1 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: May 26, 1998                       By:        /s/ Xxxx-Xxxxx Xxxx
                                                    ----------------------------
                                         Name:      Xxxx-Xxxxx Xxxx
                                                    Signatory Authority


Date: May 26, 1998                                  By:  /s/ Xx. Xxxxxx Xxxxxxxx
                                                    ----------------------------
                                         Name:      Xx. Xxxxxx Xxxxxxxx
                                                    Vice Chairman and Director



                                         BIOTECH TARGET, S.A.

Date: May 26, 1998                       By:        /s/ Xx. Xxxxxxx Xxxxxx
                                                    ----------------------------
                                         Name:      Xx. Xxxxxxx Xxxxxx
                                                    Signatory Authority


Date: May 26, 1998                       By:        /s/ Dr. Xxxxxx Xxxx
                                                    ----------------------------
                                         Name:      Dr. Xxxxxx Xxxx
                                                    Signatory Authority


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