in reply to
What is the (greatest|biggest|largest|supreme|most known) project made (in|with) perl?
You don't have the word 'significant' in your alternation, but if it were there, then I would have to rate How Perl saved the Human Genome Project as likely to prove one of the most significant in the long term.
Examine what is said, not who speaks -- Silence betokens consent -- Love the truth but pardon error.
"Science is about questioning the status quo. Questioning authority".
In the absence of evidence, opinion is indistinguishable from prejudice.