1 EXHIBIT 4 JOINT FILING AGREEMENT

   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: November 19, 1997           By: /s/ ▇▇▇▇-▇▇▇▇▇ ▇▇▇▇     
                                     -------------------------
                                  Name: ▇▇▇▇-▇▇▇▇▇ ▇▇▇▇       
                                       -----------------------

Date: November 19, 1997           By: /s/ ▇▇. ▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇ 
                                     -------------------------
                                  Name: ▇▇. ▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇   
                                       -----------------------


                                           BIOTECH TARGET, S.A.

Date: November 19, 1997           By: /s/ ▇▇. ▇▇▇▇▇▇▇ ▇▇▇▇▇▇  
                                     -------------------------
                                  Name: ▇▇. ▇▇▇▇▇▇▇ ▇▇▇▇▇▇    
                                       -----------------------

Date: November 19, 1997           By: /s/ Dr. ▇▇▇▇▇▇ ▇▇▇▇     
                                     -------------------------
                                  Name: Dr. ▇▇▇▇▇▇ ▇▇▇▇       
                                       -----------------------





                                        Page 14 of 14