JOINT FILING AGREEMENT

   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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