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                                  EXHIBIT 10.1

                          TRANSKARYOTIC THERAPIES, INC.

                          1993 LONG-TERM INCENTIVE PLAN

                                TABLE OF CONTENTS

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<S>                                                                       <C>
1.       PURPOSE                                                           1

2.       DEFINITIONS                                                       1
            2.1.  Affiliate                                                1
            2.2.  Award                                                    1
            2.3.  Board                                                    1
            2.4.  Code                                                     1
            2.5.  Committee                                                1
            2.6.  Company                                                  1
            2.7.  Employment Agreement                                     1
            2.8.  Fair Market Value                                        2
            2.9.  Incentive Option                                         2
            2.10. Long-Term Performance Award or Long-Term Award           2
            2.11. Nonstatutory Option                                      2
            2.12. Participant                                              2
            2.13. Plan                                                     2
            2.14. Restricted Stock                                         2
            2.15. Stock                                                    2
            2.16. Shareholders Agreement                                   2
            2.17. Stock Appreciation Right                                 2
            2.18. Stock Grant                                              2
            2.19. Stock Option or Option                                   2
            2.20. Ten Percent Owner                                        3

3.    TERM OF THE PLAN                                                     3

4.    STOCK SUBJECT TO THE PLAN                                            3

5.    ADMINISTRATION                                                       4

6.    ELIGIBILITY                                                          5

7.    STOCK OPTIONS                                                        5
            7.1.  Provision for Grant                                      5
            7.2.  Terms and Conditions                                     5

8.    STOCK APPRECIATION RIGHTS                                            8
            8.1.  Provision for Grant                                      8


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            8.2.  Termination                                              8
            8.3.  Manner and Effect of Exercise                            8
            8.4.  Other Terms and Conditions                               9

9.    RESTRICTED STOCK                                                     9
            9.1.  Provision for Grant                                      9
            9.2.  Awards and Certificates                                  9
            9.3   Additional Terms and Conditions                          9

10.   LONG-TERM PERFORMANCE AWARDS                                        11
            10.1. Provision for Grant                                     11
            10.2. Periodic Determination of Performance                   11
            10.3. Adjustment of Awards                                    11
            10.4. Effect of Termination of Employment or Association      12
            10.5. Form of Payment                                         12

11.   STOCK GRANTS                                                        12

12.   RESTRICTIONS ON ISSUANCE OF SHARES                                  12
            12.1. Securities Laws                                         12
            12.2. Investment Representation                               13
            12.3. Placement of Legends; Stop Orders; etc                  13
            12.4. Registration                                            13
            12.5. Applicability of Shareholders Agreement                 14

13.   EFFECT OF CERTAIN TRANSACTIONS                                      14
            13.1. Liquidation or Dissolution of the Company               14
            13.2. Sale of Assets, Merger or Consolidation                 14

14.   TERMINATION AND AMENDMENT OF THE PLAN AND AWARDS                    14

15.   MISCELLANEOUS PROVISIONS                                            15
            15.1  Unfunded Status of Plan                                 15
            15.2. Adoption of Other Plans                                 15
            15.3. Payments on Death                                       15
            15.4. Tax Withholding                                         15
            15.5. Limitation of Rights in Stock                           16
            15.6. No Special Employment or Other Rights                   16
            15.7. Notices and Other Communications                        16
            15.8. Governing Law.                                          16

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                          TRANSKARYOTIC THERAPIES, INC.

                          1993 LONG-TERM INCENTIVE PLAN

1.    PURPOSE

      The purpose of this Plan is to enable key employees of and consultants to
Transkaryotic Therapies, Inc. (the "Company") to (i) own shares of stock in the
Company, (ii) participate in the shareholder value which has been created, (iii)
have a mutuality of interest with other shareholders and (iv) enable the Company
to attract, retain and motivate key employees and consultants of particular
merit.

2.    DEFINITIONS

      For the purposes of the Plan, the following terms shall have the meanings
set forth below:

      2.1. Affiliate means a parent or subsidiary corporation of the Company, as
defined in Sections 424(e) and (f), respectively, of the Code.

      2.2. Award means the grant or sale pursuant to the Plan of any of Stock
Options, Restricted Stock, Stock Appreciation Rights, Stock Grants, and Long
Term Awards.

      2.3. Board means the Board of Directors of the Company.

      2.4. Code means the federal Internal Revenue Code of 1986, as amended from
time to time, or any statute successor thereto, and any regulations issued from
time to time thereunder.

      2.5. Committee means a committee appointed by the Board, responsible for
the administration of the Plan, as provided in Section 5 of the Plan. No member
of the Committee shall be eligible to receive an Award under the Plan, and no
individual shall be eligible for membership on the Committee within one year of
having received an Award under the Plan. For any period during which no such
committee is in existence all authority and responsibility assigned the
Committee under the Plan shall be exercised, if at all, by the Board.

      2.6. Company means Transkaryotic Therapies, Inc., a corporation organized
under the laws of the State of Delaware.

      2.7. Employment Agreement means an agreement, if any, between the Company
and a Participant, setting forth, inter alia, conditions and restrictions upon
the transfer of shares of Stock.

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                                       -2-


      2.8. Fair Market Value means, as of any given date, the last reported
sales price of the Stock as reported in The Wall Street Journal for such date
or, if either no such sale is reported or the Stock is not publicly traded on or
as of such date, the fair market value of the Stock as determined by the
Committee in good faith based on the available facts and circumstances at the
time.

      2.9. Incentive Option means an Option which by its terms is to be treated
as an "incentive stock option" within the meaning of Section 422 of the Code.

      2.10. Long-Term Performance Award or Long-Term Award means an award made
pursuant to Section 10 below that is payable in cash and/or Stock (including
Restricted Stock) in accordance with the terms of the grant, based on Company,
business unit and/or individual performance.

      2.11. Nonstatutory Option means any Option that is not an Incentive
Option.

      2.12. Participant means an employee or consultant to whom an Award, as
provided in Section 6, shall have been granted under the Plan.

      2.13. Plan means this 1993 Long-Term Incentive Plan of the Company, as
amended from time to time.

      2.14. Restricted Stock means an Award pursuant to Section 9 below of
shares of Stock subject to restrictions or other forfeiture conditions.

      2.15. Stock means Common Stock, par value $.01 per share of the Company.

      2.16. Shareholders Agreement means the agreement, if any, between the
Company and certain shareholders, setting forth, inter alia, certain
restrictions upon the transfer of shares of Stock.

      2.17. Stock Appreciation Right means the right, pursuant to an Award
granted under Section 8 below, to surrender to the Company all (or a portion) of
a Stock Option in exchange for an amount equal to the difference between (i) the
Fair Market Value, as of the date such Stock Option (or such portion thereof) is
surrendered, of the shares of Stock covered by such Stock Option (or such
portion thereof), and (ii) the aggregate exercise price of such Stock Option (or
such portion thereof).

      2.18. Stock Grant means an Award pursuant to Section 11 below of shares of
Stock not subject to restrictions or other forfeiture conditions.

      2.19. Stock Option or Option means any option to purchase shares of Stock
(including Restricted Stock) granted pursuant to Section 7 below.
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                                       -3-


      2.20. Ten Percent Owner means a person who owns, or is deemed within the
meaning of Section 422(b)(6) of the Code to own, stock possessing more than 10%
of the total combined voting power of all classes of stock of the Company (or
any Affiliate). Whether a person is a Ten Percent Owner shall be determined with
respect to an Incentive Option based on the facts existing immediately prior to
the grant date of such Option.

3.    TERM OF THE PLAN

      Unless the Plan shall have been earlier terminated by the Board, Awards
may be granted hereunder at any time in the period commencing on the approval of
the Plan by the Board and ending on the tenth anniversary of the earlier of the
adoption of the Plan by the Board or approval of the Plan by the Company's
shareholders. Awards granted pursuant to the Plan within such period shall not
expire solely by reason of the termination of the Plan.

4.    STOCK SUBJECT TO THE PLAN

      (a) Aggregate Limit On Awards. At no time shall the number of shares of
Stock issued pursuant to Awards granted under the Plan exceed 1,250,000 shares,
subject, however, to the provisions of subsection (c) below. Such shares may be
either authorized but unissued shares or shares held by the Company in its
treasury. The Company shall at all times reserve and make available in
sufficient number of shares to meet the requirements of the Plan, provided that
following termination of the Plan the number of shares reserved need not exceed
the number of Shares issuable under Awards outstanding from time to time
thereafter.

      (b) Computation of Available Shares. For the purpose of computing the
total number of shares of Stock available for Plan purposes at any time during
which the Plan is in effect, there shall be debited against the total number of
shares determined to be available pursuant to paragraphs (a) and (c) of this
Section 4(i) any outstanding Restricted Stock and Stock Grants, (ii) the maximum
number of shares of Stock subject to issuance upon exercise of Options or upon
settlement of other Awards theretofore made under the Plan, (iii) the shares
related to the unexercised or undistributed portion of any terminated, expired
or forfeited Award for which a material benefit was received by a Participant
(e.g. dividends, but not including voting rights), and the equivalent number of
shares (determined as of the date of settlement) of any portion of any Award
settled in cash.

      (c) Other Adjustment. In the event of any merger, reorganization,
consolidation, recapitalization, Stock dividend, or other change in corporate
structure affecting the Stock, such substitution or adjustment shall be made in
the character and aggregate number of shares reserved for issuance under the
Plan, and in the number and option price of shares subject to outstanding
Options and other stock based Awards granted under the Plan, as may be
determined to be appropriate by the Committee, provided that the number of
shares subject to any Award shall

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                                       -4-


always be a whole number. Any such adjusted option price shall also be used to
determine the amount payable by the Company upon the exercise of any Stock
Appreciation Right associated with any Stock Option.

5.    ADMINISTRATION

      The Plan shall be administered by the Committee. Subject to the provisions
of the Plan, the Committee shall have complete authority, in its sole
discretion, to make or to select the manner of making any and all determinations
required for the operation of the Plan, and without limiting the generality of
the foregoing, shall have the authority to

      (a) grant to eligible individuals, pursuant to the terms of the Plan: (i)
Stock Options, (ii) Stock Appreciation Rights, (iii) Restricted Stock, (iv)
Long-Term Performance Awards, and (v) Stock Grants;

      (b) select from time to time the officers, other employees and consultants
of the Company and its Affiliates to whom Awards shall be granted hereunder;

      (c) determine whether and to what extent Incentive Options, Nonstatutory
Options, Stock Appreciation rights, Restricted Stock, Long-Term Performance
Awards and Stock Grants or any combination thereof, are to be granted hereunder;

      (d) determine the number of shares of Stock to be covered by each Award
granted hereunder;

       (e) determine the terms and conditions, not inconsistent with the terms
of the Plan, of any Award (which need not be identical in every case),
including, but not limited to, the share price and any restriction or
limitation, or any vesting acceleration or forfeiture waiver regarding any Stock
Option or other Award and the shares of Stock relating thereto, based on such
factors as the Committee shall determine;

      (f) determine whether and under what circumstances a Stock Option may be
settled in cash or Stock, including Restricted Stock, as provided in Section
7.2;

      (g) determine whether and under what circumstances a Stock Option may be
exercised without a payment of cash as provided in Section 7.2; and

      (h) determine whether, to what extent and under what circumstances Stock
and other amounts payable with respect to an Award under this Plan shall be
deferred either automatically or at the election of the Participant.

      In making such determinations, the Committee may take into account the
nature of the services rendered by the respective employees and consultants,
their

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                                       -5-


present and potential contributions to the success of the Company and its
Affiliates, and such other factors as the Committee in its discretion shall deem
relevant. Subject to the provisions of the Plan, the Committee shall also have
complete authority, in its sole discretion, to interpret the Plan, to prescribe,
amend and rescind rules and regulations relating to it, to determine the terms
and provisions of any Award issued under the Plan (and any agreements relating
thereto), to resolve all disputes arising under the Plan, and to make all other
determinations necessary or advisable for the administration of the Plan. The
Committee's determinations shall be conclusive, final and binding upon all
persons having or claiming any interest in the Plan or in any Award pursuant to
the Plan.

6.    ELIGIBILITY

      Awards shall be granted under the Plan only to employees of or consultants
to one or more of the Company or an Affiliate (but excluding members of the
Committee) who are responsible for or contribute to, as determined by the
Committee, the management, growth and profitability of the business of the
Company and its Affiliates. A director of one or more of the Company or any
Affiliate who is not also an employee or consultant of one or more of the
Company or an Affiliate shall not be eligible to receive an Award under the
Plan.

7.    STOCK OPTIONS

      7.1. Provision for Grant. Stock Options may be granted alone, in addition
to or in tandem with other Awards under the Plan. Any Stock Option granted under
the Plan shall be in such form as the Committee may from time to time approve.
The Committee shall have the authority to grant any optionee who is an employee
of the Company, or an Affiliate, Incentive Options, Nonstatutory Options, or
both types of Stock Options (in each case with or without Stock Appreciation
Rights). To the extent that any Stock Option does not qualify as an Incentive
Option, it shall constitute a separate Nonstatutory Option. In the case of any
other person eligible for an Award under the Plan, any Stock Option granted
under the Plan shall be a Nonstatutory Option (with or without Stock
Appreciation Rights).

      Anything in the Plan to the contrary notwithstanding, no term of this Plan
relating to Incentive Options shall be interpreted, amended or altered, nor
shall any discretion or authority granted under the Plan be so exercised, so as
to disqualify the Plan under Section 422 of the code, or, without the consent of
the optionee(s) affected, to disqualify any Incentive Option under such Section
422.

      7.2. Terms and Conditions. Options granted under the Plan shall be subject
to the following terms and conditions and shall contain such additional terms
and conditions, not inconsistent with the terms of the Plan, as the Committee
shall deem appropriate:

            (a) Option Price. The option price per share of Stock purchasable 

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                                      -6-


under a Stock Option shall be determined by the Committee at the time of grant
but in the case of any Incentive Option shall be not less than 100% of the Fair
Market Value of the Stock at the time of grant (110% of Fair Market Value, in
the case of any grant of an Incentive Option to a Ten Percent Owner).

            (b) Option Term. The term of each Stock Option shall be fixed by the
Committee, but not Incentive Option shall be exercisable more than ten years
after the date the Option is granted (or, more than five years after the date
the Option is granted, in the case of any grant of an Incentive Option to a Ten
Percent Owner). No Stock Option may be exercised by any person after expiration
of the term of the Option.

            (c) Exercisability. Stock Options shall be exercisable at such time
or times and subject to such terms and conditions as shall be determined by the
Committee at or after grant, provided, however, that, except as provided in this
Section 7 and Section 13, at or after grant no Stock Option shall be exercisable
during the six months following the date of the granting of the Option. If the
Committee provides, in its discretion, that any Stock Option is exercisable only
in installments, the Committee may waive such installment exercise provisions at
any time at or after grant in whole or in part, based on such factors as the
Committee shall determine.

            (d) Method of Exercise. Subject to whatever installment exercise
provisions may apply, Stock Options may be exercised in whole or in part at any
time and from time to time during the option period, by giving written notice of
exercise to the Company, in the manner set out in Section 15.7, specifying the
number of shares to be purchased. Such notice shall be accompanied by payment in
full of the purchase price, either by certified or bank check, or such other
instrument as the Committee may accept. As determined by the Committee, at or
after grant, payment in full or in part may also be made in the form of
unrestricted Stock already owned by the optionee or, in the case of the exercise
of a Nonstatutory Option, Restricted Stock subject to an Award hereunder (based,
in each case, on the Fair Market Value of the Stock on the date the option is
exercised, as determined by the Committee); provided, however, that, in the case
of an Incentive Option, the right to make a payment in the form of already owned
shares may be authorized only at the time the option is granted.

      If payment of the option exercise price of a Nonstatutory Option is made
in whole or in part in the form of Restricted Stock, such Restricted Stock (and
any replacement shares relating thereto) shall remain (or be) restricted in
accordance with the original terms of the Restricted Stock Award in question,
and any additional Stock received upon the exercise shall be subject to the same
forfeiture restrictions, unless otherwise determined by the Committee, at or
after grant.

      If payment of the Option exercise price of a Stock Option is made in whole
or in part in the form of unrestricted Stock already owned by the Participant,
the

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                                       -7-


Company may require that the Stock has been owned by the Participant for a
specified minimum period of time, for the purpose of avoiding any charge to the
Company's earnings, limiting the pyramiding of Stock Option exercises, or such
other purposes as the Company deems appropriate.

            (e) Replacement Options. If a Nonstatutory Option granted pursuant
to the Plan may be exercised by an optionee by means of the delivery of
previously acquired Stock, then the Committee may, at the time of the original
option grant, authorize the Participant to automatically receive a replacement
Nonstatutory Option to the extent shares are available under Section 4 at the
time such replacement Option would be issued. Any such replacement Option shall
cover such number of shares as may be determined by the Committee, but in no
event more than the number of shares equal to the difference, if any, between
the number of shares for which the original Option is exercised and the net
shares received by the Participant from such exercise. Any such replacement
Option shall have an exercise price equal to the then Fair Market Value of
Stock, and a term extending to the expiration date of the original Option. The
Committee shall have the right at any time to discontinue the automatic grant of
replacement Options.

            (f) Transferability. No Stock Option shall be transferable by the
optionee other than by will or by the laws of descent and distribution, and all
Stock Options shall be exercisable, during the optionee's lifetime, only by the
optionee.

            (g) Effect of Termination of Employment Or Association. If an
optionee's employment by or association with the Company and its Affiliates
terminates for any reason whatsoever, unless the Committee shall have provided
otherwise, any Stock Option held by such optionee shall thereupon terminate;
provided, however, that military or sick leave shall not be deemed a termination
of employment or other association, if it does not exceed the longer of 90 days
or the period during which the absent optionee's reemployment rights, if any,
are guaranteed by statute or by contract.

            (h) Incentive Option Limitations. To the extent required for
"Incentive Option" status under Section 422 of the Code, the aggregate Fair
Market Value (determined as of the date of grant) of the Stock with respect to
which Incentive Options become exercisable for the first time by the optionee
during any calendar year under the Plan and any other stock option plan of the
Company and any Affiliate shall not exceed $100,000. In the event shares of
Stock in excess of the preceding limitation become exercisable for the first
time in a calendar year under any such Options or options, such shares shall be
considered to have become exercisable under separate Nonstatutory Options (with
the Options or options granted earliest in time considered to constitute to the
maximum extent possible the Incentive Options).

            (i) Cash-out of Option; Settlement of Spread Value in Restricted
Stock. On receipt of written notice to exercise, the Committee may elect to cash
out

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                                       -8-


all or part of the portion of the Option(s) to be exercised by paying the
optionee an amount, in cash or Stock, equal to the excess of the Fair Market
Value of the Stock over the option price (the "Spread Value") on the effective
date of such exercise. In addition, if the Option agreement so provides at grant
or is amended after grant and prior to exercise to so provide (with the
optionee's consent), the Committee may require that all or part of the shares to
be issued with respect to the Spread Value of an exercised Option take the form
of Restricted Stock, which shall be valued on the date of exercise on the basis
of the Fair Market Value of such Restricted Stock determined without regard to
the forfeiture restrictions involved.

            (j) Cashless Exercise. To the extent permitted under the applicable
laws and regulations and the terms of a Participant's Option agreement, at the
request of the Participant and with the consent of the Committee, the Company
agrees to cooperate in a "cashless exercise" of an Option. The cashless exercise
shall be effected by the Participant delivering to a registered securities
broker acceptable to the Company instructions to sell a sufficient number of
shares of Stock from which such Option is then exercisable to cover the costs
and expenses associated with such exercise and sale.

            (k) Grant Date. The granting of an Option shall take place at the
time specified in the agreement set forth the terms of such Option. Only if
expressly so provided in the Option agreement, shall the grant date be the date
on which an Option agreement shall have been duly executed and delivered by the
Company and the Participant.

8.    STOCK APPRECIATION RIGHTS

      8.1. Provision for Grant. Stock Appreciation Rights may be granted in
conjunction with all or part of any Stock Option granted under the Plan. In the
case of a Nonstatutory Option, such rights may be granted either at or after the
time of the grant of such Stock Option. In the case of an Incentive Option, such
rights may be granted only at the time of the grant of such Stock Option.

      8.2. Termination. A Stock Appreciation Right or applicable portion thereof
granted with respect to a given Stock Option shall terminate and no longer be
exercisable upon the termination or exercise of the related Stock Option, except
that, unless otherwise determined by the Committee at the time of grant, a Stock
Appreciation Right granted with respect to less than the full number of shares
covered by a related Stock Option shall not be reduced until the number of
shares covered by an exercise or termination of the related Stock Option exceeds
the number of shares not covered by the Stock Appreciation Right.

      8.3. Manner and Effect of Exercise. A Stock Appreciation Right may be
exercised by an optionee, in accordance with Section 8.4, by surrendering the
applicable portion of the related Stock Option. Upon such exercise and
surrender, the optionee shall be entitled to receive an amount determined in the
manner

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                                       -9-


prescribed in Section 8.4. Stock Options which have been so surrendered, in
whole or in part, shall no longer be exercisable to the extent the related Stock
Appreciation Right has been exercised.

      8.4. Other Terms and Conditions. Stock Appreciation Rights granted under
the Plan shall be subject to the following terms and conditions, and shall
contain such additional terms and conditions, not inconsistent with the
provisions of the Plan, as the Committee shall deem appropriate:

            (a) Exercisability. Stock Appreciation Rights shall be exercisable
only at such time or times and to the extent that the Stock Options to which
they relate, if any, shall be exercisable in accordance with the provisions of
Section 7 and this Section 8.4 of the Plan; provided, however, that any Stock
Appreciation Right granted subsequent to the grant of the related Stock Option
shall not be exercisable during the first six months of its term; and provided,
further, however, that a Stock Appreciation Right granted in connection with an
Incentive Option may be exercised only if and when the market price of the Stock
subject to the Incentive Option exceeds the exercise price of such Stock Option.

            (b) Amount Payable. Upon the exercise of a Stock Appreciation Right,
an optionee shall be entitled to receive up to, but not more than, an amount in
cash or shares of Stock equal in value to the excess of the Fair Market Value of
one share of Stock over the option price per share specified in the related
Stock Option, multiplied by the number of shares in respect of which the Stock
Appreciation Right shall have been exercised. The Committee shall determine the
form of payment.

            (c) Transferability. Stock Appreciation Rights shall be transferable
only when and to the extent that the underlying Stock Option would be
transferable under Section 7.2 of the Plan.

9.    RESTRICTED STOCK

      9.1. Provision for Grant. Shares of Stock may be issued either alone or in
addition to other Awards granted under the Plan at such price, if any, as the
Committee may determine. The Committee may condition the grant of Restricted
Stock upon the completion of additional service, attainment of specified
performance goals or such other factors as the Committee may determine.

      9.2. Awards and Certificates. The prospective recipient of a Restricted
Stock Award shall not have any rights with respect to such Award, unless and
until such recipient has executed an agreement evidencing the Award and has
delivered a fully executed copy thereof to the Company, and has otherwise
complied with the applicable terms and conditions of such Award.

      9.3. Additional Terms and Conditions. Grants of Restricted Stock may be

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                                      -10-


made under the following additional terms and conditions:

            (a) Purchase Price. The purchase price for shares of Restricted
Stock shall be equal to or less than their Fair Market Value and may be zero, as
determined by the Committee.

            (b) Acceptance of Awards. Awards of Restricted Stock must be
accepted within a period of 60 days (or such shorter period as the Committee may
specify at grant) after the Award date, by executing a Restricted Stock Award
agreement and paying whatever price (if any) is required pursuant to the terms
of the Award.

            (c) Issuance of Certificates. Each Participant receiving a
Restricted Stock Award shall be issued a stock certificate in respect of such
shares of Restricted Stock. Such certificate shall be registered in the name of
such Participant and, if applicable, shall bear an appropriate legend referring
to the terms, conditions, and restrictions applicable to such Award, in addition
to legends authorized pursuant to Section 12, substantially in the following
form:

                        "The transferability of this certificate and the shares
            of stock represented hereby are subject to the terms and conditions
            (including forfeiture) of the Transkaryotic Therapies, Inc. 1993
            Long-Term Incentive Plan and an Agreement entered into between the
            registered owner and Transkaryotic Therapies, Inc. Copies of such
            Plan and Agreement are on file in the offices of Transkaryotic
            Therapies, Inc. at 195 Albany Street, Cambridge, MA 02139."

            (d) Escrow of Shares. The Committee may require that the stock
certificates evidencing shares of Restricted Stock be held in custody by the
Company until the restrictions thereon shall have lapsed, and that the
Participant deliver a stock power, endorsed in blank, relating to the Stock
covered by such Award.

             (e) Transferability. Subject to the provisions of this Plan and the
Award agreement, during the period set by the Committee commencing with the date
of such Award (the "Restriction Period"), the Participant shall not be permitted
to sell, transfer, pledge, assign or otherwise encumber shares of Restricted
Stock awarded under the Plan. Within these limits, the Committee may provide for
the lapse of such restrictions in installments and may accelerate or waive such
restrictions in whole or in part, based on service, performance and/or such
other factors or criteria as the Committee may determine.

            (f) Rights Pending Lapse of Restrictions or Forfeiture of Award.
Except as provided in this subsection (f) and subsection (e) above, the
Participant shall have, with respect to the shares of Restricted Stock, all of
the rights of a shareholder of the Company, including the right to vote the
shares, and the right to receive any cash dividends. The Committee, as
determined at the time of Award,

<PAGE>

                                      -11-


may permit or require the payment of cash dividends to be deferred and, if the
Committee so determines, reinvested in additional Restricted Stock to the extent
shares are available under Section 4.

            (g) Effect of Termination of Employment or Association. Unless
otherwise determined by the Committee and subject to the applicable provisions
of the Award agreement and this Section 9, upon termination of a Participant's
employment or other association with the Company and its Affiliates for any
reason during the Restriction Period, all shares still subject to restriction
shall be forfeited by the Participant; provided, however, that military or sick
leave shall not be deemed a termination of employment or other association, if
it does not exceed the longer of 90 days or the period during which the absent
optionee's reemployment rights, if any, are guaranteed by statute or by
contract.

            (h) Lapse of Restrictions. If and when the Restriction Period
expires without a prior forfeiture of the Restricted Stock subject to such
Restriction Period, the certificates for such shares shall be delivered to the
Participant promptly if not theretofore so delivered.

10.   LONG-TERM PERFORMANCE AWARDS

      10.1. Provision for Grant. Long-Term Performance Awards may be awarded
either alone or in addition to other Awards granted under the Plan. The
Committee shall determine the nature, length and starting date of the
performance period (the "Performance Period") for each Long-Term Performance
Award, which subject to Section 13 below shall be a period of at least two
years, and shall determine the performance objectives to be used in valuing
Long-Term Performance Awards and determining the extent to which such Long-Term
Performance Awards have been earned. Performance objectives may vary from
Participant to Participant and between groups of Participants and shall be based
upon such Company, business unit and/or individual performance factors and
criteria as the Committee may deem appropriate, including, but not limited to,
earnings per share or return on equity. Performance Periods may overlap and
Participants may participate simultaneously with respect to Long-Term
Performance Awards that are subject to different Performance Periods and/or
different performance factors and criteria.

      10.2. Periodic Determination of Performance. At the beginning of each
Performance Period, the Committee shall determine for each Long-Term Performance
Award subject to such Performance period the range of dollar values or number of
shares of Stock to be awarded to the Participant at the end of the Performance
period if and to the extent that the relevant measure(s) of performance for such
Long Term Performance is (are) met. Such dollar values or number of shares of
Stock may be fixed or may vary in accordance with such performance or other
criteria as may be specified by the Committee.

      10.3. Adjustment of Awards. In the event of special or unusual events or

<PAGE>

                                      -12-


circumstances affecting the application of one or more performance objectives to
a Long-Term Performance Award, the Committee may revise the performance
objectives or underlying factors and criteria applicable to the Long-Term
Performance Awards affected, to the extent deemed appropriate by the Committee,
to avoid unintended windfalls or hardship.

      10.4. Effect of Termination of Employment or Association. Unless otherwise
determined by the Committee, upon termination of a Participant's employment or
other association with the Company and its Affiliates for any reason during a
Performance period, the Participant shall not be entitled to any payment with
respect to the Long-Term Performance Awards subject to such Performance period;
provided, however, that military or sick leave shall not be deemed a termination
of employment or other association, if it does not exceed the longer of 90 days
or the period during which the absent Participant's reemployment rights, if any,
are guaranteed by statute or by contract.

      10.5. Form of Payment. The earned portion of a Long-Term Performance Award
may be paid currently or on a deferred basis with such interest or earnings
equivalent as may be determined by the Committee. Payment shall be made in the
form of cash or whole shares of Stock, including Restricted Stock, either in a
lump sum payment or in annual installments commencing as soon as practicable
after the end of the relevant Performance Period, all as the Committee shall
determine at or after grant.

11.   STOCK GRANTS

      In recognition of significant contributions to the success of the Company
or its Affiliates, and in such other circumstances as the Committee deems
appropriate shares of Stock may be issued either alone or in addition to other
stock or cash-based Awards granted under the Plan at such price, if any, as the
Committee may determine. Subject to adjustment pursuant to Section 4(c) above,
the number of shares awarded as Stock Grants shall not exceed 125,000 of the
1,250,000 shares of Stock subject to this Plan. Stock Grant Awards shall be made
without forfeiture conditions of any kind and otherwise pursuant to such terms
and conditions as the Committee may determine.

12.   RESTRICTIONS ON ISSUANCE OF SHARES

      12.1. Securities Laws. Notwithstanding any other provision of the Plan,
if, at any time, in the reasonable opinion of the Company the issuance of shares
of Stock covered by any Award granted under the Plan may constitute a violation
of law, then the Company may delay such issuance and the delivery of a
certificate for such shares until (i) approval shall have been obtained from
such governmental agencies, other than the Securities and Exchange Commission,
as may be required under any applicable law, rule, or regulation; and (ii) in
the case where such issuance would constitute a violation of a law administered
by or a regulation of the


<PAGE>

                                      -13-


Securities and Exchange Commission, one of the following conditions shall have
been satisfied:

            (a) the shares with respect to which such Option has been exercised
are at the time of the issue of such shares effectively registered under the
Securities Act of 1933, as amended (the "Securities Act"); or

            (b) a no-action letter in form and substance reasonably satisfactory
to the Company with respect to the issuance of such shares shall have been
obtained by the Company from the Securities and Exchange Commission. The Company
shall make all reasonable efforts to bring about the occurrence of said events.

      12.2. Investment Representation. Unless the shares to be issued in
connection with any Award granted under the Plan have been effectively
registered under the Securities Act, the Company shall be under no obligation to
issue any shares covered by such Award unless the person to acquire such shares
shall give a written representation to the Company which is satisfactory in form
and substance to its counsel and upon which the Company may reasonably rely,
that he or she is acquiring the shares issued pursuant to such Award as an
investment and not with a view to, or for sale in connection with, the
distribution of any such shares.

      12.3. Placement of Legends; Stop Orders; etc. Each share of Stock issued
pursuant to an Award granted under this Plan may bear a reference to the
investment representation made in accordance with Section 12.2 in addition to
any other applicable restriction under the Plan, the terms of the Award, and any
applicable Shareholders Agreement and Employment Agreement, and to the fact that
no registration statement has been filed with the Securities and Exchange
Commission in respect to said Stock. All certificates for shares of Stock or
other securities delivered under the Plan shall be subject to such
stock-transfer orders and other restrictions as the Committee may deem advisable
under the rules, regulations, and other requirements of any stock exchange upon
which the Stock is then listed, and any applicable Federal or state securities
law, and the Committee may cause a legend or legends to be put on any such
certificates to make appropriate reference to such restrictions.

      12.4. Registration. If the Company shall deem it necessary or desirable to
register under the Securities Act or other applicable statutes any shares with
respect to which an Option shall have been granted or to qualify any such shares
for exemption from the Securities Act or other applicable statutes, then the
Company shall take such action at its own expense. The Company may require from
each Participant, and each holder of shares of Stock acquired pursuant to an
Award granted under the Plan such information in writing for use in any
registration statement, prospectus, preliminary prospectus or offering circular
as is reasonably necessary for such purpose and may require reasonable indemnity
to the Company and its officers and directors from such holder against all
losses, claims, damage and liabilities arising from such use of the information
so furnished and caused by any


<PAGE>

                                      -14-

untrue statement of any material fact therein or caused by the omission to state
a material fact required to be stated therein or necessary to make the
statements therein not misleading in the light of the circumstances under which
they were made.

      12.5. Applicability of Shareholders Agreement. Whenever shares are to be
issued pursuant to an Award granted hereunder, the Company shall have the right
to require the Participant to execute and deliver and otherwise become a party
to the Shareholders Agreement in respect of such shares.

13.   EFFECT OF CERTAIN TRANSACTIONS

      13.1. Liquidation or Dissolution of the Company. In the event of a
proposed dissolution or liquidation of the Company, each outstanding Award
granted hereunder shall terminate (i.e., Options and Stock Appreciation Rights
shall lapse, Restricted Stock shall be forfeited and any Performance Awards
cancelled) immediately prior to the consummation of such action, without any
payment therefore, unless otherwise provided by the Committee. As to outstanding
Options, the Committee may, in the exercise of its sole discretion in such
instances, declare that any such Option shall terminate as of a date fixed by
the Committee and give each Optionee the right to exercise his option as to all
or any part of the shares of Stock covered by an Option for a period of twenty
(20) days following such date, including shares of Stock as to which the Option
would not otherwise be exercisable.

      13.2. Sale of Assets, Merger or Consolidation. In the event of a proposed
sale of all or substantially all of the assets of the Company, or the merger or
consolidation of the Company with or into another corporation in a transaction
in which the Company does not survive, the Committee may, in the exercise of its
sole discretion in such instances, give each Participant the right to exercise
his Option as to all or any part of the shares of Stock covered by an Option,
including shares of Stock as to which the Option would not otherwise be
exercisable, waive any remaining restrictions applicable to Restricted Stock and
provide for the pro rata payment of Performance Awards based on performance
through the date of such transaction. In the event the Committee elects to
authorize the exercise of outstanding and otherwise unexercisable Options, the
Committee shall notify the Participant that the Option shall be fully
exercisable for a period of not less than twenty (20) nor more than sixty (60)
days from the date of such notice, and if such Option shall not be exercised,
the Committee may, in the exercise of its sole discretion in such instances,
determine that the Option shall terminate upon the expiration of such period and
be of no further force or effect.

14.   TERMINATION AND AMENDMENT OF THE PLAN AND AWARDS

      The Board may at any time terminate the Plan or make such modifications of
the Plan as it shall deem advisable. No termination or amendment of the Plan
may, without the consent of the Participant to whom any Award shall theretofore
have


<PAGE>

                                      -15-


been granted, adversely affect the rights of such Participant under such Award.

      The Committee may amend the terms of any Award theretofore granted,
prospectively or retroactively, but no such amendment shall impair the rights of
any Participant without the Participant's consent.

15.   MISCELLANEOUS PROVISIONS

      15.1. Unfunded Status of Plan. The Plan is intended to constitute an
"unfunded" plan for incentive and deferred compensation. With respect to any
payments not yet made to a Participant by the Company, nothing contained herein
shall give any such Participant any rights that are greater than those of any
other general creditor of the Company. The Committee may authorize the creation
of trusts or other arrangements to meet the obligations created under the Plan
to deliver Stock or payments in lieu of or with respect to Awards hereunder,
provided, however, unless the Committee otherwise determines with the consent of
the affected participant, the existence of such trusts or other arrangements is
consistent with the "unfunded" status of the Plan.

      15.2. Adoption of Other Plans. Nothing contained in this Plan shall
prevent the Board of Directors from adopting other or additional compensation
arrangements, subject to stockholder approval if such approval is required; and
such arrangements may be either generally applicable or applicable only in
specific cases.

      15.3. Payments on Death. The Committee shall establish such procedures as
it deems appropriate for a Participant to designate a beneficiary to whom any
amounts payable in the event of the Participant's death are to be paid.

      15.4. Tax Withholding.

            (a) In General. No later than the date as of which an amount first
becomes includable in the gross income of the Participant for federal income tax
purposes with respect to any Award, the Participant shall pay to the Company, or
make arrangements satisfactory to the Company regarding the payment of, any
federal, state, or local taxes of any kind required by law to be withheld
(whether so required to secure an otherwise available tax deduction or
otherwise) with respect to such amount. If authorized by the Committee at the
grant of an Award (or, other than in the case of Incentive Option, at any time
thereafter) and so elected by the Participant, the minimum required withholding
obligations may be settled with Stock, including Stock that is part of the Award
that gives rise to the withholding requirement. The obligations of the Company
under the Plan shall be conditional on such payment or arrangements and the
Company shall, to the extent permitted by law, have the right to deduct any such
taxes from any payment of any kind otherwise due to the Participant.

            (b) Disqualifying Dispositions. The Company may require as a

<PAGE>

                                      -16-


condition to the issuance of shares covered by any Incentive Option that the
party exercising such Option give a written representation to the Company which
is satisfactory in form and substance to its counsel and upon which the Company
may reasonably rely, that he or she will report to the Company any disposition
of such shares prior to the expiration of the holding periods specified by
Section 422(a)(1) of the Code. If and to the extent that the realization of
income in such a disposition imposes upon the Company federal, state, local or
other withholding tax requirements, or any such withholding is required to
secure for the Company an otherwise available tax deduction, the Company shall
have the right to require that the recipient remit to the Company an amount
sufficient to satisfy those requirements.

      15.5. Limitation of Rights in Stock. No Participant shall not be deemed
for any purpose to be a stockholder of the Company with respect to any of the
shares of Stock covered by an Award, except to the extent any payment required
therefor shall have been received by the Company and a certificate shall have
been issued therefor and delivered to the Participant or his or her agent (or,
in the case of Restricted Stock, the Company as escrow agent). Any Stock issued
pursuant to an Award shall be subject to all restrictions upon the transfer
thereof which may be now or hereafter imposed by the Certificate of
Incorporation, the By-laws of the Company, the Shareholders Agreement and the
Employment Agreement.

      15.6. No Special Employment or Other Rights. Nothing contained in the Plan
or in any Award shall confer upon any Participant any right with respect to the
continuation of his or her employment or other association with the Company (or
any Affiliate), or interfere in any way with the right of the Company (or any
Affiliate), subject to the terms of any separate employment or consulting
agreement or provision of law or corporate articles or by-laws to the contrary,
at any time to terminate such employment or consulting agreement or to increase
or decrease the compensation of the Participant from the rate in existence at
the time of the grant of an Award under the Plan.

      15.7. Notices and Other Communications. All notices and other
communications required or permitted under the Plan shall be effective if in
writing and if delivered or sent by certified or registered mail, return receipt
requested (a) if to the Participant, at his or her residence address last filed
with the Company, and (b) if to the Company, at 195 Albany Street, Cambridge, MA
02139 Attention: Treasurer or to such other persons or addresses as the
Participant or the Company may specify by a written notice to the other from
time to time.

      15.8. Governing Law. The Plan and all Awards and actions taken thereunder
shall be governed by and construed in accordance with the laws of the
Commonwealth of Massachusetts, without regard to the conflict of laws principles
thereof.

<PAGE>

                                     -17-


            Date of Board Approval: June 16, 1993

            Date of Shareholder Approval: June 24, 1993

<PAGE>

                          TRANSKARYOTIC THERAPIES, INC.

               Amendment No. 1 to 1993 Long Term Incentive Plan


            Section 7.2(c) of the Plan is amended and restated in its entirety
            to read as follows:

            "(c) Exercisability. Stock Options shall be exercisable at such time
            or times and subject to such terms and conditions as shall be
            determined by the Committee at or after grant. If the Committee
            provides, in its discretion, that any Stock Option is exercisable
            only in installments, the Committee may waive such installment
            exercise provisions at any time at or after grant in whole or in
            part, based on such factors as the Committee may determine."



                                    Adopted by the Board of Directors on
                                    January 22, 1998