File size: 111,240 Bytes
a3be5d0
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
631
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
654
655
656
657
658
659
660
661
662
663
664
665
666
667
668
669
670
671
672
673
674
675
676
677
678
679
680
681
682
683
684
685
686
687
688
689
690
691
692
693
694
695
696
697
698
699
700
701
702
703
704
705
706
707
708
709
710
711
712
713
714
715
716
717
718
719
720
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735
736
737
738
739
740
741
742
743
744
745
746
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
766
767
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
821
822
823
824
825
826
827
828
829
830
831
832
833
834
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
865
866
867
868
869
870
871
872
873
874
875
876
877
878
879
880
881
882
883
884
885
886
887
888
889
890
891
892
893
894
895
896
897
898
899
900
901
902
903
904
905
906
907
908
909
910
911
912
913
914
915
916
917
918
919
920
921
922
923
924
925
926
927
928
929
930
931
932
933
934
935
936
937
938
939
940
941
942
943
944
945
946
947
948
949
950
951
952
953
954
955
956
957
958
959
960
961
962
963
964
965
966
967
968
969
970
971
972
973
974
975
976
977
978
979
980
981
982
983
984
985
986
987
988
989
990
991
992
993
994
995
996
997
998
999
1000
1001
1002
1003
1004
1005
1006
1007
1008
1009
1010
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
1022
1023
1024
1025
1026
1027
1028
1029
1030
1031
1032
1033
1034
1035
1036
1037
1038
1039
1040
1041
1042
1043
1044
1045
1046
1047
1048
1049
1050
1051
1052
1053
1054
1055
1056
1057
1058
1059
1060
1061
1062
1063
1064
1065
1066
1067
1068
1069
1070
1071
1072
1073
1074
1075
1076
1077
1078
1079
1080
1081
1082
1083
1084
1085
1086
1087
1088
1089
1090
1091
1092
1093
1094
1095
1096
1097
1098
1099
1100
1101
1102
1103
1104
1105
1106
1107
1108
1109
1110
1111
1112
1113
1114
1115
1116
1117
1118
1119
1120
1121
1122
1123
1124
1125
1126
1127
1128
1129
1130
1131
1132
1133
1134
1135
1136
1137
1138
1139
1140
1141
1142
1143
1144
1145
1146
1147
1148
1149
1150
1151
1152
1153
1154
1155
1156
1157
1158
1159
1160
1161
1162
1163
1164
1165
1166
1167
1168
1169
1170
1171
1172
1173
1174
1175
1176
1177
1178
1179
1180
1181
1182
1183
1184
1185
1186
1187
1188
1189
1190
1191
1192
1193
1194
1195
1196
1197
1198
1199
1200
1201
1202
1203
1204
1205
1206
1207
1208
1209
1210
1211
1212
1213
1214
1215
1216
1217
1218
1219
1220
1221
1222
1223
1224
1225
1226
1227
1228
1229
1230
1231
1232
1233
1234
1235
1236
1237
1238
1239
1240
1241
1242
1243
1244
1245
1246
1247
1248
1249
1250
1251
1252
1253
1254
1255
1256
1257
1258
1259
1260
1261
1262
1263
1264
1265
1266
1267
1268
1269
1270
1271
1272
1273
1274
1275
1276
1277
1278
1279
1280
1281
1282
1283
1284
1285
1286
1287
1288
1289
1290
1291
1292
1293
1294
1295
1296
1297
1298
1299
1300
1301
1302
1303
1304
1305
1306
1307
1308
1309
1310
1311
1312
1313
1314
1315
1316
1317
1318
1319
1320
1321
1322
1323
1324
1325
1326
1327
1328
1329
1330
1331
1332
1333
1334
1335
1336
1337
1338
1339
1340
1341
1342
1343
1344
1345
1346
1347
1348
1349
1350
1351
1352
1353
1354
1355
1356
1357
1358
1359
1360
1361
1362
1363
1364
1365
1366
1367
1368
1369
1370
1371
1372
1373
1374
1375
1376
1377
1378
1379
1380
1381
1382
1383
1384
1385
1386
1387
1388
1389
1390
1391
1392
1393
1394
1395
1396
1397
1398
1399
1400
1401
1402
1403
1404
1405
1406
1407
1408
1409
1410
1411
1412
1413
1414
1415
1416
1417
1418
1419
1420
1421
1422
1423
1424
1425
1426
1427
1428
1429
1430
1431
1432
1433
1434
1435
1436
1437
1438
1439
1440
1441
1442
1443
1444
1445
1446
1447
1448
1449
1450
1451
1452
1453
1454
1455
1456
1457
1458
1459
1460
1461
1462
1463
1464
1465
1466
1467
1468
1469
1470
1471
1472
1473
1474
1475
1476
1477
1478
1479
1480
1481
1482
1483
1484
1485
1486
1487
1488
1489
1490
1491
1492
1493
1494
1495
1496
1497
1498
1499
1500
1501
1502
1503
1504
1505
1506
1507
1508
1509
1510
1511
1512
1513
1514
1515
1516
1517
1518
1519
1520
1521
1522
1523
1524
1525
1526
1527
1528
1529
1530
1531
1532
1533
1534
1535
1536
1537
1538
1539
1540
1541
1542
1543
1544
1545
1546
1547
1548
1549
1550
1551
1552
1553
1554
1555
1556
1557
1558
1559
1560
1561
1562
1563
1564
1565
1566
1567
1568
1569
1570
1571
1572
1573
1574
1575
1576
1577
1578
1579
1580
1581
1582
1583
1584
1585
1586
1587
1588
1589
1590
1591
1592
1593
1594
1595
1596
1597
1598
1599
1600
1601
1602
1603
1604
1605
1606
1607
1608
1609
1610
1611
1612
1613
1614
1615
1616
1617
1618
1619
1620
1621
1622
1623
1624
1625
1626
1627
1628
1629
1630
1631
1632
1633
1634
1635
1636
1637
1638
1639
1640
1641
1642
1643
1644
1645
1646
1647
1648
1649
1650
1651
1652
1653
1654
1655
1656
1657
1658
1659
1660
1661
1662
1663
1664
1665
1666
1667
1668
1669
1670
1671
1672
1673
1674
1675
1676
1677
1678
1679
1680
1681
1682
1683
1684
1685
1686
1687
1688
1689
1690
1691
1692
1693
1694
1695
1696
1697
1698
1699
1700
1701
1702
1703
1704
1705
1706
1707
1708
1709
1710
1711
1712
1713
1714
1715
1716
1717
1718
1719
1720
1721
1722
1723
1724
1725
1726
1727
1728
1729
1730
1731
1732
1733
1734
1735
1736
1737
1738
1739
1740
1741
1742
1743
1744
1745
1746
1747
1748
1749
1750
1751
1752
1753
1754
1755
1756
1757
1758
1759
1760
1761
1762
1763
1764
1765
1766
1767
1768
1769
1770
1771
1772
1773
1774
1775
1776
1777
1778
1779
1780
1781
1782
1783
1784
1785
1786
1787
1788
1789
1790
1791
1792
1793
1794
1795
1796
1797
1798
1799
1800
1801
1802
1803
1804
1805
1806
1807
1808
1809
1810
1811
1812
1813
1814
1815
1816
1817
1818
1819
1820
1821
1822
1823
1824
1825
1826
1827
1828
1829
1830
1831
1832
1833
1834
1835
1836
1837
1838
1839
1840
1841
1842
1843
1844
1845
1846
1847
1848
1849
1850
1851
1852
1853
1854
1855
1856
1857
1858
1859
1860
1861
1862
1863
1864
1865
1866
1867
1868
1869
1870
1871
1872
1873
1874
1875
1876
1877
1878
1879
1880
1881
1882
1883
1884
1885
1886
1887
1888
1889
1890
1891
1892
1893
1894
1895
1896
1897
1898
1899
1900
1901
1902
1903
1904
1905
1906
1907
1908
1909
1910
1911
1912
1913
1914
1915
1916
1917
1918
1919
1920
1921
1922
1923
1924
1925
1926
1927
1928
1929
1930
1931
1932
1933
1934
1935
1936
1937
1938
1939
1940
1941
1942
1943
1944
1945
1946
1947
1948
1949
1950
1951
1952
1953
1954
1955
1956
1957
1958
1959
1960
1961
1962
1963
1964
1965
1966
1967
1968
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
1979
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
2027
2028
2029
2030
2031
2032
2033
2034
2035
2036
2037
2038
2039
2040
2041
2042
2043
2044
2045
2046
2047
2048
2049
2050
2051
2052
2053
2054
2055
2056
2057
2058
2059
2060
2061
2062
2063
2064
2065
2066
2067
2068
2069
2070
2071
2072
2073
2074
2075
2076
2077
2078
2079
2080
2081
2082
2083
2084
2085
2086
2087
2088
2089
2090
2091
2092
2093
2094
2095
2096
2097
2098
2099
2100
2101
2102
2103
2104
2105
2106
2107
2108
2109
2110
2111
2112
2113
2114
2115
2116
2117
2118
2119
2120
2121
2122
2123
2124
2125
2126
2127
2128
2129
2130
2131
2132
2133
2134
2135
2136
2137
2138
2139
2140
2141
2142
2143
2144
2145
2146
2147
2148
2149
2150
2151
2152
2153
2154
2155
2156
2157
2158
2159
2160
2161
2162
2163
2164
2165
2166
2167
2168
2169
2170
2171
2172
2173
2174
2175
2176
2177
2178
2179
2180
2181
2182
2183
2184
2185
2186
2187
2188
2189
2190
2191
2192
2193
2194
2195
2196
2197
2198
2199
2200
2201
2202
2203
2204
2205
2206
2207
2208
2209
2210
2211
2212
2213
2214
2215
2216
2217
2218
2219
2220
2221
2222
2223
2224
2225
2226
2227
2228
2229
2230
2231
2232
2233
2234
2235
2236
2237
2238
2239
2240
2241
2242
2243
2244
2245
2246
2247
2248
2249
2250
2251
2252
2253
2254
2255
2256
2257
2258
2259
2260
2261
2262
2263
2264
2265
2266
2267
2268
2269
2270
2271
2272
2273
2274
2275
2276
2277
2278
2279
2280
2281
2282
2283
2284
2285
2286
2287
2288
2289
2290
2291
2292
2293
2294
2295
2296
2297
2298
2299
2300
2301
2302
2303
2304
2305
2306
2307
2308
2309
2310
2311
2312
2313
2314
2315
2316
2317
2318
2319
2320
2321
2322
2323
2324
2325
2326
2327
2328
2329
2330
2331
2332
2333
2334
2335
2336
2337
2338
2339
2340
2341
2342
2343
2344
2345
2346
2347
2348
2349
2350
2351
2352
2353
2354
2355
2356
2357
2358
2359
2360
2361
2362
2363
2364
2365
2366
2367
2368
2369
2370
2371
2372
2373
2374
2375
2376
2377
2378
2379
2380
2381
2382
2383
2384
2385
2386
2387
2388
2389
2390
2391
2392
2393
2394
2395
2396
2397
2398
2399
2400
2401
2402
2403
2404
2405
2406
2407
2408
2409
2410
2411
2412
2413
2414
2415
2416
2417
2418
2419
2420
2421
2422
2423
2424
2425
2426
2427
2428
2429
2430
2431
2432
2433
2434
2435
2436
2437
2438
2439
2440
2441
2442
2443
2444
2445
2446
2447
2448
2449
2450
2451
2452
2453
2454
2455
2456
2457
2458
2459
2460
2461
2462
2463
2464
2465
2466
2467
2468
2469
2470
2471
2472
2473
2474
2475
2476
2477
2478
2479
2480
2481
2482
2483
2484
2485
2486
2487
2488
2489
2490
2491
2492
2493
2494
2495
2496
2497
2498
2499
2500
2501
2502
2503
2504
2505
2506
2507
2508
2509
2510
2511
2512
2513
2514
2515
2516
2517
2518
2519
2520
2521
2522
2523
2524
2525
2526
2527
2528
2529
2530
2531
2532
2533
2534
2535
2536
2537
2538
2539
2540
2541
2542
2543
2544
2545
2546
2547
2548
2549
2550
2551
2552
2553
2554
2555
2556
2557
2558
2559
2560
2561
2562
2563
2564
2565
2566
2567
2568
2569
2570
2571
2572
2573
2574
2575
2576
2577
2578
2579
2580
2581
2582
2583
2584
2585
2586
2587
2588
2589
2590
2591
2592
2593
2594
2595
2596
2597
2598
2599
2600
2601
2602
2603
2604
2605
2606
2607
2608
2609
2610
2611
2612
2613
2614
2615
2616
2617
2618
2619
2620
2621
2622
2623
2624
2625
2626
2627
2628
2629
2630
2631
2632
2633
2634
2635
2636
2637
2638
2639
2640
2641
2642
2643
2644
2645
2646
2647
2648
2649
2650
2651
2652
2653
2654
2655
2656
2657
2658
2659
2660
2661
2662
2663
2664
2665
2666
2667
2668
2669
2670
2671
2672
2673
2674
2675
2676
2677
2678
2679
2680
2681
2682
2683
2684
2685
2686
2687
2688
2689
2690
2691
2692
2693
2694
2695
2696
2697
2698
2699
2700
2701
2702
2703
2704
2705
2706
2707
2708
2709
2710
2711
2712
2713
2714
2715
2716
2717
2718
2719
2720
2721
2722
2723
2724
2725
2726
2727
2728
2729
2730
2731
2732
2733
2734
2735
2736
2737
2738
2739
2740
2741
2742
2743
2744
2745
2746
2747
2748
2749
2750
2751
2752
2753
2754
2755
2756
2757
2758
2759
2760
2761
2762
2763
2764
2765
2766
2767
2768
2769
2770
2771
2772
2773
2774
2775
2776
2777
2778
2779
2780
2781
2782
2783
2784
2785
2786
2787
2788
2789
2790
2791
2792
2793
2794
2795
2796
2797
2798
2799
2800
2801
2802
2803
2804
2805
2806
2807
2808
2809
2810
2811
2812
2813
2814
2815
2816
2817
2818
2819
2820
2821
2822
2823
2824
2825
2826
2827
2828
2829
2830
2831
2832
2833
2834
2835
2836
2837
2838
2839
2840
2841
2842
2843
2844
2845
2846
2847
2848
2849
2850
2851
2852
2853
2854
2855
2856
2857
2858
2859
2860
2861
2862
2863
2864
2865
2866
2867
2868
2869
2870
2871
2872
2873
2874
2875
2876
2877
2878
2879
2880
2881
2882
2883
2884
2885
2886
2887
2888
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
2911
2912
2913
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
2944
2945
2946
2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
2977
2978
2979
2980
2981
2982
2983
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009
3010
3011
3012
3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
3043
3044
3045
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
3076
3077
3078
3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
3109
3110
3111
3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
3142
3143
3144
3145
3146
3147
3148
3149
3150
3151
3152
3153
3154
3155
3156
3157
3158
3159
3160
3161
3162
3163
3164
3165
3166
3167
3168
3169
3170
3171
3172
3173
3174
3175
3176
3177
3178
3179
3180
3181
3182
3183
3184
3185
3186
3187
3188
3189
3190
3191
3192
3193
3194
3195
3196
3197
3198
3199
3200
3201
3202
3203
3204
3205
3206
3207
3208
3209
3210
3211
3212
3213
3214
3215
3216
3217
3218
3219
3220
3221
3222
3223
3224
3225
3226
3227
3228
3229
3230
3231
3232
3233
3234
3235
3236
3237
3238
3239
3240
3241
3242
3243
3244
3245
3246
3247
3248
3249
3250
3251
3252
3253
3254
3255
3256
3257
3258
3259
3260
3261
3262
3263
3264
3265
3266
3267
3268
3269
3270
3271
3272
3273
3274
3275
3276
3277
3278
3279
3280
3281
3282
3283
3284
3285
3286
3287
3288
3289
3290
3291
3292
3293
3294
3295
3296
3297
3298
3299
3300
3301
3302
3303
3304
3305
3306
3307
3308
3309
3310
3311
3312
3313
3314
3315
3316
3317
3318
3319
3320
3321
3322
3323
3324
3325
3326
3327
3328
3329
3330
3331
3332
3333
3334
3335
3336
3337
3338
3339
3340
3341
3342
3343
3344
3345
3346
3347
3348
3349
3350
3351
3352
3353
3354
3355
3356
3357
3358
3359
3360
3361
3362
3363
3364
3365
3366
3367
3368
3369
3370
3371
3372
3373
3374
3375
3376
3377
3378
3379
3380
3381
3382
3383
3384
3385
3386
3387
3388
3389
3390
3391
3392
3393
3394
3395
3396
3397
3398
3399
3400
3401
3402
3403
3404
3405
3406
3407
3408
3409
3410
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3421
3422
3423
3424
3425
3426
3427
3428
3429
3430
3431
3432
3433
3434
3435
3436
3437
3438
3439
3440
3441
3442
3443
3444
3445
3446
3447
3448
3449
3450
3451
3452
3453
3454
3455
3456
3457
3458
3459
3460
3461
3462
3463
3464
3465
3466
3467
3468
3469
3470
3471
3472
3473
3474
3475
3476
3477
3478
3479
3480
3481
3482
3483
3484
3485
3486
3487
3488
3489
3490
3491
3492
3493
3494
3495
3496
3497
3498
3499
3500
3501
3502
3503
3504
3505
3506
3507
3508
3509
3510
3511
3512
3513
3514
3515
3516
3517
3518
3519
3520
3521
3522
3523
3524
3525
3526
3527
3528
3529
3530
3531
3532
3533
3534
3535
3536
3537
3538
3539
3540
3541
3542
3543
3544
3545
3546
3547
3548
3549
3550
3551
3552
3553
3554
3555
3556
3557
3558
3559
3560
3561
3562
3563
3564
3565
3566
3567
3568
3569
3570
3571
3572
3573
3574
3575
3576
3577
3578
3579
3580
3581
3582
3583
3584
3585
3586
3587
3588
3589
3590
3591
3592
3593
3594
3595
3596
3597
3598
3599
3600
3601
3602
3603
3604
3605
3606
3607
3608
3609
3610
3611
3612
3613
3614
3615
3616
3617
3618
3619
3620
3621
3622
3623
3624
3625
3626
3627
3628
3629
3630
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
3641
3642
3643
3644
3645
3646
3647
3648
3649
3650
3651
3652
3653
3654
3655
3656
3657
3658
3659
3660
3661
3662
3663
3664
3665
3666
3667
3668
3669
3670
3671
3672
3673
3674
3675
3676
3677
3678
3679
3680
3681
3682
3683
3684
3685
3686
3687
3688
3689
3690
3691
3692
3693
3694
3695
3696
3697
3698
3699
3700
3701
3702
3703
3704
3705
3706
3707
3708
3709
3710
3711
3712
3713
3714
3715
3716
3717
3718
3719
3720
3721
3722
3723
3724
3725
3726
3727
3728
3729
3730
3731
3732
3733
3734
3735
3736
3737
3738
3739
3740
3741
3742
3743
3744
3745
3746
3747
3748
3749
3750
3751
3752
3753
3754
3755
3756
3757
3758
3759
3760
3761
3762
3763
3764
3765
3766
3767
3768
3769
3770
3771
3772
3773
3774
3775
3776
3777
3778
3779
3780
3781
3782
3783
3784
3785
3786
3787
3788
3789
3790
3791
3792
3793
3794
3795
3796
3797
3798
3799
3800
3801
3802
3803
3804
3805
3806
3807
3808
3809
3810
3811
3812
3813
3814
3815
3816
3817
3818
3819
3820
3821
3822
3823
3824
3825
3826
3827
3828
3829
3830
3831
3832
3833
3834
3835
3836
3837
3838
3839
3840
3841
3842
3843
3844
3845
3846
3847
3848
3849
3850
3851
3852
3853
3854
3855
3856
3857
3858
3859
3860
3861
3862
3863
3864
3865
3866
3867
3868
3869
3870
3871
3872
3873
3874
3875
3876
3877
3878
3879
3880
3881
3882
3883
3884
3885
3886
3887
3888
3889
3890
3891
3892
3893
3894
3895
3896
3897
3898
3899
3900
3901
3902
3903
3904
3905
3906
3907
3908
3909
3910
3911
3912
3913
3914
3915
3916
3917
3918
3919
3920
3921
3922
3923
3924
3925
3926
3927
3928
3929
3930
3931
3932
3933
3934
3935
3936
3937
3938
3939
3940
3941
3942
3943
3944
3945
3946
3947
3948
3949
3950
3951
3952
3953
3954
3955
3956
3957
3958
3959
3960
3961
3962
3963
3964
3965
3966
3967
3968
3969
3970
3971
3972
3973
3974
3975
3976
3977
3978
3979
3980
3981
3982
3983
3984
3985
3986
3987
3988
3989
3990
3991
3992
3993
3994
3995
3996
3997
3998
3999
4000
4001
4002
4003
4004
4005
4006
4007
4008
4009
4010
4011
4012
4013
4014
4015
4016
4017
4018
4019
4020
4021
4022
4023
4024
4025
4026
4027
4028
4029
4030
4031
4032
4033
4034
4035
4036
4037
4038
4039
4040
4041
4042
4043
4044
4045
4046
4047
4048
4049
4050
4051
4052
4053
4054
4055
4056
4057
4058
4059
4060
4061
4062
4063
4064
4065
4066
4067
4068
4069
4070
4071
4072
4073
4074
4075
4076
4077
4078
4079
4080
4081
4082
4083
4084
4085
4086
4087
4088
4089
4090
4091
4092
4093
4094
4095
4096
4097
4098
4099
4100
4101
4102
4103
4104
4105
4106
4107
4108
4109
4110
4111
4112
4113
4114
4115
4116
4117
4118
4119
4120
4121
4122
4123
4124
4125
4126
4127
4128
4129
4130
4131
4132
4133
4134
4135
4136
4137
4138
4139
4140
4141
4142
4143
4144
4145
4146
4147
4148
4149
4150
4151
4152
4153
4154
4155
4156
4157
4158
4159
4160
4161
4162
4163
4164
4165
4166
4167
4168
4169
4170
4171
4172
4173
4174
4175
4176
4177
4178
4179
4180
4181
4182
4183
4184
4185
4186
4187
4188
4189
4190
4191
4192
4193
4194
4195
4196
4197
4198
4199
4200
4201
4202
4203
4204
4205
4206
4207
4208
4209
4210
4211
4212
4213
4214
4215
4216
4217
4218
4219
4220
4221
4222
4223
4224
4225
4226
4227
4228
4229
4230
4231
4232
4233
4234
4235
4236
4237
4238
4239
4240
4241
4242
4243
4244
4245
4246
4247
4248
4249
4250
4251
4252
4253
4254
4255
4256
4257
4258
4259
4260
4261
4262
4263
4264
4265
4266
4267
4268
4269
4270
4271
4272
4273
4274
4275
4276
4277
4278
4279
4280
4281
4282
4283
4284
4285
4286
4287
4288
4289
4290
4291
4292
4293
4294
4295
4296
4297
4298
4299
4300
4301
4302
4303
4304
4305
4306
4307
4308
4309
4310
4311
4312
4313
4314
4315
4316
4317
4318
4319
4320
4321
4322
4323
4324
4325
4326
4327
4328
4329
4330
4331
4332
4333
4334
4335
4336
4337
4338
4339
4340
4341
4342
4343
4344
4345
4346
4347
4348
4349
4350
4351
4352
4353
4354
4355
4356
4357
4358
4359
4360
4361
4362
4363
4364
4365
4366
4367
4368
4369
4370
4371
4372
4373
4374
4375
4376
4377
4378
4379
4380
4381
4382
4383
4384
4385
4386
4387
4388
4389
4390
4391
4392
4393
4394
4395
4396
4397
4398
4399
4400
4401
4402
4403
4404
4405
4406
4407
4408
4409
4410
4411
4412
4413
4414
4415
4416
4417
4418
4419
4420
4421
4422
4423
4424
4425
4426
4427
4428
4429
4430
4431
4432
4433
4434
4435
4436
4437
4438
4439
4440
4441
4442
4443
4444
4445
4446
4447
4448
4449
4450
4451
4452
4453
4454
4455
4456
4457
4458
4459
4460
4461
4462
4463
4464
4465
4466
4467
4468
4469
4470
4471
4472
4473
4474
4475
4476
4477
4478
4479
4480
4481
4482
4483
4484
4485
4486
4487
4488
4489
4490
4491
4492
4493
4494
4495
4496
4497
4498
4499
4500
4501
4502
4503
4504
4505
4506
4507
4508
4509
4510
4511
4512
4513
4514
4515
4516
4517
4518
4519
4520
4521
4522
4523
4524
4525
4526
4527
4528
4529
4530
4531
4532
4533
4534
4535
4536
4537
4538
4539
4540
4541
4542
4543
4544
4545
4546
4547
4548
4549
4550
4551
4552
4553
4554
4555
4556
4557
4558
4559
4560
4561
4562
4563
4564
4565
4566
4567
4568
4569
4570
4571
4572
4573
4574
4575
4576
4577
4578
4579
4580
4581
4582
4583
4584
4585
4586
4587
4588
4589
4590
4591
4592
4593
4594
4595
4596
4597
4598
4599
4600
4601
4602
4603
4604
4605
4606
4607
4608
4609
4610
4611
4612
4613
4614
4615
4616
4617
4618
4619
4620
4621
4622
4623
4624
4625
4626
4627
4628
4629
4630
4631
4632
4633
4634
4635
4636
4637
4638
4639
4640
4641
4642
4643
4644
4645
4646
4647
4648
4649
4650
4651
4652
4653
4654
4655
4656
4657
4658
4659
4660
4661
4662
4663
4664
4665
4666
4667
4668
4669
4670
4671
4672
4673
4674
4675
4676
4677
4678
4679
4680
4681
4682
4683
4684
4685
4686
4687
4688
4689
4690
4691
4692
4693
4694
4695
4696
4697
4698
4699
4700
4701
4702
4703
4704
4705
4706
4707
4708
4709
4710
4711
4712
4713
4714
4715
4716
4717
4718
4719
4720
4721
4722
4723
4724
4725
4726
4727
4728
4729
4730
4731
4732
4733
4734
4735
4736
4737
4738
4739
4740
4741
4742
4743
4744
4745
4746
4747
4748
4749
4750
4751
4752
4753
4754
4755
4756
4757
4758
4759
4760
4761
4762
4763
4764
4765
4766
4767
4768
4769
4770
4771
4772
4773
4774
4775
4776
4777
4778
4779
4780
4781
4782
4783
4784
4785
4786
4787
4788
4789
4790
4791
4792
4793
4794
4795
4796
4797
4798
4799
4800
4801
4802
4803
4804
4805
4806
4807
4808
4809
4810
4811
4812
4813
4814
4815
4816
4817
4818
4819
4820
4821
4822
4823
4824
4825
4826
4827
4828
4829
4830
4831
4832
4833
4834
4835
4836
4837
4838
4839
4840
4841
4842
4843
4844
4845
4846
4847
4848
4849
4850
4851
4852
4853
4854
4855
4856
4857
4858
4859
4860
4861
4862
4863
4864
4865
4866
WEBVTT

00:00.000 --> 00:03.220
 The following is a conversation with Regina Barzilay.

00:03.220 --> 00:06.700
 She's a professor at MIT and a world class researcher

00:06.700 --> 00:08.340
 in natural language processing

00:08.340 --> 00:12.460
 and applications of deep learning to chemistry and oncology

00:12.460 --> 00:15.340
 or the use of deep learning for early diagnosis,

00:15.340 --> 00:18.300
 prevention and treatment of cancer.

00:18.300 --> 00:21.020
 She has also been recognized for teaching

00:21.020 --> 00:24.700
 of several successful AI related courses at MIT,

00:24.700 --> 00:26.840
 including the popular Introduction

00:26.840 --> 00:28.920
 to Machine Learning course.

00:28.920 --> 00:32.160
 This is the Artificial Intelligence podcast.

00:32.160 --> 00:34.560
 If you enjoy it, subscribe on YouTube,

00:34.560 --> 00:37.840
 give it five stars on iTunes, support it on Patreon

00:37.840 --> 00:39.840
 or simply connect with me on Twitter

00:39.840 --> 00:43.760
 at Lex Friedman spelled F R I D M A N.

00:43.760 --> 00:47.760
 And now here's my conversation with Regina Barzilay.

00:48.840 --> 00:50.320
 In an interview you've mentioned

00:50.320 --> 00:51.960
 that if there's one course you would take,

00:51.960 --> 00:54.600
 it would be a literature course with a friend of yours

00:54.600 --> 00:56.360
 that a friend of yours teaches.

00:56.360 --> 00:59.160
 Just out of curiosity, because I couldn't find anything

00:59.160 --> 01:04.160
 on it, are there books or ideas that had profound impact

01:04.400 --> 01:07.200
 on your life journey, books and ideas perhaps

01:07.200 --> 01:10.800
 outside of computer science and the technical fields?

01:11.780 --> 01:14.680
 I think because I'm spending a lot of my time at MIT

01:14.680 --> 01:18.280
 and previously in other institutions where I was a student,

01:18.280 --> 01:21.040
 I have limited ability to interact with people.

01:21.040 --> 01:22.640
 So a lot of what I know about the world

01:22.640 --> 01:24.220
 actually comes from books.

01:24.220 --> 01:27.240
 And there were quite a number of books

01:27.240 --> 01:31.380
 that had profound impact on me and how I view the world.

01:31.380 --> 01:35.820
 Let me just give you one example of such a book.

01:35.820 --> 01:39.660
 I've maybe a year ago read a book

01:39.660 --> 01:42.500
 called The Emperor of All Melodies.

01:42.500 --> 01:45.740
 It's a book about, it's kind of a history of science book

01:45.740 --> 01:50.740
 on how the treatments and drugs for cancer were developed.

01:50.740 --> 01:54.580
 And that book, despite the fact that I am in the business

01:54.580 --> 01:59.580
 of science, really opened my eyes on how imprecise

01:59.780 --> 02:03.060
 and imperfect the discovery process is

02:03.060 --> 02:05.820
 and how imperfect our current solutions

02:06.980 --> 02:11.060
 and what makes science succeed and be implemented.

02:11.060 --> 02:14.100
 And sometimes it's actually not the strengths of the idea,

02:14.100 --> 02:17.420
 but devotion of the person who wants to see it implemented.

02:17.420 --> 02:19.780
 So this is one of the books that, you know,

02:19.780 --> 02:22.300
 at least for the last year, quite changed the way

02:22.300 --> 02:24.940
 I'm thinking about scientific process

02:24.940 --> 02:26.700
 just from the historical perspective

02:26.700 --> 02:31.700
 and what do I need to do to make my ideas really implemented.

02:33.460 --> 02:36.060
 Let me give you an example of a book

02:36.060 --> 02:39.580
 which is not kind of, which is a fiction book.

02:40.620 --> 02:43.100
 It's a book called Americana.

02:44.420 --> 02:48.780
 And this is a book about a young female student

02:48.780 --> 02:53.260
 who comes from Africa to study in the United States.

02:53.260 --> 02:57.740
 And it describes her past, you know, within her studies

02:57.740 --> 03:02.020
 and her life transformation that, you know,

03:02.020 --> 03:06.540
 in a new country and kind of adaptation to a new culture.

03:06.540 --> 03:11.220
 And when I read this book, I saw myself

03:11.220 --> 03:13.540
 in many different points of it,

03:13.540 --> 03:18.540
 but it also kind of gave me the lens on different events.

03:20.140 --> 03:22.060
 And some of it that I never actually paid attention.

03:22.060 --> 03:24.700
 One of the funny stories in this book

03:24.700 --> 03:29.700
 is how she arrives to her new college

03:30.420 --> 03:32.900
 and she starts speaking in English

03:32.900 --> 03:35.700
 and she had this beautiful British accent

03:35.700 --> 03:39.860
 because that's how she was educated in her country.

03:39.860 --> 03:40.980
 This is not my case.

03:40.980 --> 03:45.460
 And then she notices that the person who talks to her,

03:45.460 --> 03:47.220
 you know, talks to her in a very funny way,

03:47.220 --> 03:48.340
 in a very slow way.

03:48.340 --> 03:51.460
 And she's thinking that this woman is disabled

03:51.460 --> 03:54.500
 and she's also trying to kind of to accommodate her.

03:54.500 --> 03:56.700
 And then after a while, when she finishes her discussion

03:56.700 --> 03:58.580
 with this officer from her college,

03:59.860 --> 04:02.100
 she sees how she interacts with the other students,

04:02.100 --> 04:03.020
 with American students.

04:03.020 --> 04:08.020
 And she discovers that actually she talked to her this way

04:08.020 --> 04:11.020
 because she saw that she doesn't understand English.

04:11.020 --> 04:14.180
 And I thought, wow, this is a funny experience.

04:14.180 --> 04:16.940
 And literally within few weeks,

04:16.940 --> 04:20.820
 I went to LA to a conference

04:20.820 --> 04:23.180
 and I asked somebody in the airport,

04:23.180 --> 04:25.580
 you know, how to find like a cab or something.

04:25.580 --> 04:28.380
 And then I noticed that this person is talking

04:28.380 --> 04:29.220
 in a very strange way.

04:29.220 --> 04:31.100
 And my first thought was that this person

04:31.100 --> 04:34.500
 have some, you know, pronunciation issues or something.

04:34.500 --> 04:36.060
 And I'm trying to talk very slowly to him

04:36.060 --> 04:38.580
 and I was with another professor, Ernst Frankel.

04:38.580 --> 04:42.180
 And he's like laughing because it's funny

04:42.180 --> 04:44.860
 that I don't get that the guy is talking in this way

04:44.860 --> 04:46.060
 because he thinks that I cannot speak.

04:46.060 --> 04:49.100
 So it was really kind of mirroring experience.

04:49.100 --> 04:53.300
 And it led me think a lot about my own experiences

04:53.300 --> 04:56.060
 moving, you know, from different countries.

04:56.060 --> 04:59.300
 So I think that books play a big role

04:59.300 --> 05:01.780
 in my understanding of the world.

05:01.780 --> 05:06.420
 On the science question, you mentioned that

05:06.420 --> 05:09.780
 it made you discover that personalities of human beings

05:09.780 --> 05:12.420
 are more important than perhaps ideas.

05:12.420 --> 05:13.660
 Is that what I heard?

05:13.660 --> 05:15.740
 It's not necessarily that they are more important

05:15.740 --> 05:19.180
 than ideas, but I think that ideas on their own

05:19.180 --> 05:20.460
 are not sufficient.

05:20.460 --> 05:24.660
 And many times, at least at the local horizon,

05:24.660 --> 05:29.140
 it's the personalities and their devotion to their ideas

05:29.140 --> 05:32.980
 is really that locally changes the landscape.

05:32.980 --> 05:37.500
 Now, if you're looking at AI, like let's say 30 years ago,

05:37.500 --> 05:39.180
 you know, dark ages of AI or whatever,

05:39.180 --> 05:42.420
 what is symbolic times, you can use any word.

05:42.420 --> 05:44.660
 You know, there were some people,

05:44.660 --> 05:46.620
 now we're looking at a lot of that work

05:46.620 --> 05:48.780
 and we're kind of thinking this was not really

05:48.780 --> 05:52.220
 maybe a relevant work, but you can see that some people

05:52.220 --> 05:54.900
 managed to take it and to make it so shiny

05:54.900 --> 05:59.260
 and dominate the academic world

05:59.260 --> 06:02.380
 and make it to be the standard.

06:02.380 --> 06:05.180
 If you look at the area of natural language processing,

06:06.420 --> 06:09.140
 it is well known fact that the reason that statistics

06:09.140 --> 06:13.980
 in NLP took such a long time to become mainstream

06:13.980 --> 06:16.860
 because there were quite a number of personalities

06:16.860 --> 06:18.460
 which didn't believe in this idea

06:18.460 --> 06:22.060
 and didn't stop research progress in this area.

06:22.060 --> 06:25.900
 So I do not think that, you know,

06:25.900 --> 06:28.940
 kind of asymptotically maybe personalities matters,

06:28.940 --> 06:33.940
 but I think locally it does make quite a bit of impact

06:33.940 --> 06:36.900
 and it's generally, you know,

06:36.900 --> 06:41.340
 speeds up the rate of adoption of the new ideas.

06:41.340 --> 06:43.500
 Yeah, and the other interesting question

06:43.500 --> 06:46.540
 is in the early days of particular discipline,

06:46.540 --> 06:50.460
 I think you mentioned in that book

06:50.460 --> 06:52.340
 is ultimately a book of cancer.

06:52.340 --> 06:55.100
 It's called The Emperor of All Melodies.

06:55.100 --> 06:58.580
 Yeah, and those melodies included the trying to,

06:58.580 --> 07:00.740
 the medicine, was it centered around?

07:00.740 --> 07:04.900
 So it was actually centered on, you know,

07:04.900 --> 07:07.180
 how people thought of curing cancer.

07:07.180 --> 07:10.660
 Like for me, it was really a discovery how people,

07:10.660 --> 07:14.140
 what was the science of chemistry behind drug development

07:14.140 --> 07:17.220
 that it actually grew up out of dying,

07:17.220 --> 07:19.780
 like coloring industry that people

07:19.780 --> 07:23.780
 who developed chemistry in 19th century in Germany

07:23.780 --> 07:28.140
 and Britain to do, you know, the really new dyes.

07:28.140 --> 07:30.180
 They looked at the molecules and identified

07:30.180 --> 07:32.140
 that they do certain things to cells.

07:32.140 --> 07:34.500
 And from there, the process started.

07:34.500 --> 07:35.740
 And, you know, like historically saying,

07:35.740 --> 07:36.900
 yeah, this is fascinating

07:36.900 --> 07:38.700
 that they managed to make the connection

07:38.700 --> 07:42.300
 and look under the microscope and do all this discovery.

07:42.300 --> 07:44.340
 But as you continue reading about it

07:44.340 --> 07:48.780
 and you read about how chemotherapy drugs

07:48.780 --> 07:50.500
 which were developed in Boston,

07:50.500 --> 07:52.500
 and some of them were developed.

07:52.500 --> 07:57.500
 And Farber, Dr. Farber from Dana Farber,

07:57.500 --> 08:00.460
 you know, how the experiments were done

08:00.460 --> 08:03.340
 that, you know, there was some miscalculation,

08:03.340 --> 08:04.540
 let's put it this way.

08:04.540 --> 08:06.740
 And they tried it on the patients and they just,

08:06.740 --> 08:09.980
 and those were children with leukemia and they died.

08:09.980 --> 08:11.660
 And then they tried another modification.

08:11.660 --> 08:15.020
 You look at the process, how imperfect is this process?

08:15.020 --> 08:17.500
 And, you know, like, if we're again looking back

08:17.500 --> 08:19.180
 like 60 years ago, 70 years ago,

08:19.180 --> 08:20.780
 you can kind of understand it.

08:20.780 --> 08:23.020
 But some of the stories in this book

08:23.020 --> 08:24.620
 which were really shocking to me

08:24.620 --> 08:27.980
 were really happening, you know, maybe decades ago.

08:27.980 --> 08:30.660
 And we still don't have a vehicle

08:30.660 --> 08:35.100
 to do it much more fast and effective and, you know,

08:35.100 --> 08:38.220
 scientific the way I'm thinking computer science scientific.

08:38.220 --> 08:40.420
 So from the perspective of computer science,

08:40.420 --> 08:43.780
 you've gotten a chance to work the application to cancer

08:43.780 --> 08:44.860
 and to medicine in general.

08:44.860 --> 08:48.420
 From a perspective of an engineer and a computer scientist,

08:48.420 --> 08:51.780
 how far along are we from understanding the human body,

08:51.780 --> 08:55.140
 biology of being able to manipulate it

08:55.140 --> 08:57.940
 in a way we can cure some of the maladies,

08:57.940 --> 08:59.740
 some of the diseases?

08:59.740 --> 09:02.220
 So this is very interesting question.

09:03.460 --> 09:06.020
 And if you're thinking as a computer scientist

09:06.020 --> 09:09.820
 about this problem, I think one of the reasons

09:09.820 --> 09:11.900
 that we succeeded in the areas

09:11.900 --> 09:13.980
 we as a computer scientist succeeded

09:13.980 --> 09:16.260
 is because we don't have,

09:16.260 --> 09:18.980
 we are not trying to understand in some ways.

09:18.980 --> 09:22.260
 Like if you're thinking about like eCommerce, Amazon,

09:22.260 --> 09:24.220
 Amazon doesn't really understand you.

09:24.220 --> 09:27.700
 And that's why it recommends you certain books

09:27.700 --> 09:29.580
 or certain products, correct?

09:30.660 --> 09:34.660
 And, you know, traditionally when people

09:34.660 --> 09:36.380
 were thinking about marketing, you know,

09:36.380 --> 09:39.780
 they divided the population to different kind of subgroups,

09:39.780 --> 09:41.740
 identify the features of this subgroup

09:41.740 --> 09:43.140
 and come up with a strategy

09:43.140 --> 09:45.580
 which is specific to that subgroup.

09:45.580 --> 09:47.340
 If you're looking about recommendation system,

09:47.340 --> 09:50.580
 they're not claiming that they're understanding somebody,

09:50.580 --> 09:52.700
 they're just managing to,

09:52.700 --> 09:54.780
 from the patterns of your behavior

09:54.780 --> 09:57.540
 to recommend you a product.

09:57.540 --> 09:59.580
 Now, if you look at the traditional biology,

09:59.580 --> 10:03.180
 and obviously I wouldn't say that I

10:03.180 --> 10:06.180
 at any way, you know, educated in this field,

10:06.180 --> 10:09.300
 but you know what I see, there's really a lot of emphasis

10:09.300 --> 10:10.660
 on mechanistic understanding.

10:10.660 --> 10:12.540
 And it was very surprising to me

10:12.540 --> 10:13.820
 coming from computer science,

10:13.820 --> 10:17.580
 how much emphasis is on this understanding.

10:17.580 --> 10:20.740
 And given the complexity of the system,

10:20.740 --> 10:23.220
 maybe the deterministic full understanding

10:23.220 --> 10:27.380
 of this process is, you know, beyond our capacity.

10:27.380 --> 10:29.460
 And the same ways in computer science

10:29.460 --> 10:31.540
 when we're doing recognition, when you do recommendation

10:31.540 --> 10:32.780
 and many other areas,

10:32.780 --> 10:35.940
 it's just probabilistic matching process.

10:35.940 --> 10:40.100
 And in some way, maybe in certain cases,

10:40.100 --> 10:42.940
 we shouldn't even attempt to understand

10:42.940 --> 10:45.780
 or we can attempt to understand, but in parallel,

10:45.780 --> 10:48.060
 we can actually do this kind of matchings

10:48.060 --> 10:51.060
 that would help us to find key role

10:51.060 --> 10:54.100
 to do early diagnostics and so on.

10:54.100 --> 10:55.860
 And I know that in these communities,

10:55.860 --> 10:59.060
 it's really important to understand,

10:59.060 --> 11:00.700
 but I'm sometimes wondering, you know,

11:00.700 --> 11:02.940
 what exactly does it mean to understand here?

11:02.940 --> 11:05.500
 Well, there's stuff that works and,

11:05.500 --> 11:07.620
 but that can be, like you said,

11:07.620 --> 11:10.340
 separate from this deep human desire

11:10.340 --> 11:12.700
 to uncover the mysteries of the universe,

11:12.700 --> 11:16.140
 of science, of the way the body works,

11:16.140 --> 11:17.620
 the way the mind works.

11:17.620 --> 11:19.540
 It's the dream of symbolic AI,

11:19.540 --> 11:24.540
 of being able to reduce human knowledge into logic

11:25.220 --> 11:26.900
 and be able to play with that logic

11:26.900 --> 11:28.700
 in a way that's very explainable

11:28.700 --> 11:30.300
 and understandable for us humans.

11:30.300 --> 11:31.780
 I mean, that's a beautiful dream.

11:31.780 --> 11:34.860
 So I understand it, but it seems that

11:34.860 --> 11:37.900
 what seems to work today and we'll talk about it more

11:37.900 --> 11:40.780
 is as much as possible, reduce stuff into data,

11:40.780 --> 11:43.900
 reduce whatever problem you're interested in to data

11:43.900 --> 11:47.060
 and try to apply statistical methods,

11:47.060 --> 11:49.100
 apply machine learning to that.

11:49.100 --> 11:51.140
 On a personal note,

11:51.140 --> 11:54.140
 you were diagnosed with breast cancer in 2014.

11:55.380 --> 11:58.420
 What did facing your mortality make you think about?

11:58.420 --> 12:00.260
 How did it change you?

12:00.260 --> 12:01.860
 You know, this is a great question

12:01.860 --> 12:03.820
 and I think that I was interviewed many times

12:03.820 --> 12:05.740
 and nobody actually asked me this question.

12:05.740 --> 12:09.700
 I think I was 43 at a time.

12:09.700 --> 12:12.860
 And the first time I realized in my life that I may die

12:12.860 --> 12:14.460
 and I never thought about it before.

12:14.460 --> 12:17.260
 And there was a long time since you're diagnosed

12:17.260 --> 12:18.580
 until you actually know what you have

12:18.580 --> 12:20.180
 and how severe is your disease.

12:20.180 --> 12:23.500
 For me, it was like maybe two and a half months.

12:23.500 --> 12:28.340
 And I didn't know where I am during this time

12:28.340 --> 12:30.660
 because I was getting different tests

12:30.660 --> 12:33.380
 and one would say it's bad and I would say, no, it is not.

12:33.380 --> 12:34.900
 So until I knew where I am,

12:34.900 --> 12:36.300
 I really was thinking about

12:36.300 --> 12:38.220
 all these different possible outcomes.

12:38.220 --> 12:39.700
 Were you imagining the worst

12:39.700 --> 12:41.940
 or were you trying to be optimistic or?

12:41.940 --> 12:43.540
 It would be really,

12:43.540 --> 12:47.340
 I don't remember what was my thinking.

12:47.340 --> 12:51.100
 It was really a mixture with many components at the time

12:51.100 --> 12:54.100
 speaking in our terms.

12:54.100 --> 12:59.100
 And one thing that I remember,

12:59.340 --> 13:01.500
 and every test comes and then you're saying,

13:01.500 --> 13:03.300
 oh, it could be this or it may not be this.

13:03.300 --> 13:04.700
 And you're hopeful and then you're desperate.

13:04.700 --> 13:07.660
 So it's like, there is a whole slew of emotions

13:07.660 --> 13:08.700
 that goes through you.

13:09.820 --> 13:14.820
 But what I remember is that when I came back to MIT,

13:15.100 --> 13:17.780
 I was kind of going the whole time through the treatment

13:17.780 --> 13:19.780
 to MIT, but my brain was not really there.

13:19.780 --> 13:21.820
 But when I came back, really finished my treatment

13:21.820 --> 13:23.860
 and I was here teaching and everything,

13:24.900 --> 13:27.060
 I look back at what my group was doing,

13:27.060 --> 13:28.820
 what other groups was doing.

13:28.820 --> 13:30.820
 And I saw these trivialities.

13:30.820 --> 13:33.260
 It's like people are building their careers

13:33.260 --> 13:36.900
 on improving some parts around two or 3% or whatever.

13:36.900 --> 13:38.380
 I was, it's like, seriously,

13:38.380 --> 13:40.740
 I did a work on how to decipher ugaritic,

13:40.740 --> 13:42.860
 like a language that nobody speak and whatever,

13:42.860 --> 13:46.140
 like what is significance?

13:46.140 --> 13:49.020
 When all of a sudden, I walked out of MIT,

13:49.020 --> 13:51.860
 which is when people really do care

13:51.860 --> 13:54.500
 what happened to your ICLR paper,

13:54.500 --> 13:57.900
 what is your next publication to ACL,

13:57.900 --> 14:01.860
 to the world where people, you see a lot of suffering

14:01.860 --> 14:04.900
 that I'm kind of totally shielded on it on daily basis.

14:04.900 --> 14:07.460
 And it's like the first time I've seen like real life

14:07.460 --> 14:08.660
 and real suffering.

14:09.700 --> 14:13.260
 And I was thinking, why are we trying to improve the parser

14:13.260 --> 14:18.260
 or deal with trivialities when we have capacity

14:18.340 --> 14:20.700
 to really make a change?

14:20.700 --> 14:24.620
 And it was really challenging to me because on one hand,

14:24.620 --> 14:27.420
 I have my graduate students really want to do their papers

14:27.420 --> 14:29.860
 and their work, and they want to continue to do

14:29.860 --> 14:31.900
 what they were doing, which was great.

14:31.900 --> 14:36.300
 And then it was me who really kind of reevaluated

14:36.300 --> 14:37.460
 what is the importance.

14:37.460 --> 14:40.260
 And also at that point, because I had to take some break,

14:42.500 --> 14:47.500
 I look back into like my years in science

14:47.740 --> 14:50.460
 and I was thinking, like 10 years ago,

14:50.460 --> 14:52.940
 this was the biggest thing, I don't know, topic models.

14:52.940 --> 14:55.340
 We have like millions of papers on topic models

14:55.340 --> 14:56.500
 and variation of topics models.

14:56.500 --> 14:58.580
 Now it's totally like irrelevant.

14:58.580 --> 15:02.460
 And you start looking at this, what do you perceive

15:02.460 --> 15:04.500
 as important at different point of time

15:04.500 --> 15:08.900
 and how it fades over time.

15:08.900 --> 15:12.980
 And since we have a limited time,

15:12.980 --> 15:14.900
 all of us have limited time on us,

15:14.900 --> 15:18.380
 it's really important to prioritize things

15:18.380 --> 15:20.540
 that really matter to you, maybe matter to you

15:20.540 --> 15:22.020
 at that particular point.

15:22.020 --> 15:24.380
 But it's important to take some time

15:24.380 --> 15:26.940
 and understand what matters to you,

15:26.940 --> 15:28.860
 which may not necessarily be the same

15:28.860 --> 15:31.700
 as what matters to the rest of your scientific community

15:31.700 --> 15:34.580
 and pursue that vision.

15:34.580 --> 15:38.460
 So that moment, did it make you cognizant?

15:38.460 --> 15:42.500
 You mentioned suffering of just the general amount

15:42.500 --> 15:44.340
 of suffering in the world.

15:44.340 --> 15:45.620
 Is that what you're referring to?

15:45.620 --> 15:47.420
 So as opposed to topic models

15:47.420 --> 15:50.780
 and specific detailed problems in NLP,

15:50.780 --> 15:54.460
 did you start to think about other people

15:54.460 --> 15:56.940
 who have been diagnosed with cancer?

15:56.940 --> 16:00.020
 Is that the way you started to see the world perhaps?

16:00.020 --> 16:00.860
 Oh, absolutely.

16:00.860 --> 16:04.980
 And it actually creates, because like, for instance,

16:04.980 --> 16:05.820
 there is parts of the treatment

16:05.820 --> 16:08.500
 where you need to go to the hospital every day

16:08.500 --> 16:11.620
 and you see the community of people that you see

16:11.620 --> 16:16.100
 and many of them are much worse than I was at a time.

16:16.100 --> 16:20.460
 And you all of a sudden see it all.

16:20.460 --> 16:23.940
 And people who are happier someday

16:23.940 --> 16:25.300
 just because they feel better.

16:25.300 --> 16:28.500
 And for people who are in our normal realm,

16:28.500 --> 16:30.820
 you take it totally for granted that you feel well,

16:30.820 --> 16:32.940
 that if you decide to go running, you can go running

16:32.940 --> 16:35.900
 and you're pretty much free

16:35.900 --> 16:37.620
 to do whatever you want with your body.

16:37.620 --> 16:40.180
 Like I saw like a community,

16:40.180 --> 16:42.820
 my community became those people.

16:42.820 --> 16:47.460
 And I remember one of my friends, Dina Katabi,

16:47.460 --> 16:50.420
 took me to Prudential to buy me a gift for my birthday.

16:50.420 --> 16:52.340
 And it was like the first time in months

16:52.340 --> 16:54.980
 that I went to kind of to see other people.

16:54.980 --> 16:58.180
 And I was like, wow, first of all, these people,

16:58.180 --> 16:59.820
 they are happy and they're laughing

16:59.820 --> 17:02.620
 and they're very different from these other my people.

17:02.620 --> 17:04.620
 And second of thing, I think it's totally crazy.

17:04.620 --> 17:06.620
 They're like laughing and wasting their money

17:06.620 --> 17:08.420
 on some stupid gifts.

17:08.420 --> 17:12.540
 And they may die.

17:12.540 --> 17:15.940
 They already may have cancer and they don't understand it.

17:15.940 --> 17:20.060
 So you can really see how the mind changes

17:20.060 --> 17:22.340
 that you can see that,

17:22.340 --> 17:23.180
 before that you can ask,

17:23.180 --> 17:24.380
 didn't you know that you're gonna die?

17:24.380 --> 17:28.340
 Of course I knew, but it was a kind of a theoretical notion.

17:28.340 --> 17:31.060
 It wasn't something which was concrete.

17:31.060 --> 17:33.900
 And at that point, when you really see it

17:33.900 --> 17:38.060
 and see how little means sometimes the system has

17:38.060 --> 17:41.740
 to have them, you really feel that we need to take a lot

17:41.740 --> 17:45.420
 of our brilliance that we have here at MIT

17:45.420 --> 17:48.020
 and translate it into something useful.

17:48.020 --> 17:50.540
 Yeah, and you still couldn't have a lot of definitions,

17:50.540 --> 17:53.620
 but of course, alleviating, suffering, alleviating,

17:53.620 --> 17:57.460
 trying to cure cancer is a beautiful mission.

17:57.460 --> 18:01.940
 So I of course know theoretically the notion of cancer,

18:01.940 --> 18:06.940
 but just reading more and more about it's 1.7 million

18:07.100 --> 18:09.860
 new cancer cases in the United States every year,

18:09.860 --> 18:13.460
 600,000 cancer related deaths every year.

18:13.460 --> 18:18.460
 So this has a huge impact, United States globally.

18:19.340 --> 18:24.340
 When broadly, before we talk about how machine learning,

18:24.340 --> 18:27.180
 how MIT can help,

18:27.180 --> 18:32.100
 when do you think we as a civilization will cure cancer?

18:32.100 --> 18:34.980
 How hard of a problem is it from everything you've learned

18:34.980 --> 18:35.940
 from it recently?

18:37.260 --> 18:39.300
 I cannot really assess it.

18:39.300 --> 18:42.100
 What I do believe will happen with the advancement

18:42.100 --> 18:45.940
 in machine learning is that a lot of types of cancer

18:45.940 --> 18:48.500
 we will be able to predict way early

18:48.500 --> 18:53.420
 and more effectively utilize existing treatments.

18:53.420 --> 18:57.540
 I think, I hope at least that with all the advancements

18:57.540 --> 19:01.180
 in AI and drug discovery, we would be able

19:01.180 --> 19:04.700
 to much faster find relevant molecules.

19:04.700 --> 19:08.220
 What I'm not sure about is how long it will take

19:08.220 --> 19:11.940
 the medical establishment and regulatory bodies

19:11.940 --> 19:14.780
 to kind of catch up and to implement it.

19:14.780 --> 19:17.420
 And I think this is a very big piece of puzzle

19:17.420 --> 19:20.420
 that is currently not addressed.

19:20.420 --> 19:21.780
 That's the really interesting question.

19:21.780 --> 19:25.460
 So first a small detail that I think the answer is yes,

19:25.460 --> 19:30.460
 but is cancer one of the diseases that when detected earlier

19:33.700 --> 19:37.820
 that's a significantly improves the outcomes?

19:37.820 --> 19:41.020
 So like, cause we will talk about there's the cure

19:41.020 --> 19:43.020
 and then there is detection.

19:43.020 --> 19:45.180
 And I think where machine learning can really help

19:45.180 --> 19:46.660
 is earlier detection.

19:46.660 --> 19:48.580
 So does detection help?

19:48.580 --> 19:49.660
 Detection is crucial.

19:49.660 --> 19:53.940
 For instance, the vast majority of pancreatic cancer patients

19:53.940 --> 19:57.300
 are detected at the stage that they are incurable.

19:57.300 --> 20:02.300
 That's why they have such a terrible survival rate.

20:03.740 --> 20:07.300
 It's like just few percent over five years.

20:07.300 --> 20:09.820
 It's pretty much today the sentence.

20:09.820 --> 20:13.620
 But if you can discover this disease early,

20:14.500 --> 20:16.740
 there are mechanisms to treat it.

20:16.740 --> 20:20.740
 And in fact, I know a number of people who were diagnosed

20:20.740 --> 20:23.580
 and saved just because they had food poisoning.

20:23.580 --> 20:25.020
 They had terrible food poisoning.

20:25.020 --> 20:28.540
 They went to ER, they got scan.

20:28.540 --> 20:30.660
 There were early signs on the scan

20:30.660 --> 20:33.540
 and that would save their lives.

20:33.540 --> 20:35.820
 But this wasn't really an accidental case.

20:35.820 --> 20:40.820
 So as we become better, we would be able to help

20:41.260 --> 20:46.260
 to many more people that are likely to develop diseases.

20:46.540 --> 20:51.020
 And I just want to say that as I got more into this field,

20:51.020 --> 20:53.620
 I realized that cancer is of course terrible disease,

20:53.620 --> 20:56.700
 but there are really the whole slew of terrible diseases

20:56.700 --> 21:00.820
 out there like neurodegenerative diseases and others.

21:01.660 --> 21:04.580
 So we, of course, a lot of us are fixated on cancer

21:04.580 --> 21:06.420
 because it's so prevalent in our society.

21:06.420 --> 21:08.540
 And you see these people where there are a lot of patients

21:08.540 --> 21:10.340
 with neurodegenerative diseases

21:10.340 --> 21:12.540
 and the kind of aging diseases

21:12.540 --> 21:17.100
 that we still don't have a good solution for.

21:17.100 --> 21:22.100
 And I felt as a computer scientist,

21:22.860 --> 21:25.460
 we kind of decided that it's other people's job

21:25.460 --> 21:29.340
 to treat these diseases because it's like traditionally

21:29.340 --> 21:32.420
 people in biology or in chemistry or MDs

21:32.420 --> 21:35.340
 are the ones who are thinking about it.

21:35.340 --> 21:37.420
 And after kind of start paying attention,

21:37.420 --> 21:40.340
 I think that it's really a wrong assumption

21:40.340 --> 21:42.940
 and we all need to join the battle.

21:42.940 --> 21:46.460
 So how it seems like in cancer specifically

21:46.460 --> 21:49.140
 that there's a lot of ways that machine learning can help.

21:49.140 --> 21:51.860
 So what's the role of machine learning

21:51.860 --> 21:54.100
 in the diagnosis of cancer?

21:55.260 --> 21:58.700
 So for many cancers today, we really don't know

21:58.700 --> 22:03.460
 what is your likelihood to get cancer.

22:03.460 --> 22:06.300
 And for the vast majority of patients,

22:06.300 --> 22:07.940
 especially on the younger patients,

22:07.940 --> 22:09.580
 it really comes as a surprise.

22:09.580 --> 22:11.140
 Like for instance, for breast cancer,

22:11.140 --> 22:13.860
 80% of the patients are first in their families,

22:13.860 --> 22:15.380
 it's like me.

22:15.380 --> 22:18.460
 And I never saw that I had any increased risk

22:18.460 --> 22:20.820
 because nobody had it in my family.

22:20.820 --> 22:22.300
 And for some reason in my head,

22:22.300 --> 22:24.820
 it was kind of inherited disease.

22:26.580 --> 22:28.380
 But even if I would pay attention,

22:28.380 --> 22:32.420
 the very simplistic statistical models

22:32.420 --> 22:34.540
 that are currently used in clinical practice,

22:34.540 --> 22:37.460
 they really don't give you an answer, so you don't know.

22:37.460 --> 22:40.380
 And the same true for pancreatic cancer,

22:40.380 --> 22:45.380
 the same true for non smoking lung cancer and many others.

22:45.380 --> 22:47.340
 So what machine learning can do here

22:47.340 --> 22:51.620
 is utilize all this data to tell us early

22:51.620 --> 22:53.140
 who is likely to be susceptible

22:53.140 --> 22:55.980
 and using all the information that is already there,

22:55.980 --> 22:59.980
 be it imaging, be it your other tests,

22:59.980 --> 23:04.860
 and eventually liquid biopsies and others,

23:04.860 --> 23:08.180
 where the signal itself is not sufficiently strong

23:08.180 --> 23:11.300
 for human eye to do good discrimination

23:11.300 --> 23:12.940
 because the signal may be weak,

23:12.940 --> 23:15.620
 but by combining many sources,

23:15.620 --> 23:18.100
 machine which is trained on large volumes of data

23:18.100 --> 23:20.700
 can really detect it early.

23:20.700 --> 23:22.500
 And that's what we've seen with breast cancer

23:22.500 --> 23:25.900
 and people are reporting it in other diseases as well.

23:25.900 --> 23:28.260
 That really boils down to data, right?

23:28.260 --> 23:30.980
 And in the different kinds of sources of data.

23:30.980 --> 23:33.740
 And you mentioned regulatory challenges.

23:33.740 --> 23:35.180
 So what are the challenges

23:35.180 --> 23:39.260
 in gathering large data sets in this space?

23:40.860 --> 23:42.660
 Again, another great question.

23:42.660 --> 23:45.500
 So it took me after I decided that I want to work on it

23:45.500 --> 23:48.740
 two years to get access to data.

23:48.740 --> 23:50.580
 Any data, like any significant data set?

23:50.580 --> 23:53.580
 Any significant amount, like right now in this country,

23:53.580 --> 23:57.060
 there is no publicly available data set

23:57.060 --> 23:58.820
 of modern mammograms that you can just go

23:58.820 --> 24:01.860
 on your computer, sign a document and get it.

24:01.860 --> 24:03.180
 It just doesn't exist.

24:03.180 --> 24:06.860
 I mean, obviously every hospital has its own collection

24:06.860 --> 24:07.700
 of mammograms.

24:07.700 --> 24:11.300
 There are data that came out of clinical trials.

24:11.300 --> 24:13.220
 What we're talking about here is a computer scientist

24:13.220 --> 24:17.140
 who just wants to run his or her model

24:17.140 --> 24:19.060
 and see how it works.

24:19.060 --> 24:22.900
 This data, like ImageNet, doesn't exist.

24:22.900 --> 24:27.900
 And there is a set which is called like Florida data set

24:28.620 --> 24:30.860
 which is a film mammogram from 90s

24:30.860 --> 24:32.420
 which is totally not representative

24:32.420 --> 24:33.860
 of the current developments.

24:33.860 --> 24:35.780
 Whatever you're learning on them doesn't scale up.

24:35.780 --> 24:39.300
 This is the only resource that is available.

24:39.300 --> 24:42.780
 And today there are many agencies

24:42.780 --> 24:44.460
 that govern access to data.

24:44.460 --> 24:46.300
 Like the hospital holds your data

24:46.300 --> 24:49.260
 and the hospital decides whether they would give it

24:49.260 --> 24:52.340
 to the researcher to work with this data or not.

24:52.340 --> 24:54.180
 Individual hospital?

24:54.180 --> 24:55.020
 Yeah.

24:55.020 --> 24:57.220
 I mean, the hospital may, you know,

24:57.220 --> 24:59.220
 assuming that you're doing research collaboration,

24:59.220 --> 25:01.980
 you can submit, you know,

25:01.980 --> 25:05.060
 there is a proper approval process guided by RB

25:05.060 --> 25:07.820
 and if you go through all the processes,

25:07.820 --> 25:10.140
 you can eventually get access to the data.

25:10.140 --> 25:13.540
 But if you yourself know our OEI community,

25:13.540 --> 25:16.100
 there are not that many people who actually ever got access

25:16.100 --> 25:20.260
 to data because it's very challenging process.

25:20.260 --> 25:22.780
 And sorry, just in a quick comment,

25:22.780 --> 25:25.780
 MGH or any kind of hospital,

25:25.780 --> 25:28.100
 are they scanning the data?

25:28.100 --> 25:29.740
 Are they digitally storing it?

25:29.740 --> 25:31.580
 Oh, it is already digitally stored.

25:31.580 --> 25:34.180
 You don't need to do any extra processing steps.

25:34.180 --> 25:38.340
 It's already there in the right format is that right now

25:38.340 --> 25:41.180
 there are a lot of issues that govern access to the data

25:41.180 --> 25:46.180
 because the hospital is legally responsible for the data.

25:46.180 --> 25:51.020
 And, you know, they have a lot to lose

25:51.020 --> 25:53.140
 if they give the data to the wrong person,

25:53.140 --> 25:56.460
 but they may not have a lot to gain if they give it

25:56.460 --> 26:00.580
 as a hospital, as a legal entity has given it to you.

26:00.580 --> 26:02.740
 And the way, you know, what I would imagine

26:02.740 --> 26:05.220
 happening in the future is the same thing that happens

26:05.220 --> 26:06.780
 when you're getting your driving license,

26:06.780 --> 26:09.820
 you can decide whether you want to donate your organs.

26:09.820 --> 26:13.100
 You can imagine that whenever a person goes to the hospital,

26:13.100 --> 26:17.540
 they, it should be easy for them to donate their data

26:17.540 --> 26:19.420
 for research and it can be different kind of,

26:19.420 --> 26:22.420
 do they only give you a test results or only mammogram

26:22.420 --> 26:25.900
 or only imaging data or the whole medical record?

26:27.060 --> 26:28.980
 Because at the end,

26:30.540 --> 26:33.860
 we all will benefit from all this insights.

26:33.860 --> 26:36.060
 And it's not like you say, I want to keep my data private,

26:36.060 --> 26:38.780
 but I would really love to get it from other people

26:38.780 --> 26:40.740
 because other people are thinking the same way.

26:40.740 --> 26:45.740
 So if there is a mechanism to do this donation

26:45.740 --> 26:48.020
 and the patient has an ability to say

26:48.020 --> 26:50.820
 how they want to use their data for research,

26:50.820 --> 26:54.100
 it would be really a game changer.

26:54.100 --> 26:56.460
 People, when they think about this problem,

26:56.460 --> 26:58.460
 there's a, it depends on the population,

26:58.460 --> 27:00.140
 depends on the demographics,

27:00.140 --> 27:03.420
 but there's some privacy concerns generally,

27:03.420 --> 27:05.860
 not just medical data, just any kind of data.

27:05.860 --> 27:09.620
 It's what you said, my data, it should belong kind of to me.

27:09.620 --> 27:11.660
 I'm worried how it's going to be misused.

27:12.540 --> 27:15.620
 How do we alleviate those concerns?

27:17.100 --> 27:19.460
 Because that seems like a problem that needs to be,

27:19.460 --> 27:22.980
 that problem of trust, of transparency needs to be solved

27:22.980 --> 27:27.260
 before we build large data sets that help detect cancer,

27:27.260 --> 27:30.180
 help save those very people in the future.

27:30.180 --> 27:31.940
 So I think there are two things that could be done.

27:31.940 --> 27:34.460
 There is a technical solutions

27:34.460 --> 27:38.220
 and there are societal solutions.

27:38.220 --> 27:40.180
 So on the technical end,

27:41.460 --> 27:46.460
 we today have ability to improve disambiguation.

27:48.140 --> 27:49.740
 Like, for instance, for imaging,

27:49.740 --> 27:54.740
 it's, you know, for imaging, you can do it pretty well.

27:55.620 --> 27:56.780
 What's disambiguation?

27:56.780 --> 27:58.540
 And disambiguation, sorry, disambiguation,

27:58.540 --> 27:59.860
 removing the identification,

27:59.860 --> 28:02.220
 removing the names of the people.

28:02.220 --> 28:04.820
 There are other data, like if it is a raw tax,

28:04.820 --> 28:08.180
 you cannot really achieve 99.9%,

28:08.180 --> 28:10.060
 but there are all these techniques

28:10.060 --> 28:12.460
 that actually some of them are developed at MIT,

28:12.460 --> 28:15.460
 how you can do learning on the encoded data

28:15.460 --> 28:17.420
 where you locally encode the image,

28:17.420 --> 28:22.420
 you train a network which only works on the encoded images

28:22.420 --> 28:24.940
 and then you send the outcome back to the hospital

28:24.940 --> 28:26.580
 and you can open it up.

28:26.580 --> 28:28.020
 So those are the technical solutions.

28:28.020 --> 28:30.660
 There are a lot of people who are working in this space

28:30.660 --> 28:33.780
 where the learning happens in the encoded form.

28:33.780 --> 28:36.180
 We are still early,

28:36.180 --> 28:39.260
 but this is an interesting research area

28:39.260 --> 28:41.900
 where I think we'll make more progress.

28:43.340 --> 28:45.620
 There is a lot of work in natural language processing

28:45.620 --> 28:48.620
 community how to do the identification better.

28:50.380 --> 28:54.020
 But even today, there are already a lot of data

28:54.020 --> 28:55.900
 which can be deidentified perfectly,

28:55.900 --> 28:58.780
 like your test data, for instance, correct,

28:58.780 --> 29:00.980
 where you can just, you know the name of the patient,

29:00.980 --> 29:04.300
 you just want to extract the part with the numbers.

29:04.300 --> 29:07.460
 The big problem here is again,

29:08.420 --> 29:10.420
 hospitals don't see much incentive

29:10.420 --> 29:12.660
 to give this data away on one hand

29:12.660 --> 29:14.220
 and then there is general concern.

29:14.220 --> 29:17.700
 Now, when I'm talking about societal benefits

29:17.700 --> 29:19.660
 and about the education,

29:19.660 --> 29:24.340
 the public needs to understand that I think

29:25.700 --> 29:29.420
 that there are situation and I still remember myself

29:29.420 --> 29:33.380
 when I really needed an answer, I had to make a choice.

29:33.380 --> 29:35.220
 There was no information to make a choice,

29:35.220 --> 29:36.660
 you're just guessing.

29:36.660 --> 29:41.060
 And at that moment you feel that your life is at the stake,

29:41.060 --> 29:44.820
 but you just don't have information to make the choice.

29:44.820 --> 29:48.740
 And many times when I give talks,

29:48.740 --> 29:51.300
 I get emails from women who say,

29:51.300 --> 29:52.820
 you know, I'm in this situation,

29:52.820 --> 29:55.940
 can you please run statistic and see what are the outcomes?

29:57.100 --> 30:01.300
 We get almost every week a mammogram that comes by mail

30:01.300 --> 30:03.460
 to my office at MIT, I'm serious.

30:04.380 --> 30:07.860
 That people ask to run because they need to make

30:07.860 --> 30:10.020
 life changing decisions.

30:10.020 --> 30:12.980
 And of course, I'm not planning to open a clinic here,

30:12.980 --> 30:16.660
 but we do run and give them the results for their doctors.

30:16.660 --> 30:20.100
 But the point that I'm trying to make,

30:20.100 --> 30:23.780
 that we all at some point or our loved ones

30:23.780 --> 30:26.620
 will be in the situation where you need information

30:26.620 --> 30:28.860
 to make the best choice.

30:28.860 --> 30:31.860
 And if this information is not available,

30:31.860 --> 30:35.100
 you would feel vulnerable and unprotected.

30:35.100 --> 30:37.860
 And then the question is, you know, what do I care more?

30:37.860 --> 30:40.380
 Because at the end, everything is a trade off, correct?

30:40.380 --> 30:41.700
 Yeah, exactly.

30:41.700 --> 30:45.580
 Just out of curiosity, it seems like one possible solution,

30:45.580 --> 30:47.420
 I'd like to see what you think of it,

30:49.340 --> 30:50.660
 based on what you just said,

30:50.660 --> 30:52.500
 based on wanting to know answers

30:52.500 --> 30:55.060
 for when you're yourself in that situation.

30:55.060 --> 30:58.420
 Is it possible for patients to own their data

30:58.420 --> 31:01.020
 as opposed to hospitals owning their data?

31:01.020 --> 31:04.100
 Of course, theoretically, I guess patients own their data,

31:04.100 --> 31:06.620
 but can you walk out there with a USB stick

31:07.580 --> 31:10.620
 containing everything or upload it to the cloud?

31:10.620 --> 31:14.500
 Where a company, you know, I remember Microsoft

31:14.500 --> 31:17.820
 had a service, like I try, I was really excited about

31:17.820 --> 31:19.260
 and Google Health was there.

31:19.260 --> 31:21.900
 I tried to give, I was excited about it.

31:21.900 --> 31:24.780
 Basically companies helping you upload your data

31:24.780 --> 31:27.940
 to the cloud so that you can move from hospital to hospital

31:27.940 --> 31:29.260
 from doctor to doctor.

31:29.260 --> 31:32.700
 Do you see a promise of that kind of possibility?

31:32.700 --> 31:34.660
 I absolutely think this is, you know,

31:34.660 --> 31:38.180
 the right way to exchange the data.

31:38.180 --> 31:41.700
 I don't know now who's the biggest player in this field,

31:41.700 --> 31:45.940
 but I can clearly see that even for totally selfish

31:45.940 --> 31:49.300
 health reasons, when you are going to a new facility

31:49.300 --> 31:52.620
 and many of us are sent to some specialized treatment,

31:52.620 --> 31:55.740
 they don't easily have access to your data.

31:55.740 --> 31:59.420
 And today, you know, we might want to send this mammogram,

31:59.420 --> 32:01.780
 need to go to the hospital, find some small office

32:01.780 --> 32:04.820
 which gives them the CD and they ship as a CD.

32:04.820 --> 32:08.340
 So you can imagine we're looking at kind of decades old

32:08.340 --> 32:10.100
 mechanism of data exchange.

32:11.340 --> 32:15.620
 So I definitely think this is an area where hopefully

32:15.620 --> 32:20.380
 all the right regulatory and technical forces will align

32:20.380 --> 32:23.220
 and we will see it actually implemented.

32:23.220 --> 32:27.500
 It's sad because unfortunately, and I need to research

32:27.500 --> 32:30.620
 why that happened, but I'm pretty sure Google Health

32:30.620 --> 32:32.940
 and Microsoft Health Vault or whatever it's called

32:32.940 --> 32:36.100
 both closed down, which means that there was

32:36.100 --> 32:39.100
 either regulatory pressure or there's not a business case

32:39.100 --> 32:41.820
 or there's challenges from hospitals,

32:41.820 --> 32:43.260
 which is very disappointing.

32:43.260 --> 32:46.500
 So when you say you don't know what the biggest players are,

32:46.500 --> 32:50.540
 the two biggest that I was aware of closed their doors.

32:50.540 --> 32:53.140
 So I'm hoping, I'd love to see why

32:53.140 --> 32:54.780
 and I'd love to see who else can come up.

32:54.780 --> 32:59.620
 It seems like one of those Elon Musk style problems

32:59.620 --> 33:01.300
 that are obvious needs to be solved

33:01.300 --> 33:02.980
 and somebody needs to step up and actually do

33:02.980 --> 33:07.540
 this large scale data collection.

33:07.540 --> 33:09.620
 So I know there is an initiative in Massachusetts,

33:09.620 --> 33:11.740
 I think, which you led by the governor

33:11.740 --> 33:15.460
 to try to create this kind of health exchange system

33:15.460 --> 33:17.860
 where at least to help people who kind of when you show up

33:17.860 --> 33:20.220
 in emergency room and there is no information

33:20.220 --> 33:23.540
 about what are your allergies and other things.

33:23.540 --> 33:26.140
 So I don't know how far it will go.

33:26.140 --> 33:28.180
 But another thing that you said

33:28.180 --> 33:30.780
 and I find it very interesting is actually

33:30.780 --> 33:33.780
 who are the successful players in this space

33:33.780 --> 33:37.260
 and the whole implementation, how does it go?

33:37.260 --> 33:40.300
 To me, it is from the anthropological perspective,

33:40.300 --> 33:44.660
 it's more fascinating that AI that today goes in healthcare,

33:44.660 --> 33:50.380
 we've seen so many attempts and so very little successes.

33:50.380 --> 33:54.220
 And it's interesting to understand that I've by no means

33:54.220 --> 33:56.700
 have knowledge to assess it,

33:56.700 --> 33:59.620
 why we are in the position where we are.

33:59.620 --> 34:02.940
 Yeah, it's interesting because data is really fuel

34:02.940 --> 34:04.980
 for a lot of successful applications.

34:04.980 --> 34:08.500
 And when that data acquires regulatory approval,

34:08.500 --> 34:12.940
 like the FDA or any kind of approval,

34:12.940 --> 34:15.740
 it seems that the computer scientists

34:15.740 --> 34:17.460
 are not quite there yet in being able

34:17.460 --> 34:18.900
 to play the regulatory game,

34:18.900 --> 34:21.220
 understanding the fundamentals of it.

34:21.220 --> 34:26.500
 I think that in many cases when even people do have data,

34:26.500 --> 34:31.300
 we still don't know what exactly do you need to demonstrate

34:31.300 --> 34:33.860
 to change the standard of care.

34:35.500 --> 34:37.180
 Like let me give you an example

34:37.180 --> 34:41.100
 related to my breast cancer research.

34:41.100 --> 34:45.500
 So in traditional breast cancer risk assessment,

34:45.500 --> 34:47.140
 there is something called density,

34:47.140 --> 34:50.500
 which determines the likelihood of a woman to get cancer.

34:50.500 --> 34:51.700
 And this pretty much says,

34:51.700 --> 34:54.220
 how much white do you see on the mammogram?

34:54.220 --> 34:58.980
 The whiter it is, the more likely the tissue is dense.

34:58.980 --> 35:03.660
 And the idea behind density, it's not a bad idea.

35:03.660 --> 35:08.100
 In 1967, a radiologist called Wolf decided to look back

35:08.100 --> 35:09.780
 at women who were diagnosed

35:09.780 --> 35:12.420
 and see what is special in their images.

35:12.420 --> 35:14.700
 Can we look back and say that they're likely to develop?

35:14.700 --> 35:16.180
 So he come up with some patterns.

35:16.180 --> 35:20.660
 And it was the best that his human eye can identify.

35:20.660 --> 35:22.060
 Then it was kind of formalized

35:22.060 --> 35:24.220
 and coded into four categories.

35:24.220 --> 35:26.940
 And that's what we are using today.

35:26.940 --> 35:31.020
 And today this density assessment

35:31.020 --> 35:34.620
 is actually a federal law from 2019,

35:34.620 --> 35:36.180
 approved by President Trump

35:36.180 --> 35:40.100
 and for the previous FDA commissioner,

35:40.100 --> 35:43.620
 where women are supposed to be advised by their providers

35:43.620 --> 35:45.100
 if they have high density,

35:45.100 --> 35:47.260
 putting them into higher risk category.

35:47.260 --> 35:49.460
 And in some states,

35:49.460 --> 35:51.260
 you can actually get supplementary screening

35:51.260 --> 35:53.700
 paid by your insurance because you're in this category.

35:53.700 --> 35:56.780
 Now you can say, how much science do we have behind it?

35:56.780 --> 36:00.820
 Whatever, biological science or epidemiological evidence.

36:00.820 --> 36:05.140
 So it turns out that between 40 and 50% of women

36:05.140 --> 36:06.660
 have dense breasts.

36:06.660 --> 36:11.140
 So about 40% of patients are coming out of their screening

36:11.140 --> 36:15.020
 and somebody tells them, you are in high risk.

36:15.020 --> 36:16.860
 Now, what exactly does it mean

36:16.860 --> 36:19.620
 if you as half of the population in high risk?

36:19.620 --> 36:22.060
 It's from saying, maybe I'm not,

36:22.060 --> 36:23.700
 or what do I really need to do with it?

36:23.700 --> 36:27.220
 Because the system doesn't provide me

36:27.220 --> 36:28.340
 a lot of the solutions

36:28.340 --> 36:30.140
 because there are so many people like me,

36:30.140 --> 36:34.620
 we cannot really provide very expensive solutions for them.

36:34.620 --> 36:38.740
 And the reason this whole density became this big deal,

36:38.740 --> 36:40.820
 it's actually advocated by the patients

36:40.820 --> 36:42.500
 who felt very unprotected

36:42.500 --> 36:44.900
 because many women went and did the mammograms

36:44.900 --> 36:46.260
 which were normal.

36:46.260 --> 36:49.460
 And then it turns out that they already had cancer,

36:49.460 --> 36:50.580
 quite developed cancer.

36:50.580 --> 36:54.420
 So they didn't have a way to know who is really at risk

36:54.420 --> 36:56.300
 and what is the likelihood that when the doctor tells you,

36:56.300 --> 36:58.060
 you're okay, you are not okay.

36:58.060 --> 37:02.140
 So at the time, and it was 15 years ago,

37:02.140 --> 37:06.820
 this maybe was the best piece of science that we had.

37:06.820 --> 37:11.820
 And it took quite 15, 16 years to make it federal law.

37:12.180 --> 37:15.660
 But now this is a standard.

37:15.660 --> 37:17.620
 Now with a deep learning model,

37:17.620 --> 37:19.660
 we can so much more accurately predict

37:19.660 --> 37:21.580
 who is gonna develop breast cancer

37:21.580 --> 37:23.700
 just because you're trained on a logical thing.

37:23.700 --> 37:26.060
 And instead of describing how much white

37:26.060 --> 37:27.380
 and what kind of white machine

37:27.380 --> 37:30.140
 can systematically identify the patterns,

37:30.140 --> 37:32.780
 which was the original idea behind the thought

37:32.780 --> 37:33.700
 of the cardiologist,

37:33.700 --> 37:35.740
 machines can do it much more systematically

37:35.740 --> 37:38.260
 and predict the risk when you're training the machine

37:38.260 --> 37:42.140
 to look at the image and to say the risk in one to five years.

37:42.140 --> 37:45.060
 Now you can ask me how long it will take

37:45.060 --> 37:46.460
 to substitute this density,

37:46.460 --> 37:48.620
 which is broadly used across the country

37:48.620 --> 37:53.620
 and really is not helping to bring this new models.

37:54.380 --> 37:56.700
 And I would say it's not a matter of the algorithm.

37:56.700 --> 37:58.780
 Algorithms use already orders of magnitude better

37:58.780 --> 38:00.460
 than what is currently in practice.

38:00.460 --> 38:02.500
 I think it's really the question,

38:02.500 --> 38:04.380
 who do you need to convince?

38:04.380 --> 38:07.460
 How many hospitals do you need to run the experiment?

38:07.460 --> 38:11.500
 What, you know, all this mechanism of adoption

38:11.500 --> 38:15.180
 and how do you explain to patients

38:15.180 --> 38:17.580
 and to women across the country

38:17.580 --> 38:20.460
 that this is really a better measure?

38:20.460 --> 38:22.740
 And again, I don't think it's an AI question.

38:22.740 --> 38:25.940
 We can work more and make the algorithm even better,

38:25.940 --> 38:29.300
 but I don't think that this is the current, you know,

38:29.300 --> 38:32.060
 the barrier, the barrier is really this other piece

38:32.060 --> 38:35.260
 that for some reason is not really explored.

38:35.260 --> 38:36.860
 It's like anthropological piece.

38:36.860 --> 38:39.860
 And coming back to your question about books,

38:39.860 --> 38:42.980
 there is a book that I'm reading.

38:42.980 --> 38:47.980
 It's called American Sickness by Elizabeth Rosenthal.

38:48.260 --> 38:51.580
 And I got this book from my clinical collaborator,

38:51.580 --> 38:53.100
 Dr. Connie Lehman.

38:53.100 --> 38:54.820
 And I said, I know everything that I need to know

38:54.820 --> 38:56.020
 about American health system,

38:56.020 --> 38:59.220
 but you know, every page doesn't fail to surprise me.

38:59.220 --> 39:03.140
 And I think there is a lot of interesting

39:03.140 --> 39:06.860
 and really deep lessons for people like us

39:06.860 --> 39:09.660
 from computer science who are coming into this field

39:09.660 --> 39:13.660
 to really understand how complex is the system of incentives

39:13.660 --> 39:17.660
 in the system to understand how you really need to play

39:17.660 --> 39:18.780
 to drive adoption.

39:19.740 --> 39:21.180
 You just said it's complex,

39:21.180 --> 39:23.980
 but if we're trying to simplify it,

39:23.980 --> 39:27.380
 who do you think most likely would be successful

39:27.380 --> 39:29.540
 if we push on this group of people?

39:29.540 --> 39:30.780
 Is it the doctors?

39:30.780 --> 39:31.820
 Is it the hospitals?

39:31.820 --> 39:34.300
 Is it the governments or policymakers?

39:34.300 --> 39:37.380
 Is it the individual patients, consumers?

39:38.860 --> 39:43.860
 Who needs to be inspired to most likely lead to adoption?

39:45.180 --> 39:47.100
 Or is there no simple answer?

39:47.100 --> 39:48.260
 There's no simple answer,

39:48.260 --> 39:51.980
 but I think there is a lot of good people in medical system

39:51.980 --> 39:55.180
 who do want to make a change.

39:56.460 --> 40:01.460
 And I think a lot of power will come from us as consumers

40:01.540 --> 40:04.260
 because we all are consumers or future consumers

40:04.260 --> 40:06.500
 of healthcare services.

40:06.500 --> 40:11.500
 And I think we can do so much more

40:12.060 --> 40:15.500
 in explaining the potential and not in the hype terms

40:15.500 --> 40:17.900
 and not saying that we now killed all Alzheimer

40:17.900 --> 40:20.500
 and I'm really sick of reading this kind of articles

40:20.500 --> 40:22.100
 which make these claims,

40:22.100 --> 40:24.780
 but really to show with some examples

40:24.780 --> 40:29.060
 what this implementation does and how it changes the care.

40:29.060 --> 40:30.020
 Because I can't imagine,

40:30.020 --> 40:33.220
 it doesn't matter what kind of politician it is,

40:33.220 --> 40:35.220
 we all are susceptible to these diseases.

40:35.220 --> 40:37.740
 There is no one who is free.

40:37.740 --> 40:41.060
 And eventually, we all are humans

40:41.060 --> 40:44.860
 and we're looking for a way to alleviate the suffering.

40:44.860 --> 40:47.260
 And this is one possible way

40:47.260 --> 40:49.300
 where we currently are under utilizing,

40:49.300 --> 40:50.940
 which I think can help.

40:51.860 --> 40:55.100
 So it sounds like the biggest problems are outside of AI

40:55.100 --> 40:57.980
 in terms of the biggest impact at this point.

40:57.980 --> 41:00.420
 But are there any open problems

41:00.420 --> 41:03.780
 in the application of ML to oncology in general?

41:03.780 --> 41:07.540
 So improving the detection or any other creative methods,

41:07.540 --> 41:09.620
 whether it's on the detection segmentations

41:09.620 --> 41:11.780
 or the vision perception side

41:11.780 --> 41:16.260
 or some other clever of inference?

41:16.260 --> 41:19.620
 Yeah, what in general in your view are the open problems

41:19.620 --> 41:20.460
 in this space?

41:20.460 --> 41:22.460
 Yeah, I just want to mention that beside detection,

41:22.460 --> 41:24.820
 not the area where I am kind of quite active

41:24.820 --> 41:28.580
 and I think it's really an increasingly important area

41:28.580 --> 41:30.940
 in healthcare is drug design.

41:32.260 --> 41:33.100
 Absolutely.

41:33.100 --> 41:36.900
 Because it's fine if you detect something early,

41:36.900 --> 41:41.100
 but you still need to get drugs

41:41.100 --> 41:43.860
 and new drugs for these conditions.

41:43.860 --> 41:46.740
 And today, all of the drug design,

41:46.740 --> 41:48.300
 ML is non existent there.

41:48.300 --> 41:52.980
 We don't have any drug that was developed by the ML model

41:52.980 --> 41:54.900
 or even not developed,

41:54.900 --> 41:57.060
 but at least even knew that ML model

41:57.060 --> 41:59.260
 plays some significant role.

41:59.260 --> 42:03.300
 I think this area with all the new ability

42:03.300 --> 42:05.780
 to generate molecules with desired properties

42:05.780 --> 42:10.780
 to do in silica screening is really a big open area.

42:11.460 --> 42:12.740
 To be totally honest with you,

42:12.740 --> 42:14.900
 when we are doing diagnostics and imaging,

42:14.900 --> 42:17.260
 primarily taking the ideas that were developed

42:17.260 --> 42:20.460
 for other areas and you applying them with some adaptation,

42:20.460 --> 42:25.460
 the area of drug design is really technically interesting

42:26.820 --> 42:27.980
 and exciting area.

42:27.980 --> 42:30.380
 You need to work a lot with graphs

42:30.380 --> 42:34.580
 and capture various 3D properties.

42:34.580 --> 42:37.420
 There are lots and lots of opportunities

42:37.420 --> 42:39.820
 to be technically creative.

42:39.820 --> 42:44.820
 And I think there are a lot of open questions in this area.

42:46.820 --> 42:48.820
 We're already getting a lot of successes

42:48.820 --> 42:52.700
 even with kind of the first generation of these models,

42:52.700 --> 42:56.500
 but there is much more new creative things that you can do.

42:56.500 --> 42:59.260
 And what's very nice to see is that actually

42:59.260 --> 43:04.180
 the more powerful, the more interesting models

43:04.180 --> 43:05.460
 actually do do better.

43:05.460 --> 43:10.460
 So there is a place to innovate in machine learning

43:11.300 --> 43:12.540
 in this area.

43:13.900 --> 43:16.820
 And some of these techniques are really unique to,

43:16.820 --> 43:19.620
 let's say, to graph generation and other things.

43:19.620 --> 43:20.820
 So...

43:20.820 --> 43:23.980
 What, just to interrupt really quick, I'm sorry,

43:23.980 --> 43:28.980
 graph generation or graphs, drug discovery in general,

43:30.620 --> 43:31.940
 how do you discover a drug?

43:31.940 --> 43:33.340
 Is this chemistry?

43:33.340 --> 43:37.500
 Is this trying to predict different chemical reactions?

43:37.500 --> 43:39.660
 Or is it some kind of...

43:39.660 --> 43:42.100
 What do graphs even represent in this space?

43:42.100 --> 43:43.980
 Oh, sorry, sorry.

43:43.980 --> 43:45.340
 And what's a drug?

43:45.340 --> 43:47.140
 Okay, so let's say you're thinking

43:47.140 --> 43:48.540
 there are many different types of drugs,

43:48.540 --> 43:50.580
 but let's say you're gonna talk about small molecules

43:50.580 --> 43:52.860
 because I think today the majority of drugs

43:52.860 --> 43:53.700
 are small molecules.

43:53.700 --> 43:55.020
 So small molecule is a graph.

43:55.020 --> 43:59.180
 The molecule is just where the node in the graph

43:59.180 --> 44:01.500
 is an atom and then you have the bonds.

44:01.500 --> 44:03.220
 So it's really a graph representation.

44:03.220 --> 44:05.540
 If you look at it in 2D, correct,

44:05.540 --> 44:07.460
 you can do it 3D, but let's say,

44:07.460 --> 44:09.540
 let's keep it simple and stick in 2D.

44:11.500 --> 44:14.740
 So pretty much my understanding today,

44:14.740 --> 44:18.620
 how it is done at scale in the companies,

44:18.620 --> 44:20.220
 without machine learning,

44:20.220 --> 44:22.100
 you have high throughput screening.

44:22.100 --> 44:23.740
 So you know that you are interested

44:23.740 --> 44:26.540
 to get certain biological activity of the compound.

44:26.540 --> 44:28.860
 So you scan a lot of compounds,

44:28.860 --> 44:30.700
 like maybe hundreds of thousands,

44:30.700 --> 44:32.980
 some really big number of compounds.

44:32.980 --> 44:36.060
 You identify some compounds which have the right activity

44:36.060 --> 44:39.220
 and then at this point, the chemists come

44:39.220 --> 44:43.220
 and they're trying to now to optimize

44:43.220 --> 44:45.340
 this original heat to different properties

44:45.340 --> 44:47.180
 that you want it to be maybe soluble,

44:47.180 --> 44:49.060
 you want it to decrease toxicity,

44:49.060 --> 44:51.620
 you want it to decrease the side effects.

44:51.620 --> 44:54.020
 Are those, sorry again to interrupt,

44:54.020 --> 44:55.500
 can that be done in simulation

44:55.500 --> 44:57.700
 or just by looking at the molecules

44:57.700 --> 44:59.820
 or do you need to actually run reactions

44:59.820 --> 45:02.460
 in real labs with lab coats and stuff?

45:02.460 --> 45:04.020
 So when you do high throughput screening,

45:04.020 --> 45:06.100
 you really do screening.

45:06.100 --> 45:07.020
 It's in the lab.

45:07.020 --> 45:09.140
 It's really the lab screening.

45:09.140 --> 45:10.980
 You screen the molecules, correct?

45:10.980 --> 45:12.580
 I don't know what screening is.

45:12.580 --> 45:15.060
 The screening is just check them for certain property.

45:15.060 --> 45:17.260
 Like in the physical space, in the physical world,

45:17.260 --> 45:18.740
 like actually there's a machine probably

45:18.740 --> 45:21.420
 that's actually running the reaction.

45:21.420 --> 45:22.900
 Actually running the reactions, yeah.

45:22.900 --> 45:25.420
 So there is a process where you can run

45:25.420 --> 45:26.660
 and that's why it's called high throughput

45:26.660 --> 45:29.580
 that it become cheaper and faster

45:29.580 --> 45:33.820
 to do it on very big number of molecules.

45:33.820 --> 45:35.820
 You run the screening,

45:35.820 --> 45:40.300
 you identify potential good starts

45:40.300 --> 45:42.340
 and then when the chemists come in

45:42.340 --> 45:44.060
 who have done it many times

45:44.060 --> 45:46.180
 and then they can try to look at it and say,

45:46.180 --> 45:48.260
 how can you change the molecule

45:48.260 --> 45:51.780
 to get the desired profile

45:51.780 --> 45:53.460
 in terms of all other properties?

45:53.460 --> 45:56.500
 So maybe how do I make it more bioactive and so on?

45:56.500 --> 45:59.460
 And there the creativity of the chemists

45:59.460 --> 46:03.980
 really is the one that determines the success

46:03.980 --> 46:07.460
 of this design because again,

46:07.460 --> 46:09.300
 they have a lot of domain knowledge

46:09.300 --> 46:12.900
 of what works, how do you decrease the CCD and so on

46:12.900 --> 46:15.020
 and that's what they do.

46:15.020 --> 46:17.860
 So all the drugs that are currently

46:17.860 --> 46:20.220
 in the FDA approved drugs

46:20.220 --> 46:22.140
 or even drugs that are in clinical trials,

46:22.140 --> 46:27.100
 they are designed using these domain experts

46:27.100 --> 46:30.060
 which goes through this combinatorial space

46:30.060 --> 46:31.940
 of molecules or graphs or whatever

46:31.940 --> 46:35.140
 and find the right one or adjust it to be the right ones.

46:35.140 --> 46:38.060
 It sounds like the breast density heuristic

46:38.060 --> 46:40.460
 from 67 to the same echoes.

46:40.460 --> 46:41.820
 It's not necessarily that.

46:41.820 --> 46:45.380
 It's really driven by deep understanding.

46:45.380 --> 46:46.820
 It's not like they just observe it.

46:46.820 --> 46:48.540
 I mean, they do deeply understand chemistry

46:48.540 --> 46:50.460
 and they do understand how different groups

46:50.460 --> 46:53.140
 and how does it changes the properties.

46:53.140 --> 46:56.660
 So there is a lot of science that gets into it

46:56.660 --> 46:58.740
 and a lot of kind of simulation,

46:58.740 --> 47:00.940
 how do you want it to behave?

47:01.900 --> 47:03.900
 It's very, very complex.

47:03.900 --> 47:06.140
 So they're quite effective at this design, obviously.

47:06.140 --> 47:08.420
 Now effective, yeah, we have drugs.

47:08.420 --> 47:10.780
 Like depending on how do you measure effective,

47:10.780 --> 47:13.940
 if you measure it in terms of cost, it's prohibitive.

47:13.940 --> 47:15.820
 If you measure it in terms of times,

47:15.820 --> 47:18.420
 we have lots of diseases for which we don't have any drugs

47:18.420 --> 47:20.060
 and we don't even know how to approach

47:20.060 --> 47:23.460
 and don't need to mention few drugs

47:23.460 --> 47:27.140
 or neurodegenerative disease drugs that fail.

47:27.140 --> 47:32.140
 So there are lots of trials that fail in later stages,

47:32.180 --> 47:35.180
 which is really catastrophic from the financial perspective.

47:35.180 --> 47:39.540
 So is it the effective, the most effective mechanism?

47:39.540 --> 47:42.700
 Absolutely no, but this is the only one that currently works.

47:44.300 --> 47:47.900
 And I was closely interacting

47:47.900 --> 47:49.260
 with people in pharmaceutical industry.

47:49.260 --> 47:51.340
 I was really fascinated on how sharp

47:51.340 --> 47:55.260
 and what a deep understanding of the domain do they have.

47:55.260 --> 47:57.020
 It's not observation driven.

47:57.020 --> 48:00.220
 There is really a lot of science behind what they do.

48:00.220 --> 48:02.300
 But if you ask me, can machine learning change it,

48:02.300 --> 48:05.300
 I firmly believe yes,

48:05.300 --> 48:07.860
 because even the most experienced chemists

48:07.860 --> 48:11.100
 cannot hold in their memory and understanding

48:11.100 --> 48:12.500
 everything that you can learn

48:12.500 --> 48:15.420
 from millions of molecules and reactions.

48:17.220 --> 48:19.900
 And the space of graphs is a totally new space.

48:19.900 --> 48:22.060
 I mean, it's a really interesting space

48:22.060 --> 48:23.980
 for machine learning to explore, graph generation.

48:23.980 --> 48:26.260
 Yeah, so there are a lot of things that you can do here.

48:26.260 --> 48:28.740
 So we do a lot of work.

48:28.740 --> 48:31.620
 So the first tool that we started with

48:31.620 --> 48:36.300
 was the tool that can predict properties of the molecules.

48:36.300 --> 48:39.420
 So you can just give the molecule and the property.

48:39.420 --> 48:41.340
 It can be by activity property,

48:41.340 --> 48:44.300
 or it can be some other property.

48:44.300 --> 48:46.460
 And you train the molecules

48:46.460 --> 48:50.020
 and you can now take a new molecule

48:50.020 --> 48:52.180
 and predict this property.

48:52.180 --> 48:54.860
 Now, when people started working in this area,

48:54.860 --> 48:55.980
 it is something very simple.

48:55.980 --> 48:58.580
 They do kind of existing fingerprints,

48:58.580 --> 49:00.740
 which is kind of handcrafted features of the molecule.

49:00.740 --> 49:02.980
 When you break the graph to substructures

49:02.980 --> 49:05.980
 and then you run it in a feed forward neural network.

49:05.980 --> 49:08.500
 And what was interesting to see that clearly,

49:08.500 --> 49:11.020
 this was not the most effective way to proceed.

49:11.020 --> 49:14.060
 And you need to have much more complex models

49:14.060 --> 49:16.300
 that can induce a representation,

49:16.300 --> 49:19.220
 which can translate this graph into the embeddings

49:19.220 --> 49:21.300
 and do these predictions.

49:21.300 --> 49:23.220
 So this is one direction.

49:23.220 --> 49:25.260
 Then another direction, which is kind of related

49:25.260 --> 49:29.180
 is not only to stop by looking at the embedding itself,

49:29.180 --> 49:32.780
 but actually modify it to produce better molecules.

49:32.780 --> 49:36.020
 So you can think about it as machine translation

49:36.020 --> 49:38.140
 that you can start with a molecule

49:38.140 --> 49:40.580
 and then there is an improved version of molecule.

49:40.580 --> 49:42.860
 And you can again, with encoder translate it

49:42.860 --> 49:45.380
 into the hidden space and then learn how to modify it

49:45.380 --> 49:49.340
 to improve the in some ways version of the molecules.

49:49.340 --> 49:52.620
 So that's, it's kind of really exciting.

49:52.620 --> 49:54.740
 We already have seen that the property prediction

49:54.740 --> 49:56.140
 works pretty well.

49:56.140 --> 49:59.780
 And now we are generating molecules

49:59.780 --> 50:01.820
 and there is actually labs

50:01.820 --> 50:04.180
 which are manufacturing this molecule.

50:04.180 --> 50:06.340
 So we'll see where it will get us.

50:06.340 --> 50:07.780
 Okay, that's really exciting.

50:07.780 --> 50:08.860
 There's a lot of promise.

50:08.860 --> 50:11.820
 Speaking of machine translation and embeddings,

50:11.820 --> 50:15.580
 I think you have done a lot of really great research

50:15.580 --> 50:17.540
 in NLP, natural language processing.

50:19.260 --> 50:21.540
 Can you tell me your journey through NLP?

50:21.540 --> 50:25.100
 What ideas, problems, approaches were you working on?

50:25.100 --> 50:28.180
 Were you fascinated with, did you explore

50:28.180 --> 50:33.180
 before this magic of deep learning reemerged and after?

50:34.020 --> 50:37.180
 So when I started my work in NLP, it was in 97.

50:38.180 --> 50:39.460
 This was very interesting time.

50:39.460 --> 50:42.620
 It was exactly the time that I came to ACL.

50:43.500 --> 50:46.140
 And at the time I could barely understand English,

50:46.140 --> 50:48.500
 but it was exactly like the transition point

50:48.500 --> 50:53.500
 because half of the papers were really rule based approaches

50:53.500 --> 50:56.180
 where people took more kind of heavy linguistic approaches

50:56.180 --> 51:00.060
 for small domains and try to build up from there.

51:00.060 --> 51:02.220
 And then there were the first generation of papers

51:02.220 --> 51:04.500
 which were corpus based papers.

51:04.500 --> 51:06.420
 And they were very simple in our terms

51:06.420 --> 51:07.900
 when you collect some statistics

51:07.900 --> 51:10.020
 and do prediction based on them.

51:10.020 --> 51:13.100
 And I found it really fascinating that one community

51:13.100 --> 51:18.100
 can think so very differently about the problem.

51:19.220 --> 51:22.820
 And I remember my first paper that I wrote,

51:22.820 --> 51:24.460
 it didn't have a single formula.

51:24.460 --> 51:25.740
 It didn't have evaluation.

51:25.740 --> 51:28.340
 It just had examples of outputs.

51:28.340 --> 51:32.020
 And this was a standard of the field at the time.

51:32.020 --> 51:35.860
 In some ways, I mean, people maybe just started emphasizing

51:35.860 --> 51:38.940
 the empirical evaluation, but for many applications

51:38.940 --> 51:42.780
 like summarization, you just show some examples of outputs.

51:42.780 --> 51:45.460
 And then increasingly you can see that how

51:45.460 --> 51:48.300
 the statistical approaches dominated the field

51:48.300 --> 51:52.100
 and we've seen increased performance

51:52.100 --> 51:56.020
 across many basic tasks.

51:56.020 --> 52:00.420
 The sad part of the story maybe that if you look again

52:00.420 --> 52:05.100
 through this journey, we see that the role of linguistics

52:05.100 --> 52:07.460
 in some ways greatly diminishes.

52:07.460 --> 52:11.580
 And I think that you really need to look

52:11.580 --> 52:14.540
 through the whole proceeding to find one or two papers

52:14.540 --> 52:17.260
 which make some interesting linguistic references.

52:17.260 --> 52:18.100
 It's really big.

52:18.100 --> 52:18.920
 Today, yeah.

52:18.920 --> 52:19.760
 Today, today.

52:19.760 --> 52:20.600
 This was definitely one of the.

52:20.600 --> 52:23.140
 Things like syntactic trees, just even basically

52:23.140 --> 52:26.180
 against our conversation about human understanding

52:26.180 --> 52:30.300
 of language, which I guess what linguistics would be

52:30.300 --> 52:34.300
 structured, hierarchical representing language

52:34.300 --> 52:37.140
 in a way that's human explainable, understandable

52:37.140 --> 52:39.500
 is missing today.

52:39.500 --> 52:42.380
 I don't know if it is, what is explainable

52:42.380 --> 52:43.620
 and understandable.

52:43.620 --> 52:47.360
 In the end, we perform functions and it's okay

52:47.360 --> 52:50.140
 to have machine which performs a function.

52:50.140 --> 52:53.200
 Like when you're thinking about your calculator, correct?

52:53.200 --> 52:56.100
 Your calculator can do calculation very different

52:56.100 --> 52:57.620
 from you would do the calculation,

52:57.620 --> 52:58.860
 but it's very effective in it.

52:58.860 --> 53:02.560
 And this is fine if we can achieve certain tasks

53:02.560 --> 53:05.760
 with high accuracy, doesn't necessarily mean

53:05.760 --> 53:09.300
 that it has to understand it the same way as we understand.

53:09.300 --> 53:11.260
 In some ways, it's even naive to request

53:11.260 --> 53:14.940
 because you have so many other sources of information

53:14.940 --> 53:17.900
 that are absent when you are training your system.

53:17.900 --> 53:19.220
 So it's okay.

53:19.220 --> 53:20.060
 Is it delivered?

53:20.060 --> 53:21.500
 And I would tell you one application

53:21.500 --> 53:22.780
 that is really fascinating.

53:22.780 --> 53:25.060
 In 97, when it came to ACL, there were some papers

53:25.060 --> 53:25.900
 on machine translation.

53:25.900 --> 53:27.440
 They were like primitive.

53:27.440 --> 53:31.060
 Like people were trying really, really simple.

53:31.060 --> 53:34.260
 And the feeling, my feeling was that, you know,

53:34.260 --> 53:36.260
 to make real machine translation system,

53:36.260 --> 53:39.580
 it's like to fly at the moon and build a house there

53:39.580 --> 53:41.580
 and the garden and live happily ever after.

53:41.580 --> 53:42.600
 I mean, it's like impossible.

53:42.600 --> 53:46.740
 I never could imagine that within, you know, 10 years,

53:46.740 --> 53:48.540
 we would already see the system working.

53:48.540 --> 53:51.420
 And now, you know, nobody is even surprised

53:51.420 --> 53:54.420
 to utilize the system on daily basis.

53:54.420 --> 53:56.220
 So this was like a huge, huge progress,

53:56.220 --> 53:57.860
 saying that people for very long time

53:57.860 --> 54:00.820
 tried to solve using other mechanisms.

54:00.820 --> 54:03.220
 And they were unable to solve it.

54:03.220 --> 54:06.140
 That's why coming back to your question about biology,

54:06.140 --> 54:10.800
 that, you know, in linguistics, people try to go this way

54:10.800 --> 54:13.500
 and try to write the syntactic trees

54:13.500 --> 54:17.500
 and try to abstract it and to find the right representation.

54:17.500 --> 54:22.240
 And, you know, they couldn't get very far

54:22.240 --> 54:26.580
 with this understanding while these models using,

54:26.580 --> 54:29.640
 you know, other sources actually capable

54:29.640 --> 54:31.680
 to make a lot of progress.

54:31.680 --> 54:33.960
 Now, I'm not naive to think

54:33.960 --> 54:36.780
 that we are in this paradise space in NLP.

54:36.780 --> 54:38.580
 And sure as you know,

54:38.580 --> 54:40.860
 that when we slightly change the domain

54:40.860 --> 54:42.620
 and when we decrease the amount of training,

54:42.620 --> 54:44.740
 it can do like really bizarre and funny thing.

54:44.740 --> 54:46.500
 But I think it's just a matter

54:46.500 --> 54:48.540
 of improving generalization capacity,

54:48.540 --> 54:51.500
 which is just a technical question.

54:51.500 --> 54:54.340
 Wow, so that's the question.

54:54.340 --> 54:57.720
 How much of language understanding can be solved

54:57.720 --> 54:59.180
 with deep neural networks?

54:59.180 --> 55:03.740
 In your intuition, I mean, it's unknown, I suppose.

55:03.740 --> 55:07.660
 But as we start to creep towards romantic notions

55:07.660 --> 55:10.620
 of the spirit of the Turing test

55:10.620 --> 55:14.220
 and conversation and dialogue

55:14.220 --> 55:18.340
 and something that maybe to me or to us,

55:18.340 --> 55:21.620
 so the humans feels like it needs real understanding.

55:21.620 --> 55:23.500
 How much can that be achieved

55:23.500 --> 55:27.180
 with these neural networks or statistical methods?

55:27.180 --> 55:32.180
 So I guess I am very much driven by the outcomes.

55:33.340 --> 55:35.420
 Can we achieve the performance

55:35.420 --> 55:40.420
 which would be satisfactory for us for different tasks?

55:40.700 --> 55:43.020
 Now, if you again look at machine translation system,

55:43.020 --> 55:46.020
 which are trained on large amounts of data,

55:46.020 --> 55:48.780
 they really can do a remarkable job

55:48.780 --> 55:51.300
 relatively to where they've been a few years ago.

55:51.300 --> 55:54.620
 And if you project into the future,

55:54.620 --> 55:59.380
 if it will be the same speed of improvement, you know,

55:59.380 --> 56:00.220
 this is great.

56:00.220 --> 56:01.060
 Now, does it bother me

56:01.060 --> 56:04.860
 that it's not doing the same translation as we are doing?

56:04.860 --> 56:06.620
 Now, if you go to cognitive science,

56:06.620 --> 56:09.460
 we still don't really understand what we are doing.

56:10.460 --> 56:11.860
 I mean, there are a lot of theories

56:11.860 --> 56:13.840
 and there's obviously a lot of progress and studying,

56:13.840 --> 56:17.540
 but our understanding what exactly goes on in our brains

56:17.540 --> 56:21.020
 when we process language is still not crystal clear

56:21.020 --> 56:25.460
 and precise that we can translate it into machines.

56:25.460 --> 56:29.220
 What does bother me is that, you know,

56:29.220 --> 56:31.700
 again, that machines can be extremely brittle

56:31.700 --> 56:33.980
 when you go out of your comfort zone

56:33.980 --> 56:36.060
 of when there is a distributional shift

56:36.060 --> 56:37.300
 between training and testing.

56:37.300 --> 56:39.020
 And it have been years and years,

56:39.020 --> 56:41.320
 every year when I teach an LP class,

56:41.320 --> 56:43.560
 now show them some examples of translation

56:43.560 --> 56:47.300
 from some newspaper in Hebrew or whatever, it was perfect.

56:47.300 --> 56:51.300
 And then I have a recipe that Tomi Yakel's system

56:51.300 --> 56:53.900
 sent me a while ago and it was written in Finnish

56:53.900 --> 56:55.720
 of Karelian pies.

56:55.720 --> 56:59.280
 And it's just a terrible translation.

56:59.280 --> 57:01.460
 You cannot understand anything what it does.

57:01.460 --> 57:04.180
 It's not like some syntactic mistakes, it's just terrible.

57:04.180 --> 57:07.020
 And year after year, I tried and will translate

57:07.020 --> 57:08.980
 and year after year, it does this terrible work

57:08.980 --> 57:10.980
 because I guess, you know, the recipes

57:10.980 --> 57:14.580
 are not a big part of their training repertoire.

57:14.580 --> 57:19.020
 So, but in terms of outcomes, that's a really clean,

57:19.020 --> 57:20.240
 good way to look at it.

57:21.100 --> 57:23.140
 I guess the question I was asking is,

57:24.060 --> 57:27.700
 do you think, imagine a future,

57:27.700 --> 57:30.540
 do you think the current approaches can pass

57:30.540 --> 57:32.460
 the Turing test in the way,

57:34.700 --> 57:37.060
 in the best possible formulation of the Turing test?

57:37.060 --> 57:39.460
 Which is, would you wanna have a conversation

57:39.460 --> 57:42.340
 with a neural network for an hour?

57:42.340 --> 57:45.820
 Oh God, no, no, there are not that many people

57:45.820 --> 57:48.380
 that I would want to talk for an hour, but.

57:48.380 --> 57:51.500
 There are some people in this world, alive or not,

57:51.500 --> 57:53.260
 that you would like to talk to for an hour.

57:53.260 --> 57:56.700
 Could a neural network achieve that outcome?

57:56.700 --> 57:58.860
 So I think it would be really hard to create

57:58.860 --> 58:02.300
 a successful training set, which would enable it

58:02.300 --> 58:04.980
 to have a conversation, a contextual conversation

58:04.980 --> 58:05.820
 for an hour.

58:05.820 --> 58:08.140
 Do you think it's a problem of data, perhaps?

58:08.140 --> 58:09.940
 I think in some ways it's not a problem of data,

58:09.940 --> 58:13.620
 it's a problem both of data and the problem of

58:13.620 --> 58:15.780
 the way we're training our systems,

58:15.780 --> 58:18.060
 their ability to truly, to generalize,

58:18.060 --> 58:19.300
 to be very compositional.

58:19.300 --> 58:23.220
 In some ways it's limited in the current capacity,

58:23.220 --> 58:27.980
 at least we can translate well,

58:27.980 --> 58:32.540
 we can find information well, we can extract information.

58:32.540 --> 58:35.180
 So there are many capacities in which it's doing very well.

58:35.180 --> 58:38.000
 And you can ask me, would you trust the machine

58:38.000 --> 58:39.820
 to translate for you and use it as a source?

58:39.820 --> 58:42.580
 I would say absolutely, especially if we're talking about

58:42.580 --> 58:45.660
 newspaper data or other data which is in the realm

58:45.660 --> 58:47.900
 of its own training set, I would say yes.

58:48.900 --> 58:52.900
 But having conversations with the machine,

58:52.900 --> 58:56.460
 it's not something that I would choose to do.

58:56.460 --> 58:59.420
 But I would tell you something, talking about Turing tests

58:59.420 --> 59:02.940
 and about all this kind of ELISA conversations,

59:02.940 --> 59:05.540
 I remember visiting Tencent in China

59:05.540 --> 59:07.620
 and they have this chat board and they claim

59:07.620 --> 59:10.780
 there is really humongous amount of the local population

59:10.780 --> 59:12.940
 which for hours talks to the chat board.

59:12.940 --> 59:15.340
 To me it was, I cannot believe it,

59:15.340 --> 59:18.000
 but apparently it's documented that there are some people

59:18.000 --> 59:20.760
 who enjoy this conversation.

59:20.760 --> 59:24.540
 And it brought to me another MIT story

59:24.540 --> 59:26.980
 about ELISA and Weisenbaum.

59:26.980 --> 59:29.340
 I don't know if you're familiar with the story.

59:29.340 --> 59:31.020
 So Weisenbaum was a professor at MIT

59:31.020 --> 59:32.580
 and when he developed this ELISA,

59:32.580 --> 59:34.620
 which was just doing string matching,

59:34.620 --> 59:38.540
 very trivial, like restating of what you said

59:38.540 --> 59:41.260
 with very few rules, no syntax.

59:41.260 --> 59:43.740
 Apparently there were secretaries at MIT

59:43.740 --> 59:48.180
 that would sit for hours and converse with this trivial thing

59:48.180 --> 59:50.180
 and at the time there was no beautiful interfaces

59:50.180 --> 59:51.820
 so you actually need to go through the pain

59:51.820 --> 59:53.540
 of communicating.

59:53.540 --> 59:56.940
 And Weisenbaum himself was so horrified by this phenomenon

59:56.940 --> 59:59.300
 that people can believe enough to the machine

59:59.300 --> 1:00:00.820
 that you just need to give them the hint

1:00:00.820 --> 1:00:03.940
 that machine understands you and you can complete the rest

1:00:03.940 --> 1:00:05.420
 that he kind of stopped this research

1:00:05.420 --> 1:00:08.660
 and went into kind of trying to understand

1:00:08.660 --> 1:00:11.480
 what this artificial intelligence can do to our brains.

1:00:12.740 --> 1:00:14.380
 So my point is, you know,

1:00:14.380 --> 1:00:19.300
 how much, it's not how good is the technology,

1:00:19.300 --> 1:00:22.620
 it's how ready we are to believe

1:00:22.620 --> 1:00:25.580
 that it delivers the goods that we are trying to get.

1:00:25.580 --> 1:00:27.200
 That's a really beautiful way to put it.

1:00:27.200 --> 1:00:29.800
 I, by the way, I'm not horrified by that possibility,

1:00:29.800 --> 1:00:33.140
 but inspired by it because,

1:00:33.140 --> 1:00:35.920
 I mean, human connection,

1:00:35.920 --> 1:00:38.220
 whether it's through language or through love,

1:00:39.860 --> 1:00:44.860
 it seems like it's very amenable to machine learning

1:00:44.900 --> 1:00:49.340
 and the rest is just challenges of psychology.

1:00:49.340 --> 1:00:52.460
 Like you said, the secretaries who enjoy spending hours.

1:00:52.460 --> 1:00:55.020
 I would say I would describe most of our lives

1:00:55.020 --> 1:00:58.020
 as enjoying spending hours with those we love

1:00:58.020 --> 1:01:00.820
 for very silly reasons.

1:01:00.820 --> 1:01:02.780
 All we're doing is keyword matching as well.

1:01:02.780 --> 1:01:05.100
 So I'm not sure how much intelligence

1:01:05.100 --> 1:01:08.140
 we exhibit to each other with the people we love

1:01:08.140 --> 1:01:09.820
 that we're close with.

1:01:09.820 --> 1:01:12.660
 So it's a very interesting point

1:01:12.660 --> 1:01:16.020
 of what it means to pass the Turing test with language.

1:01:16.020 --> 1:01:16.860
 I think you're right.

1:01:16.860 --> 1:01:18.220
 In terms of conversation,

1:01:18.220 --> 1:01:20.180
 I think machine translation

1:01:21.420 --> 1:01:24.420
 has very clear performance and improvement, right?

1:01:24.420 --> 1:01:28.020
 What it means to have a fulfilling conversation

1:01:28.020 --> 1:01:32.660
 is very person dependent and context dependent

1:01:32.660 --> 1:01:33.580
 and so on.

1:01:33.580 --> 1:01:36.340
 That's, yeah, it's very well put.

1:01:36.340 --> 1:01:40.740
 But in your view, what's a benchmark in natural language,

1:01:40.740 --> 1:01:43.640
 a test that's just out of reach right now,

1:01:43.640 --> 1:01:46.020
 but we might be able to, that's exciting.

1:01:46.020 --> 1:01:49.100
 Is it in perfecting machine translation

1:01:49.100 --> 1:01:51.900
 or is there other, is it summarization?

1:01:51.900 --> 1:01:52.740
 What's out there just out of reach?

1:01:52.740 --> 1:01:55.820
 I think it goes across specific application.

1:01:55.820 --> 1:01:59.500
 It's more about the ability to learn from few examples

1:01:59.500 --> 1:02:03.300
 for real, what we call few short learning and all these cases

1:02:03.300 --> 1:02:05.940
 because the way we publish these papers today,

1:02:05.940 --> 1:02:09.900
 we say, if we have like naively, we get 55,

1:02:09.900 --> 1:02:12.500
 but now we had a few example and we can move to 65.

1:02:12.500 --> 1:02:13.540
 None of these methods

1:02:13.540 --> 1:02:15.980
 actually are realistically doing anything useful.

1:02:15.980 --> 1:02:18.540
 You cannot use them today.

1:02:18.540 --> 1:02:23.540
 And the ability to be able to generalize and to move

1:02:25.460 --> 1:02:28.940
 or to be autonomous in finding the data

1:02:28.940 --> 1:02:30.300
 that you need to learn,

1:02:31.340 --> 1:02:34.280
 to be able to perfect new tasks or new language,

1:02:35.300 --> 1:02:38.100
 this is an area where I think we really need

1:02:39.200 --> 1:02:43.020
 to move forward to and we are not yet there.

1:02:43.020 --> 1:02:45.060
 Are you at all excited,

1:02:45.060 --> 1:02:46.540
 curious by the possibility

1:02:46.540 --> 1:02:48.520
 of creating human level intelligence?

1:02:49.900 --> 1:02:52.540
 Is this, cause you've been very in your discussion.

1:02:52.540 --> 1:02:54.340
 So if we look at oncology,

1:02:54.340 --> 1:02:58.100
 you're trying to use machine learning to help the world

1:02:58.100 --> 1:02:59.700
 in terms of alleviating suffering.

1:02:59.700 --> 1:03:02.340
 If you look at natural language processing,

1:03:02.340 --> 1:03:05.300
 you're focused on the outcomes of improving practical things

1:03:05.300 --> 1:03:06.820
 like machine translation.

1:03:06.820 --> 1:03:09.880
 But human level intelligence is a thing

1:03:09.880 --> 1:03:13.800
 that our civilization has dreamed about creating,

1:03:13.800 --> 1:03:15.740
 super human level intelligence.

1:03:15.740 --> 1:03:16.940
 Do you think about this?

1:03:16.940 --> 1:03:19.040
 Do you think it's at all within our reach?

1:03:20.380 --> 1:03:22.660
 So as you said yourself, Elie,

1:03:22.660 --> 1:03:26.140
 talking about how do you perceive

1:03:26.140 --> 1:03:28.980
 our communications with each other,

1:03:28.980 --> 1:03:31.940
 that we're matching keywords and certain behaviors

1:03:31.940 --> 1:03:33.020
 and so on.

1:03:33.020 --> 1:03:36.860
 So at the end, whenever one assesses,

1:03:36.860 --> 1:03:38.680
 let's say relations with another person,

1:03:38.680 --> 1:03:41.460
 you have separate kind of measurements and outcomes

1:03:41.460 --> 1:03:43.620
 inside your head that determine

1:03:43.620 --> 1:03:45.860
 what is the status of the relation.

1:03:45.860 --> 1:03:48.580
 So one way, this is this classical level,

1:03:48.580 --> 1:03:49.600
 what is the intelligence?

1:03:49.600 --> 1:03:51.860
 Is it the fact that now we are gonna do the same way

1:03:51.860 --> 1:03:52.940
 as human is doing,

1:03:52.940 --> 1:03:55.500
 when we don't even understand what the human is doing?

1:03:55.500 --> 1:03:59.100
 Or we now have an ability to deliver these outcomes,

1:03:59.100 --> 1:04:01.300
 but not in one area, not in NLP,

1:04:01.300 --> 1:04:03.940
 not just to translate or just to answer questions,

1:04:03.940 --> 1:04:05.380
 but across many, many areas

1:04:05.380 --> 1:04:08.100
 that we can achieve the functionalities

1:04:08.100 --> 1:04:11.060
 that humans can achieve with their ability to learn

1:04:11.060 --> 1:04:12.380
 and do other things.

1:04:12.380 --> 1:04:15.500
 I think this is, and this we can actually measure

1:04:15.500 --> 1:04:17.560
 how far we are.

1:04:17.560 --> 1:04:21.580
 And that's what makes me excited that we,

1:04:21.580 --> 1:04:23.780
 in my lifetime, at least so far what we've seen,

1:04:23.780 --> 1:04:25.840
 it's like tremendous progress

1:04:25.840 --> 1:04:28.700
 across these different functionalities.

1:04:28.700 --> 1:04:32.260
 And I think it will be really exciting

1:04:32.260 --> 1:04:35.540
 to see where we will be.

1:04:35.540 --> 1:04:39.300
 And again, one way to think about it,

1:04:39.300 --> 1:04:41.820
 there are machines which are improving their functionality.

1:04:41.820 --> 1:04:44.940
 Another one is to think about us with our brains,

1:04:44.940 --> 1:04:46.420
 which are imperfect,

1:04:46.420 --> 1:04:51.420
 how they can be accelerated by this technology

1:04:51.420 --> 1:04:55.900
 as it becomes stronger and stronger.

1:04:55.900 --> 1:04:57.260
 Coming back to another book

1:04:57.260 --> 1:05:01.060
 that I love, Flowers for Algernon.

1:05:01.060 --> 1:05:02.100
 Have you read this book?

1:05:02.100 --> 1:05:02.940
 Yes.

1:05:02.940 --> 1:05:05.700
 So there is this point that the patient gets

1:05:05.700 --> 1:05:07.980
 this miracle cure, which changes his brain.

1:05:07.980 --> 1:05:11.020
 And all of a sudden they see life in a different way

1:05:11.020 --> 1:05:13.300
 and can do certain things better,

1:05:13.300 --> 1:05:14.860
 but certain things much worse.

1:05:14.860 --> 1:05:19.860
 So you can imagine this kind of computer augmented cognition

1:05:22.400 --> 1:05:24.800
 where it can bring you that now in the same way

1:05:24.800 --> 1:05:28.120
 as the cars enable us to get to places

1:05:28.120 --> 1:05:30.080
 where we've never been before,

1:05:30.080 --> 1:05:31.640
 can we think differently?

1:05:31.640 --> 1:05:33.600
 Can we think faster?

1:05:33.600 --> 1:05:36.680
 And we already see a lot of it happening

1:05:36.680 --> 1:05:38.260
 in how it impacts us,

1:05:38.260 --> 1:05:42.200
 but I think we have a long way to go there.

1:05:42.200 --> 1:05:45.040
 So that's sort of artificial intelligence

1:05:45.040 --> 1:05:47.280
 and technology affecting our,

1:05:47.280 --> 1:05:50.440
 augmenting our intelligence as humans.

1:05:50.440 --> 1:05:55.440
 Yesterday, a company called Neuralink announced,

1:05:55.520 --> 1:05:56.800
 they did this whole demonstration.

1:05:56.800 --> 1:05:57.980
 I don't know if you saw it.

1:05:57.980 --> 1:06:01.000
 It's, they demonstrated brain computer,

1:06:01.000 --> 1:06:02.680
 brain machine interface,

1:06:02.680 --> 1:06:06.360
 where there's like a sewing machine for the brain.

1:06:06.360 --> 1:06:11.120
 Do you, you know, a lot of that is quite out there

1:06:11.120 --> 1:06:14.040
 in terms of things that some people would say

1:06:14.040 --> 1:06:16.340
 are impossible, but they're dreamers

1:06:16.340 --> 1:06:18.080
 and want to engineer systems like that.

1:06:18.080 --> 1:06:20.360
 Do you see, based on what you just said,

1:06:20.360 --> 1:06:23.820
 a hope for that more direct interaction with the brain?

1:06:25.120 --> 1:06:27.040
 I think there are different ways.

1:06:27.040 --> 1:06:29.000
 One is a direct interaction with the brain.

1:06:29.000 --> 1:06:30.900
 And again, there are lots of companies

1:06:30.900 --> 1:06:32.280
 that work in this space

1:06:32.280 --> 1:06:35.080
 and I think there will be a lot of developments.

1:06:35.080 --> 1:06:36.600
 But I'm just thinking that many times

1:06:36.600 --> 1:06:39.080
 we are not aware of our feelings,

1:06:39.080 --> 1:06:41.400
 of motivation, what drives us.

1:06:41.400 --> 1:06:44.200
 Like, let me give you a trivial example, our attention.

1:06:45.520 --> 1:06:47.260
 There are a lot of studies that demonstrate

1:06:47.260 --> 1:06:49.200
 that it takes a while to a person to understand

1:06:49.200 --> 1:06:51.080
 that they are not attentive anymore.

1:06:51.080 --> 1:06:52.160
 And we know that there are people

1:06:52.160 --> 1:06:54.520
 who really have strong capacity to hold attention.

1:06:54.520 --> 1:06:57.080
 There are other end of the spectrum people with ADD

1:06:57.080 --> 1:06:58.800
 and other issues that they have problem

1:06:58.800 --> 1:07:00.760
 to regulate their attention.

1:07:00.760 --> 1:07:03.520
 Imagine to yourself that you have like a cognitive aid

1:07:03.520 --> 1:07:06.280
 that just alerts you based on your gaze,

1:07:06.280 --> 1:07:09.280
 that your attention is now not on what you are doing.

1:07:09.280 --> 1:07:10.560
 And instead of writing a paper,

1:07:10.560 --> 1:07:12.760
 you're now dreaming of what you're gonna do in the evening.

1:07:12.760 --> 1:07:16.360
 So even this kind of simple measurement things,

1:07:16.360 --> 1:07:17.840
 how they can change us.

1:07:17.840 --> 1:07:22.400
 And I see it even in simple ways with myself.

1:07:22.400 --> 1:07:26.480
 I have my zone app that I got in MIT gym.

1:07:26.480 --> 1:07:28.800
 It kind of records, you know, how much did you run

1:07:28.800 --> 1:07:29.800
 and you have some points

1:07:29.800 --> 1:07:32.880
 and you can get some status, whatever.

1:07:32.880 --> 1:07:35.840
 Like, I said, what is this ridiculous thing?

1:07:35.840 --> 1:07:38.800
 Who would ever care about some status in some app?

1:07:38.800 --> 1:07:39.640
 Guess what?

1:07:39.640 --> 1:07:41.560
 So to maintain the status,

1:07:41.560 --> 1:07:44.640
 you have to do set a number of points every month.

1:07:44.640 --> 1:07:48.040
 And not only is that I do it every single month

1:07:48.040 --> 1:07:50.560
 for the last 18 months,

1:07:50.560 --> 1:07:54.160
 it went to the point that I was injured.

1:07:54.160 --> 1:07:56.160
 And when I could run again,

1:07:58.120 --> 1:08:02.560
 in two days, I did like some humongous amount of running

1:08:02.560 --> 1:08:04.080
 just to complete the points.

1:08:04.080 --> 1:08:05.920
 It was like really not safe.

1:08:05.920 --> 1:08:08.440
 It was like, I'm not gonna lose my status

1:08:08.440 --> 1:08:10.240
 because I want to get there.

1:08:10.240 --> 1:08:13.320
 So you can already see that this direct measurement

1:08:13.320 --> 1:08:15.160
 and the feedback is, you know,

1:08:15.160 --> 1:08:16.320
 we're looking at video games

1:08:16.320 --> 1:08:18.720
 and see why, you know, the addiction aspect of it,

1:08:18.720 --> 1:08:21.200
 but you can imagine that the same idea can be expanded

1:08:21.200 --> 1:08:23.640
 to many other areas of our life.

1:08:23.640 --> 1:08:25.960
 When we really can get feedback

1:08:25.960 --> 1:08:28.480
 and imagine in your case in relations,

1:08:29.880 --> 1:08:31.240
 when we are doing keyword matching,

1:08:31.240 --> 1:08:36.120
 imagine that the person who is generating the keywords,

1:08:36.120 --> 1:08:37.720
 that person gets direct feedback

1:08:37.720 --> 1:08:39.560
 before the whole thing explodes.

1:08:39.560 --> 1:08:42.000
 Is it maybe at this happy point,

1:08:42.000 --> 1:08:44.000
 we are going in the wrong direction.

1:08:44.000 --> 1:08:48.040
 Maybe it will be really a behavior modifying moment.

1:08:48.040 --> 1:08:51.360
 So yeah, it's a relationship management too.

1:08:51.360 --> 1:08:54.200
 So yeah, that's a fascinating whole area

1:08:54.200 --> 1:08:56.120
 of psychology actually as well,

1:08:56.120 --> 1:08:58.240
 of seeing how our behavior has changed

1:08:58.240 --> 1:09:01.840
 with basically all human relations now have

1:09:01.840 --> 1:09:06.200
 other nonhuman entities helping us out.

1:09:06.200 --> 1:09:09.440
 So you teach a large,

1:09:09.440 --> 1:09:12.600
 a huge machine learning course here at MIT.

1:09:14.000 --> 1:09:15.360
 I can ask you a million questions,

1:09:15.360 --> 1:09:17.560
 but you've seen a lot of students.

1:09:17.560 --> 1:09:20.920
 What ideas do students struggle with the most

1:09:20.920 --> 1:09:23.920
 as they first enter this world of machine learning?

1:09:23.920 --> 1:09:26.520
 Actually, this year was the first time

1:09:26.520 --> 1:09:28.480
 I started teaching a small machine learning class.

1:09:28.480 --> 1:09:31.160
 And it came as a result of what I saw

1:09:31.160 --> 1:09:34.640
 in my big machine learning class that Tomi Yakel and I built

1:09:34.640 --> 1:09:36.640
 maybe six years ago.

1:09:38.040 --> 1:09:40.360
 What we've seen that as this area become more

1:09:40.360 --> 1:09:43.440
 and more popular, more and more people at MIT

1:09:43.440 --> 1:09:45.360
 want to take this class.

1:09:45.360 --> 1:09:48.320
 And while we designed it for computer science majors,

1:09:48.320 --> 1:09:50.760
 there were a lot of people who really are interested

1:09:50.760 --> 1:09:52.600
 to learn it, but unfortunately,

1:09:52.600 --> 1:09:55.720
 their background was not enabling them

1:09:55.720 --> 1:09:57.200
 to do well in the class.

1:09:57.200 --> 1:09:59.360
 And many of them associated machine learning

1:09:59.360 --> 1:10:01.360
 with the word struggle and failure,

1:10:02.480 --> 1:10:04.640
 primarily for non majors.

1:10:04.640 --> 1:10:06.840
 And that's why we actually started a new class

1:10:06.840 --> 1:10:10.800
 which we call machine learning from algorithms to modeling,

1:10:10.800 --> 1:10:15.000
 which emphasizes more the modeling aspects of it

1:10:15.000 --> 1:10:20.000
 and focuses on, it has majors and non majors.

1:10:20.000 --> 1:10:23.480
 So we kind of try to extract the relevant parts

1:10:23.480 --> 1:10:25.560
 and make it more accessible,

1:10:25.560 --> 1:10:27.800
 because the fact that we're teaching 20 classifiers

1:10:27.800 --> 1:10:29.240
 in standard machine learning class,

1:10:29.240 --> 1:10:32.200
 it's really a big question to really need it.

1:10:32.200 --> 1:10:34.520
 But it was interesting to see this

1:10:34.520 --> 1:10:36.480
 from first generation of students,

1:10:36.480 --> 1:10:39.080
 when they came back from their internships

1:10:39.080 --> 1:10:42.320
 and from their jobs,

1:10:42.320 --> 1:10:45.560
 what different and exciting things they can do.

1:10:45.560 --> 1:10:47.600
 I would never think that you can even apply

1:10:47.600 --> 1:10:50.800
 machine learning to, some of them are like matching,

1:10:50.800 --> 1:10:53.480
 the relations and other things like variety.

1:10:53.480 --> 1:10:56.080
 Everything is amenable as the machine learning.

1:10:56.080 --> 1:10:58.320
 That actually brings up an interesting point

1:10:58.320 --> 1:11:00.680
 of computer science in general.

1:11:00.680 --> 1:11:03.520
 It almost seems, maybe I'm crazy,

1:11:03.520 --> 1:11:06.520
 but it almost seems like everybody needs to learn

1:11:06.520 --> 1:11:08.160
 how to program these days.

1:11:08.160 --> 1:11:11.400
 If you're 20 years old, or if you're starting school,

1:11:11.400 --> 1:11:14.200
 even if you're an English major,

1:11:14.200 --> 1:11:19.200
 it seems like programming unlocks so much possibility

1:11:20.480 --> 1:11:21.880
 in this world.

1:11:21.880 --> 1:11:25.000
 So when you interacted with those non majors,

1:11:25.000 --> 1:11:30.000
 is there skills that they were simply lacking at the time

1:11:30.280 --> 1:11:33.000
 that you wish they had and that they learned

1:11:33.000 --> 1:11:34.680
 in high school and so on?

1:11:34.680 --> 1:11:37.520
 Like how should education change

1:11:37.520 --> 1:11:41.320
 in this computerized world that we live in?

1:11:41.320 --> 1:11:44.320
 I think because I knew that there is a Python component

1:11:44.320 --> 1:11:47.000
 in the class, their Python skills were okay

1:11:47.000 --> 1:11:49.160
 and the class isn't really heavy on programming.

1:11:49.160 --> 1:11:52.400
 They primarily kind of add parts to the programs.

1:11:52.400 --> 1:11:55.440
 I think it was more of the mathematical barriers

1:11:55.440 --> 1:11:58.200
 and the class, again, with the design on the majors

1:11:58.200 --> 1:12:01.200
 was using the notation, like big O for complexity

1:12:01.200 --> 1:12:04.520
 and others, people who come from different backgrounds

1:12:04.520 --> 1:12:05.800
 just don't have it in the lexical,

1:12:05.800 --> 1:12:09.120
 so necessarily very challenging notion,

1:12:09.120 --> 1:12:11.480
 but they were just not aware.

1:12:12.360 --> 1:12:16.240
 So I think that kind of linear algebra and probability,

1:12:16.240 --> 1:12:19.120
 the basics, the calculus, multivariate calculus,

1:12:19.120 --> 1:12:20.840
 things that can help.

1:12:20.840 --> 1:12:23.520
 What advice would you give to students

1:12:23.520 --> 1:12:25.280
 interested in machine learning,

1:12:25.280 --> 1:12:29.240
 interested, you've talked about detecting,

1:12:29.240 --> 1:12:31.360
 curing cancer, drug design,

1:12:31.360 --> 1:12:34.520
 if they want to get into that field, what should they do?

1:12:36.320 --> 1:12:39.040
 Get into it and succeed as researchers

1:12:39.040 --> 1:12:42.080
 and entrepreneurs.

1:12:43.320 --> 1:12:45.240
 The first good piece of news is that right now

1:12:45.240 --> 1:12:47.400
 there are lots of resources

1:12:47.400 --> 1:12:50.160
 that are created at different levels

1:12:50.160 --> 1:12:54.800
 and you can find online in your school classes

1:12:54.800 --> 1:12:57.560
 which are more mathematical, more applied and so on.

1:12:57.560 --> 1:13:01.320
 So you can find a kind of a preacher

1:13:01.320 --> 1:13:02.760
 which preaches in your own language

1:13:02.760 --> 1:13:04.520
 where you can enter the field

1:13:04.520 --> 1:13:06.720
 and you can make many different types of contribution

1:13:06.720 --> 1:13:09.640
 depending of what is your strengths.

1:13:10.760 --> 1:13:13.720
 And the second point, I think it's really important

1:13:13.720 --> 1:13:18.160
 to find some area which you really care about

1:13:18.160 --> 1:13:20.240
 and it can motivate your learning

1:13:20.240 --> 1:13:22.640
 and it can be for somebody curing cancer

1:13:22.640 --> 1:13:25.360
 or doing self driving cars or whatever,

1:13:25.360 --> 1:13:29.680
 but to find an area where there is data

1:13:29.680 --> 1:13:31.320
 where you believe there are strong patterns

1:13:31.320 --> 1:13:33.600
 and we should be doing it and we're still not doing it

1:13:33.600 --> 1:13:35.280
 or you can do it better

1:13:35.280 --> 1:13:39.680
 and just start there and see where it can bring you.

1:13:40.800 --> 1:13:45.600
 So you've been very successful in many directions in life,

1:13:46.480 --> 1:13:48.840
 but you also mentioned Flowers of Argonon.

1:13:51.200 --> 1:13:53.840
 And I think I've read or listened to you mention somewhere

1:13:53.840 --> 1:13:55.360
 that researchers often get lost

1:13:55.360 --> 1:13:56.720
 in the details of their work.

1:13:56.720 --> 1:14:00.240
 This is per our original discussion with cancer and so on

1:14:00.240 --> 1:14:02.200
 and don't look at the bigger picture,

1:14:02.200 --> 1:14:05.320
 bigger questions of meaning and so on.

1:14:05.320 --> 1:14:07.440
 So let me ask you the impossible question

1:14:08.640 --> 1:14:11.560
 of what's the meaning of this thing,

1:14:11.560 --> 1:14:16.560
 of life, of your life, of research.

1:14:16.720 --> 1:14:21.440
 Why do you think we descendant of great apes

1:14:21.440 --> 1:14:24.480
 are here on this spinning ball?

1:14:26.800 --> 1:14:30.320
 You know, I don't think that I have really a global answer.

1:14:30.320 --> 1:14:32.800
 You know, maybe that's why I didn't go to humanities

1:14:33.760 --> 1:14:36.480
 and I didn't take humanities classes in my undergrad.

1:14:39.480 --> 1:14:43.560
 But the way I'm thinking about it,

1:14:43.560 --> 1:14:48.200
 each one of us inside of them have their own set of,

1:14:48.200 --> 1:14:51.120
 you know, things that we believe are important.

1:14:51.120 --> 1:14:53.360
 And it just happens that we are busy

1:14:53.360 --> 1:14:56.240
 with achieving various goals, busy listening to others

1:14:56.240 --> 1:15:00.960
 and to kind of try to conform and to be part of the crowd,

1:15:00.960 --> 1:15:03.680
 that we don't listen to that part.

1:15:04.600 --> 1:15:09.600
 And, you know, we all should find some time to understand

1:15:09.600 --> 1:15:11.840
 what is our own individual missions.

1:15:11.840 --> 1:15:14.080
 And we may have very different missions

1:15:14.080 --> 1:15:18.200
 and to make sure that while we are running 10,000 things,

1:15:18.200 --> 1:15:21.920
 we are not, you know, missing out

1:15:21.920 --> 1:15:26.800
 and we're putting all the resources to satisfy

1:15:26.800 --> 1:15:28.440
 our own mission.

1:15:28.440 --> 1:15:32.400
 And if I look over my time, when I was younger,

1:15:32.400 --> 1:15:35.000
 most of these missions, you know,

1:15:35.000 --> 1:15:38.600
 I was primarily driven by the external stimulus,

1:15:38.600 --> 1:15:41.520
 you know, to achieve this or to be that.

1:15:41.520 --> 1:15:46.520
 And now a lot of what I do is driven by really thinking

1:15:47.640 --> 1:15:51.360
 what is important for me to achieve independently

1:15:51.360 --> 1:15:55.160
 of the external recognition.

1:15:55.160 --> 1:16:00.080
 And, you know, I don't mind to be viewed in certain ways.

1:16:01.400 --> 1:16:05.760
 The most important thing for me is to be true to myself,

1:16:05.760 --> 1:16:07.520
 to what I think is right.

1:16:07.520 --> 1:16:08.680
 How long did it take?

1:16:08.680 --> 1:16:13.240
 How hard was it to find the you that you have to be true to?

1:16:14.160 --> 1:16:15.520
 So it takes time.

1:16:15.520 --> 1:16:17.760
 And even now, sometimes, you know,

1:16:17.760 --> 1:16:20.880
 the vanity and the triviality can take, you know.

1:16:20.880 --> 1:16:22.560
 At MIT.

1:16:22.560 --> 1:16:25.080
 Yeah, it can everywhere, you know,

1:16:25.080 --> 1:16:26.960
 it's just the vanity at MIT is different,

1:16:26.960 --> 1:16:28.160
 the vanity in different places,

1:16:28.160 --> 1:16:30.920
 but we all have our piece of vanity.

1:16:30.920 --> 1:16:35.920
 But I think actually for me, many times the place

1:16:38.720 --> 1:16:43.720
 to get back to it is, you know, when I'm alone

1:16:43.800 --> 1:16:45.800
 and also when I read.

1:16:45.800 --> 1:16:47.760
 And I think by selecting the right books,

1:16:47.760 --> 1:16:52.760
 you can get the right questions and learn from what you read.

1:16:54.880 --> 1:16:58.080
 So, but again, it's not perfect.

1:16:58.080 --> 1:17:02.040
 Like vanity sometimes dominates.

1:17:02.040 --> 1:17:04.800
 Well, that's a beautiful way to end.

1:17:04.800 --> 1:17:06.400
 Thank you so much for talking today.

1:17:06.400 --> 1:17:07.240
 Thank you.

1:17:07.240 --> 1:17:08.080
 That was fun.

1:17:08.080 --> 1:17:28.080
 That was fun.