The Origins of Synthetic Life. - Rambling... (May/31/2010 )

In the beginning there was a man, and the man was Craig Venter. Through him all history would follow, without him nothing would be made. For Craig Venter had opened his wallet and his wallet poured forth USD 40 million into a DNA synthesizer. And from this machine, DNA strands were made, but the many DNA strands were short. And so Craig Venter and his team stitched the many fibres together until single a thread was spun. 1.08 million base pairs long and far thinner than a hair, he placed this thread with cytoplasm embed within an agar block. Then Craig Venter looked down upon this block and said ‘let there be life’. And there was life. And thus was born the AL, and all others who would follow..

Creation of a Bacterial Cell Controlled by a Chemically Synthesized. Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, Benders GA, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi ZQ, Segall-Shapiro TH, Calvey CH, Parmar PP, Hutchison CA 3rd, Smith HO, Venter JC. Science.1190719


But enough of pseudo religious paraphrasing…. Although it does tickle the imagination of a pastor citing a very long paper title, followed by 25 author names, journal name, edition number and page numbers.

We have witness history. A point in time that future generations will recognise as the beginning.

In my mind what Craig Venter has done for biology, is comparable to only one other event in science, the work of Friedrich Wöhler in chemistry.

In the early to mid 19th century, it was widely believed that while organic and inorganic compounds shared many of the same atoms, compounds derived from living origins were somehow different. Vitalism was the idea of the day and it was believed that organic chemicals required a vital spark, a soul, a touch of god for their creation. And it was this spark that was missing in chemicals derived from nonliving sources, separating the chemistry of the living from the non-living.

What Friedrich Wöhler did was to synthesis urea, an organic compound from ammonium cynate, an inorganic compound. And what he did for chemistry was to show that no such spark of divine energy was needed to create an organic compound. His synthetic urea showed that the line between chemicals derived from the living and nonliving was an imaginary one.

Still it took another 20 more years before the ideas of vitalism even contemplated the act of dying. Eminent contemporaries such as Louis Pasteur and Justus von Liebig refused to let go of vitalism. Nevertheless Wöhler got the ball rolling.

And laugh as one might, the ideas of vitalism was so strong that until today we have phrases like “organic compound” and “inorganic compound” and that the teaching of chemistry is arbitrary divided into organic chemistry and inorganic chemistry, even when there are many perfectly happy metalloorganic compounds.

And now we have Craig Venter and his manmade carbon copy of Mycoplasma mycoides.

Unlike Wöhler’s time, I believe the current scientific community is unhampered by the belief that there is something supernatural to life. Life is but a very large group of self replicating chemical reaction of eye catching complexity, working on iterations of simpler rules and reactions. It has had 3.4 billion years to reach the state we see today.

However Venter’s very public unveiling that a cell is nothing more and nothing less that a machine (which he could reprogram in totality), would have a great effect on the general public. Most people I feel would accept this new feat of mankind as similar although less spectacular as going to the moon, and leave at that. Most people have other more tangible concerns. Those like myself would probably be amaze how far we have come, but this feat only reinforces our understanding of the nature of life.

For those who are religious, I believe, like a slow moving tide, Craig Venter’s work and the work of others who will undoubtedly follow, will force them into a corner to examine their belief in the divinity of life. It is sticky theological question as it ask, ‘if only God could create life, what does that make Craig Venter?’ (God’ s understudy – as my labmate replied)

On grounds closer to earth, we have creationist who are every bit as staunch in their belief as the vitalist of old. It will take decades but eventually, as new discoveries, new inventions pile up and coupled with the birth of a new generation, the ideas of creationism would eventually fade. And religion retreats another step up the beach against the oncoming tide of science. I would predict that religion will then make another stand, claiming sentience is a product of the divine, until that challenge too is eventually answered.

(Notice that the 20 year it took vitalism to end, is about the same amount of time for the birth of a new generation and the death or retirement of the previous one.)

On another note if AL (Artificial life) ever did become intelligent, their book of creation stories, might just justifiably begin with “In the beginning there was a man, and the man was Craig Venter.” And how odd, yet truthful would that be

And then it was back (this thread, I mean...and the dragon too) ...hey perneseblue....nice to see you back here. When this news broke, I thought that there would be one happy dragon somewhere....I agree, it was pretty amazing but media hype aside, did he really create life, a bacterial cell? Because we'd be back to the age-old philosopher's dilemma of what life is....Nice to revisit the mechanistic/vitalistic debate that went on for years on end. Life reduced to the building blocks or the more modern view of function, processes and organisation?

And I guess what many people esp the philosophers are more interested in would be the ethics of creating artificial life? Cui bono? consider its potential for the greatest benefit to mankind as well as the greatest risk? And I guess he has all the patents for all these? Do we have the right to produce organisms that would exist independently in the future? Sorry I'm rambling too ...need to read that paper again....

I'm a pleased dragon.

To be more precise, all Craig Venter actually did was a highly efficient, PEG based, chemical transfection of a circular YAC into a Mycoplasma capricolum. But unlike any YAC, this YAC was a super size beasty, 1.08Mb in size and happened to encode the genome of a different species of mycoplasma, Mycoplasma mycoides. Which also mean that the YAC is self replicating. It also happened that this YAC was painfully synthesized from synthetic oligoes (as some of us have done with small genes)

Once the "YAC" got transformed into the cell, its genes started being expressed. And after selection, Venter managed to get the "YAC" isolated in its own pool of cytoplasm. And with the genes this YAC carried, the cytosol pool changed to the point where all its proteins were replaced with that of M. mycoides. And if you have a YAC encoding a M.mycoides genome sitting in cytosol containing M.mycoides protein, you have a M.mycodes cell.

I believe this a point for the mechanistic view of life.I do see parallels here with state chemistry nearly 200 year ago.


Did Craig Venter create life?

On one level he did not. Life requires a set up. And Venter did not create his cell from base chemical and first principles. He did not synthesizing the 250 proteins required to replicate a cell by chemical synthesis (which can be done at great cost), nor create any artificial bilayer bubble of phospholipids (which has also been done before). And he did not encase all these component, proteins, DNA, micromolecules in said membrane, creating what would have truly been an artificial cell.

On another level. Yes he did. He reprogram a cell's cytoplasm so completely that it became something else, a different organism in its own right. Only in science fiction.. do have incidence such as these. And what was is no longer.

As for the potential for the greatest benefit to mankind as well as the greatest risk?
I can't glimpse what the potential benefit might be, for the future is far away. But I believe them to be great. And what an optimistic belief it is.

As for the potential risk... well my supervisor and I spoke about Venter's cell. He had this to say. As a young man, in the days of the cold war, he work in bi0l0gical weapons development. And after 20 year, it became clear that the most horrible of bugs man could create was no match for what nature had already produced. (and this lead to different avenues... weaponisation/dispersion rather than creation)

We should take a moment to reflect on this. We live in an environment of a biological arms race that has been going on for the last 3.4 billion years. Every weakness is going to be exploited.

Now the legal stand point and moral stand point is interesting.
At this point in time, you can legally own an entire species, even an entire genus. Yes, just go look up the patent office and you will be amazed how many species are actually owned by so and so. So what can one say about an artificial species you made?

Although at this point in time, nobody has challenged the patent claims on these species. After all, who really cares for a species that is completely unknown, with no known use. And until somebody does and makes said challenge, we won't know for sure.

Quite a nice read, pernesebleu, thanks…I read the paper again (or at least tried to ) and in the end, I was actually gonna ask for a Artificial Life/Synthetic Biology for Idiots summary. One wrong base pair and it rendered the whole genome inactive, I guess this speaks of nature’s precision. Anyways, the debate would still continue if Venter indeed created life or produced a new life form. Even David Baltimore commented that "Venter overplayed the importance of his work, he didn’t create life, only mimicked it.” Well, for sure he didn’t create from scratch and this organism is not really new but still found in nature….perhaps just a matter of semantics, in the end?

Correct me if I’m wrong (bowing to your superior knowledge here) but what would be the major difference here is that in nature, the organism is neither good nor bad, knows no right nor wrong…and yup, will always struggle or adapt for survival and propagation but a synthetic organism will do what it is programmed/designed for in the first place and if it’s for nefarious purposes, it's what's giving some people sleepless nights. Is this another expression of our obsession to control nature and the environment?

Or what could maybe be more worrisome is that this organism might do something unexpected. When released in the environment…to mop up excess CO2 or clean up oil spills, etc. can we really predict what it's gonna do or what it will end up being? So aside from the ethical aspects , some philosophers are bringing up the ontological question…what is it? Can we really “know” it? If we can create it, does that mean we can understand it? Do we know enough about biology that we'd start manipulating genomes so we can produce organisms which will cough up drugs, vaccines, diamonds? And if we don’t consider these questions now, then it would be a clear oversight or short-sightedness on our part.

And this is probably a very bum analogy….but I’d like to whine about this anyhow….BP has all the technology to extract humongous volumes of oil from the deep…a rig goes down, and already more than a month has passed and they can not fix this catastrophe…just spread blame all around….if one of these bugs escape, will there be enough guards in place, proper regulations etc to prevent a disaster, but yup, probably a bum analogy…

But it isn’t only this organism that he’s gonna want to own the rights for, for sure he would patent (or probably already did) the technology or isn’t it novel at all? Is it the same one done for the polio virus earlier? He wouldn’t invest 40 million of his own money and for what? To feed his vanity, just to prove that he could do it….well, actually, this is the guy who challenged the human genome project to sequencing race so who knows? These patenting issues are the sticky points- science for commercial gain. The ETC Group based here in Canada, and others, claims this is an unfair attempt by Ventor’s group to dominate synthetic life....how did they put it- Venter would end up having "Microbesoft" monopoly which doesn't seem right.

casandra on Jun 1 2010, 07:20 PM said:

I believe we are approaching the area of fussy greyness.

Imagine for a moment that Venter had taken genes from various organisms and put them together to form a functional genome for his organism. On one hand, you could say he had created a new species. For no organism had previously existed containing that combination of genes. On the other hand you could easily argue that Venter is merely copying nature. Nature had already perfect the proteins which these genes encode and Venter was merely using them. Venter has no more created life than one becomes a fashion designer by picking clothes out form a supermarket.

Personally I think Venter has created synthetic life. But he has not done so in a controlled and rational manner. He is missing one last step to truly claim to have created artificial life. And that last step in my mind is the production of a functional synthetic genome where the presence of every DNA sequence and gene is there because you know its function and that it is required.

Venter's organism is a human-made carbon copy. It is a synthetic organism, but it is the way a glider is to an airplane. It has master some of the rules but not enough for controlled and sustained flight.

Human love controlling nature.. i think it is in our nature (See our best friend the dog... which is rather close to my hypothetical happy slave species as we currently have). Personally I think the near extinction of our species some 80,000 year ago strongly selected for individuals who where driven to control their surroundings.

We only need to look at computers. We created them and we know everything that goes into them. And without human intention (programming) all they do is sit. Yet their effect, a one way, human to machine relationship has been enormous, far greater than people in the 1960s would have imagined. So for any disruptive technology, we are unlikely to be able to predict their effects.. good or ill

You have a point. But at the same time, I believe our only real option is to confront the the problem head on. And by "head on" it will be by trial and error. The prize that is real genetic engineering is too great to be ignored.... and too deep to completely puzzle out simply by looking at its potential from the outside.

As for oversight,... such a great prize means that the field will be difficult if not impossible to regulate completely. Once the field begins to reach maturity, I can imagine that many governments would be all too happy to play with the more dangerous aspect in the name of national security. We will be like any other engineers. Some engineers build roads others build cluster bombs and megaton nuclear warheads. At most we can appeal for the community to follow a few set of rules and ethical guides.

Undoubtedly this action of exploring the potential of genetic engineering (for good or ill) will cost humanity greatly. And even with foresight it doesn't stop people from acting dumb.

So why do it? I liken genetic engineering (or any great and disruptive human advancement) to an imaginary scene where fire was first discovered by two cave men (or cave women). Upon seeing the blaze, the immediate application of the new discovery was obvious to the two cavemen. It could keep people warm and scare animals away. At the same time its immediate dangers were obvious, it could injure a man so greatly as to be fatal. It could go out of control and set the camp ablaze. So should they adopt this new discovery? And what if the cave men were to somehow be informed that fire would lead to other development which would bring about more deaths and woe than any lion or tiger could.

How should they decide? And their answer is our answer.

You do have a point. But I have to play the devil's advocate here. If Venter had not done what he did, it would be be years if not a decade for another group to achieve what his group did. He did risk $40 million chasing a dream. Should he not be rewarded for such a risk. It could all have been a big waste of money and time. And few people would have been surprised if Venter had failed. Most team had gone another way, leaving them with the problem of inactivating the host genome which had been full integrated with the new genome. A problem that after half a decade has not been solved.

The ability to manipulate YAC within the >500kb is rare. Not impossible but very few people ever bother to optimize the protocol to manipulate these giants. The protocol as you can see can now reach 1Mb.

So, yes, Venter deserves the patents and any money he can make from his work. It is the capitalist system after all. Yet it doesn't "feel" right. But then again we don't grumble about oil oligopolies or pharma cartels, or monopoly of nuclear technology by selected nations. (who are only trustworthy because it is our own nations)

perneseblue on Jun 5 2010, 02:08 AM said:

Fussy? A spelling error but an apt one..…a man claims to have created a bacteria cell solely controlled by an artificial genome thus blurring the boundaries between life and non-life, nature and artefact, the evolved and the designed…so I guess folks are allowed to be fussy about it, starting with the fundamental definition of life. Where before, we only had In-Vivo and In-Vitro, now, we’ve got In-Venter (ETC’s le mot nouveau).

"WHAT I CANNOT BUILD, I CANNOT UNDERSTAND." - Richard Feynman's dictum..…cleverly encoded in one of the watermarks (?) of the artificial genome. And your perspective is the classic, mechanistic reductionist approach of SB, the DNA-centric view of life. But isn’t a living cell a complex system and the power which drive cellular events is shared equally by the cell membranes, the cytoplasmic organelles and the genome?

Ah, but there’s the rub and is nit-picked by some disputing his claims….if he has indeed created a live cell, he shld’ve started with the cell itself not merely synthesising the genome and inserting it into a live recipient cell (although the construction of a long functional DNA and the subsequent booting up of a cell is acknowledged as a technological feat). So some had liken what he did to changing the transmission of a car but not that of building the car itself. Or as geneticist Steve Jones (voicing out his scepticism) has commented this in the Guardian. “What he has done in genetic terms would be analogous to taking an Apple Mac programme and making it work on a PC — and then saying you have created a computer. It’s not trivial, but it is utterly absurd the claims that are being made about it.”

Gibson, the primary author of the study said the same thing (sorry if I’m mangling this) i.e., that any technology is dual purpose but in the case of these synthetic organisms, for every linear increase in its ability to do harm, there’s a logarithmic increase to do good and he’s probably right. These bugs have the potential to solve urgent problems of energy and climate change, they can be platforms for new drugs, vaccines etc. and compared with its ability to do evil which is mainly bioterrorism, we’d suppose that the benefits far outweigh the risks. But perhaps we shld also add another factor to this cost analysis and compare which is easier to do (technically i.e.): design a bioweapon or a biofuel? Perhaps by the time we have produced one beneficial organism, the evildoers have already produced 10…but that’s probably the stuff of sci fi dystopias…

Confront it head-on and with Venter the bio-entrepenuer leading the assault? The guy who sequenced his own genome, named the institute after himself, with the goal of creating a trillion-dollar organism and who joked that from gene king, he wants to be the oil king.…. he’s the one who’s gonna hand us this prize? ETC calls this hubris and a slew of ad homs from others. If this breakthrough with all that media blitz is perceived not only as scientists playing God or producing franskenstein monsters but more as a profit-driven venture, can we blame the public for being wary? Shouldn’t we advocate the Precautionary Principle here?

And acting as the ETC advocate here ….check this out : men and money behind Synthia

And to add their two cents :

Because the science can be privatized and monopolized it becomes more attractive to companies seeking profit rather than addressing social needs.

The synthetic biology community has also ignored blatant conflicts of interest - most of the scientific leaders in synthetic biology have established their own synthetic biology start-ups. Synthetic biology must not be governed by those seeking to profit from it.

Would you then favour self-governance or strict regulation (governmental etc) right now?

I like this analogy but it’s not a fair one, IMHO. The cave people had very basic survival needs. I wonder if they had even imagined travelling to the moon or dropping a nuclear bomb or procreating without the act of procreation. But modern men with his modern needs, challenges and ambitions would have a different answer.

really rambling ....

I missed this discussion but somehow I did start to read a part of it because of the venter boat thingie...

And I wanted to ask you something about this:

One of the biggest goals in science this day is the creation of a cell from scratch...


You mention that it can be done at great cost, but is this really true? Do you mean maybe we can indeed replicate those 250 proteints , but dont manage (yet) to let them work together? Or?
Do you think we have the knowledge and techology allready to do this?
If so: who arent we doing it? It cant be because of the money?

What he did is big, but still "not that big" in the end.. he replaced something (living, allready there) by something else (artificial, created from scratch in the lab).
This might sound weird (and I am not saying its no big deal what he did, its a big deal) but when you explain what he did to small children they notice or make the following remark: Oh, he just replaced what was in the cell by something he made and the cell stayed alive... its a bit like putting a "plastic" bone in your arm when you lost your real arm.. so why is that special?
Or another child said: "hey, but you told us that you can make DNA before, so why is this so special, its just more DNA ?"


(I use the above sentence since this was a remark a child made during a "lecture" on microbiology for kids where venters creation was explained.. And the funny part was the the professors giving the lectures received a lot o "weird" questions, very simple ones, that made them think harder then ever...)


I know I oversimplify it, but its an easy way to make my point.



BTW: I noticed that a majority of peope still think/believe that venter created an entire cell from scratch.. Even in the news they mentioned it like : "venter created a cell, life" ....

Thanks Pito for bringing this to conversation to light (or did I mean Life ? ).

I really like the Fire analogy. For the future, we are cavemen. Not only this, but all technology has to be treated like a double edged sword. Net banking was not developed, so that some creep could steal away someone's life savings. "With great power, come great responsibilities" (Spiderman et al.,2002). How to utilise this technology, is for us to decide.

So what, if Venter wants to use this technology to make 40 billion dollars, we have not even used 10% of what he put on the internet 10 years ago. If economic profits drive today's science, let it drive. After a few years, these discoveries can have worldwide applications. Isn't that what we are aiming for? Its better late than Never.

gt_ameya on Fri Apr 8 07:12:48 2011 said:

but you forgot to thank me for bringing up that Venter boat thingie, Ameya....perhaps it's time to start a new thread here:

Should economic profits drive today's science?

casandra on Fri Apr 8 16:11:19 2011 said:

Hey Casandra, I dint see the post that directed Pito here... so NO credit given to you.

Science today is being driven, largely from funds coming from Big pharma companies.
People are aware of what drug development involves and all this does cost a lot of money.


Often, govt aided projects are slow and inefficient. Although, profit driven, privately funded projects are much more efficient. Venter's work is a global example. So, if it takes money to drive people at full efficiency, then let money drive this vehicle. The role of the governmental offices should be limited to providing vision and granting approvals. Rest all should be delegated.