Natalie Abrams
November 08, 2017 AT 04:04 PM EST

On Thursday, Grey’s Anatomy will do what few shows have done before, hitting the landmark 300th episode.

Hot off the immediate successes of Lost and Desperate Housewives, ABC launched the Ellen Pompeo-starring Grey’s Anatomy as a midseason replacement on March 27, 2005. Kicking off with decent numbers in its nine-episode first season, the Shonda Rhimes medical drama became a runaway hit by season 2, partially thanks to the post-Super Bowl episode that helped cement the show in the pop culture zeitgeist.

“It’s been pretty special,” says original cast member James Pickens Jr. “I’m in a fraternity that most actors will never get into, and that’s to be in one show for this long. Most actors will go their whole career and never experience 14 seasons. We’re lucky to get a job and go several episodes, but to have something that has gone this long and had the kind of impact it’s had with our fans, it’s been pretty amazing, it’s been a true blessing.”

It’s a blessing many in the cast didn’t think would ever happen. In fact, fellow original Chandra Wilson kept her day job into season 2. “I [had] done a sitcom for ABC in 2001 and it’s the whole, don’t put all your eggs in one basket scenario,” Wilson says. “I said bye to everybody, packed up, moved to L.A., came out to do the show, and the show didn’t work out. I was like, ‘Oh no, what do I do now? Do I stay?’ I hadn’t planned on being in L.A. not working and had to go back to New York. I said, ‘Okay, I learned from that.’ So this next opportunity came up three years later, and I’m like, ‘Sure, I’ll go back and forth, I’ll commute, I won’t move — give me a chance to see what happens.’ I basically flew back and forth. I came to work and went back home on the weekends. Once season 2 started, my job said, ‘Do not call in this weekend, because you’re not coming. Your show is doing very well, you’re not coming.'”

Paul Hebert/ABC

While Wilson says she’s constantly amazed by Rhimes’ ability to reshape the show and evolve these characters — the story originally centered on five interns in their first year, most of whom have since left — for their fearless leader herself, Rhimes says she’s also changed a lot over the last 300 episodes. “I’m not such an introvert as I was anymore,” Rhimes says. “I think I’ve grown a lot as a businesswoman and as a leader. I said yes a lot, I started having a little bit more fun, although [my daughter] feels that I’m a nerd, I think I’ve started to enjoy this. I’ve learned how to enjoy it and I’ve stopped thinking it’s going to go away. That only happened a couple years ago, where I thought that this is all going to stop at any minute.”

Rhimes certainly shows no signs of slowing down, either. Over the last 14 seasons, as Grey’s has continued to be a ratings juggernaut for ABC, the uber-producer launched six-season spin-off Private Practice, critically acclaimed Scandal and Viola Davis vehicle How to Get Away with Murder, along with short-lived fare Off the Map, The Catch, and Still Star-Crossed. She also recently signed a lucrative Netflix deal, while ABC has another spin-off of Grey’s in the works that will be set in a Seattle firehouse, with flagship star Jason George set to star. Mix that with actually reaching 300 episodes, and executive producer Debbie Allen says it’s all a testament to Rhimes’ staying power. “How many shows get to do 300?” Allen says. “It is a real point in the legacy of Shonda Rhimes and who she is, this is home base for her, this show is the beginning and it speaks volumes about what might come and what is coming.”

Part of the show’s own staying power came from Rhimes and the writers introducing new characters each year, from initial love interests-turned-beloved faces like Arizona (Jessica Capshaw) and Owen (Kevin McKidd) to legacy characters like Amelia Shepherd (Caterina Scorsone) and Maggie Pierce (Kelly McCreary). “Everything that can be implied by the number 300, should be implied,” Capshaw says. “It’s weighty, it’s a lot, it’s incredible, it’s fortunate, it’s earned, it’s a ton of things — above and beyond all that, it’s sort of magical, it’s definitely a unicorn, it doesn’t happen often.”

“I’m so unbelievably grateful, it’s a gift,” adds Sarah Drew, whose character April Kepner joined Grey’s in season 6 when then-Seattle Grace literally merged with another hospital, therefore introducing a slew of new characters. “It’s not something I ever expected that I would have in my life. Before I did this show, I was just guest-starring from show to show to show, and so many shows start and go for maybe three seasons, maybe three episodes, but to be on a show this long-lasting, I’ve been able to have both my kids while being on this show, in a completely and amazing supportive environment of female leadership, who really lifted all of us up and never once made us feel like we were a nuisance for getting pregnant. All of that, I just feel like I have been nurtured and protected and cared for this whole time. It’s just a privilege to be a part of something that’s so huge and so far-reaching, and has affected so many people’s lives.”

It doesn’t hurt that the series tends to include a dozen or so series regulars at any moment — this season includes 14 — allowing for more ensemble stories despite the show’s title. “What’s wonderful is that it’s such a collaboration,” Scorsone says. “I think everybody turns in such beautiful performances and we all appreciate the work and the talent that all of our compatriots bring to the table. We get to go in and play, and do our bit. It really is a company of players and it’s greater than the sum of its parts. It’s an honor to be part of it.”

As for the actual episode, the milestone hour — which aptly pulls its name from Hamilton’s closing number, “Who Lives, Who Dies, Who Tells Your Story” — brings the Shondaland roller coaster to life. Literally. After a nightmare accident involving a county fair ride, it’s all hands on deck as Meredith and the docs of Grey Sloan tend to patients who ignite memories of ghosts from their past. Those ghosts include patients who look like original Fab Five members Cristina (Sandra Oh), George (T.R. Knight), and Izzie (Katherine Heigl). “Cristina, George, and Izzie we’re thinking about a lot during this episode because our three guest actors on the show actually really look like them and remind the rest of the doctors of those characters,” Drew says. “That causes the original group to really remember those people well and want to fight for these ones to live.”

But those originals won’t be the only ones mentioned over the hour. Executive producer Krista Vernoff included an Easter egg hunt that will honor the beloved characters who have since left the show. Drew also mentions nods to characters including Mark Sloan (Eric Dane) and Callie (Sara Ramirez), which Capshaw seems to confirm. “There’s just familiar faces that sort of re-conjure some lifelong loves that we might have had during the course of love in the show, and so they come up and they make you very happy,” Capshaw says. And certainly Meredith’s late-love Derek’s (Patrick Dempsey) presence will also loom large during the hour. “There are definitely some echoes of my brother,” Scorsone teases. “There’s a situation that happens that has some similarities to a situation with him.”

Grey’s Anatomy‘s 300th episode airs Thursday at 8 p.m. ET on ABC.

—With reporting by Abby Stern

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