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The Best TV 'I Love You' Scenes Of All Time

Three simple words, so many variations. TV's greatest couples have all exchanged "I love yous" at some point, taking their relationships to a new level. We simply can't resist the sweeping romance of when one half of the couple realizes they simply can't contain their feelings any longer and pours their heart out to the other. In other instances, both halves express their love for each other at the same time, confirming their unending bond for life.

Here are some of our favorite "I love you" moments from TV that reduce us to a puddle of tears every time.

Rory and Dean on Gilmore Girls ("Love, Daisies and Troubadours," season 1, episode 21) Alexis Bledel on 'Gilmore Girls'. Warner Bros. Television Dean Forester (Jared Padalecki) was Rory Gilmore's (Alexis Bledel) first love, but it took her a second to realize it. After Dean's unreciprocated "I love you" led to the couple's first breakup, Rory couldn't quite find a way to make things right. But, when Dean showed up at her school, she realized she couldn't let him go again. Best part: "Because I love you, you idiot!" Jamie and Claire on Outlander ("Lallybroch," season 1, episode 12) Sam Heughan and Caitríona Balfe on 'Outlander'. Starz The story of Outlander is the story of Claire (Caitríona Balfe) trying to find her home, the place she belongs. And the moment she started to feel that at Lallybroch, Jamie (Sam Heughan) launched into a sentimental conversation about the reasons why he married her, and, furthermore, the moment he first fell in love with her. It caught Claire — and the viewers — off guard in the most welcome way possible. Best part: Jamie telling Claire, "I wanted you from the first moment I saw you, but... I loved you when you wept in my arms that first night at Leoch. Now, I wake up every day and I find that I love you more than I did the day before." Booth to Bones on Bones ("The Parts in the Sum of the Whole," season 5, episode 16) Emily Deschanel and David Boreanaz on 'Bones'. Greg Gayne/Fox Booth (David Boreanaz) had put his heart on the line twice and been shot down, well, twice. (Then it happened a third time with Katheryn Winnick's Hanna.) While we're thrilled Booth and Bones (Emily Deschanel) got together, we're baffled as to how Bones — or any woman for that matter — would have the strength to turn down a guy who delivered a speech like Booth's "I'm the gambler" in the show's 100th episode. And you can bet that we still cry when watching this scene. Best part: "You know when you talk to older couples who've been in love for 30 or 40 or 50 years. It's always the guy who said 'I knew.' I knew right from the beginning... I'm that guy. Bones, I'm that guy. I know." Jim to Pam on The Office ("Casino Night," season 2, episode 22) Jenna Fischer and John Krasinski on 'The Office'. NBC Two seasons of will-they-won't-they tension led up to Jim's (John Krasinski) sincere and simply put parking lot confession of love. But then-engaged Pam's (Jenna Fischer) reaction was — at least initially — less than ideal and drove Jim (and us!) to tears. And you know what? It still gets us every time. Best part: [Pause] "I'm in love with you." Desmond and Penny on Lost ("The Constant," season 4, episode 5) Henry Ian Cusick on 'Lost'. ABC He never stopped trying to reach her. She never stopped looking for him. And ever since this aired, we never stopped dissolving into tears whenever we see it. Best part: The. Whole. Thing. Ryan and Marissa on The O.C. ("The Countdown," season 1, episode 14) Ben McKenzie and Mischa Barton on 'The O.C.'. Fox After nearly half a season of build-up, Ryan (Ben McKenzie) and Marissa (Mischa Barton) finally decided to give the relationship thing a try, but neither of them expected to fall for the other so quickly. So, when Marissa found herself saying "I love you" after a movie date, all Ryan could manage to say back was "Thank you." But, when he found himself locked in a pool house on New Year's Eve, he had some time to realize his mistake. In an iconic moment, Ryan raced to find Marissa, running up the stairs to Oliver's (Taylor Handley) penthouse, where he arrived just as the clock hit midnight to confess his love. Best part: Marissa's "thank you" in response to Ryan's "I love you." Carol to Luka re: Doug on ER ("Such Sweet Sorrow," season 6, episode 21) Julianna Margulies on 'ER'. NBC A patient's husband's emotional speech about his everlasting love for his dead wife prompted Carol (Julianna Margulies) to pack her things and rush off to meet longtime love Doug (George Clooney) in Seattle during season 6. But she didn't leave without explaining her rush exit to Luka (Goran Višnjić), who had been standing beside her loyally since the birth of her and Doug's twins. We don't even blame her for not saying her speech directly to Doug because, honestly, would you waste time with words if you were with that man? That's what we thought. Best part: "I'm still in love with him; I am," she said. "I've been in love with him since I was 23 years old. He's...He's everything to me. He's my life. I feel complete when I'm with him, and I feel empty when we're apart. He's the father of my children...And he's my soulmate." Meredith to Derek on Grey's Anatomy ("Bring the Pain," season 2, episode 5) Ellen Pompeo and Patrick Dempsey on 'Grey's Anatomy'. ABC We don't like to remind ourselves about those times when all wasn't about happy Post-it marriages for Grey's most famous couple. But we do like to remember this scene, where Meredith (Ellen Pompeo) spilled her heart in a very Meredith way. And while Derek (Patrick Dempsey) didn't "pick" her that time — eventually he did. That's what counts. Best part: "Derek, I love you. In a really, really big, pretend to like your taste in music, let you eat the last piece of cheesecake, hold a radio over my head outside your window, unfortunate way that makes me hate you, love you. So pick me. Choose me. Love me." Chuck to Sarah on Chuck ("Chuck Versus the Three Words," season 3, episode 2) Zachary Levi and Yvonne Strahovski on 'Chuck'. NBC Choosing the best Chuck (Zachary Levi) and Sarah (Yvonne Strahovski) moment is like choosing the best piece of chocolate from a variety pack — it's all good. But when Sarah learned (via video confession) that Chuck chose to be a spy because he loved her, we got more teary-eyed than she did. To use a rom-com cliché, she made him want to be a better man. Sigh. Best part: "You're the one that taught me that being a spy is about choosing something bigger. It's about putting aside your own personal feelings for the greater good, and that's what I chose. I chose to be a spy for my family and friends and you. I chose to be a spy because...Sarah, I love you." Buffy to Angel on Angel ("I Will Remember You," season 1, episode 8) Sarah Michelle Gellar and David Boreanaz on 'Angel'. The WB We have to make this quick because just thinking about the tragedy of this episode and those bitchy oracles makes us hurt in ways only this couple can. The most wrenching part, of course, is when the seconds inched by and Buffy (Sarah Michelle Gellar) repeated, "I'll never forget. I'll never forget." We never did. Best part: "How am I supposed to go on with my life, knowing what we had? What we could have had?" Damon to Elena on The Vampire Diaries ("Rose," season 2, episode 8) Nina Dobrev and Ian Somerhalder on 'The Vampire Diaries'. The CW He might have thought he didn't "deserve" Elena (Nina Dobrev), but after this uncharacteristically tender moment, Damon (Ian Somerhalder) at least deserves some lauds for putting someone else's happiness before his own. Best part: "I love you, Elena...And it's because I love you that I can't be selfish with you." Alicia and Will on The Good Wife ("End," season 7, episode 22) Julianna Margulies and Josh Charles on 'The Good Wife'. CBS Alicia (Julianna Margulies) and Will's (Josh Charles) love story was tragically cut short when Will was killed in The Good Wife's fifth season. But the series finale saw his return...At least in Alicia's head. And as she sought closure so that she could go after Jason (Jeffrey Dean Morgan), she confessed what we all knew to be true: Her love for Will will always remain. Best part: "I'll love you forever." —Alicia "I'm okay with that." —Will Joey to Pacey on Dawson's Creek ("A Winter's Tale," season 4, episode 14) Katie Holmes and Joshua Jackson on 'Dawson's Creek'. The WB Joey (Katie Holmes) was all about the little things in life, which explains why that's exactly what mattered most to her when it came to her relationship with Pacey (Joshua Jackson), as she pointed out in her sex preamble. We give it a 10, darling. Best part: "Pacey, this is about how you carried my bag off the bus yesterday. This is about how...When we go to the movies and you go and you buy popcorn, you always make sure you bring back a napkin so I don't wipe all the grease on my jeans. And this is about how, just last week, when we were at miniature golf, you took all of the shots first so I would know the correct path." Chandler and Monica on Friends ("The One With the Proposal, Part Two," season 6, episode 25) Matthew Perry and Courteney Cox on 'Friends'. NBCU Photo Bank Monica (Courteney Cox) only got through a few lines, but we give her some credit for providing the romantic setup and getting the ball rolling. But credit goes to Chandler (Matthew Perry) for being able to sweetly express himself — without a terrible joke at the end! Oh, Bing-a-ling. Best part: "I thought...That it mattered, what I said or where I said it. Then I realized, the only thing that matters is that you... You make me happier than I ever thought I could be. And if you let me, I will spend the rest of my life trying to make you feel the same way." —Chandler Olivia and Fitz on Scandal ("Happy Birthday, Mr. President," season 2, episode 8) Kerry Washington and Tony Goldwyn on 'Scandal'. ABC In the middle of Scandal's second season, viewers were treated to a flashback that showed just how much love once existed between Olivia (Kerry Washington) and Fitz (Tony Goldwyn). As she found herself frustrated with the feeling that her love for him controlled her, the most powerful man in the country admitted that he felt the same in one of the greatest confessions of love TV's ever seen. Best part: "I love you. I'm in love with you. You're the love of my life. My every feeling is controlled by the look on your face. I can't breathe without you. I can't sleep without you. I wait for you. I watch for you. I exist for you." —Fitz Chuck to Blair on Gossip Girl ("The Goodbye Gossip Girl," season 2, episode 25) Leighton Meester and Ed Westwick on 'Gossip Girl'. The CW When Chuck (Ed Westwick) showed up in a limo with Blair's (Leighton Meester) favorite spoils from around the world in hand at the end of season 2, he won Blair's heart. He won ours, however, with three little words: "You were right." Kidding. It was four words: "I love you, too." Best part: See latter line. Homer to Marge on The Simpsons ("The Way We Was," season 2, episode 12) Homer and Marge on 'The Simpsons'. Fox This cartoon couple has no shortage of sweet moments, but it's Homer's car confession post-prom disaster in this flashback episode that never fails to choke us up. A-d'oh-able. Best part: "I've got a problem. Once you stop this car, I'm going to hug you, and kiss you, and then I'll never be able to let you go. [Cut to present day] And I never have." Kevin to Scotty on Brothers & Sisters ("Moral Hazard," season 2, episode 15) Matthew Rhys and Luke Macfarlane on 'Brothers & Sisters'. ABC A moment of clarity amid family chaos led Kevin (Matthew Rhys) to pop the question to Scotty (Luke Macfarlane) without a ring, but with sincerity. Best part: "I'm completely, completely in love with you. I even love the things about you that I hate because you make me feel like I don't have to be anyone other than who I am." Fleabag to Hot Priest on Fleabag ("Season 2, Episode 6") Andrew Scott and Phoebe Waller-Bridge on 'Fleabag'. Prime Video What started as a naughty love affair between Fleabag (Phoebe Waller-Bridge) and "Hot Priest" (Andrew Scott) turned devastating in the final episode of the series. At a bus stop, Fleabag uttered a sincere "I love you," to which the priest took her hand and heartbreakingly replied, "It'll pass."  (Minutes later, though, he tells her, "I love you, too." It still hurts.) Best part: "You know, the worst thing is...That I f---ing love you. I love you. No, no, don't. No, let's just leave that out there just for a second on its own. I love you." Sam to Diane on Cheers ("The Proposal," season 5, episode 1) Shelley Long and Ted Danson on 'Cheers'. NBCU Photo Bank Okay, it was once sour and eventually turned even more sour, but, in the moment, Sam (Ted Danson) knew exactly what to say. It was simple, sweet, and Sam. Yes, he got shot down in the end, but let's just pretend that last part didn't happen. Deal? Best part: "From the very start, down deep inside, I have been crazy about you. Crazier about you than any other woman I've ever met. Hell, I was crazy about you even when I hated you." Niles to Daphne on Frasier ("Mixed Doubles," season 4, episode 6) David Hyde Pierce and Jane Leeves on 'Frasier'. NBC The tension had been building for years, so an eventual acknowledgment of Niles' (David Hyde Pierce) feelings for Daphne (Jane Leeves) was inevitable. He finally got his chance when Daphne asked what his pickup line would have been had they crossed paths in a singles' bar. While the too-subtle confession of love that followed went right over Daphne's head, it was stored in ours as one of the best ever. Best part: "Well, I would have said, 'Is this seat taken?' And you would have said 'No.' You would have said 'My name is Daphne,' and I would have said, 'My name is Niles.' And then I would have said... 'What are you doing for the rest of your life?'" Steve to Miranda on Sex and the City ("One," season 6, episode 12) David Eigenberg and Cynthia Nixon on 'Sex and the City'. HBO He was no one-night stand — even though she wanted him to be. Over the years Steve (David Eigenberg) had gone above and beyond for Miranda (Cynthia Nixon). (Remember when he showed up for her mom's funeral?!) Who knew that it'd be a small pantry encounter that sealed the deal? Best part: "I love you, too. I mean, c'mon...Miranda, you're the one." Alison to Emily on Pretty Little Liars ("The Glove That Rocks the Cradle," season 7, episode 16) Sasha Pieterse on 'Pretty Little Liars'. Freeform It took them long enough! It wasn't until Pretty Little Liars' final season that Alison (Sasha Pieterse) was finally ready to tell Emily (Shay Mitchell) why all of her past relationships failed...Because she was in love with Emily! Best part: "I wanna do this, together.... I want to be a family." David to Maddie's Dad re: Maddie on Moonlighting ("Father Knows Last," season 4, episode 7) Bruce Willis and Cybill Shepherd on 'Moonlighting'. ABC; ABC/Courtesy Everett Collection Ah, another third-person confession. Only David (Bruce Willis) took a major risk choosing Maddie's (Cybill Shepherd) no-nonsense father, Alexander (Robert Webber), as the receiving end of his candor. The bold move paid off, however, as his confession was as genuine as it was frantic — kinda like love, eh? Best part: "Four billion people in the world, half of them built for comfort, and I gotta pick this one to wanna grow old with." Clark to Lois on Smallville ("Harvest," season 10, episode 6) Tom Welling on 'Smallville'. The CW Arguably one of pop culture's most famous couples, the bar is set pretty high for declarations of love. But this one ranks up there because it's nice to see that even a man of steel has a soft spot. Best part: "I want you to know me completely with no secrets because you're the one. You always will be." Cory to Topanga on Boy Meets World ("What I Meant to Say," season 3, episode 3) Danielle Fishel and Ben Savage on 'Boy Meets World'. ABC They were still itty-bitty high schoolers when Cory (Ben Savage) first told Topanga (Danielle Fishel) he loved her, but the innocent take on the meaning of love still strikes a chord with us even now. Kids say the darnedest — and sometimes wisest — things. Best part: "All I know is you and I belong together. I mean, I have always been able to talk to you, to make you laugh, and I've always, always wanted to take care of you." Marshall and Lily on How I Met Your Mother ("Something Borrowed," season 2, episode 21) Alyson Hannigan, Neil Patrick Harris, and Jason Segel on 'How I Met Your Mother'. Ron Tom/CBS Arguably the cutest, cuddliest couple on our list, Marshall (Jason Segel) and Lily (Alyson Hannigan) were not short on gestures of affection (marching bands at the airport!), but lengthy speeches weren't their style. Their wedding was the exception, though, and we couldn't have penned more fitting — or adorably personal — vows for the plucky pair. Best part: "Marshall, I love you because you're funny, and you make me feel loved, and you make me feel safe. And, for our anniversary, you gave me a sweatshirt that says, 'Lily & Marshall Rockin' It Since '96.' I kinda wish I was wearing it right now because it smells like you." —Lily Amy to Ephram on Everwood ("Foreverwood [Part 2]," season 4, episode 22) Emily VanCamp and Gregory Smith on 'Everwood'. The WB The romantic Ferris wheel in the background certainly didn't hurt the impact of the speeches exchanged in the final episode of Everwood. But, above all, Amy's (Emily VanCamp) rambling speech to Ephram (Gregory Smith) provided the perfect closure for the pair — and fans. Best part: "Four years ago, you came to my little town and you changed my life. I never thought that one person could do that to another, but you did." Blaine to Kurt on Glee ("New York," season 2, episode 22) Darren Criss and Chris Colfer on 'Glee'. Disney Some of the best proclamations of love come about in the most casual of settings. After Kurt (Chris Colfer) regaled his boyfriend Blaine (Darren Criss) with stories about his trip to New York, Blaine looked at Kurt with hearts in his eyes and professed his love. Klaine 4eva! Best part: "I love you, too. You know, when you stop and think about it, Kurt Hummel has had a pretty good year." —Kurt Stefan to Elena on The Vampire Diaries ("Daddy Issues," season 2, episode 13) Paul Wesley on 'The Vampire Diaries'. The CW By the middle of season 2, Stefan (Paul Wesley) and Elena had said "I love you" more than once — including Elena's epic first declaration — but there was something so simple and powerful about this moment. After Caroline (Candice King) had a bad day, Stefan surprised her with a girls' night when he brought Bonnie (Kat Graham) and Elena over to her house for a sleepover. As Elena hugged her friend, she mouthed "I love you" to her thoughtful boyfriend, who mouthed it back. Best part: It's a tie between the way Stefan pauses before mouthing it back and the look on his face when he does. It's as if he can't believe how much he loves Elena. Juliet to Sawyer on Lost ("The Incident, Part 2," season 5, episode 17) Josh Holloway and Elizabeth Mitchell on 'Lost'. ABC Sawyer's (Josh Holloway) desperate plea to a chain-trapped Juliet (Elizabeth Mitchell) was enough to tear us up, but her response made it rain on our faces. The love speech lesson here is when you really mean it, forget the nicknames. Best part: "I love you, James. I love you so much." Eric and Tami Taylor on Friday Night Lights ("Best Laid Plans," season 1, episode 21) Kyle Chandler and Connie Britton on 'Friday Night Lights'. NBC Eric (Kyle Chandler) and Tami Taylor (Connie Britton) will always be one of the greatest couples in television history, but that's not to say they agreed on everything. Rather, their disagreement was what made their portrayal of marriage all the more realistic. The perfect example? After Eric was offered a coaching job at TMU in season 1, Tami told him that, as much as she loves him, she and Julie (Aimee Teegarden) were going to stay in Dillon. He, however, needed to chase his dream. Best part: Eric putting his arms around Tami and telling her, seemingly out of the blue, "I love you, I respect you, I'm proud of you, and I am in love with you completely." Uncle Jesse to Becky on Full House ("The House Meets the Mouse: Part 2," season 6, episode 24) John Stamos and Lori Loughlin on 'Full House'. ABC So, it technically wasn't a speech, but who doesn't want a song dedicated to them? A Disney song, no less! Yes, we're corny. Best part: "This is a song for dreamers everywhere." Uncle Jesse (John Stamos), along with the Rippers, then proceeds to play "A Dream Is a Wish Your Heart Makes" on piano in front of Cinderella's castle while fireworks go off. Robert to Sol on Grace and Frankie ("The Vows," season 1, episode 13) Martin Sheen on 'Grace and Frankie'. Netflix Though Sol (Sam Waterston) wouldn't actually get to hear the vows until four episodes into the following season, hearing Robert (Martin Sheen) let down his emotional guard while writing his vows to his husband-to-be can give anyone at any age #relationshipgoals. (Let's just forget about the fact that Sol just cheated on Robert with his ex-wife, Lily Tomlin's Frankie, moments earlier since — spoiler alert — it all worked out in the end.) Best part: "Sol, I love you for who you are and who I am with you." Mulder to Scully on The X-Files ("The Sixth Extinction II: Amor Fati," season 7, episode 2) David Duchovny and Gillian Anderson on 'The X-Files'. Fox There are almost too many moments from this pair to choose just one, but when Mulder (David Duchovny) returned from an odd journey in this season 7 episode, he made a heartfelt revelation about Scully's (Gillian Anderson) role in his life that left us with goosebumps. Best part: "The end of my world was unrecognizable and upside down. There was one thing that remained the same. You...Were my friend, and you told me the truth. Even when the world was falling apart, you were my constant...My touchstone." Alex to Izzie on Grey's Anatomy ("What a Difference a Day Makes," season 5, episode 22) Katherine Heigl and Justin Chambers on 'Grey's Anatomy'. Scott Garfield/ABC Talk about creating a moment. Ingrid Michaelson's "Turn to Stone" playing in the background only added more emotional punch to Alex's (Justin Chambers) all-too-fitting vows (which he technically borrowed from a patient, but we forgive him). Best part: "Today's the day my life begins. All my life I've been just me — just a smart-mouthed kid. Today, I become a man. Today, I become a husband. Today, I become accountable to someone other than myself. Today, I become accountable to you, to our future." David and Patrick to each other on Schitt's Creek ("Singles Week," season 4, episode 12) Dan Levy and Noah Reid on 'Schitt's Creek'. CBC Television Patrick (Noah Reid) knew full well how hard it was for boyfriend David (Dan Levy) to say "I love you" — he's only ever said it three times, including once at a Mariah Carey concert. But that didn't stop Patrick from telling David he loved him at their store, and while David was as overwhelmed as we were, he ultimately reciprocated that love later in the day. And we love that for them. Best part: "I don't expect you to say it back right now. Say it when you're ready. Just felt right to me in the moment. You're my Mariah Carey."

Who Went Home On Week 2 Of 'The Golden Bachelorette'? Here's Who Got Roses, Dates

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Medical Sleuthing Identified The Dangers Of Thalidomide

It's the early 1960s, and Widukind Lenz, a German pediatrician, is going door to door in his efforts to find out what is causing an epidemic of babies born with shortened limbs and other serious medical conditions.

In the U.S. The drug company Richardson-Merrell is battling with Frances Oldham Kelsey at the Food and Drug Administration about the pending approval of thalidomide. She's asking for data that show it's safe to use during pregnancy (spoiler alert: it's not).

Meanwhile Merrell continues to send what will add up to millions of thalidomide pills to doctors in so-called clinical trials. In November 1961 Lenz goes public with the results of his medical sleuthing and, as host Katie Hafner puts it, "the proverbial shit hits the proverbial fan."

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LISTEN TO THE PODCAST

TRANSCRIPT

Katie Hafner: The fall of 1961 was a happening time.

President John F. Kennedy: Time for this great nation to take a leading role in space achievement…

Katie Hafner: There was a glamorous young couple in the White House with a president hell bent on going to the moon. The civil rights movement was gaining momentum.

James Farmer: The ride had become a symbol of the fight against segregation not only in southern bus terminals but everywhere.

Katie Hafner: The swinging sixties were just revving up. Bob Dylan gave his first concert at Carnegie Hall and Brian Epstein heard the Beatles for the first time in Liverpool, England.

In Germany and elsewhere around the world , a sedative called thalidomide had been selling like mad for several years. Chemie-Grünenthal, the manufacturer of that sedative, was profiting wildly.

But there was a pocket of people in a world of hurt.

I'm Katie Hafner, and this is the third chapter of The Devil in the Details, a special series from Lost Women of Science. In this episode, we explore the proverbial shit hitting the proverbial fan.

Katie Hafner: In the fall of 1961 in the United States, Dr. Frances Kelsey continued to stall the application for thalidomide, much to the frustration of the manufacturer, William S. Merrell.

At the same time, in Europe, women by the thousands had given birth to children severely injured while in the womb.

And several doctors had taken notice.

Most notably, Widukind Lenz, the skeptical pediatrician, had been investigating for several months. He and Karl Schulte-Hillen, the father of one of these babies, were talking to as many affected families as they could find.

But there was no obvious culprit.

Then, on November 11, the story began to shift. That day, Widukind had gone to meet a family, this time on his own. They were the parents of a girl born without arms. The mother mentioned she had taken Contergan, Grünenthal's thalidomide-based sedative.

The following day, Widukind visited another family. As usual, he introduced himself and explained that he was trying to figure out what was causing these strange births. And for the second time in as many days, Contergan came up. The father told Widukind plainly he thought Contergan was the cause.

Okay, Contergan had come up before, but it had never been at the top of Widukind's list. Maybe because many of the families he'd interviewed did not mention Contergan. Or maybe he too had been influenced by the company's bold safety claims.

But two days in a row? This time, Widukind paid attention. He asked the father, what made him suspect Contergan? The father said he'd read that these tablets could cause nerve damage. (bBy then, the news about peripheral neuritis had reached the popular press.)

After the meeting, Widukind called up Karl and he asked him this: Had his wife, Linde, taken Contergan during her pregnancy with Jan? Karl wasn't sure. He'd have to find out.

Katie Hafner: While Widukind Lenz was investigating in Germany, over in the United States, Frances Kelsey was still jousting with Merrell's liaison, Joseph Murray.

And if she was feeling the heat…well, Frances, in typical Frances "dare-me-to-raise-my-voice" fashion, didn't let on.

Katie Hafner: Yes. That's all you're gonna get out of the stoic Frances Kelsey.

So, in the fall of 1961, Frances wasn't letting Joseph Murray get to her. She wasn't going to rush this product through if the application was incomplete. But Murray was DONE waiting.

A full year had passed since the company had first submitted its application for Kevadon, Merrell's thalidomide drug. And with another holiday season looming and visions of pill bottles dancing in the heads of Merrell's executives— Murray decided to call in the big guns.

He brought a group of clinical investigators to the FDA to talk about their experiences with Kevadon. They were physicians and some professors who were consulting for the company or working in some capacity under contract.

The idea was to show Frances that credentialed doctors and researchers backed Merrell's claims about Kevadon, and put more pressure on the FDA to bring the drug to market quickly.

But as pro-Kevadon as these hand-picked attendees were, some of them asked questions about Kevadon.

Questions Frances had been asking for months.

And one of her questions was about the safety of this drug in pregnancy.

Katie Hafner: Frances happened to know quite a bit about how drugs could affect embryos… Because during World War II, Frances and her future husband, Ellis, worked in Eugene Geiling's lab investigating new antimalarial treatments. It was part of a nationwide effort to treat soldiers fighting in malaria zones.

Trent Stephens: It put her in a unique, an absolutely unique position in my opinion.

Katie Hafner: Trent Stephens is the co-author of "Dark Remedy," a book about the history of thalidomide. He's also a developmental biologist, who's studied thalidomide's effects on embryos. And he says that during her time in Geiling's lab, Frances got to work with quinine—a well-known antimalarial medication. She and Ellis Kelsey were testing how rabbits broke it down in their livers. And that included pregnant rabbits.

Trent Stephens: One of the things they learned during their research on quinine is that it passes the so-called placental barrier.

Katie Hafner: In quinine's case, Frances was fascinated to discover that rabbits in utero processed quinine very differently than adult rabbits did.

Adult rabbit livers are very good at breaking down quinine. Which is important because if your body doesn't break down a drug, it can accumulate in your system beyond what's safe.

And it turned out that fetal rabbits cannot break down quinine at all.

Katie Hafner: So Frances Kelsey knew that just because a drug didn't seem to hurt an adult, that didn't mean it wouldn't hurt a developing embryo. In fact, during her own pregnancies, she was very careful about taking ANY drugs.

And actually, around the time Frances joined the FDA, there was a growing understanding of this: children, babies, and fetuses aren't just adults in miniature. Their bodies work differently. So you can't assume that because a drug is safe for an adult, it will be safe at other stages of development. So even though in the fall of 1961, Frances knew nothing about what was happening in Europe, she asked Merrell about safety during pregnancy. And it wasn't the first time. She'd asked about it a few months earlier too, and she didn't get a satisfactory answer.

Now, Merrell did have some evidence about the use of thalidomide in pregnancy. The company told Frances they weren't aware of any problems—but the company only tried it out in late pregnancy.

Frances didn't think that was good enough. The FDA needed to know what happened if thalidomide was taken throughout pregnancy. And she was right to insist on that. As we know now, thalidomide is most damaging when taken in the first few weeks. But Merrell refused to conduct such a study, of course, conducting another study would mean yet another delay in getting this drug to market. But Merrell did agree to add a warning to its labels indicating that thalidomide's effects on pregnancy were not known.

Still, Frances Kelsey was not ready to approve the drug. And that should have been enough to keep Americans safe, right? The drug wasn't for sale in the US.

But here's the problem: while Merrell and the FDA went back and forth about labeling and studies and paperwork, hundreds of pregnant women were already taking thalidomide in the United States. Some had brought it back from overseas. But many of them got thalidomide from their doctors. Because Merrell had distributed Kevadon, its thalidomide pill, across the United States, without any FDA approval or oversight… And back then, that was completely legal.

Gwen Riechmann: The dogs are going to, this is going to take a moment. Sorry.

Elah Feder: It's okay. I think- I think it's inevitable the pets are going to feature in this.

Katie Hafner: Gwen Riechmann lives in Cincinnati with a menagerie of pets.

Gwen Riechmann: I have two Shelties. And two cats.

Katie Hafner: Elah, our senior producer, called Gwen up on Zoom a few months ago. Gwen closed the door to keep the pets out, but some were insisting on joining anyway.

Gwen Riechmann: Um, that sounds like Arwen. The small female who's making all the noise at the moment. She has to say something about everything.

Katie Hafner: Gwen is in her early 60s now, and she's a thalidomide survivor. She was born in Cincinnati in May 1962. And pay attention to that date. May 1962, at least a year after Frances Kelsey first asked Merrell for evidence that thalidomide was safe to take during pregnancy.

Gwen Riechmann: I was born with phocomelia of both arms, which means my arms are short and misshapen. One arm is eight inches. The other arm is 12 inches in length. And both feet are clubbed, meaning they literally look like golf clubs.

Katie Hafner: Until she was about five, Gwen could walk and play tee ball with her brothers in the backyard by moving around on her knees. But later, surgery that was meant to help her actually made it harder for her to walk, and she started using a wheelchair. Gwen says that when she was growing up, her parents encouraged her to be as independent as possible, and in general, took a "tough love" approach to raising a child with a disability.

Gwen Riechmann: For instance, if I tried to get them to do something like go get something for me that my parents knew I could do, my parents would say, are you handicapped or something? Go do it yourself.

Katie Hafner: Gwen says she didn't ask her parents a lot of questions about her disability because it was clear they didn't want to talk about it. So, for years, she assumed her phocomelia was genetic. There are, in fact, very rare genetic conditions that cause phocomelia—the shortening of the limbs. But Gwen's condition wasn't genetic.

Gwen Riechmann: I didn't actually hear the word thalidomide until I was like 7th, 8th grade.

Katie Hafner: Gwen went to a public school for kids with physical disabilities. And, like at most schools, around middle school, the teachers split up the boys and the girls to talk about sex education.

Gwen Riechmann: And they said if anybody wants to, find out if you could pass your disability on to a baby we'll be happy to talk to you. And so when I came home that night, mom said, "So how did it go?"

Katie Hafner: So Gwen told her mom about the baby conversation, and she said she didn't have a lot of questions for the nurse because she already knew her condition was genetic.

Gwen Riechmann: And my mom said, well, that's not actually the case. And I said, well, what is it then? And that's when she said, it's from a drug called thalidomide that I was given when I was pregnant with you. And that was it. Conversation over.

Katie Hafner: Gwen eventually learned that her mom had been given thalidomide sometime around October, 1961, during her first weeks of pregnancy.

In October, 1961, Kevadon was, of course, not for sale in the United States. Frances Kelsey hadn't approved the drug. But just because the drug wasn't approved, didn't mean the company couldn't distribute it in "clinical trials."

Now, when I use the phrase "clinical trials," you might be imagining a rigorous, placebo-controlled study, with patients systematically recruited, and symptoms carefully tracked on clipboards.

Well, that's not how things worked back then.

Drug companies didn't actually need approval from the FDA to conduct a clinical trial. All they had to do was turn in whatever results they had come up with when they submitted the drug to the FDA for approval. Okay, we don't know for sure, but theoretically, for instance, they could ask, you know, a hundred, a thousand, ten people. Gee, how do you feel on this drug? And somebody could say, Oh, yeah, pretty darn good. …

But what Merrell had done to come up with its results…. Well…it almost defies belief.

Katie Hafner: In 1958, after Merrell first got the license from Grünenthal to sell thalidomide, the company got busy recruiting doctors to test the drug. Merrrell was based out of Cincinnati, and one of those doctors was a Cincinnati obstetrician named Ray Nulsen. He just happened to be a friend of Merrell's director of clinical research, Raymond Pogge. And I think the Nulsen/Pogge story tells you everything you need to know about these so-called clinical trials.

Nulsen treated a few hundred pregnant women each year, and Pogge asked Nulsen to try out thalidomide with these patients to help calm their nerves at night. In June 1961, Nulsen published a paper in the American Journal of Obstetrics and Gynecology titled

"Trial of thalidomide in insomnia associated with the third trimester". The paper had a very upbeat conclusion: thalidomide was a safe and effective sleeping agent for use in late pregnancy.

But here's what would eventually come out: Ray Nulsen didn't actually write that paper. Later on, in a legal deposition he admitted that Raymond Pogge, his buddy at Merrell, had written the whole thing. The lawyer doing the deposition asked him, how about all the papers cited in that article? Did you read those? Nope. Okay, so what about all the data—do you have copies of the reports you sent to Merrell?

Nulsen said, no, it was all verbal and he explained it was quote "by telephone, or it may have been that we had lunch together, or it may have been when we played golf."

Dr. Ray Nulsen… was the doctor who treated Gwen Riechmann's mom.

Gwen Riechmann: she did say that she had only taken one dose of the thalidomide that she was given.

Katie Hafner: But that one pill was enough.

Neil Vargesson: There are studies going back to1990s, early 1990s that suggest just one tablet is enough to cause damage to the embryo.

Katie Hafner: Neil Vargesson is a professor of developmental biology at the University of Aberdeen in Scotland. He's done extensive research on thalidomide's effects. We now know that one of the main ways that thalidomide harms embryos is by blocking angiogenesis, the development of blood vessels.

Neil Vargesson: It's the action of the drug on the blood vessels that's causing the damage. And as you destroy the blood vessels, you then get cells dying off. And it does it in a time dependent way.

Katie Hafner: So if an embryo is exposed to thalidomide when the arms are forming, the blood vessels feeding those tissues will die and the arms won't grow. Same with the ears, the heart, the brain…

Neil Vargesson: It's as simple as that. You've got to remember that, oads of things are forming at that point. It's not like the limbs form, and then the ears form and then the nose forms.Now, they're all forming at the same time. So that's why many survivors have got multiple damages and no two survivors look the same. They all look unique because it was depending on when their mum took the medicine.

Katie Hafner: There's a critical two-week window for the kind of harm typically associated with thalidomide, and that window starts roughly three weeks after fertilization. When thalidomide is taken in that window, you can find effects on arms, legs, hearts… all the symptoms we've mentioned before. But harm isn't restricted to that two-week window.

Neil Vargesson: if you took the drug before the so-called time sensitive window, you'd end up in a miscarriage because you can imagine all the blood vessels will be destroyed.

There will be no blood vessels, so there's no embryo. And if you took it after the so-called time sensitive window, you might not see damage to limbs. But you would see internal organ damage and possibly brain damage as well.

Katie Hafner: In October 1961, when Gwen Riechmann's mother took that pill early in her pregnancy, she wouldn't have known any of this. Her doctor wouldn't have known either. At the time there were, at most, suspicions about thalidomide. But it was only a few weeks later, across the Atlantic, that Widukind Lenz had two fateful interviews with two families in Germany, both naming the same suspect: Contergan. So after years of women taking this damn drug, Finally Widukind Lenz was about to set things in motion

And here's how it all unfolded. In November of 1961, after months of investigating these mysterious births, aggrieved father, Karl Schulte-Hillen, and dogged pediatrician, Widukind Lenz, had gumshoed their way to a prime suspect: Contergan.

Here's author Jennifer Vanderbes again:

Jennifer Vanderbes: The tough part of this story is that once Karl realizes it's this drug, he has to go back and ask his wife if she took it.

Katie Hafner: At first Linde Schulte-Hillen couldn't remember even taking Contergan—the German version of thalidomide. But then a memory surfaced. A year earlier, when Linde was only one month pregnant, her father had died. The family had traveled to attend his funeral. It was a stressful time, nerves were frayed, and at the end of the day, the whole family took a sedative, including Linde who was pregnant.

Jennifer Vanderbes: She took one or two and that, in the first trimester of pregnancy early on, immediately affected Jan in his development.

Katie Hafner: On November 15, 1961 Widukind called Grünenthal. He reached a man named Heinrich Mückter. We could dedicate an entire episode to just this guy. But the important thing to know right now is that he wasn't just any Grünenthal employee. He was the company's chief science officer, and he had played a key early role in thalidomide, and he got a cut of every package of thalidomide sold.

Widukind told Muckter that Grünenthal needed to take the drug off the market immediately, and the next day, he put that request in writing. And he did not mince words. He wrote in his letter that simply waiting for proof that the drug was harmless was indefensible. This drug should not be sold until it was conclusively shown to be SAFE.

And then, that weekend, Widukind attended a pediatricians' conference. And during a session about the uptick in phocomelia cases being seen around the country, he stood up. Widukind said that he had identified a substance that might be to blame. He couldn't yet prove that it was the cause of these injuries, but it was conceivable, and so as a citizen he could no longer remain silent.

Jennifer Vanderbes: He didn't want to name the drug, but he says there is a drug. We're pretty sure it's causing this epidemic of phocomelia.

Katie Hafner: And he made an urgent plea–right there in public–that the unnamed "substance" be withdrawn from the market immediately. He warned that each month's delay meant dozens more babies would be harmed.

Early the following week, Grünenthal sent three representatives to meet with Widukind Lenz in person. He was ready to present his case, but he wanted witnesses present for this conversation, and so in the afternoon of November 20th, they met along with three representatives from the Hamburg University clinics and four from the Hamburg health authorities.

It was, by all accounts, a tense meeting. Grünenthal wanted Widukind to hand over all of his materials. But some of that was confidential patient information, and some was property of the Hamburg clinic, and it wasn't his to hand over. The Grünenthal side said if he didn't turn the material over to them, then any delay in action would be his fault. He said he'd consult with a lawyer and the group would reconvene the next morning.

The following morning, he gave them copies of his redacted notes. Now Grünenthal tightened the screws. The representatives said there would be legal ramifications if Widukind made false accusations against the company. And Widukind asked them flat out— would they guarantee they would not use the material he presented in lawsuit against him? No, they said, they couldn't guarantee it.

So They scheduled another meeting for later in the week Friday, November 24th, this time in Dusseldorf with representatives of the regional health ministry. Widukind later described being repeatedly interrupted by the Grünenthal's representatives as he tried to present his evidence, but this time, he took an even firmer stand. No, he said, he couldn't say the case was definitively proven, but the evidence was overwhelming and there could be no reasonable doubt.

Katie Hafner: I want to take a minute – or maybe a minute and half - to talk about this man, Widukind Lenz. Here you have the son of a Nazi, and not just some run-of-the-mill Nazi… Fritz Lenz, let me remind you, was a prominent eugenics specialist who endorsed racial cleansing even before Hitler. And he believed that disabled people should be sterilized – i.E. Forcibly prevented from reproducing. Fritz Lenz was still very much alive and espousing his eugenic theories when his son took on Chemie Grünenthal, in the name of every single infant severely disabled at the hands of bad medicine.

Like his father, Widukind later became a geneticist. But not only did this apple fall far from the tree, it rolled as far away as possible. I can only imagine the courage it must have taken for the younger Dr. Lenz to do what he did in 1961, still not even a generation removed from the Third Reich.

Like Frances Kelsey, Widukind Lenz was no grandstander. The two people hadn't met each other, of course. From what we can tell from the scant bit of audio we've heard, Widukind was soft-spoken but self-assured. And like Frances, he came across as …. Maybe a little dry… a thorough dot-all-your-i's-and-cross-all-your-t's person.

Katie Hafner: So you can imagine the level tones he must have used when meeting with Grünenthal's representatives. In the end, the Grünenthal people did agree to add a label warning not to use Contergan during pregnancy.

But then they left, and Widukind kept talking to the government people. This time, without the Grünenthal crew in the room, Widukind