The Primitive Streak

Summary

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Radiolab: "The Primitive Streak"

Date: September 23, 2016
Hosts: Molly Webster & Robert Krulwich
Theme:
This episode delves into the science, ethics, and history surrounding the “14-day rule”—a legal and moral boundary governing how long scientists can grow human embryos in the lab. The show explores why this line was drawn, what happens just before and after 14 days of development, and the scientific advances that now make this rule especially urgent and relevant.

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Episode Overview

Radiolab embarks on an investigative journey into how we understand human development at its earliest stages, what “the primitive streak” is and why the 14-day rule has become a flashpoint for science, ethics, law, and philosophy. Featuring interviews with pioneering scientists and ethicists, the episode delves into how new breakthroughs challenge society's boundaries about experimenting with human origins.

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Key Discussion Points & Insights

1. Setting the Stage: The 14-Day Rule

• Introduction to the Rule: There is an international guideline that human embryos can only be grown for 14 days in the lab (01:12, 02:51).
• Host Curiosity: Molly admits she didn’t know about this rule or any of the details behind human embryo research, sparking the episode's investigation (02:04, 02:08).

"In this universe are twins and souls and mice and something called the primitive streak. And they're all gathered together around a certain rule."
— Molly Webster (02:17)

2. Historical Backdrop: Law, Ethics, and Early Science

• Roe v Wade and Medical Ethics: 1973’s Roe v. Wade and scandals in medical research (Tuskegee Study, forced sterilizations) brought ethical questions around human experimentation to the forefront (03:52, 04:32).
• Rise of IVF: The birth of “test tube baby” Louise Brown via IVF in 1978 created new fears and possibilities regarding reproduction (05:05, 05:32).
• Committee Formation & Leroy Walters: The government created the Ethics Advisory Board, bringing together various experts (including ethicist Leroy Walters) to set the first boundaries on embryo research (06:13, 06:38).

3. Why 14 Days?

• Leroy Walters' Reasoning: Walters outlined arguments leading to the 14-day rule (07:27):
  • Natural Loss: Before 14 days, ~50% of embryos are lost naturally (07:34, 07:54).
  • Biological Identity: Before 14 days, embryos can still split (twinning) or recombine; only at 14 days do they become truly unique individuals (08:11, 08:20).
  • The Primitive Streak: Around day 14, the “primitive streak” appears—marking the first organizational sign of a body’s axis/spinal cord (08:33, 08:47).
• Global Impact: Although Walters’ report gathered dust, its recommendations spread as a guideline internationally (09:48, 09:56).
• Practicality: The rule felt safe, as labs weren't technologically able to grow embryos that long—until recently (10:11).

"It also seemed like a safe marker, a safe boundary."
— Leroy Walters (09:56)

4. The Scientific Black Box: What Happens Between Days 7 and 14?

• Invisibility of Early Development: No one has witnessed this phase, as detection of pregnancy often happens too late, and imaging is impossible at this time (10:31, 11:33).
• Textbook 'Black Box': The period between implantation and the “primitive streak” is termed a "black box" in textbooks (11:42).

5. Breakthrough in the Lab: Growing the Embryo to Day 13

• Pioneering Work of Magdalena Zernicka-Goetz: At Cambridge, she and her team spent years recreating the womb’s environment in a dish, succeeded with mice, then two human embryos (11:47, 13:01, 13:40).
• Success: One embryo survived and developed to day 13 (13:40).
• Observation: For the first time, scientists could watch previously unseen stages of human development (13:55).

6. Firsthand Glimpse into the Lab

• Visit to Rockefeller University: Molly tours Ollie Rivenloo’s lab in New York, observing actual embryos at day 12 and using advanced microscopes to view them at different stages (16:31, 18:16).
• The Embryo's Appearance: Embryos at this stage are minuscule—just a “grain of sand,” or like “a pinpoint of light” (18:23).

"Holy crap. That’s really small. That's like a grain of sand." — Molly Webster (18:30)

• Day-by-Day Changes: The lab team guides Molly through images showing the embryo’s rapid complexity from day 8 to day 13, noting cell specialization and the emergence of the epiblast—the precursor to all tissues (19:12, 20:59), and the origin of the placenta (20:50).

7. Scientific Revelations and Mysteries

• Embryo's Self-Organization: It turns out that, up to day 14, embryos can organize themselves without maternal input—a surprising result (21:42, 22:08).
• Preparing for Maternal Connection: Between days 12 and 14, embryos begin developing pathways for maternal attachment, starting the “hookup” to the network of the mother’s body (22:39).
• Pregnancy Hormone (hCG): At day 10, the embryo starts releasing the hormone that pregnancy tests detect, essentially broadcasting its presence (23:12, 23:30).

"The thing it's reading is that hormone... boom, boom, boom, boom, boom... I'm here, I'm here. Look at this hormone." — Molly Webster (23:35)

8. The Human Experience of Scientific Discovery

• Awe of the Unknown: Scientists liken seeing these early developmental stages for the first time to receiving “the digital image of the Hubble telescope” (23:59).
• The Abrupt Stop: To comply with the rule, experiments are halted and embryos preserved at day 14 (24:43). There’s a strange emotional dynamic: a desire to keep going is tempered by an ethical line (25:28).

"You want to open it, but you have to be ready to see what's in it." — Ollie Rivenloo (25:53)

9. The Rule Under Pressure: What Now?

• Technological Advance Outpacing Law: Now that 14 days is attainable, a debate emerges: should we extend the limit? (26:13, 26:40).
• Ethical and Religious Diversity: Scientists express humility and reluctance to decide where the line should be, recognizing various religious beliefs and societal attitudes (28:12, 28:20):
  • Catholicism: Soul at conception
  • Judaism/Islam: Significance of heartbeat
  • Buddhism: Individuality at cord cutting
  • Hinduism: Life as a circle, not a linear origin

"What origin? A circle does not have an origin." — Ollie Rivenloo (28:20)

• The Desire for Knowledge vs. Social Responsibility: Scientists voice their intrinsic curiosity but stress the importance of societal consensus and sensitivity.

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Notable Quotes & Memorable Moments

• "There is a place in the development of the human being that no scientist has seen? ... No."
  — Robert Krulwich & Molly Webster (11:33)
• "This is this kind of period, which in the textbook you will find described as a black box."
  — Magdalena Zernicka-Goetz (11:42)
• "The human embryo will behave in a self organizing manner in a complete absence of maternal inputs, at least for 14 days."
  — Ollie Rivenloo (21:55)
• "When people receive the digital image of the Hubble telescope… when I look inside of our own anatomy at the time where nobody knows that we even exist, it’s the same as looking at dimensions that we have never imagined we will ever see because we didn’t even know they exist."
  — Ollie Rivenloo (23:59)
• "If technology has now moved it a whole other week... does that mean the rule’s going to have to change?"
  — Robert Krulwich (26:13)

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Timestamps for Key Segments

• Introduction to 14 Day Rule: [01:12]–[03:02]
• Leroy Walters and Committee History: [06:13]–[09:48]
• Defining the Primitive Streak and Embryo Individuality: [08:33]–[09:05]
• What Happens Between Days 7 and 14: [10:31]–[11:47]
• Magdalena’s Breakthrough Growing the Embryo: [13:01]–[13:55]
• Lab Tour and First Glimpse of Embryos: [16:31]–[19:11]
• Interpreting Embryo Images and Key Discoveries: [19:12]–[23:12]
• Debate on Extending the Rule and Societal Implications: [26:13]–[30:02]

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Closing Thoughts

The episode closes with a sense of wonder, humility, and caution: modern science, while making the invisible visible, must continually balance its curiosity with deep ethical wisdom and respect for varying beliefs about what it means to be human. The intersection of scientific possibility and human values is only getting more intense as technology advances.

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Transcript

[Molly Webster]

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[Unidentified Female Participant]

Oh, wait, you're listening.

[Unidentified Male Participant]

Okay.

[Molly Webster]

All right.

[Magdalena Zernicka-Goetz]

Okay.

[Molly Webster]

All right.

[Alex Honnold]

You're listening to Radiolab Radio Lab from wny.

[Molly Webster]

See?

[Unidentified Female Participant]

Yep.

[Molly Webster]

We're gonna start with a conversation that I had with Jad a few weeks ago.

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

Okay.

[Molly Webster]

So I like medical stories.

[Unidentified Female Participant]

This I know about you.

[Molly Webster]

This you know. And so I read this website called statnews.com which does sort of really. It's like a new website out of Boston.

[Unidentified Female Participant]

It's new, right?

[Molly Webster]

And they basically, it's this collection of really amazing, like, medical reporters. And I will click on stories that look interesting. And there was one about, we've just grown embryos, human embryos, for a long time in a lab. And that was when I read the phrase the 14 day rule for the first time. And it was that apparently there's this thing that you can't grow an embryo in a lab past 14 days.

[Unidentified Female Participant]

Huh.

[Molly Webster]

Which I didn't even know you could grow an embryo in a lab at all. Right. Or that people were. Or that. I mean, I guess I knew IVF happened.

[Unidentified Female Participant]

Sure.

[Molly Webster]

Like test tube babies.

[Unidentified Female Participant]

How long, if in the average IVF situation, how long is an embryo in a dish for?

[Molly Webster]

And then I realized I didn't actually even know that either. So then I just spun out. So, like, the whole article is just interesting because I was like, I don't know about any of this.

[Unidentified Male Participant]

Right, Right.

[Molly Webster]

I'm Molly Webster.

[Robert Krulwich]

Oh, and I'm Robert Krulwich. This is Radiolab.

[Molly Webster]

And today on Radiolab, we're gonna zip down a wormhole into another universe. And Robert, you're coming with me.

[Robert Krulwich]

Okay, Tell me about this before I buy a ticket.

[Molly Webster]

Yeah, okay, you're gonna want to buy a ticket. Because in this universe are twins and souls and mice and something called the primitive streak. And they're all gathered together around a certain rule.

[Robert Krulwich]

Oh, and remind me again, what the.

[Molly Webster]

So you know how you can fertilize an egg? You get an egg and a sperm and you put them together.

[Robert Krulwich]

Yes.

[Molly Webster]

Fertilizes the Egg, Right. And then the egg, the fertilized egg, it multiplies. Multiplies. Cell divides. So a scientist could take it to watch it grow, to learn about human development, but then they have to stop at day 14. That's the rule.

[Robert Krulwich]

Is this a medical kind of thing or a science limitation? Why do they.

[Molly Webster]

It's all those things. It's medical and it's science, and there's, like, philosophy and ethics and obviously religion and.

[Robert Krulwich]

And that's it.

[Molly Webster]

Yeah. You're buying it now.

[Robert Krulwich]

I see the whole shebang.

[Unidentified Male Participant]

I have water. Okay, I'll take a sip.

[Molly Webster]

Okay, we're gonna begin with this guy Leroy Walters.

[Unidentified Male Participant]

Okay.

[Molly Webster]

He was an ethicist at Georgetown University, now retired. And to me, he is sort of the father of the 14 day rule.

[Unidentified Male Participant]

I never. I never thought of myself as the father of the 14 day rule, but he is.

[Molly Webster]

He totally is.

[Unidentified Male Participant]

Well, we shouldn't forget the context of 73.

[Molly Webster]

All right, so 1973. Leroy has recently graduated with a doctorate in ethics from Yale University and settling into his job. And at the time, medicine and ethics were on a sort of collision course.

[Unidentified Male Participant]

Yes. Yes.

[Molly Webster]

Mm.

[Unidentified Male Narrator or Scientist]

Good evening.

[Molly Webster]

January 1973.

[Unidentified Male Narrator or Scientist]

In a landmark ruling, the Supreme Court today legalized abortion.

[Molly Webster]

Wade happens. It is clear, at least under present law, that an unborn fetus is not a person within the meaning of the Constitution. But just six months after that decision, the issue of fetuses and research done.

[Unidentified Male Participant]

With them, fetal research, became a hot topic.

[Unidentified Male Narrator or Scientist]

Some of the testimony in here is shocking.

[Molly Webster]

There were news reports of butchering and cutting up about dissecting fetuses. Even an instance of decapitating fetuses.

[Unidentified Male Participant]

Oh, man.

[Molly Webster]

And then, around the same time, used.

[Unidentified Male Participant]

As human guinea pigs, the research involving human beings.

[Unidentified Male Narrator or Scientist]

The controversial Tuskegee syphilis study.

[Molly Webster]

News reports of the syphilis studies that were done on African American men without their knowledge.

[Unidentified Male Participant]

There was the sterilization of two daughters.

[Unidentified Male Narrator or Scientist]

Had been sterilized without their informed consent.

[Unidentified Male Participant]

Women with intellectual disabilities.

[Molly Webster]

Experiments in genetic research. Genetic engineering was coming into its own. You have all these questions whirling about, like how we feel about the human body, whether or not we want to experiment on it. What do we protect and what don't we protect? It's just sort of this whirlwind.

[Unidentified Male Narrator or Scientist]

And you are about to see a historic birth.

[Molly Webster]

Then, most relevant for our story, we.

[Unidentified Male Narrator or Scientist]

Are going to deliver her by caesarean.

[Molly Webster]

Sect on July 25, 1978.

[Unidentified Male Participant]

Scientists in the UK and we are now incising.

[Unidentified Male Narrator or Scientist]

The uterus itself.

[Unidentified Male Participant]

Produced a child with the aid of in vitro Fertilization.

[Molly Webster]

The first baby that was born from an embryo that was grown inside a tube.

[Unidentified Male Participant]

Baby Louise Brown.

[Unidentified Male Narrator or Scientist]

Baby's not opened her eyes yet.

[Unidentified Male Participant]

Everyone in the world was fascinated, but there were people who predicted doom.

[Molly Webster]

What was the doom?

[Unidentified Male Participant]

That in vitro fertilization would lead to reproduction as a form of manufacture.

[Molly Webster]

So the government was grappling with, we need more regulations or we need, as a country, to think about, like, what our ethical guidelines are, right?

[Unidentified Male Narrator or Scientist]

So the Department of Health, Education and.

[Molly Webster]

Welfare, and they put together something called the Ethics Advisory Board, a panel of.

[Unidentified Male Narrator or Scientist]

Doctors, laymen, academics, even a Jesuit priest.

[Molly Webster]

To consider some fundamental moral and ethical.

[Unidentified Male Narrator or Scientist]

Questions, questions involved in test tube human fertilization. Its meetings and discussions open today.

[Molly Webster]

Now, as part of those meetings, the board would call on these expert witnesses. And one of those witnesses was our.

[Unidentified Male Participant]

Boy Leroy, right, The staff director.

[Molly Webster]

And they asked Leroy, like, ethically, tell us what we should be thinking about when it comes to embryos and how.

[Unidentified Male Participant]

We are to regard them.

[Molly Webster]

And he says, well, there's a spectrum. And on the one side, you could.

[Unidentified Male Participant]

Argue that human embryos should be protected from the time of fertilization forward.

[Molly Webster]

We shouldn't even be growing embryos in a lab at all. But then there's the other side.

[Unidentified Male Participant]

The most permissive position was that research could be done until about eight weeks. A fetus at about eight weeks can have a reflex response to a stimulus.

[Molly Webster]

And then at some point, a committee member turns to leroy and she says, where would you draw the line? He pauses and he says, well.

[Unidentified Male Participant]

Well, I would say for me, 14 days.

[Robert Krulwich]

Why 14?

[Molly Webster]

Well, Leroy had a couple different arguments. For one, before 14 days, about 50%.

[Unidentified Male Participant]

Of early human embryos are simply sloughed off.

[Molly Webster]

They're just sort of shed from the.

[Unidentified Male Participant]

Woman'S uterus and don't develop further.

[Molly Webster]

So the thinking was, if we are already losing 50% of them naturally, we.

[Unidentified Male Participant]

Don'T have strong moral obligations toward early human embryos.

[Unidentified Female Participant]

I see.

[Unidentified Male Participant]

You can even pose it as a metaphysical question. If these are important beings, why do 50% of them disappear and we never have any knowledge of them?

[Molly Webster]

Argument number two.

[Unidentified Male Participant]

Early embryos can split into two, as in twins, or two separate embryos can.

[Molly Webster]

Recombine into one embryo.

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

Right?

[Molly Webster]

Like before 14 days, an embryo doesn't know if it's one embryo or if it's, like, going to be one person or if it's going to be two people. So as Leroy put it, it doesn't.

[Unidentified Male Participant]

Have a biological identity.

[Molly Webster]

And that happens right around 14 days.

[Unidentified Male Participant]

Argument number three, the primitive streak appears.

[Unidentified Female Participant]

The primitive streak appears.

[Unidentified Male Participant]

The primitive streak is the first indication of an axis of the future body.

[Molly Webster]

People see it as, like, the body starting to organize itself.

[Unidentified Male Participant]

You might say it's the outline of the spinal cord that will develop later on.

[Unidentified Female Participant]

It's the first hint of like, shape.

[Unidentified Male Participant]

All of those seem to kind of converge around 14 days.

[Molly Webster]

Eventually, the committee decides to take Leroy's suggestion and recommend that all research on human embryos be stopped at 14 days.

[Unidentified Male Participant]

With high expectations, we submitted the report to Secretary of Health, Education, and Welfare Joseph Califano on May 4, 1979. And on July 19, 1979, before he could respond, Secretary Califano was fired by President Jimmy Carter.

[Molly Webster]

It was part of a whole cabinet shakeup.

[Unidentified Male Participant]

And so the report has been sitting on shelves, gathering dust, and there has never been a formal response.

[Molly Webster]

It did end up becoming a guideline in the US it's actually an international guideline, but we never actually needed it, because 14 days, that was so far.

[Unidentified Male Participant]

Beyond the capacity of researchers to culture early embryos that it also seemed like a safe marker, a safe boundary.

[Molly Webster]

Because. And this is the interesting thing with IVF, we're familiar with, like, Days 012345 6, which is about the time they put the embryo into the mother. So nobody had ever really seen how an embryo develops from day seven through 14.

[Unidentified Female Participant]

Oh, interesting.

[Molly Webster]

You can't photograph it through the body for, like, various reasons. For one, no one ever knows they're pregnant that early. Like, when did you and your wife realize you were pregnant? It's like a month after the fertilization happens. Yeah.

[Unidentified Female Participant]

It's funny. It's like when she.

[Molly Webster]

You.

[Unidentified Female Participant]

Even if you're trying, you don't actually know for weeks until.

[Molly Webster]

Yeah. And it's so small that even if you did know, the way it attaches to the uterus, it sort of burrows in, and you kind of can't see it. And at the same time, scientists are pretty sure that this is a very important moment in development, and they just can't get to it.

[Robert Krulwich]

Wait a second. Life magazine 50 years ago published these gorgeous pictures of a fertilized cell. And then beautiful little baby with eyes, you know, just.

[Molly Webster]

Yeah, but that they have pictures of sperms and eggs, then there's a blank spot until at least three and a half weeks. So that magazine spread.

[Robert Krulwich]

So Life didn't show the first few, the second or third.

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

No.

[Robert Krulwich]

Really?

[Molly Webster]

Yes.

[Robert Krulwich]

You're saying that there is a place in the development of the human being that no scientist has seen?

[Molly Webster]

No.

[Robert Krulwich]

Ever?

[Molly Webster]

No. Really? Yeah.

[Magdalena Zernicka-Goetz]

So this is this kind of period, which in the textbook you will find described as a black box.

[Molly Webster]

Which brings us to Magdalena.

[Magdalena Zernicka-Goetz]

So I'm Magdalena Jernicka Goetz at the University of Cambridge in uk.

[Molly Webster]

She for years had been trying to figure out how to grow embryos during this period.

[Magdalena Zernicka-Goetz]

But for those experiments, and the problem.

[Molly Webster]

Was at this point, the embryo is beginning to attach to the mother's uterus. And so it just need certain things from the mother. And if you try and grow it in a dish, it just shrivels up and dies.

[Magdalena Zernicka-Goetz]

Yes, yes. So at the time, we were trying really scratch our heads and come up with the most enriching environment we could imagine.

[Molly Webster]

Like, maybe I can, like, recreate that really warm, cozy home, but in a dish without the mom.

[Unidentified Female Participant]

Interesting. So it's like experimenting, like, what is the right bath that the growing embryo needs to sort of get what it needs.

[Molly Webster]

Yeah. And they decided that while they were still trying to figure it out, they would just do it on mice embryos first. And so she started essentially just coming up with, like, chemistry concoctions. They started with the gel, which was of particular elasticity, sort of gloppy and gooey. And then they toss in a serum made from human placentas, added some hormones.

[Magdalena Zernicka-Goetz]

Like progesterone, along with fibroblast growth factors.

[Molly Webster]

And of course, a dash of selamin, fibronectin. This sounds like someone would sell this as like a face cream or something. They even tried serum from that's placentas that actually really didn't work.

[Magdalena Zernicka-Goetz]

It was not so good as the serum from the human placement. Yes.

[Molly Webster]

You know, so for five years, they put stuff in, they pulled stuff out, they tried everything, until they ended up was something that, at least on mice, seemed to work really well. So they thought, okay, maybe it's time we try this with human embryos.

[Magdalena Zernicka-Goetz]

We took two embryos, just two human blastocysts, put them in a dish with.

[Molly Webster]

Their chemical concoction, and amazingly, it worked. One of them did make it to 13 days. The other one didn't.

[Magdalena Zernicka-Goetz]

But one made it right.

[Molly Webster]

Suddenly they had an embryo that was growing happily into day 8, day 9, day 10, day 11. And they were able to see all of these moments in human development that no one had ever seen before. And guess what, Robert?

[Robert Krulwich]

Yeah.

[Molly Webster]

I got to see them too.

[Robert Krulwich]

You did?

[Molly Webster]

I did. You want to come?

[Robert Krulwich]

Of course I want to come.

[Molly Webster]

Okay, good.

[Robert Krulwich]

They should go right now.

[Molly Webster]

We are going to go, but we're going to actually have to take a break first.

[Robert Krulwich]

Oh, God.

[Molly Webster]

So we'll be back in a bit.

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

Okay.

[Molly Webster]

Hi, this is Lizzie from Arlington, Texas. Radiolab is supported in part by the Alfred P. Sloan foundation, enhancing public understanding of science and technology in the modern world. More information about [e-mail]. radiolab is supported by Planet Visionaries, the podcast created in partnership with the Rolex Perpetual Planet Initiative. Stay tuned for a trailer and subscribe wherever you get your podcasts.

[Alex Honnold]

I'm Alex Honnold, professional rock climber and founder of the Honl Foundation. I wanted to let you know about a brand new season of the Planet Visionaries podcast in partnership with the Rolex Perpetual Planet Initiative. This is the podcast exploring bold ideas and big solutions from the people leading the way in conservation. Join me in conversation with the likes of climate champion Mark Ruffalo, biologist and photographer Christina Mittermeier, and one of the most successful conservations of our time, Chris Tompkins. Join us on Planet Visionaries. Wherever you get your podcasts, you should.

[Molly Webster]

Tell the people who we are and.

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

What our new show is.

[Molly Webster]

I'm Robert Smith and this is Jacob Goldstein.

[Robert Krulwich]

And we used to host a show.

[Molly Webster]

Called Planet Money and now we're back making this new podcast podcast about the best ideas and people and businesses in history and some of the worst people, horrible ideas and destructive companies in the history of business. We struggled to come up with a name, decided to call it business history.

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

You know why?

[Robert Krulwich]

Why?

[Molly Webster]

Because it's a show about the history of business. Available everywhere you get your podcast.

[Robert Krulwich]

Okay, we're back. I am Robert Krulwich. I'm Molly Webster, this is Radiolab. And today the 14 day rule.

[Molly Webster]

Last we left you, we had just met a woman who managed to grow a human embryo in a lab right up to the 14 day line.

[Robert Krulwich]

And now we get to see it, right? That's what you promised.

[Molly Webster]

Yes. One earphone on, one earphone off.

[Magdalena Zernicka-Goetz]

Good luck.

[Molly Webster]

Good luck. Lucky enough for me, there is an embryology lab right here in New York at Rockefeller University. Hi, how are you? Nice to meet you. Run by this guy.

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

So you're a radio scientist?

[Molly Webster]

Ollie Rivenloo. I fake being a scientist, but Ollie's team building off of Magdalena's work. They were also growing human embryos in the lab to the 14 day mark. So he invited me up to see them.

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

You would realize that your eyes are seeing something that no other human beings has ever seen except the group in.

[Molly Webster]

This lab and obviously Magda's lab. How many people are in this lab that you think saw it?

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

I think we're a total of 25.

[Molly Webster]

So then I'll be like, 26. So Ali has to step out of the room. I'm excited. Thank you, Ali. And he passes me off to the guy that runs, like, the human embryology research at the lab.

[Unidentified Male Narrator or Scientist]

Guest Croft.

[Molly Webster]

And a lab technician, Cecilia Pellegrini. Cecilia Pellegrini. Okay, we got. We go into the lab. We're walking through a cool lab. It's very big, and everyone's looking at me. Lots of benches and microscopes and people pipetting and so a fridge. There's a little sticky note on the fridge that says, experiment 27 embryos here. So we keep them in the tip box, and Cecilia pulls out, like, a plastic box that has a blue bottom and, like a white, opaque top. The lid just came off, and inside there was kind of like a microscope slide, and the embryos were attached to that, but there's condensation on it. So we had to wait, like, 10 minutes. I got weirdly nervous, but eventually you, like, look down into this, like, little square. Well, okay. It's like 10 millimeters by 10 millimeters. And it has a little bit of liquid in it, and then inside that liquid.

[Unidentified Female Participant]

Wow.

[Molly Webster]

This is a human embryo.

[Unidentified Male Participant]

Yeah.

[Unidentified Female Participant]

How big is it? How big is an embryo?

[Molly Webster]

Oh, my God, it's so small.

[Unidentified Female Participant]

I was like. We talk about 14 days, and in my mind, I do imagine a tiny little human. Is it even human? Like, at that point?

[Molly Webster]

Tiny dot right there? No, it's just the little white dot. Holy crap. That's really small. That's like a grain of sand. Yeah, it's about that size. And it looks like. I kept also thinking that it looked like if you took a sheet of typing paper and you took a pin and you poked a hole in the paper and a little pinpoint of light came through.

[Unidentified Male Participant]

That's what it looks like.

[Molly Webster]

It looks like that. I cannot believe that goes into a 5 foot 9 tall human being. So that was a day 12 embryo we were looking at with our naked eye. But Gist and Cecilia also took me over to this badass microscope. What do I. I don't want to break anything.

[Unidentified Male Narrator or Scientist]

Yeah, you're not gonna break it. I'll show you how to do this.

[Molly Webster]

So we could look at a bunch of images and. And see the development of an embryo day by day, starting with day eight. You see right here, like, you have the embryo mass.

[Robert Krulwich]

What are you. What does it look like?

[Molly Webster]

It looks very lunar to me. Blown out gray sphere that has, like, mottled surfaces, but inside of it are hundreds and hundreds and hundreds of cells.

[Unidentified Male Narrator or Scientist]

There's trophectoderm, primitive endoderm, and there's epiblast.

[Molly Webster]

There were like three different types of cells, but to me, it like, looks. Looked like a simple structure. And then this is the same embryo. The next day. Wait, is this day nine? Oh, whoa. It looks totally different. So it starts to get a little more complex.

[Unidentified Male Narrator or Scientist]

Now we can see nuclei.

[Molly Webster]

Is that what all those bright spots are?

[Unidentified Male Narrator or Scientist]

Yeah, there's the nucleus. There's the nucleus.

[Molly Webster]

Huh. And then can we switch from 9 to 10? Mm. So what are those, like, oil droplet looking things?

[Unidentified Male Narrator or Scientist]

Those look like oil droplets, don't they?

[Molly Webster]

Now there are these, like, spherical balls around the edges. And it could be any number of things, but guess thinks they might be fat, like lipid. And the embryo, it starts forming, like the asymmetry. Like, you see things move to different areas of the cell.

[Unidentified Male Narrator or Scientist]

It makes a hollow shell inside.

[Molly Webster]

And then your inner gut cavity that starts to form.

[Unidentified Male Narrator or Scientist]

There's all of a sudden a new cell type we've never seen. The yolk sac trophectoderm cells.

[Molly Webster]

So a totally new type of cell no one's ever seen before.

[Unidentified Male Narrator or Scientist]

So we don't know where it comes from, and neither does anyone else.

[Molly Webster]

And then day 11, I get excited every time you open one of them. Okay. Day 11. Day 11 didn't really, like, look that different to me. Day 12, Day 12 has a lot more going on.

[Unidentified Male Narrator or Scientist]

That's the origin of the placenta.

[Magdalena Zernicka-Goetz]

Cool.

[Molly Webster]

Day 13, there's all this brightness at the bottom in the upper left hand corner.

[Unidentified Male Narrator or Scientist]

These could be epiblast cells.

[Molly Webster]

Remind me again, the epiblast is.

[Unidentified Male Narrator or Scientist]

That is the cell type from which the entire body eventually emerges.

[Molly Webster]

Gist says those are the cells that all of the body comes from. Like, all the other stuff is mostly just support.

[Unidentified Female Participant]

Oh, wow. So it's like the primal, like, primordial cells.

[Molly Webster]

Foundational cells. Foundational cells, yeah.

[Unidentified Female Participant]

Yeah.

[Molly Webster]

So I actually got there on day 13 of the experiment. So all of the embryos were just sort of waiting to get to day 14. And so that was it.

[Unidentified Male Narrator or Scientist]

So let's shut this down and get this guy back in the incubator.

[Molly Webster]

And then I was just sort of spit back out into the real world.

[Unidentified Female Participant]

Are they learning fantastically new amazing things based on this?

[Molly Webster]

Well, like, the big takeaway that both of the groups had was that this embryo grew for another week without any maternal input. And it grew basically as it should.

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

Have grown, which was mind blowing to me and to all of my colleagues that the human embryo will behave in a self organizing manner in a complete absence of maternal inputs, at least for 14 days.

[Molly Webster]

Like I think they always thought even if they got the chemistry right, there'd be some sort of system breakdown because it wasn't getting input from the moment.

[Unidentified Female Participant]

Interesting.

[Molly Webster]

I always keep thinking of it as like the anti Mother's Day message. The embryo doesn't need you. Happy Mother's Day. But the one pro mom thing is by the end, in between day like 12 to 14, it became clear that it started needing maternal input. I see.

[Unidentified Female Participant]

Like, what do they know?

[Molly Webster]

Well, so this is the part I thought was cool, was like they saw that the embryo started forming tunnels and pathways for the mom to like infiltrate. So there were little tubes and pathways that formed where like nerve attachment could happen and like circulation. So it prepares itself in this week for the mom and the connection.

[Unidentified Female Participant]

That's really cool. It's like hooking itself up to the network in a way.

[Molly Webster]

I know, it's funny. It's like coming online as like a human being.

[Unidentified Female Participant]

Yeah, that's a good way to put it. Yeah, that's cool.

[Molly Webster]

The other cool thing was Gist told me that right around day 10, along the edges of the embryo, this hormone shows up that your body doesn't have before. It's called like a gonadotrophin. So you know when you take a pregnancy test, the thing it's reading is that hormone.

[Unidentified Female Participant]

Oh, is that, he thinks, like the embryo broadcasting.

[Molly Webster]

Yes. It's like boom, boom, boom, boom, boom, boom. Like out to the rest of the body, like, I'm here, I'm here. Look at this hormone.

[Unidentified Female Participant]

Wow, that's super cool.

[Molly Webster]

What is it like to look through a microscope and see day eight when we've been stopped at day seven since the 1970s, or day nine or day 10?

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

It's hard to describe it. When people receive the digital image of the Hubble telescope, those first few eyes who are getting it in their screens. I guess it has to be something very similar to that. When I look inside of our own anatomy at the time where nobody knows that we even exist, it's the same as looking at dimensions that we have never imagined we will ever see because we didn't even know they exist.

[Molly Webster]

But then at day 14, you have to essentially embalm it. You, like, can make it stop growing and freeze in the place that it's at. They call it fixing.

[Robert Krulwich]

But if they wanted to, could they go past 14 days?

[Molly Webster]

Maybe. But Ollie, he said that as they got closer to day 14, they noticed changes in the embryo that made it clear that it started needing more than just the current B it was in. But, like. And Brivanloo says this too, and Magdalena says this. It's like every day feels like an accomplishment. You're like, oh, my gosh, it grew another day. And then you start, like, cheering it on. You're like, grow another day, grow another day. Oh, my gosh, you're at day 12 and it becomes like, you're like, championing it. And then you're like, okay, stop, you're done.

[Unidentified Male Participant]

Right?

[Molly Webster]

And I felt like when I was standing there, I was like, oh, that's abrupt. Because I wanted it to grow, grow, grow, grow, grow. But obviously I don't want it to grow, grow, grow too far. So I was like, go to day 15. And I'm like, go to day 16. And then I'm like, when does the joy in my voice stop? Eventually, I'm going to hit a. Don't worry. Eventually I'm going to hit a point where I'm like, that's uncomfortable.

[Unidentified Male Participant]

Right?

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

This is something that touches us in the root of our own definition of our being and existence and individuality. It becomes a little bit like a Pandora box. So, yes, you want to open it, but you have to be ready to see what's in it.

[Robert Krulwich]

If technology has now moved it a whole other week, so we can go for 14 days, maybe it's pretty soon you can go a whole nother week and then a whole nother week. Does that mean the rule's going to have to change?

[Molly Webster]

That is the conversation that's happening right now, basically. Once this research was published, there were commentaries and articles and columns about, what do we do about the 14 day rule. And there's conferences. There's a conference in Boston that's happening in the fall.

[Robert Krulwich]

But what are your choices, though? Like, you could choose.

[Molly Webster]

You could do any number of things. It depends on where you sort of throw down a biological or moral marker that you feel comfortable with. Like, you could keep it at 14 days and sort of keep it around. Like this idea of twinning and the primitive streak. You could move it a week out to, say, to day 21, when there's interesting sort of neural folds and divisions that are starting to happen in the brain. You could go to eight weeks, but it could also go back to zero.

[Robert Krulwich]

So there's no consensus on.

[Molly Webster]

No, no, there's no consensus. And the scientists are the first to say, like, they don't want to make this decision. They just think, like, maybe we should have this conversation as a group. So the society decides, not us.

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

So, yeah, and then.

[Molly Webster]

But it's just like, if you say that, like, it's as amazing as, like, the Hubble telescope. How does it feel when you're like, I've gotten this far and now I have to end it?

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

So that's the toughest question you're going to ask me today. For me, for sure, it was important to stop the experiment where there was still a message that we could convey that would not offend people. This is more than just science. One of the greatest challenges in reproductive biology, especially in human reproductive biology, is to make sure that you don't offend people's sense of identity, dignity, religion.

[Molly Webster]

And so Ali, he finds himself trying to keep all of these different perspectives in his head all at once.

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

So, for example, if the Catholic point of view is human origins, conception, then I have to respect also the Jewish point of view that says, you know, what is that heartbeat? I also have to respect the Muslim point of view about the origin of human life, which surprisingly, for one, seems to be similar than the Jewish point of view. It's also heartbeat. I also have to respect the Buddhist point of view. And what about the Hindus? The Buddhist says, if you don't cut the umbilical cord in, you're not independent, you're not a human being. You don't call an organ a human being because it's attached to you. A Hindu says, I don't know what you guys are talking about. There is no origin or end. We're circles within circles within circles. I'm a butterfly today I'm going to die and come back as a tiger. I'm going to die and come back as a human. Die and come back as an elephant. What origin? A circle does not have an origin. So I am for the progress of science. I am for gaining knowledge. It's my job. It's the way I'm wired as a human being. I satisfy our sense of curiosity, and there is nothing more curious to me than our own origin.

[Molly Webster]

So then that would be like. You would love to know, like, what happens on day 21.

[Unidentified Male Scientist (possibly Ollie Rivenloo or another lab member)]

Absolutely. And I like to think that before I die, we will know what happens on day 21.

[Molly Webster]

This episode was Produced by Annie McKeown, with help from Matt Kilty and Brenna Farrell and Simon Adler. And I actually think the entire Radiolab staff had something to do with this episode. So thanks, guys. And I want to thank the research library at Georgetown University.

[Robert Krulwich]

Thank you for listening.

[Molly Webster]

See you later.

[Leroy Walters]

To play the message, press 2. This is Leroy Walters. I'm a retired faculty member from Georgetown University, where I was part of the Kennedy Institute of Ethics and the Philosophy department. Radiolab is produced by Jad Abumrad. Dylan Keith is our director of sound design. Thorin Wheeler is senior editor. Jamie York is our senior producer. Our staff includes Simon Adler, Brenna Farrell, David Giebel, Matt Chielty, Robert Krulwich, Annie McEwen, Latif Nasser, Melissa O', Donnell, Arianne Wack and Molly Webster, with help from Nigar Fatali, Alexandra Lee Young, Charu Sinha, Persia Verlin and W. Harry Fortuna. Our fact checkers are Eva Dasher and Michelle Harris. That's it. Thanks. Bye. End of message.