The Dubious Consent Question At The Heart Of The Human Genome Project

This episode of "Short Wave" delves into the ethical and procedural controversies surrounding the Human Genome Project, particularly focusing on issues of donor consent and representation.

1. The Human Genome Project was a monumental scientific endeavor with ambitious goals similar to the Apollo missions.
2. Ethical concerns have arisen due to the reliance on the DNA of a single anonymous donor, identified only as RP eleven.
3. The project’s shift to using primarily one donor's DNA was driven by technical challenges and time pressures, exacerbated by competition from the private sector.
4. There is an ongoing need to address the ethical considerations of genetic research, especially concerning informed consent.
5. The episode underscores the importance of transparency and ethics in scientific research, impacting future genetic studies.

1. Introduction to the Human Genome Project

This chapter outlines the origins and goals of the Human Genome Project, likened to a biological moonshot. Ashley Smart: "It was something wildly unprecedented and hugely ambitious."

2. The Shift in Genetic Material Usage

Discussion on how the project deviated from using a mosaic of donors to primarily one donor’s DNA. Emily Kwong: "But in reality, one person’s DNA made up the bulk of the final sequence."

3. Ethical Implications and Insights

Explores the ethical implications of the consent process and the impact of using DNA predominantly from one donor. Ashley Smart: "None of the Roswell park donors know... RP eleven was never told of this change."

1. Always ensure informed consent in research studies.
2. Promote transparency in the processes and outcomes of scientific research.
3. Engage in continuous dialogue about ethical standards in science.
4. Advocate for diversity in scientific research to avoid biases.
5. Support oversight and ethical review in all stages of scientific projects.

The Human Genome Project was a massive undertaking that took more than a decade and billions of dollars to complete. For it, scientists collected DNA samples from anonymous volunteers who were told the final project would be a mosaic of DNA. Instead, over two-thirds of the DNA comes from one person: RP11. No one ever told him. Science journalist Ashley Smart talks to host Emily Kwong about his recent investigation into the decision to make RP11 the major donor — and why unearthing this history matters to genetics today.

People

Ashley Smart, Emily Kwong

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Undark magazine

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Guest Name(s):

Ashley Smart

Content Warnings:

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Emily Kwong
You're listening to short wave from NPR.

In 1990, the Department of Energy and the National Institutes of Health launched a massive undertaking called the Human Genome Project.

Ashley Smart
People in the biology community and the genetics community refer to it as a moonshot for biology, if you will, kind of on par with the Apollo mission.

Emily Kwong
Because for the first time ever, scientists were going to sequence the human genome as fully as possible.

Ashley Smart
That is, they were going to read all of the DNA from a person. That kind of makes us a person.

Emily Kwong
Ashley Smart is a senior editor at Undark magazine, where he recently wrote about this landmark effort. Genetic sequencing and testing may be widely available nowadays, but back then it was.

Ashley Smart
Something wildly unprecedented and something hugely ambitious.

Emily Kwong
Which is why the human genome project took several scientific teams over a decade and $3 billion to complete.

But there's one part of the legacy that Ashley believes doesn't get talked about enough, and that is the donors.

Ashley Smart
To sequence human DNA, you need actual DNA from humans. And so one of the questions that people, people have been asking pretty much since the completion of the human genome project was where did this genetic sequence come from? Who were the humans whose DNA we were looking at? And that's a complicated story.

Emily Kwong
That complicated story is the focus of.

Emily Kwong
Ashley's recent article in Undark magazine, an article which investigates how the human genome project veered from its initial plan in one particular way. The final genome sequence was supposed to be made up of many peoples DNA, a mosaic of genetic material. But instead, 70% of the sequence comes from just one donor. And Ashley wanted to know how, how.

Ashley Smart
Did we end up specifically with 70%? You know, why not 100%? Why not a smaller percentage?

I was curious to know why that changed.

Emily Kwong
I today on the show revisiting the ethics of the human genome project.

It fundamentally shifted the field of biology, but also succumbed to intense pressure along the way, resulting in an over dependence on one anonymous male RP eleven.

Emily Kwong
Who was he?

Emily Kwong
And why does unearthing this history matter to the genetics research we do today? I'm Emily Kwong. You're listening to short wave, the science podcast from NPRDH.

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Emily Kwong
To the late nineties. What was the power back then of sequencing the entire human genome? What could scientists do with that information that they couldn't do before?

Ashley Smart
Yeah, so a lot of people I've talked to have kind of emphasized that we didn't exactly know what the power was without having this sequence.

Emily Kwong
So it was first like, can we do it at all?

Ashley Smart
Can we do it at all? And I think there was certainly an anticipation, certainly a hope that kind of understanding our genetics at this level would lead to better understanding of diseases and would lead to new medicines and treatments, treatments that can be kind of tailored to work specifically for a person based on their genetic profile.

And I think it's debatable how much and to what extent the project delivered on that promise.

But I think what pretty much everyone I've talked to would agree on is that the project really launched us into a new era of biology of the way we kind of understand living things.

Emily Kwong
Yeah. And when you say genome, you're talking about all the genetic material in an organism. In this case, the organism is human beings, and that's made up of our friend DNA. I know that most people are probably aware it's like a double helix. It's too stranded, and it is made up of all these molecules with, like, different letters. Why would knowing the order of the letters matter, right?

Ashley Smart
So the letters that make up our DNA, A's, C's, T's, G's, kind of the order of those letters is basically a code for building proteins, and the proteins are kind of one of the fundamental building blocks of our cells.

They help determine things like eye color and hair color, and they perform all of these functions in cells and tissues.

And so, in theory, if you can understand that sequence, that code of A's, C's, T's, and G's, and if you can do that across all of our 23 pairs of chromosomes, then you can unearth in what some would call kind of a blueprint for what makes us us.

But there are places where our genes vary, and so that's one of the things, I think, that the scientists in the human genome project wanted to do. By teasing out this code, can we better understand the differences that we see in when it comes to health and medicine and things related to those issues.

Emily Kwong
And how they did this? You write about this in the piece, is basically by taking these blood samples and grabbing fragments of the DNA, which they then clone. How does that work? And why are they trying to create clones of pieces of people's DNA?

Ashley Smart
Yeah. So, essentially, in order to sequence DNA.

Emily Kwong
For this project, just to know the order of the letters.

Ashley Smart
Yeah. To read out the order of the A, Cs, and T's and G's, you can't just stick an entire person's DNA or chromosome through a reader and get out the whole answer that way. So you kind of have to read it in little short segments.

And so they intentionally fragmented the DNA, and then they'd stick each fragment into a bacterium, and the bacteria would basically replicate that fragment as it reproduced.

And so you could basically take an entire person's genome, cut it up into little pieces, and then create copies of all of those pieces, essentially let them have multiple groups around the world work on the sequencing at the same time.

So in my. In my story, I describe it as distributing identical sets of a puzzle to researchers all over the world who are really good at doing puzzles.

It allows them to work on different parts of the puzzle at the same time, and then they can also check each other's work.

Emily Kwong
Yeah.

Emily Kwong
So at this point in the project, it was time to recruit volunteers to the Roswell Park Cancer Institute to donate their DNA. And I understand from your piece that the consent forms at the time said to the donors, you know, we expect no more than 10% of the final sequence to be any one volunteer's DNA.

Emily Kwong
But in reality, what ended up happening.

Emily Kwong
Is one person's DNA made up the bulk of the final sequence.

Ashley, how did that happen.

Ashley Smart
So it's complicated. And different people that I've talked to have given me different answers.

But what seems to be clear is that sometime after March 1997, after that recruitment process, the project shifted course and it decided that the mosaic genome that it had aspired to was either not going to be feasible or not going to be practical. And it decided to shift to focusing on primarily one donor. Why did they shift course?

Well, some people I've talked to have told me that there were technical reasons, that there was a worry that those places where our DNA differs could create challenges when you're trying to stitch together a coherent genome.

But other people I've talked to have pointed to time being the bigger issue.

And one of the important developments here was that in early 1998, the Human Genome project got competition, essentially from the private sector.

So there was Craig Venter, who is kind of a noted scientist and entrepreneur, and who had actually done some work with the human genome project. In the early days, he kind of splintered off and announced a new private project that would be done with a company called Celera Genomics.

And they said that they were going to complete the genome even faster than the human genome project and at a lower cost.

And so people I've talked to said that really lit a fire under the human genome project to say, how can we do this thing faster?

Emily Kwong
But did any of the donors know about this shift in focus to one.

Emily Kwong
Person'S DNA being most of the data?

Ashley Smart
None of the Roswell park donors know. And so RP eleven, the anonymous male donor who makes up 70% to 75% of the genome, was never told of this change.

Emily Kwong
And to this day, does he have any idea?

Ashley Smart
I haven't spoken to him, so I don't know. But I know that to this day, Francis Collins, who led the project, never attempted to tell RP eleven of this change.

And I should point out that there was an ethics panel, an institutional review board, who basically decided that none of the donors should be told about this change.

Emily Kwong
Tell me more about what we know about RP eleven.

Ashley Smart
Yeah. So years after the human genome project ended, the sequence that came out of it remained kind of a central resource in genetics and has been the subject of a ton of analysis and study.

And one of those studies in that was done in 2010, analyzed the sequence, what we call the reference genome, and concluded that RP eleven, just based on the genetic patterns they saw in his sequence, showed a mix of african ancestry and european ancestry, consistent with likely identifying as african american.

And so when I thought about RP eleven, and how they might feel knowing that their genome, one, played such an important part in the march of genetic science. And two, you know, when they realized that what the project scientists did was something different than what they told them, you know, those realizations were colored by the fact that, you know, there's kind of a long history of, of tension and ethical missteps. Maybe you'd even say ethical mistreatment or ethical wrongs being done to the african american community here. And me as a black person who covers science and was once upon a time ago a scientist, when I think about RP eleven possibly being a black person who made this big contribution to science, I think about myself when I think about him, you know, and I think about kind of this big contribution hasn't been acknowledged. Right.

And it may be the case that RP eleven doesn't want it to be acknowledged. It may be the case that RP eleven, you know, would rather no one know, you know, that he was behind this genome.

But I guess I feel sympathetic for him and in one, for him to at least be able to make that choice for himself.

Emily Kwong
Yeah, you quote many of the scientists involved, and the one that really keeps sticking with me is Aristides Patrinos, who says to you, I think at this point it probably would be a good idea to come out in the open.

Emily Kwong
And tell everybody what happened and give.

Emily Kwong
As many specifics as possible.

How does society stand to benefit from knowing fully the story of the human genome project?

Ashley Smart
I mean, as a journalist, I feel like my goal is always to tell a true story and to help provide an honest record of what happened. This is an aspect of the project that had never really been documented for the record, and I wanted to do that. And so I guess one hope that I would have for this piece of would be to kind of foster more of a discussion between people who are thinking about genomics from a very technical point of view and the people who are thinking about the ethics of how we do this work. I think really for the field to thrive, both of those communities probably need to be talking openly with each other and also respecting what the other side has to say.

Emily Kwong
Ashley Smart is the associate director of the Knight science Journalism program at Mitz and a senior editor at Undark. Thank you so much for coming on.

Emily Kwong
Shortwave to talk about this reporting.

Emily Kwong
You did.

Ashley Smart
Thank you so much for having me.

Emily Kwong
And you can read the piece yourself. We highly encourage it at the link in our show notes.

Emily Kwong
This episode was produced by Burleigh McCoy. It was edited by our showrunner Rebecca Ramirez and fact checked by Burley and Rebecca. The audio engineer was Kwesi Lee. Beth Donovan is our senior director and Colin Campbell is our senior vice president of podcasting strategy. I'm Emily Kwong. Thanks for listening to short wave from NPR.

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