diff --git a/lib/galaxy/datatypes/binary.py b/lib/galaxy/datatypes/binary.py
index f8dfa4b58bc8..0db1eb270fab 100644
--- a/lib/galaxy/datatypes/binary.py
+++ b/lib/galaxy/datatypes/binary.py
@@ -28,6 +28,7 @@
 )
 from galaxy.datatypes.metadata import DictParameter, ListParameter, MetadataElement, MetadataParameter
 from galaxy.datatypes.sniff import build_sniff_from_prefix
+from galaxy.datatypes.util.generic_util import call_pysam_index
 from galaxy.util import nice_size, sqlite
 from galaxy.util.checkers import is_bz2, is_gzip
 from . import data, dataproviders
@@ -488,13 +489,8 @@ def dataset_content_needs_grooming(self, file_name):
             # If pysam fails to index a file it will write to stderr,
             # and this causes the set_meta script to fail. So instead
             # we start another process and discard stderr.
-            if index_flag == '-b':
-                # IOError: No such file or directory: '-b' if index_flag is set to -b (pysam 0.15.4)
-                cmd = ['python', '-c', f"import pysam; pysam.set_verbosity(0); pysam.index('{file_name}', '{index_name}')"]
-            else:
-                cmd = ['python', '-c', f"import pysam; pysam.set_verbosity(0); pysam.index('{index_flag}', '{file_name}', '{index_name}')"]
-            with open(os.devnull, 'w') as devnull:
-                subprocess.check_call(cmd, stderr=devnull, shell=False)
+            call_pysam_index(file_name, index_name, index_flag=index_flag,
+                             stderr=os.devnull)
             needs_sorting = False
         except subprocess.CalledProcessError:
             needs_sorting = True
@@ -516,11 +512,7 @@ def set_meta(self, dataset, overwrite=True, **kwd):
             index_file = dataset.metadata.bam_csi_index
         if not index_file:
             index_file = dataset.metadata.spec[spec_key].param.new_file(dataset=dataset)
-        if index_flag == '-b':
-            # IOError: No such file or directory: '-b' if index_flag is set to -b (pysam 0.15.4)
-            pysam.index(dataset.file_name, index_file.file_name)
-        else:
-            pysam.index(index_flag, dataset.file_name, index_file.file_name)
+        call_pysam_index(dataset.file_name, index_file.file_name, index_flag=index_flag)
         dataset.metadata.bam_index = index_file
 
     def sniff(self, file_name):
@@ -691,7 +683,7 @@ def get_cram_version(self, filename):
 
     def set_index_file(self, dataset, index_file):
         try:
-            pysam.index(dataset.file_name, index_file.file_name)
+            call_pysam_index(dataset.file_name, index_file.file_name)
             return True
         except Exception as exc:
             log.warning('%s, set_index_file Exception: %s', self, exc)
diff --git a/lib/galaxy/datatypes/util/generic_util.py b/lib/galaxy/datatypes/util/generic_util.py
index 574f09586c09..a41dbf3888a0 100644
--- a/lib/galaxy/datatypes/util/generic_util.py
+++ b/lib/galaxy/datatypes/util/generic_util.py
@@ -16,3 +16,21 @@ def count_special_lines(word, filename, invert=False):
     except commands.CommandLineException:
         return 0
     return int(out)
+
+
+def call_pysam_index(self, file_name, index_name, index_flag=None, stderr=None):
+    """
+    The pysam.index call can block the GIL, which can pause all threads, including
+    the heartbeat thread. Therefore, start it as an external process.
+    """
+    if index_flag == '-b' or not index_flag:
+        # IOError: No such file or directory: '-b' if index_flag is set to -b (pysam 0.15.4)
+        cmd = ['python', '-c', f"import pysam; pysam.set_verbosity(0); pysam.index('{file_name}', '{index_name}')"]
+    else:
+        cmd = ['python', '-c',
+               f"import pysam; pysam.set_verbosity(0); pysam.index('{index_flag}', '{file_name}', '{index_name}')"]
+    if stderr:
+        with open(stderr, 'w') as stderr:
+            subprocess.check_call(cmd, stderr=stderr, shell=False)
+    else:
+        subprocess.check_call(cmd, shell=False)