A Synthetic Human Genome? Not So Fast

12:06 minutes

When scientists and entrepreneurs held an invite-only meeting at Harvard last week to discuss the prospect of manufacturing a complete human genome and inserting it into a cell line, ethicists and biologists alike responded with swift and cautionary advice. “The creation of new human life is one of the last human-associated processes that has not yet been industrialised or fully commodified,” wrote Drew Endy and Laurie Zoloth in Cosmos. “Discussions to synthesise, for the first time, a human genome should not occur in closed rooms.”

Aside from the ethical discussions that may ultimately determine the fate of such a project, biologist Jeff Way, who attended the meeting, says building human chromosomes from scratch would be a huge technological leap. “It’s not really feasible. Part of the idea is you have to invent the technology to make it feasible.” Zoloth and Way join Ira to discuss the scientific and ethical challenges that lie ahead for large genome synthesis.

Segment Guests

Jeffrey Way

Jeffrey Way is a Senior Staff Scientist at the Wyss Institute for Biologically Inspired Engineering, at Harvard Medical School in Boston, Massachusetts.

Laurie Zoloth

Laurie Zoloth is a professor at Northwestern University. She is Past president of the American Academy of Religion, and of theAmerican Society of Bioethics and Humanities. She’s based in Evanston, Illinois.

Segment Transcript

IRA FLATOW: This is Science Friday. I’m Ira Flatow.

Last week, scientists and entrepreneurs held a closed-door invite only meeting at Harvard to discuss an idea from the realm of science fiction. Manufacturing a human genome. Human cells with the genetic instructions made from scratch. No parents needed.

You can imagine what happened next. Biologists, ethicists, theologians responded swiftly and forcefully, saying it’s not up to scientists and industry to make this sort of decision, especially behind closed doors. Scientist may have the expertise to pursue these projects, the critics said, but not the authority.

The organizers of the conference later dialed it back a little. They stressed that the idea was not to build a person with the technology, just cells in a dish. And they said the focus would not be on synthetic human genomes. They’d study creating synthetic animal and plant genomes too.

But who would that work benefit? If it was publicly funded, would all the taxpayers footing the bill, including most underrepresented members of our society, ever see a benefit?

By the way, building a synthetic genome as big as a human isn’t that easy to pull off either. Even if a project like this did you get the green light, it would face a lot of technical and economic challenges.

So where do you weigh in on this? Give us a call, 844-724-8255, 844-SCI-TALK. The meetings organizers declined an invitation to join us today. So we’re going to have to catch up with them next time hopefully.

My next guests are Jeffrey Way, senior staff scientist at the Wyss Institute for Biologically Inspired Engineering. That’s at Harvard Med School. Welcome to Science Friday.

JEFFREY WAY: Thank you.

IRA FLATOW: Laurie Zoloth is a professor at Northwestern University. And she’s also past president of both the American Academy of Religion and the American Society of Bioethics and Humanities. Welcome to Science Friday.

LAURIE ZOLOTH: Thanks for having.

IRA FLATOW: Dr. Way, you were at the meeting at the Wyss. What was the purpose? To hash out technical details, discuss the fundamental model, public or private? What was going on there?

JEFFREY WAY: What was going on primarily was scientific talks by people who were doing research related to the potential synthesis of the human genome. And so there were talks about making DNA, talks about some of the medical uses that people might be able to attack with if you have this technology. Diseases like Duchenne’s muscular dystrophy, various genetic disorders, organ transplants, and so forth. And also people working on the basic technologies that might underlie being able to do this.

IRA FLATOW: So no one was going to the meeting saying, hey, we’re coming here to learn how to build a human genome?

JEFFREY WAY: No. The people who came want to do, are interested in doing it, and maybe have something to offer. But I think the main spirit of the meeting was that this is in fact a daunting process. The idea of doing this is technologically really impossible right now.

And it’s a very desirable goal because as you rattled off, synthesis of a variety of different genomes would be extremely useful. Especially plant genomes to solve potential world hunger issues, animal genomes for making better agricultural animals, and so forth. And also just for studying the basics of how genomes work.

But really doing it from scratch is just daunting. The expense, the time, the effort, whether it’s possible or not is an open question. And that was really the spirit of the meeting is how challenging it is. And how should we organize such a large project.

IRA FLATOW: So why was the meeting closed to the press and the public then?

JEFFREY WAY: I think the project is at such an early stage that if you have the press present, then there would be a certain level of self-censorship because people would be basically afraid of saying something stupid that would then end up the next day in the press and create all sorts of unnecessary controversy. When really you want to be able to think out loud. Say things that upon reflection or upon just hearing them articulated might be a little silly or might sound like you’re trying to create a monster and so forth.

But you want an atmosphere of freedom to have those discussions. And then once you coalesce around a plan, then that would be kind of presented to the public.

IRA FLATOW: Dr. Zoloth, you and the biologist Drew Endy responded to the meeting news with an essay that says, hold on. This project is not ready for prime time yet.

LAURIE ZOLOTH: Correct. We had three points, and one of which is just a factual thing. There was a press release put out by Autodesk three or four weeks before the meeting was held saying exactly that. We’re going to make a human genome. We’re going to set up this process this year. And within a decade, we’ll have this project underway.

So we were alarmed because the meeting had a clear intent to create a human genome. That’s why it was called Human Genome Project Two. Like 0.2 of a science project.

And we were concerned about several things. One is who is invited to have this discussion? What is it ever asked not how could we do this, but if we should do it or not? The ethical question, is this the right act and what makes it so?

And finally, synthetic biology has been marked from the very beginning by including a wide swath of people including bioethicists, including theologians, including civil society groups who had something to say. Bioethics has never been excluded, and theologians and civil scientists have never been excluded to this extent before. We’ve always known that there was meetings going on. Many meetings were open. People were invited to make presentations.

Because we believe that science from the very beginning is a public project, is a project of a whole society. And that’s why ethics has begun– has to be asked and queried at the very beginning of any project in science. There’s no such thing as a privatized science project.

IRA FLATOW: Jeff, how do you answer that? You don’t seem to believe from what you said that this should be close eventually, all the way.

JEFFREY WAY: Of course not. Of course not. First of all, if it remains closed, we’ll never get the money to do it.

What we need to do is create a concrete plan. The idea, as Dr. Zoloth said, is already out there. And people are welcome to debate it. Should we create a cell?

And that’s all we’re doing. Just a cell with a synthetic human genome in it. Should we do that? That’s something that people can talk about right now.

How to do it. is a difficult question. Simply coming up with a roadmap. It’s like building a bridge, or a huge building, or a battleship. It really is expensive. It requires a lot of planning. And everybody would like to come up with that plan before essentially asking various sources for money. You need to hear a sensible plan to put forth to the public.

IRA FLATOW: Dr. Zoloth, we had the Human Genome Project, sequencing of the human genome. And I don’t recall there being this much pushback on that idea.

LAURIE ZOLOTH: Well, I’m going to say two things. One is the reason there wasn’t pushback. Because from the beginning, it was conceived as a project that had a certain proportion of public funds for ethical, legal, and social implications of the science itself.

This was called the Elsi Projects. This was an attempt to say, in the beginning, as we begin to discover this, let’s think with bioethicists, and theologians, and social scientists, and lawyers about the implications of such a project. So it was never separate. It was never put in place and then asked about it afterward. Science welcomed ethical discourse in the very beginning of the Human Genome Project.

And as I said, that’s been commonplace ever since. To include bioethicist and theologians and in their many and diverse numbers into the formation of the project itself. So that the parameters, the epistemological considerations, what is of value and what is not a value are set as part of a collaborative discourse.

And that was absent in this meeting. And that’s actually, ironically enough Ira, here’s what’s happened. We wanted two things. One was you wanted it to be an open meeting and have a full public discourse. And a conversation like this is clearly the beginning of that discourse.

And secondly, we said don’t do humans. Build the tools and the technologies. Create this science around not human biological cells. Around cells would have some meaning for public health. That there be a strong reason to create, for instance, an adaptive rice genome or a mosquito genome.

Other things besides humans, because the creation of humans is not a scientific problem. It’s a theological problem it goes to the core of the question, what does it mean to be human? What does it mean to be free? And those assumptions have to be built into any efforts at creating a human genome.

IRA FLATOW: Jeff Way, your reaction?

JEFFREY WAY: My reaction is that, first of all, if we called this project the Rice Genome Project we would have a lot more difficulty getting funding. And honestly, that was part of the consideration. We will develop technologies that will be applicable to all these different organisms. But implicit in that is the capability of synthesizing a human genome.

If we say, we’re going to make the rice genome or the cow genome, then hidden in there is the same technology that would allow you to build a human genome. And so they all go together.

And I think calling it the Human Genome Project Two or the Human Genome Project write instead of read just makes plain. It’s a kind of an honest admission that that technology is embedded in what we’re trying to do.

IRA FLATOW: What kind of funding, Jeff? What kind of money in terms of a budget are we talking about here? Let’s say if you want a complex large genome in 10 years, what ballpark?

JEFFREY WAY: The ballpark discussion is in the range of $100 million. But honestly, I mean I realize I’m on the radio. I want to say don’t quote me. This is why we need to plan.

It could be a little bit less than that. It’s hard to imagine much less than that. It’s easy to imagine a lot more than that.

Because right now, you can do calculations about simply the cost of chemical synthesis of a human genome. Just how much chemicals do you need to make all those base pairs, three billion base pairs. And it’s a lot. It’s a few cents a base.

And so already you’re talking at today’s prices tens or hundreds of millions of dollars. And then there’s the lab work to assemble it into bigger pieces, and put it into the cells, and so forth.

IRA FLATOW: Dr. Zoloth would you welcome another more inclusive meeting?

LAURIE ZOLOTH: I would welcome another more inclusive meeting. And I’d like the meeting to begin not with how we do this and how do we enact it and how do we fund it, but if we should do it or not. Should $100 million be spent with this sort of science project? Admittedly, very difficult with an unclear goal, a hand waving goal of human health.

Or should there be a $100 million spent to figure out how to get clean water to millions of people around the world that don’t have clean water? Or how to do something about malaria. Every 30 seconds a child dies of malaria. $100 million in scientific research could go a long way towards that.

IRA FLATOW: In all fairness, you could make that argument about every sort of project there is.

LAURIE ZOLOTH: And that’s why every single project there has an IRB review, has a social implications thoughtful discussion surrounding it. A major new project to create a human genome needs to have a public discussion to decide if it’s worth it and if it’s ethical.

IRA FLATOW: I think we’ve started it here today. Jeff Way, senior staff scientist at the Wyss Institute of Biological Inspired Engineering at Harvard. And Laurie Zoloth, professor at Northwestern University. And she’s also past president of the American Academy of Religion and American Society of Bioethics and Humanities.

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About Christopher Intagliata

Christopher Intagliata is Science Friday’s senior producer. He once served as a prop in an optical illusion and speaks passable Ira Flatowese.

  • Warren

    The discussion reminds me of a book written with following movie – The Island of Doctor Moreau is an 1896 science fiction novel by H. G. Wells, who called it “an exercise in youthful blasphemy”. The text of the novel is the narration of Edward Prendick, a shipwrecked man rescued by a passing boat who is left on the island home of Doctor Moreau, who creates human-like hybrid beings.

    Hope we can’t or don’t go this rout.

  • Robert Thomas

    Why should the investigators pursuing these questions care about the views of astrologers or witch doctors?

  • MikeCassady

    For me, the most telling point in the discussion about whether a program to engineer a human genome from scratch ought to be allowed to go ahead was raised by Professor Zoloth when she spoke of the way funding influences what scientific questions are worthy of investment.

    Private profit and public well being serve one another effectively in the domain of the general distribution of consumer goods and services, and, as always, particularly with respect to the production of basic material necessities and a quality material life. As much as people are treated in this domain as a mass driven and influenced by consumption drives and dreams, commercial access to our pocketbooks still must pass through the moral process of decision making. Other domains, such as public health, education, the environment and national policy interests in the evolving international sphere, including national defense, but much more than the military capability, are legitimately of general public concern are deserve the direct involvement of a public partner morally empowered to speak in behalf of all individuals, including those of the future not yet born.

    Conservative interests have, since World War II and the birth of the “military-industrial-congressional complex”, worked without a pause to starve resources to the public partner born out of the very effective public-private partnership that developed under war powers authority to coordinate US social and economic forces for the production of war materials and food supplies for many foreign coutries in ruin. The war justified public-private partnership President Eisenhower worried about as the US moved into peactime and what was expected to be business as usual, has not gone away, cannot go away, and will not go away, and should not be manipulated by private interests with no incentive to consider the good of the public as a whole.

    Professor Zoloth expressed concern that the proposed genome project was pushing research into the rightful domain of concern for general public well being and a foundational freedom to decide what is best for the society as a whole as a constituted group. A look back at the emergency-powers government of World War II shows the evolution of an effective public-private partnership, a modern form of governance for an inevitably globalizing world (World War II itself being a birth event of globalization). The individual US citizen has no standing as a moral agent in the global domain that is increasingly structuring our historic national societies and economies. He or she is represented in the growing global reality by elected representatives who constitute, in effect, our public ‘partners.’ The reality facing the federal government is the opposite to that of the age of our founding: then, self-protective and inward looking; now, outward looking, but without institutions allowing moral individuals to express thier will. As moral individuals, we operate in the global spehere through the proxy of our national partner. Economic forces operating from behind national walls are expoliting the lack of global institutions to rationalize our interpersonal dealings, but that ‘wild-west’ will not last long as nations institute new extra-national, proto-global agreements and protocols. A rational global system serving moral individuals in all tansitioning old-nations will not long tolerate short-sighted economic actors with the cherry picking instincts of natural predators.

    The public partner has a rightful role in research affecting all US persons and humanity in gerneral. As in the World War II economy, the public role should be involved in the ‘how to’ side of productivity, but should actively provide incentives and commercial protections for research clearly aligned with the public good in areas of public life that concern everyone equally. Development of much needed capacity for effective public partnership is, at least in part, one answer to the question, “Where are the jobs of the future for al thee high school and college graduates?” Protecting the environment, organizing the acquisition of integrated knowlege and skills in education, rationalizing public health, working in foreign relations and international institutions to better use the planet’s finite resources: these are necessary organizatonal tasks that are needed to make a harmonious, rather than an acrimonious “me-first”, public-private productive instrument capable of, and worthy of gaining general public support.

    When Mr. Way was asked by the moderator, Mr. Intagliata why the genome project parties believed they should do their engineering work on the human genome, instead of on some other less controversial plant or animal? Any genome would do, it turns out, because the problem is one of engineering, not basic biology; it’s a Lego problem. The answer was in words “worth a thousand pictures”, to coin a phrase: there would be no chance of getting private funding for anything other than the human genome. You’re not suffering from occular disfunction if what you see here is what is a tail wagging a dog.

  • Vimerr

    Laurie Zoloth’s ideas were very disappointing. We should not let religious leaders decide what projects make for good science!

  • David Sieving

    In a post Enlightenment world, the authority governing any project to build a human organism is a legal one, not a religious one. Churches have no legal authority to issue birth certificates and moreover no defensible authority whatsoever in deciding the ethical questions surrounding scientific activities. The only way to grant them such authority would necessarily violate the First Amendment. Religious authorities like any going concern by nature seek power. In scientific discussions, please don’t even think about letting them into the room or they’ll take whatever power you let them take because that’s what keeps their revenues flowing.