Wednesday, December 05, 2007

'Darwin's Surprise'-- ERVs

Thank you to the ERV reader from Drake that forwarded me this article from The New Yorker:
Darwin's Surprise--Why are evolutionary biologists bringing back extinct deadly viruses?

I like this article. I swear. It starts out with a **rolleyes**, and sometimes he gets a bit alarmist or messes up a bit of the science, but the ending is just fantastic, so all errors are forgiven (after I correct a few, hehe!)

First, the **rolleyes**. He ruined a perfectly good introduction on retroviruses and endogenous retroviruses by using the cursed words:

Because they no longer seem to serve a purpose or cause harm, these remnants have often been referred to as “junk DNA.”

He redeems himself by stating that ERVs are not functional, but I would like to add to that-- the fact we have no functional ERVs is interesting in and of itself. Other mammals do, so why not us?

Im also a little annoyed at the author, as well as the scientists he interviewed, perpetuated the pop-culture myth that we 'brought an extinct virus back to life!' As I discussed earlier this year, they arent bringing 'a virus' back to life. They took all the similar ERV genes they could find, made a consensus sequence, and tried to make a functional virus. Its a Frankenstein virus, not a zombie virus :P And Ive read the papers... while this is certainly cool, the virus they constructed isnt exactly 'robust.' It hobbles along, even with the addition of genes from functional viruses (they added those in hopes it would help their lame virus run a bit faster, at least fast enough to do functional experiments on).

Im also annoyed with the idea that bringing these viruses 'back to life' might harm society. First of all, retroviruses are wusses. Polio? He can hang out in dirt, happy as a clam. But HIV in that same scenario would die at the thought of being outside in sewage. Retroviruses are wusses outside of their territory. It would take a series of mistakes and improbable events for a Frankenstein retrovirus to leave a laboratory, many many many more to cause any harm. But one of the researchers interviewed tried to stress an important point:
“I understand that the idea of bringing something dead back to life is fundamentally frightening,” he went on. “It’s a power that science has come to possess and it makes us queasy, and it should. But there are many viruses that are more dangerous than these—more infectious, far riskier to work with, and less potentially useful.’’
Frankenstein viruses have an obvious place in research-- study retroviruses we naturally conquered to figure out how to stop new ones (HIV-1). Did we evolve new restriction factors? Did we lose a receptor? What happened?

Then the author starts conflating viruses a bit. He hops from retroviruses (wussy, little risk in 'resurrection') to 'building' polio. That is unfair. As I said, polio is not a baby. It is easily spread, and humans did not evolve resistance to polio 'naturally' (ie there is no cellular restriction factor that shuts down polio). We just immunized people to put out its flame so it is no longer a threat. If a homemade polio gets out of the lab, I agree, that is trouble. But confounding helpful and safe (not just harmless, helpful and safe) resurrection with obviously harmful resurrection I find offensive. Im a mad scientist. Not an idiot.

However, the last few paragraphs of that article are just brilliant-- especially for an article directed towards non-biology readers. Love it. LUV! Some highlights:
In 1968, Robin Weiss, who is now a professor of viral oncology at University College London, found endogenous retroviruses in the embryos of healthy chickens. When he suggested that they were not only benign but might actually perform a critical function in placental development, molecular biologists laughed. “When I first submitted my results on a novel ‘endogenous’ envelope, suggesting the existence of an integrated retrovirus in normal embryo cells, the manuscript was roundly rejected,’’ Weiss wrote last year in the journal Retrovirology. “One reviewer pronounced that my interpretation was impossible.’’ Weiss, who is responsible for much of the basic knowledge about how the AIDS virus interacts with the human immune system, was not deterred. He was eager to learn whether the chicken retroviruses he had seen were recently acquired infections or inheritances that had been passed down through the centuries. He moved to the Pahang jungle of Malaysia and began living with a group of Orang Asli tribesmen. Red jungle fowl, an ancestor species of chickens, were plentiful there, and the tribe was skilled at trapping them. After collecting and testing both eggs and blood samples, Weiss was able to identify versions of the same viruses. Similar tests were soon carried out on other animals. The discovery helped mark the beginning of a new approach to biology. “If Charles Darwin reappeared today, he might be surprised to learn that humans are descended from viruses as well as from apes,” Weiss wrote.


Then, in the nineteen-sixties, Howard Temin, a virologist at the University of Wisconsin, began to question the “central dogma” of molecular biology, which stated that genetic instructions moved in a single direction, from the basic blueprints contained within our DNA to RNA, which translates those blueprints and uses them to build proteins. He suggested that the process could essentially run in the other direction: an RNA tumor virus could give rise to a DNA copy, which would then insert itself into the genetic material of a cell. Temin’s theory was dismissed, like most fundamental departures from conventional wisdom. But he never wavered. Finally, in 1970, he and David Baltimore, who was working in a separate lab, at the Massachusetts Institute of Technology, simultaneously discovered reverse transcriptase, the special enzyme that can do exactly what Temin predicted: make DNA from RNA.
Not once, but TWICE, virologists made a prediction, challenged a dogma, were laughed at, and used SCIENCE to figure out who/what was right.

No PR campaigns.

No church/state issues.

Just science.

Take notes, Discovery Institute.

...nothing provides more convincing evidence for the “theory” of evolution than the viruses contained within our DNA.
Yup! Thats what I say!

Darwin’s theory makes sense, though, only if humans share most of those viral fragments with relatives like chimpanzees and monkeys. And we do, in thousands of places throughout our genome. If that were a coincidence, humans and chimpanzees would have had to endure an incalculable number of identical viral infections in the course of millions of years, and then, somehow, those infections would have had to end up in exactly the same place within each genome. The rungs of the ladder of human DNA consist of three billion pairs of nucleotides spread across forty-six chromosomes. The sequences of those nucleotides determine how each person differs from another, and from all other living things. The only way that humans, in thousands of seemingly random locations, could possess the exact retroviral DNA found in another species is by inheriting it from a common ancestor.

OMG, the whole second half of that article is orgasmic. I will probably come back to it later to hit on some of the cool stuff the author hits on (though long-time ERV readers will recognize a lot of it already!).

Thank you, reader from Drake!!


Art said...

Thank you for that article, Abbie. That is such a cool concept to think about! I agree with you, the errors are forgivable (and correctable), with such a wham-bam conclusion.

-- HalfMooner

alloy said...

It's really such an easy concept, not difficult to understand in general terms.

Which is probably why blanket (head in the sand) denial becomes the standard response.

CAE said...

That is actually one of the best popular articles on ERVs I've ever seen!

Albatrossity said...

Yeah, I was reading that article (the tree-based version, with the good cartoons) before hitting the sack last night and I wondered if you knew about it. I guess I didn't need to wonder.

Michael Specter has written some other good articles for the New Yorker. Check out this one on another evil intersection of science, sex, and conservative Republican dumbassery, the HPV vaccine and the ramifications of the conservative backlash against it.

Brett said...

Cool article. Honestly, I had never heard of ERVs before I was shown your blog.

Iron Soul said...

ERVs are fascinating. If I'd learned about them a few years earlier I might have been a biologist.

Anonymous said...

Abbie, I am sure you must have already seen this

Any reason why you dont print it out, put it in a nice hard bound binder and bludgeon creationists with it?

Tyler DiPietro said...

"Its a Frankenstein virus, not a zombie virus :P"

I would fancy a Terminator virus, but it appears nature has a perfectly easy time concocting those herself.

Torbjörn Larsson said...

Then, in the nineteen-sixties, Howard Temin, a virologist at the University of Wisconsin, began to question the “central dogma” of molecular biology, which stated that genetic instructions moved in a single direction, from the basic blueprints contained within our DNA to RNA, which translates those blueprints and uses them to build proteins. He suggested that the process could essentially run in the other direction: an RNA tumor virus could give rise to a DNA copy, which would then insert itself into the genetic material of a cell.

Ooh, Larry Moran will be so pissed that the article used Watson's later (per)version of the Central Dogma instead of Crick's own formulation:

In order to answer these questions we need to understand what the Central Dogma actually means. It was first proposed by Francis Crick in a talk given in 1957 and published in1958 (Crick, 1958). In the original paper he described all possible directions of information flow between DNA, RNA, and protein. Crick concluded that once information was transferred from nucleic acid (DNA or RNA) to protein it could not flow back to nucleic acids. In other words, the final step in the flow of information from nucleic acids to proteins is irreversible.

Crick restated the Central Dogma of Molecular Biology in a famous paper published in 1970 at a time when the premature slaying of the Central Dogma by reverse transcriptase was being announced (Crick, 1970). According to Crick, the correct, concise version of the Central Dogma is ...

... once (sequential) information has passed into protein it cannot get out again (F.H.C. Crick, 1958)

Seems from Moran's figures that Crick 1958 described Temin's and Baltimore's results as "permitted".

Torbjörn Larsson said...
This comment has been removed by the author.
Torbjörn Larsson said...

Yay! Wikipedia gets it right. (I became unsure of "Crick's own formulation", but there it is.)

Let me also add that observations of a principle of irreversibility (and, I assume, its ties to Darwinian as opposed to Lamarckian evolution) tickles my physicist fancy more than biological practical descriptions of transcription and translation. Okay, not so practical in the lab, but cool.

Philanthropologist said...

I agree with you that this is a good article but it is written by a reporter so there are some mistakes. You mention that there are no known functional ERVs in the human genome. There is one, the gene syncytin is believed to be a captive retroviral protein that aids in coding for syncytiotrophoblasts (now that is a word)involved in placental formation. The ERV belongs to the HERV-W family. Here is a link to the Nature article in Pubmed Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis