Interview. We spoke with author David Quammen about his new book about horizontal gene transfer, the little-understood evolutionary mechanism that relies on viruses; antibiotic resistance; and his new COVID-19 project.

David Quammen, after ‘Spillover’ and ‘Tangled Tree,’ is writing a book about COVID-19

During these months of lockdown, David Quammen, author of Spillover, has been the protagonist of many interviews from behind his computer screen at his workstation at home in Montana. This week, in Italy, his new book, The Tangled Tree, is being released by Adelphi. In the book, Quammen retraces the history of evolutionary science from Darwin to the recent studies of the last few decades and carries the reader into a world of discoveries about the genetics of all living beings that populate the Earth, including human beings. 

We spoke with Quammen about the implications of these discoveries, on the link between our genome and infections, both bacterial and viral, we analyzed other aspects of SARS-CoV-2, which causes the disease COVID-19 and explored how the tangled tree of life has redefined our understanding of human genetic identity.

So how are you? Are you tired of being interviewed all the time?

Well, no, it’s important and I’m grateful for the chance to spread the messages that are in Spillover. And now we’re talking about The Tangled Tree so that’s a change of pace, that’s good.

Definitely. In the book you talk about a process which is fundamental to understanding the evolution of all species, one that has been recently explored: horizontal gene transfer. Science has uncovered one of evolution’s biggest secrets, which is that genes don’t only move vertically, so from one generation to the next, but, as you say in the book, they move sideways across species boundaries. Can you tell us how you got to writing about this process?

So this process, horizontal gene transfer, most people have never heard of it, right? And even a lot of biologists had never heard of it. I write about biology all the time and I had never heard of it. And in 2013 after I had just published Spillover in the US, I was looking for my next book project and I happened to read something about horizontal gene transfer and I just thought: What? Horizontal gene transfer? Turns out it has been very important in the history of life and continues to be important for human life and for understanding human identity and human health. But it was so counterintuitive, so strange and so abstract. I couldn’t see how I could write a book about it that people would want to read. But then I came across a man, Carl Woese, who I now refer to as the most important biologist of the 20th century that you’ve never heard of, because most people still haven’t. He discovered a whole new method of looking at the history of evolution on earth, particularly the early history, and his method led to this field of drawing the tree of life using molecular evidence and that put horizontal gene transfer into perspective.

What is horizontal gene transfer and how does it happen?

As you’ve said, it’s the movement of genes, genetic material, sideways from one species into another, from one kingdom of life into another. Seems like it should be impossible. We’ve always been told that genetic material, heredity, moves vertically from parents to offspring, while this is going horizontally sideways across species boundaries. The simple explanation for how it happens is embodied in a term that scientists coined in the 1950s and that is “infective heredity.” 

So to understand horizontal gene transfer, the first thing to think about is infection; the fact that bacteria and viruses can carry genetic material with them when they infect another creature and they can drop that genetic material in the genome of another creature if they happen to infect the reproductive cells, like the STEM cells, in the testes or the ovaries that make eggs and sperm. It’s much more complicated than that, but that’s the first step toward understanding it. Infective heredity. 

A virus, for instance, can pick up genetic material in one kind of creature and then carry it and infect another kind of creature. And if the virus gets into the reproductive cells, it can drop that material there, new genes in the reproductive cells. And then it becomes heritable.

As you write in your book, 8% of our DNA comes from viral transmission. That is mind blowing. What are the implications of this?

You’re right, 8% of the human genome comes from what they call endogenous retroviruses, retroviruses that have infected humans and drop their DNA in the human genome and we know that in some cases it has been very beneficial and important to human evolution. In particular, the case that I described in the book, the most dramatic case, is a case of a gene that’s called syncytin2, responsible in humans for creating a membrane between the placenta and the fetus during human pregnancy. And without that membrane, a human pregnancy is impossible. It can’t be successful because that membrane between the placenta and the fetus is an intermediate layer that carries nutrients from the mother’s blood into the fetus to help the fetus develop and it carries waste products out to the placenta so that the mother can get rid of them in her urine. It’s very important for human pregnancy. 

This gene is a viral gene that comes from infection of mammals earlier on and that means the virus not only infects cells, but it copies itself into the genome of the cell that it infects. And if it infects stem cells of the reproductive system, it becomes heritable…If there hadn’t been a version of this early on, mammal evolution couldn’t even have begun. We would still be producing offspring by laying eggs on the ground because internal pregnancy would be impossible, right? And that’s because of viral infection and horizontal gene transfer.

There is a key word in your book: convergence. As you describe in the book, this concept of convergence has enabled us to see evolution not as a tree in the traditional sense, but as a tree redefined. What happened? How did we go from Darwin’s classical theory of evolution to HGTs?

So Darwin’s classical theory of the tree of life, as he drew it, is limbs and branches always diverging. Life comes from a single source. We thought for a long time that there were only two kingdoms of life, on one hand bacteria, single celled and simple cells, and on the other, everything else, animals, plants that have complex cells and cell nuclei, et cetera. Even the single graphic figure in Darwin’s Origin of the Species, when it was first published, was called the “diagram of divergence.” So it was all about divergence, over time, creating biological diversity. 

And then in the late 19th century, early 20th, a couple of really peculiar visionary scientists started suggesting that there were some cases of convergence, for instance, in the origin of the complex cells that we’re made of, including the chloroplasts in plants that allow them to photosynthesize and the mitochondria in all complex cells that allow us to package energy for complex processes. And that meant that there was a point of convergence when the bacteria line converged with the line of complex creatures. 

A brilliant American microbiologist named Lynn Margulis brought the idea of endosymbiosis — symbiosis, partnership; endo, inside. The idea was that we have partnerships with other forms of life that have gotten inside us, and they help ourselves be what we are. And that included the bacteria that inserted themselves into complex cells early in evolution and became the mitochondria in all of our cells, these little organelles that help package energy. 

And then with Carl Woese people started using a different kind of evidence, molecular phylogenetics, using genomes to compare one kind of life to another. And they tested her hypothesis and they found that it was correct… So now we realize that the tree of life is not all diverging limbs and branches, but some of those branches flow into another limb and that doesn’t happen with trees in the wild.

And that’s why the book title is The Tangled Tree.

Yes. The original title for five years, as I worked on the book, was: “The tree of life is not a tree.” And I use that phrase in the book “the tree of life is not a tree.” When I finally delivered the book, my editor at the publishing house here in the US said, “I love the book, but we need a new title. This title is a paradox.” And I said, “Yes, I know it’s a paradox. It’s supposed to be a paradox.” And they said, “No, readers are scared of paradoxes; let’s get another title.” So it became The Tangled Tree.

Virus mutation is also an issue you deal with in your book and we’ve been hearing a lot about SARS-CoV-2 mutation. Can you explain how virus mutation works? What are the consequences?

That’s a very important question. All viruses mutate as they replicate themselves. And that’s simply a matter of small “mistakes” that are made as the viral genome copies itself to create new viral particles — little mistakes in the alphabet of RNA, components that are symbolized by four letters and the four letters repeat themselves over and over in different combinations. And if the virus makes a mistake in copying one letter then that’s a mutation — tiny changes. 

Some viruses are RNA viruses, while some viruses are DNA viruses. Coronaviruses mutate relatively quickly because they are RNA viruses with only a single strand of RNA. The double-stranded DNA is more stable and copies itself more accurately, while single stranded RNA viruses are notoriously prone to mutation. And that’s one of the reasons why coronaviruses were at the top of the watch list of viruses that we should be concerned about. And I said that 10 years ago, in Spillover, influenza viruses, single stranded RNA, have a very, very adaptive high mutation rate, and coronaviruses are not as changeable as influenza viruses, but still very changeable. 

The fact that a virus is mutating, however, does not mean that viruses evolve in any particular direction. And the scientists, the ones that I trust, who are watching the SARS-CoV-2 genome and sampling it from different places, at different times, from different human cases, have said this virus is not evolving very much. The mutations in some cases are just a dead end, so viruses can mutate, but the mutated version might not be a successful version. 

Why is this virus mutating but not evolving very much, why would that be? Well, the answer is that a virus, like any other creature, evolves in response to challenges in an environment, to changes in an environment, in order to be more successful. This virus is already so successful it’s already adapted to the environment of the human body that it doesn’t need to change very much. And that’s the hypothesis as to why it hasn’t changed much. It’s because it’s already so successful.

The last time we spoke you told me about how some new studies are analyzing why bats are such an ideal host for coronaviruses and that’s because their immune system is toned down so that they are more accepting of the virus.

Yes, what they gained was the capacity to ignore the virus, their immune system learned to ignore the virus.

Do you think bat immunity to coronaviruses has anything to do with horizontal gene transfer at all?

I would like to believe that that’s true. That would be really interesting. And it would connect my two books together very nicely, Spillover and The Tangled Tree. But I haven’t seen evidence of that yet. The study of what’s going on with the evolution of the bat immune system is in its early days. As far as I’ve been able to see, no one yet has shown that these viruses, such as coronaviruses, transfer some of their DNA into the bat genome so that the bat then is less likely to tell its immune system to attack that virus. The hypothesis that you’re describing is an interesting hypothesis but I haven’t seen any evidence of that yet.

Do you know that any of the viruses that caused the most recent epidemic outbreaks are connected to horizontal gene transfer? Do they copy their genome into the host that they’re infecting?

HIV that causes AIDS does, but not into the genome, into the immune cells. So because HIV is a retrovirus it copies itself into the immune cells and then when the immune cells replicate, they replicate the viral genome as well as themselves. And this helps HIV to spread in a person’s body.

After reading your book I came across a study that said that horizontal gene transfer can facilitate new epidemics of bacteria. The study refers to antibiotic resistance in bacteria. Can you explain this process? Does it make us more vulnerable to epidemics?

Yes, antibiotic resistance in pathogenic bacteria. Bacteria have a process where they can trade sections of their genomes from one bacterial particle to another, one bacterium to another, even if those are bacteria of different species, so very, very different kinds of bacteria. This process is called conjugation. 

One of the three major mechanisms for horizontal gene transfer and, essentially, some people call it “bacterial sex” as a metaphor, but it’s not really sex. There is sort of a cord, like an umbilical cord that goes from one bacterial particle, to another, and then there is a little packet of DNA that goes squirting across into the second bacteria and then it becomes part of that second bacteria’s makeup. So we can acquire genes instantly that way. And one of the genetic capacities it can acquire is resistance to antibiotics. 

So that’s the reason why antibiotic resistance sweeps around the world so quickly. If one kind of bacteria slowly evolves a resistance by mutation and selection to a particular kind of antibiotic, say methicillin, then the descendants, the direct descendants of a dead bacterial type will have that resistance to methicillin. E-Coli, for example, can pass that resistance in an instant to salmonella, a different kind of bacteria, or to staphylococcus, another different kind of bacteria.

So according to the World Health Organization, resistance to antibiotics is one of the major threats to global health. Even though saying this in the middle of a pandemic is nearly a paradox…

Right, yes. No, but it really is a big issue and it’s not going away just because we’re worried with COVID-19 at the moment.

Are our antibiotics in danger of becoming obsolete?

Some scientists are saying that, yes, antibiotics are becoming obsolete because we can’t create new ones as fast as bacteria are acquiring resistance. Bacterial infections by antibiotic resistant bacteria are killing a lot of people already. Tens of thousands of people, and that’s only in the US. But if this trend continues and we can’t develop new antibiotics as fast as the bacteria are sharing their acquired resistance, then antibiotics will become obsolete. And we’ll have to find new ways of dealing with bacterial infections. I don’t know what those ways are going to be.

Are you writing a book about COVID-19?

Yes, I was busy on a book about cancer and evolution, which is a very interesting field. And I was in Tasmania all through February researching aspects of that book because Tasmania is an important part of that story, when all the COVID-19 stuff started. And then in March, my publisher, Simon and Schuster said, “David, would you please set aside cancer and evolution for now and do a book on COVID-19?” 

And my first reaction was thinking that there are going to be hundreds of books about COVID-19, and I like to write about things that other people are not writing about. But then I thought nobody’s thinking about anything but COVID-19 right now, and it’s a responsibility and I have a running start from having done Spillover. So I said, “OK, I’ll do a book on COVID-19 and I’ll try to write a book that’s different from the other books.” And [in Italy] Adelphi has already contracted to publish that book.

Can you tell us anything about the book? Without giving too much away.

I’m interested in a few things. I may have said this to you earlier, but I’m very interested to know what happened in Italy. Why Lombardy got hit so hard. I want to understand how South Korea and Singapore dealt very effectively with the virus at the beginning. I want to understand what happened in China. I want to understand why the US has done so poorly in controlling this, why we lead the world in cases and fatalities. 

I’m interested in the ultimate origins of the virus, a bat virus. Is it a bat virus that came through pangolins to humans? Pangolins, the most trafficked, illegally captured and marketed wild animal in the world, also carry a lot of coronaviruses. So I’m very interested in the origins and the evolution of the virus. And the questions that you asked me, you know, if this virus has a capacity to mutate so much, why is it not evolving? And finally, vaccines. The really interesting story is going to be which one, out of the hundreds they’re developing, works.

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