserted against
  such person and incurred by such person in any such capacity or arising out of
  such person's status as such. The Registrant maintains insurance for directors
  and officers.
  
       Article VIII, Section 8 of the Registrant's By-Laws provides that the
  Registrant shall indemnify any and all of its directors or officers, who serve
  as an officer or director of the Registrant or of any other corporation at the
  request of the Registrant, to the fullest extent permitted under and in
  accordance with the laws of the state of Delaware.
  
                                    Page 3 of 10
  4
  
  Item 7. Exemption from Registration Claimed.
  --------------------------------------------
  
       Not Applicable.
  
  Item 8. Exhibits.
  -----------------
  
       The Exhibit Index immediately preceding the exhibits is incorporated herein
  by reference.
  
  Item 9. Undertakings.
  ---------------------
  
       (a) The undersigned Registrant hereby undertakes:
  
           (1) To file, during any period in which offers or sales are being
  made, a post-effective amendment to this registration statement:
  
               (i)   To include any prospectus required by Section 10(a)(3) of
  the Securities Act of 1933;
  
               (ii)  To reflect in the prospectus any facts or events arising
  after the effective date of this Registration Statement (or the most recent
  post-effective amendment thereof) which, individually or in the aggregate,
  represents a fundamental change in the information set forth in this
  Registration Statement;
  
               (iii) To include any material information with respect to the
  plan of distribution not previously disclosed in this Registration Statement or
  any material change to such information in this Registration Statement;
  
  PROVIDED, HOWEVER, that paragraphs (a)(1)(i) and (a)(1)(ii) do not apply if the
  information required to be included in a post-effective amendment by those
  paragraphs is contained in periodic reports filed by the Registrant pursuant to
  Section 13 or Section 15(d) of the Securities Exchange Act of 1934 that are
  incorporated by reference in this Registration Statement.
  
           (2) That, for the purpose of determining any liability under the
  Securities Act of 1933, each such post-effective amendment shall be deemed to be
  a new registration statement relating to the securities offered therein, and the
  offering of such securities at that time shall be deemed to be the initial bona
  fide offering thereof.
  
           (3) To remove from registration by means of a post-effective amendment
  any of the securities being registered which remain unsold at the termination of
  the offering.
  
       (b) The undersigned Registrant hereby undertakes that, for purposes of
  determining any liability under the Securities Act of 1933, each filing of the
  Registrant's annual report pursuant to Section 13(a) or Section 15(d) of the
  Securities Exchange Act of 1934 that is incorporated by reference in this
  Registration Statement shall be deemed to be a new registration statement
  relating to the securities offered therein, and the offering of such securities
  at that time shall be deemed to be the initial bona fide offering thereof.
  
                                    Page 4 of 10
  5
  
       (c) Insofar as indemnification for liabilities arising under the Securities
  Act of 1933 may be permitted to directors, officers and controlling persons of
  the Registrant pursuant to the provisions referred to in Item 6 hereof, or
  otherwise, the Registrant has been advised that in the opinion of the Securities
  and Exchange Commission such indemnification is against public policy as
  expressed in the Act and is, therefore, unenforceable. In the event that a claim
  for indemnification against such liabilities (other than the payment by the
  Registrant of expenses incurred or paid by a director, officer or controlling
  person of the registrant in the successful defense of any action, suit or
  proceeding) is asserted by such director, officer or controlling person in
  connection with the securities being registered, the Registrant will, unless in
  the opinion of its counsel the matter has been settled by controlling precedent,
  submit to a court of appropriate jurisdiction the question whether such
  indemnification by it is against public policy as expressed in the Act and will
  be governed by the final adjudication of such issue.
  
                                    Page 5 of 10
  6
  
                                     SIGNATURES
  
       Pursuant to the requirements of the Securities Act of 1933, the Registrant
  certifies that it has reasonable grounds to believe that it meets all of the
  requirements for filing on Form S-8 and has duly caused this Registration
  Statement to be signed on its behalf by the undersigned, thereunto duly
  authorized, in the City of Cambridge, Massachusetts, on this 16th day of
  January, 1997.
  
                                         TRANSKARYOTIC THERAPIES, INC.
  
                                         By: /s/ Richard F Selden
                                             --------------------------------
                                             Richard F Selden
                                             President and Chief Executive Officer
  
                                    Page 6 of 10
  7
  
                                  POWER OF ATTORNEY
  
       We, the undersigned officers and directors of Transkaryotic Therapies, Inc.
  hereby severally constitute and appoint Richard F Selden and Michael Lytton, and
  each of them singly, our true and lawful attorneys-in-fact, with full power to
  them in any and all capacities, to sign any and all amendments to this
  Registration Statement on Form S-8 including any post-effective amendments
  thereto, and to file the same, with exhibits thereto and other documents in
  connection therewith, with the Securities and Exchange Commission, hereby
  ratifying and confirming all that each of said attorneys-in-fact may do or cause
  to be done by virtue hereof.
  
       Pursuant to the requirements of the Securities Act of 1933, this
  Registration Statement has been signed below by the following persons in the
  capacities and on the dates indicated:
  SIGNATURE                      TITLE                              DATE
           ---------                      -----                              ----
  /s/ Richard F Selden           President, Chief Executive          January 16, 1997
  ----------------------------    Officer and Director
  Richard F Selden                (Principal Executive
                                  Officer)
  
   /s/ Anthony R. Hall            Vice President, Finance and         January 16, 1997
  ----------------------------    Administration; Chief Financial
  Anthony R. Hall                 Officer (Principal Financial and
                                  Accounting Officer)
  
   /s/ William R. Miller          Director                            January 16, 1997
  ----------------------------
  William R. Miller
  
   /s/ Rodman W. Moorhead, III    Director                            January 16, 1997
  ----------------------------
  Rodman W. Moorhead, III
  
   /s/ James E. Thomas            Director                            January 16, 1997
  ---------------------------
  James E. Thomas
  Page 7 of 10
  8
                                 EXHIBIT INDEX
                                 -------------
  
  Exhibit Number                     Description                       Page Number
  --------------                     -----------                       -----------
  
       4.1       Restated Certificate of Incorporation of the
                 Registrant.                                               (1)
  
       4.2       Amended and Restated By-laws of the Registrant.           (1)
  
       4.3       Specimen certificate for shares of Common Stock,
                 $.01 par value per share of the Registrant.               (2)
  
       5.1       Opinion of Palmer & Dodge LLP as to the legality
                 of the securities registered hereunder.                    9
  
       23.1      Consent of Ernst & Young LLP, independent
                 auditors.                                                 10
  
       23.2      Consent of Palmer & Dodge LLP (contained in
                 Opinion of Palmer & Dodge LLP, filed as Exhibit
                 5.1).
  
       24.1      Power of Attorney (set forth on the signature page
                 to this Registration Statement).
  
  ------------------------------------
  (1)  Filed as an exhibit to the Registrant's Quarterly Report on Form 10-Q for
       the quarter ended September 30, 1996 (File No. 0-21481) on November 26,
       1996 and incorporated herein by reference.
  
  (2)  Filed as an exhibit to the Registrant's Registration Statement on Form S-1
       (File No. 333-10845) declared effective on October 16, 1996 and
       incorporated herein by reference.
  
                                    Page 8 of 10