1 EXHIBIT 4

   1
                                   EXHIBIT 4

                             JOINT FILING AGREEMENT


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



                                                          BB BIOTECH AG

Date: December 24, 1997                            By: /s/ Xxxx-Xxxxx Xxxx     
                                                      -------------------------
                                                   Name: Xxxx-Xxxxx Xxxx       
                                                        -----------------------

Date: December 24, 1997                            By: /s/ Xx. Xxxxxx Xxxxxxxx 
                                                      -------------------------
                                                   Name: Xx. Xxxxxx Xxxxxxxx   
                                                        -----------------------


                                                          BIOTECH TARGET S.A.

Date: December 24, 1997                            By: /s/ Xx. Xxxxxxx Xxxxxx  
                                                      -------------------------
                                                   Name: Xx. Xxxxxxx Xxxxxx    
                                                        -----------------------

Date: December 24, 1997                            By: /s/ Dr. Xxxxxx Xxxx     
                                                      -------------------------
                                                   Name: Dr. Xxxxxx Xxxx       
                                                        -----------------------





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