EXHIBIT 4

   1

                                    EXHIBIT 4

                             JOINT FILING AGREEMENT


   We, the undersigned, hereby express our agreement that the attached Schedule
13G (including all amendments thereto) is filed on behalf of each of the
undersigned.



                                          BB BIOTECH AG

Date:  November 19, 1998                  By:    /s/ XXXX-XXXXX XXXX
                                                 -------------------------------
                                          Name:      Xxxx-Xxxxx Xxxx
                                                 -------------------------------
                                                     Signatory Authority
 

Date:  November 19, 1998                  By:    /s/ XX. XXXXXX XXXXXXXX
                                                 -------------------------------
                                          Name:      Xx. Xxxxxx Xxxxxxxx
                                                 -------------------------------
                                                     Vice Chairman and Director


                                          BIOTECH TARGET S.A.

Date:  November 19, 1998                  By:    /s/ XX. XXXXXXX XXXXXX
                                                 -------------------------------
                                          Name:      Xx. Xxxxxxx Xxxxxx
                                                 -------------------------------
                                                     Signatory Authority


Date:  November 19, 1998                  By:    /s/ DR. XXXXXX XXXX
                                                 -------------------------------
                                          Name:      Dr. Xxxxxx Xxxx
                                                 -------------------------------
                                                     Signatory Authority




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