How Viruses Made Us Human
Living dead viruses - placentas - coding viruses
It’s (not) alive!
Take an empty pill capsule. A tiny one. No, tinier than that. That's good. Now, fill it with DNA or RNA, your choice. Finally, close the capsule and cover it in wax.
Congratulations, you built a virus.
All known viruses have two essential components: a capsid (a capsule made of proteins) and genetic material (there are both DNA and RNA viruses). Many have a third component called an envelope, which is a lipid layer around the capsule.
That’s it. That’s all you need to build a virus.
Unless and until it comes near a host cell, carried by the wind or a sneeze or bodily fluid, a virus doesn’t move of its own accord, doesn’t breathe, and doesn’t have a metabolism. It’s inert.
Is it alive? There is no consensus answer, even though we often talk about ‘killing’ viruses. Some researchers consider viruses to skirt the edge of life. Other scientists and philosophers remind us that we don’t have a solid definition of what counts as life and that viruses are best seen as biological replicators. Another proposal is that the unit of life that ‘counts’ is the virocell, or (virus+infected cell)1.
Viruses carry genetic material, accrue mutations, and are subject to selection. They reproduce.
Viruses don’t have a metabolism, don’t have the basic cellular structure all (other?) life has, and while they reproduce, they don’t do so through cell division but they assemble copies by hijacking the host cell’s production tools.
Regardless of whether they’re alive or not, viruses are incredibly successful. Every (other?) life form, from archaea and bacteria to plants and animals can get infected by at least some viruses. Viruses are found in almost all ecosystems2 and have probably been around since the dawn of life, before the split of life’s roots into domains.
Viruses even hide in our genome.
Meet HERV.
Meet HERV, or hey babe, how’s your placenta?
Some viruses, especially those in the family Retroviridae, have a neat trick. Within their capsule, besides the genetic material (often RNA), they carry two extra tools: reverse transcriptase and integrase.
When they inject the content of their capsule into a host cell to infect it, the reverse transcriptase starts scavenging DNA letters from inside the cell to turn the viral RNA into DNA. The integrase then integrates this newly produced viral DNA into the host cell’s genome. HIV is an example of a virus that uses this trick.
The host cell then goes about its business and runs through the usual DNA → RNA → protein production line. Only, the products include virus proteins now.
Retroviruses slide into our genomic DMs. This is where it gets delightfully weird.
Sometimes, the integrated viral DNA sticks around3 and gets passed on to the next generation. When that happens, we talk about endogenous retroviruses or ERVs. In humans, this becomes HERV — human endogenous retrovirus. And we host a lot of HERVs — about 8% of the human genome (compared to ~2% of non-viral protein-coding sequences).
Are those HERVs simply lazy bums lounging on our genomic couch? Quite the opposite. Evolution tinkers and humans are not exempt from evolution4. If HERVs are evolutionary remnants of a long-lost infection, natural selection might put them to use (an exaptation in biology jargon). That co-option of HERVs turned out to be very important for mammals in general and humans in particular.
Syncytin genes are remains of ancient viral infections, tens of millions of years ago. They were involved in building the envelope of invading viruses. Since then, however, around 60 million years ago, those syncytin HERVs were ‘domesticated’. Without syncytin-1 and syncytin-2, mammals would not be able to grow a complex placenta5. And only a few weeks ago, scientists learned that other retroviruses are involved in ramping up blood production during human pregnancy to make sure the growing fetus gets what it needs.
Complex live births, including human ones, are (probably) only possible thanks to ancient viral infections.
Sometimes, HERVs can be jerks, though.
With larger genetic databases and better analysis techniques, scientists have found HERV signatures for schizophrenia, bipolar disorder, and major depressive disorder. Changes in HERV activation can be linked to neurodegeneration, inflammation, and cancer development. And, like genomic vampires that suck us dry, some HERVs that are activated during aging speed up senescence.
Coda: Virtual, viral, and breaking walls
HERVs break the wall between virus and host.
Viruses themselves may soon break the wall between the physical and the virtual.
We already use ‘viral’ and ‘virus’ to talk about virtual phenomena. When a post, video, or essay suddenly replicates exponentially across your social media platform of choice, it goes viral. It invades host feeds and uses the host’s engagement (people comment, share, or write a response essay6) to virtually sneeze itself into others’ faces. Similarly, intentionally malicious computer viruses slip past the host’s immune system (firewall, antivirus), infect a cell (computer), and use its resources (computing power, private data) for the ends of their owners.
Of course, metaphors and analogies can only take us so far, even if they can play an important role in science when used judiciously. If you’ve ever extracted genetic material from a kiwi or tomato in science class, you’ll have seen the test tube booger that is DNA. A computer virus lacks that physicality. A flicker of electrons, maybe. Computer viruses can’t infect living organisms7.
Yet.
A computer virus is written in code. DNA is written in… code. Uh oh. For protein-coding DNA, every three ‘letters’ are known as a codon. Each codon codes for an amino acid. A string of amino acids makes a protein. In essence, DNA encodes the data required to grow a functional organism. DNA stores data and it might help us with the hungry demand for cheap and resilient data storage. DNA has a storage density better than any other storage medium so far and can be kept for millennia at room temperature.
The limiting factor (for now) is that reading and writing DNA is still comparatively slow. Especially the writing part, DNA synthesis, is in its early stages and the longer a DNA sequence gets, the more we struggle with writing it. Researchers are working on it, though. In 2019, a startup wrote the whole of Wikipedia into a little blob of DNA.
Here’s the scary part: you don’t need the entirety of Wikipedia to write a virus. Already in 2017, scientists hacked a computer with… DNA! The researchers,
… encoded malicious software in a short stretch of DNA they purchased online. They then used it to gain “full control” over a computer that tried to process the genetic data after it was read by a DNA sequencing machine.
That’s a computer virus written in DNA. Physical? Virtual? Both?
Let me finish with a science fiction scenario that isn’t far-fetched at all.
Small, affordable DNA printers are being developed as we speak. J. Craig Venter, one of the big names behind the Human Genome Project, already sees their potential for space exploration. But we don’t need to go that far. mRNA printers might soon bring vaccines to regions outside of the privileged rich countries that stockpile them for themselves. Viral genomes are relatively simple and hacking a DNA/mRNA printer is not without precedent.
I’ll let you finish the thought…
I promise this post did not contain a virus. But would it be ironic if I wanted it to go viral?
There are about 10 million viruses in a milliliter of seawater. Want to go for a swim?
Several options here: Maybe the viral DNA is close to an important host sequence and removing it is worse than keeping it, especially if it’s a mild virus; maybe it confers an unexpected advantage; maybe the host develops tolerance; maybe mutations alter or disable the function of the viral DNA, etc.
Despite what some people in the media might claim, human evolution has not ‘stopped’. Not even close. Technology, culture, and healthcare do not stop human evolution; they redistribute selection pressures.
More specifically, syncytin-1 helps build the placental barrier. Even more specifically, for extra bonus points and virtual cookies, the layer of the placenta that invades the uterine wall is the ‘syncytiotrophoblast‘, which is technically one giant cell(!) with multiple nuclei that can grow up to 13cm long. This syncytiotrophoblast is essential for allowing nutrient transport to, and waste removal from, the growing fetus. Syncytin-2 is unique to primates and is involved in the implantation of the embryo into the womb.
Popular strategy on Substack…
There are, of course, other ways in which computer viruses might be physically lethal. Screwing up emergence responses, bringing down planes… Or, as in Daniel Suarez’s 2006 novel Daemon, by taking over companies, self-driving cars, etc. to bring about its creator’s vision.
Been distracted, so I’m late to the party on this one. But this is so totally fascinating! Excellent read, Gunnar.
Excellent piece of writing. I will read it many times. x