First Reproducing Artificial Virus Created

jrrl writes "USAToday is reporting that Craig Venter's research group has synthesized a virus from scratch and that it "became bioactive" (started reproducing). Particularly interesting is that it only took them two weeks to build, rather than several years that previous attempts had taken."

Re:Chilling

[Anonymous Coward]

Maybe.

It's funded by Dept of Energy,
One of the things they're hoping to do is produce improved versions of the bacteria which eat nuclear waste.

Not really new

[wes33]

More than a year ago live polio virus was constructed from component DNA. This is not a "artificial" virus but a working copy of phi X bacteriophage. Note that this is an infringement of God's copyrights and patents and trade secrets!

(from NY times, July 2002: Scientists construct virus from scratch for first time, synthesizing live polio virus from chemicals and publicly available genetic information; work was conducted by scientists at State University of New York at Stony Brook and financed by Defense Department as part of program to develop biowarfare) countermeasures ... )

Journal Science link, NOT life

[mfago]

The article starts out:
It is the stuff of science fiction and bioethical debates: The creation of artificial life.

A virus can reproduce, but does not consume energy -> they are not alive in a technical sense.

Also see this news from Science [sciencemag.org].

Incredibly cool.

Not the first time

[Brahmastra]

This story [bbc.co.uk] indicates that it was done more than a year ago.

"irreducibly complex"? not accordin to talk.origin

[Anonymous Coward]

Claim CB200.1:

Bacterial flagella and cilia are irreducibly complex, indicating that they must have been designed.

Source:

Behe, Michael, 1996. Darwin's Black Box, The Free Press, New York, pp. 59-73.

Response:

This is an example of argument from incredulity, because irreducible complexity can evolve naturally. Many of the proteins in the flagellum are similar to each other and/or to proteins for other functions. Their origins can easily be explained by a series of gene duplications, which obviates irreducible complexity's challenge to evolution.

One plausible path for the evolution of flagella goes through the following steps:

A secretory system evolved. The type III secretory system forms a structure identical to the rod and ring structure of the flagellum [Hueck, 1998].
A proto-flagellar filament arose as part of the protein secretion structure.
An ion pump with another function in the cell fortuitously became associated with the structure, giving it some mobility.
Further refinements make the flagellum more efficient for motility.

The flagellum is not irreducible. One third of the 497 amino acids of flagellin have been cut out without harming its function [Kuwajima, 1988]. Behe claims that 240 proteins are necessary for the flagellum to function, yet only 256 genes are necessary to produce an entire survivable bacterium [ref. in Ussery, 1998]. Different bacteria have different numbers of flagellar proteins (in Helicobacter pylori, for example, only 33 proteins are necessary to produce a working flagellum), so the particular example which Behe considers might be reducible [Ussery, 1998]. Behe himself suggests (pg. 72) that taking 40 of the 240 proteins out of a flagellum leaves a working cilium.

Eubacterial flagella, archebacterial flagella, cilia, and undulopodia use entirely different designs for the same function. That is to be expected if they evolved seperately, but it makes no sense if they were the work of the same designer.

Links:

Dunkelberg, Pete, 2003. Irreducible Complexity Demystified http://www.talkdesign.org/faqs/icdmyst/ICDmyst.htm l

Musgrave, Ian, 2000. Evolution of the Bacterial Flagella. http://www.health.adelaide.edu.au/Pharm/Musgrave/e ssays/flagella.htm

References:

Hueck, C.J., 1998. Type III Protein Secretion Systems in Bacterial Pathogens of Animals and Plants. Microbiol Mol Biol Rev 62: 379-433.
Kuwajima, G, 1988. Construction of a minimum-size functional flagellin of Escherichia coli. Journal of Bacteriology 170: 3305-3309.
Ussery, D. (see below)

Further Reading:

Ussery, David, 1998. A biochemist's response to "The biochemical challenge to evolution". Bios (July 1998). http://www.cbs.dtu.dk/staff/dave/Behe.html

--------------

Life?

[Izago909]

I thought the general agreement was that viruses aren't considered life because can't metabolize energy. A virus looks like a simple lego block compared to the complex architecture of a single bacterium.

Re:eesh

[B'Trey]

Horsefeathers. Matter is not the essence of a thing. Form and function usually (but not always) are. Transformation into another form may not destroy the mass but it most certainly destroys the thing that existed before.

What they did, why it is hard

[sam_handelman]

The human genome (which is DNA), contained in each of your cells, contains the instructions needed to make a cell (much like a computer program.)

However, in order to use these instructions to make a cell, you need a cell of the same kind to read them.

Analogy: You have a computer program that tells you how to manufacture computers but this doesn't do any good unless you already have a computer OF THE SAME KIND on which to execute it.

So, even if I assemble an entire human genome, I can't use it to make a person unless I already have a human cell. Kapish?

A VIRUS, which is what was made here, is NOT A CELL. It is a parasitic piece of DNA that hijacks an existing cell and contains the instructions to make viruses. The DNA that the virus contains is, in the best case, sufficient to hijack the cell all by itself, and convert the cell into a factory for making viruses. Viruses CANNOT make more viruses by themselves. The similarity to a computer virus, I assume, is obvious.

So, if you can make VIRAL DNA, this will be sufficient to make the virus, if you have cells that the virus can infect.

Even making the genome of a virus is very difficult. The "commercially available" DNA mentioned in the article is made chemically. DNA is made up of a chain of monomers; each monomer has a 5' end and a 3' end that can attach together to form a chain. In order to add monomer n+1 to a growing chain, this is what you do (description meant to be accessible to people who don't know a lot of chemistry): ...(Monomer n-1) 3' - 5' (Monomer n) 3'(BLOCKED)
-> **add reagent to unblock**
-> wash ...(Monomer n) 3'
-> add 5' (Monomer n) 3' {BLOCKED}
-> add reagent to attach 5' and 3' together ...(Monomer n) 3' - 5' (Monomer n+1) 3' {BLOCKED}
and repeat for Monomer n+2. Recursion is good.

Now, this is done in parallel in thousands of molecules of DNA (the 5' end of each molecule is fixed to a plate.)

Every time you add the reagent to remove the BLOCKS, it has a percentage chance, which can be very small, of failing.

So, for example, if, on one paritcular molecule, it fails at position 10, then instead of:
ACGTACGTACGT
you will get,
ACGTACGTAGT.

DNA that makes proteins has something called a "reading frame", consisting of codons which are three monomers long. If you shift the reading frame over by 1 monomer, it completely changes the meaning of the message.

So, a single nucleotide deletion, which I describe above, is disastrous - the synthetic DNA becomes useless.

Even if the chance of failing to remove a block is small - typically about 0.1% - if your DNA molecule is thousands of bases long, the chance of successfully adding every base to any individual molecule is slight.

Of course, you can make two different 100-base long molecules by the above technique and then ligate them together (recursion by splitting the task in half) which is, I believe, what's been done here. This has technical difficulties of it's own, of course, but with refinements it woud allow you to make useful DNA of length n*2^m instead of DNA of length n.

This is a frightening prospect because it would allow you to make ebola "from scratch", or just from the the string of letters that represent the genome (which is so short I could write it out by hand on a stack of cocktail napkins.) We're not to that point yet but it is a scary possibility.

Re:Ebola Anyone?

[Jeremy Erwin]

Ebola Zaire: 18959 base pairs
Ebola Reston: 18891 base pairs [nih.gov]

Marburg: 19112 base pairs [nih.gov]

Not the first, and is identical to a natural virus

[Noren]

The first reproducing artificial virus was the Polio virus [nature.com] by Wimmer and colleagues.

Ventner's new virus [nature.com] is artificial in the sense that it was created from chemicals- but it is identical to a known natural virus.

Venter's team cobbled together the virus, called phi-X174, following its published genetic sequence.

Viruses, not virii

[koreth]

This will probably get modded down as flamebait, but someone has to say it: the plural of "virus" [reference.com] is "viruses." It is not "virii" [reference.com] because that isn't an actual English word.

Re:duh.. I guess humans will do it themselves

[TheSync]

The challenge here is that you can't have a genetically-targetted race-killer, because race is a social concept and not really a genetic one. Besides the vagueness of race (such as "white" or "black" when both are full of incredible genetic differentiation), even "racial" phenotypes do not always stem from identical genotypes.

There are plenty of examples of people from different races who are closer genetically to each other than to many others of the same race.

Now an individual or family target, that is a different matter...

Re:Should we really be doing things like this?

[diersing]

Yesterday, NPR's All Things Considered did a nice piece on it, you can download it here [npr.org]

Re:Viruses, not virii

[xinot]

No, not flamebait. Just ignorance on your part. You misunderstand how the english language grows and expands. It's not like the French or German or Italian which have their own institutions to determine the specifics of the words that are allowed. With English we expand the vocabulary as it is used. See email. Or many other words. You may not like virii, but if enough people use it, it is a word.

Deal with it.

Re:Should we really be doing things like this?

[mAineAc]

I am sure they take great pains to be very careful these are bacteriophages they attack bacteria. Just think they can work towards creating a virus that is hungry for cancer cells. We may be seeing the first signs of creating viruses that will eat oil spills or something equally great.

Re:Scared now

[Anonymous Coward]

The whole bit of the immune system isn't that it needs to know exactly what it's fighting [although that helps] -- it just needs to know it's *different*.

Re:Viruses and weapons

[mesocyclone]

In the same light, the US has never created a weapon it has not used.

This is absolutely not true. The US created many chemical weapons which it did not use (I don't know if we used chem weapons in WW-I, but we enver used them since then).

The US has NEVER used biological weapons (even the recorded use of smallpox against Indians was done by the British before the American Revolution).

The US has never used a hydrogen bomb.

Re:Should we really be doing things like this?

[EvilTwinSkippy]

Probably the same as handling any other virus

No, actually.

Natural viruses live with the constraint that if they kill their hosts outright they can't spread and quickly die out. (Read "The Andromeda Strain" for a great book on the subject.)

And don't think that complexity in virual structure is required to make something lethal. Ebola is a VERY simply virus. So simple that it kills it's host in weeks by rupturing all of its cells from virus production. Fortunately, Ebola generally strikes in isolated regions of Africa where an infected person only has the potential to infect a few dozen people before the outbreak is contained.

If you recall the mouse-killing viruse from a few weeks ago was actually an accident. They were working on something that would sterilize the rodents. What they ended up with is something increadibly lethal.

A simple-self replicating virus that works in human cells could be the deadliest thing we ever produce.

Ho-hum. Big deal...

[praedor]

This isn't amazing at all. It isn't even wondrous or frightening. It is merely the synthesis of enough DNA, duplicated in sequence from an extant bacteriophage, to paste together into a full phage genome. So what? Chemical DNA synthesis (as opposed to enzymatic/biological) is old news and an everyday occurrance. If you wish (and have the money) you could order "oligos" (short stretches of DNA sequence) of ANY sequence and paste them together into an ever lengthening string.

I have pasted together 6 complementary pairs of DNA oligos, each 120 bases in length and designed to have "complementary" ends. First anneal the DNA together (Heat the single strand DNAs to ~95 C in a nice buffer, paired with their complement, and then cool to just below the melting temperature of the base-paired oligos for about 30 seconds to a minute). Next, you mix together the annealed oligo pairs and incubate at room temp (or 16 C for slower reaction) with the addition of ligase (enzyme that glues DNAs together, end-to-end) for about 1 hour (or 4hrs to overnight at 16 C). If properly designed, you end up (as I did) with a long DNA sequence made up of end-to-end glued-together DNAs. In my case, the DNA sequence encoded the gene for HIV integrase, the enzyme that HIV uses to insert itself into and infected individual's DNA. Totally synthetic. Big whup.

What would have been interesting? If I had designed oligos to encode a new protein or enzyme of my own design, unique in the world, that actually functioned at doing something. All I did was produce a copy of a DNA sequence that exists already in nature. You do the same thing when you PCR DNA, fer gawd's sake. The difference is PCR is much easier and faster (yet it requires the chemical synthesis of "artificial" DNA oligos for use as primers). Now extending what I just said to the Ventner virus (phage), he didn't do anything woundrous, he did something difficult and that's it. It is difficult (more a pain in the ass) to synthesis long oligos, anneal them, ligate/glue them together, and in enough volume, to have something to work with. In my personal case, the amount of artificial gene (I changed the way the gene encodes the amino acids that make up integrase so the actual DNA sequence was ~40% different from natural HIV integrase sequence) was miniscule after the above-mentioned process. So I made lots of it by doing a...PCR on it. Simple. The PCR takes a VERY few complete, full-length sequences and copies it into a LOT of copies. At 7500 basepair, this would also be very doable with the "artificial" phage genome. You make what turns out to be very few complete genomes in a mix of mishmash and use PCR to generate lots of the complete genome. Stock molecular biology.

Do you want to know what would have been REALLY newsworthy? If the phage produced was truly artificial. That is, if it was not merely an exact copy of an already extant phage but a new, never before existing phage. Truly "life" generated artificially. As it is, they just did a lot of common molecular biology to generate a short, complete genome for a phage and, low and behold, since it is identical to the natural phage, it reproduces. Expecting otherwise would be like thinking that somehow synthetic vitamin C is different than natural vitamin C (it isn't). The chemical bonds are identical, the actual molecules in it are not different in any way, etc. Same for this phage example.

I could do something simpler. I could cut and paste a bunch of HIV DNA sequences (different strains if you wish) together into a full-length HIV DNA genome, suspend it in a buffer with DMSO and have you apply it to the skin on the inner side of either arm. There is a good chance that this will result in you contracting an HIV infection. MAGIC! If I wanted to spend the time and money to generate all the DNA oligos needed, I could anneal and paste them together and generate an HIV genome (10,000 basepairs of DNA) identical to whatever strain I chose and it would be infectious. Big deal.