The last ten days have been hectic for those in the genetic engineering field. Synthetic life has been created, scream the headlines, and well, it is no hoax.
The man at the center of it all, Craig Venter, is no stranger to those in this field, having been associated earlier with mapping the human gene.
Such a breathtaking announcement is not just of academic interest to us at Oilgae, because Venter has reportedly mentioned that the first real-world use to which he plans to try his synthetic life creation technique will be in – hold your breath – algae fuels.
Exxon Mobil entered into a partnership with Craig Venter’s Synthetic Genomics (SGI) in mid 2009 in order to explore applying SGI expertise in genetic engineering to create algae that can produce biofuels on a large scale, in an economically sustainable manner.
While ExxonMobil brings in the engineering expertise and tons of money, SGI brings in the genetic engineering knowledge. Exxon Mobil had committed to invest over $600 million in this effort to make sustainable algae fuels a reality.
Now you can well understand why all of us here at algae have been burning our midnight oil last one week over Craig Venter’s work. Well, we have been following Craig Venter since the time Exxon Mobil invested in his company, but his recent achievement added an extra level of importance to his work for all of us at Oilgae.
I hence thought that I’d dedicate this issue of the newsletter to providing inputs and perspectives on Craig Venter’s work and how it could shape algae fuel research.
The following are the sections in this detailed article:
· Background of Craig Venter and his recently breakthrough.
· Critical challenges in algae fuels
· How genetic engineering could help overcome these challenges
Craig Venter – Background and Recent Breakthrough
John Craig Venter is an American biologist and entrepreneur, most well-known until last week for his role in being the (joint) first to sequence the human genome. Two weeks back, he became equally famous for pioneering the creation of the first cell with a synthetic genome.
Venter has been a founder of companies/organizations such as Celera Genomics, The Institute for Genomic Research, the J. Craig Venter Institute and Synthetic Genomics. He was listed on Time magazine's 2007 and 2008 Time 100 list of the most influential people in the world.
His work on human genome
While working on the project to map the human genome, Craig Venter believed that shotgun sequencing (rather than a classical long-winded approach) was the fastest and most effective way to get useful human genome data. The method was controversial since some geneticists felt it would not be accurate enough for a genome as complicated as the human.
With funding from the private sector, Venter founded Celera Genomics, whose goal was to sequence the entire human genome and release it into the public domain for non-commercial use in much less time and for much less cost than the public human genome project. DNA from five demographically different individuals was used by Celera to generate the sequence of the human genome; one of them being Venter himself!
In 2000, Venter and Francis Collins of the National Institutes of Health and U.S. Public Genome Project jointly made the announcement of the mapping of the human genome. Despite some claims that shotgun sequencing was in some ways less accurate than the clone-by-clone method chosen by the Human Genome Project, the technique became widely accepted by the scientific community and is still used today.
After the human genome project, Venter founded - and is the president of - the J. Craig Venter Institute, which conducts research in synthetic biology. In June 2005, he co-founded Synthetic Genomics, a firm dedicated to using modified microorganisms to produce clean fuels and biochemicals.
The first synthetic life form
In May 2010, a team of scientists led by Venter became the first to successfully create what was described as "synthetic life".
Craig Venter and his team had succeeded in building the genome of a bacterium from scratch and had incorporated it into a cell to make what they called the world's first synthetic life form.
How exactly did they do this?
In a decade-long work, Venter and his researchers first mapped the genome of a simple bacteria, Mycoplasma mycoides. A genome is the 'brain' and control center of a cell, and contains sequences of DNA which carry all the genetic information needed for the cell — and by extension, the organism — to function. Genomes, like all other living matter, are made of chemical compounds.
Once the genome was mapped, Venter’s team manufactured the M. mycoides' genome in the lab, using chemicals. This synthetic genome was identical to the 'original' except for certain harmless 'signatures' the team put in to identify it as synthetic. The synthetic genome was then inserted into another type of bacteria after the bacteria's own genome had been taken out.
Voila! As soon as the synthetic genome was inserted into the cell, it started making new proteins encoded in its DNA and converted it into a new synthetic species. According to Craig Venter, the cell is a completely synthetic one now, having replicated over a billion times, and the only DNA that the cell has now is the synthetic one that Venter’s team made. Exciting stuff!
(For trivia buffs, the new organism has been nicknamed Synthia, and the Mycoplasma mycoides bacterium causes mastitis in goats.)
Is this really an example of synthetic life? Not everyone agrees. For instance there are some who say that the synthetic cell achievement does not fully demystify life's underlying code, the genome. They claim that the researchers built much of the bacterium's genome without fully understanding the function of many of the million-plus base pairs involved. About half of the genes, in fact, are still "a complete black box," said Richard Roberts of New England Biolabs, Inc., in a commentary after Venter's talk. (Source: http://bit.ly/ahSN4Z). In order words, some of these experts feel that it is a fairly dumb reconstruction of an existing design, with no clue of what the components of the design mean.
They might have a point after all. In an earlier instance, when the team had got just one piece out of the millions of pieces wrong, the genome simply did not work. And well, this also does not mean that the team has the ability to create a genome that is original. And some experts feel that the technical expertise and understanding required to create an entire, original cell might take a long, long time – long after folks from our generation are all dead and gone, at any rate.
A more pertinent question for us at Oilgae is: Whether or not this event qualifies as a “synthetic life creating event”, what consequences does it hold for the future of algae fuels? If scientists do not fully understand what component of genome does what but only have a “black box” understanding, isn’t their capability restricted to simply making copies of existing genomes without being able to create absolutely original ones? If that is indeed so, and all they do is to “synthetically” produce a genome that already exists in some other algal strain, isn’t it easy to simply “extract” the genome from that desired strain than painstakingly create it in the lab? Put another way, is this experiment by Venter only of academic interest or does it make a practical difference?
I had a lengthy discussion on this with my biotech team-mates, and they assured me that this event can make a practical difference.
A bit of reading helped me to identify the following advantages that synthetic genes have over their natural counterparts:
· They are obtained more quickly and less expensively than conventionally cloned genes
· They are simple to modify in order to facilitate downstream manipulations
· Any sequence you wish is possible.
To illustrate the advantages mentioned above, just because scientists have identified a desired genome in an algal strain does not mean that they will be able to extract the natural genome exactly the way they would wish to. Under such circumstances, it is worth creating the genome artificially because you can get it exactly the way you want it. Such control alone, my colleagues pointed out, could make an enormous difference.
Interesting indeed. So, I asked myself, in what specific aspects could genetic engineering, armed with this added capability to create synthetic genomes, influence algae biofuels? In order to answer this question, I first started with the critical challenges faced by the algae fuels industry.
Critical challenges in algae fuels
While a number of hurdles stand in the way of sustainable algae fuels, the following are, in my opinion, the key hurdles:
· It is difficult to selecting a suitable algae strain/species with high productivity and Oil content which can also grow well in specific environments.
· High cost of cultivation (this includes costs for mixing, CO2 (if sourced from outside), aeration, nutrients, labour and other general maintenance costs, and amortized capital costs.
· High cost of harvesting algae from the growth medium
· High costs for drying.
Some of you might point out that there are challenges in oil extraction (owing to the tough cell walls) as well as in Transesterification (owing to the high FFA content), but I reckon these are not as critical and difficult as the ones noted above.
When genetic engineering meets the algae fuel challenges…
Let’s look at each of the challenges and explore how genetic engineering could help overcome the challenge.
“Creating” optimal algae strains
This will probably be the area where SGI’s expertise will be required most. Can Venter create, using his demonstrated skills in genetic engineering, synthetic algae strains:
· with high lipid content that
· exhibit much higher productivities / yields, while
· being immune to contamination from other elements, and
· at the same time are tolerant of specific environments?
This is the trillion dollar question. I’d bet my entire wealth (sadly, not a lot) that this where Venter will put in most of his research resources.
My colleagues tell me that there’s a good amount of understanding already existing about the genomes responsible for high lipid content and for providing immunity to contamination, which will make these aspects even more interesting to Venter.
The other aspect mentioned earlier – higher yields – could be another low-hanging fruit, with considerable research likely having taken place already on genomes responsible for growth rates.
Environment tolerance is an area familiar to genetic engineering professionals. Thus, expect quick progress to be made on this aspect. Here, the efforts will be to use GM to produce strains that can grow well under existing temperatures, pH and other medium factors such as salinity.
An interesting idea came from my colleague Mathumitha Balu, who pointed out that GM could also enable mixotropic cultivation, where multiple algae strains are cultivated in the same medium. Mixotropic cultivation could be preferred in some cases because it is the natural form of algae growth in those environments – this is true especially where algae are grown in open systems. One of the hurdles to mixotropic cultivation currently is that the chemical compounds released by one strain could be “toxic” to the other strain/s. If, through GM, one were able to prevent the “toxin” being released, the possibility of mixotropic cultivation becomes enhanced to that extent.
Lowering the cost of cultivation
To a certain extent, the challenge of high cultivation cost can be taken care of if an optimal strain is chosen with high productivities & oil content, high environmental tolerance and resistance to contamination. Thus, GM plays a role here.
There’s another interesting aspect to consider – water. The amount of water required for algae cultivation is large. Still, I see few people really factoring in the criticality of water, or attaching a cost to it in their calculations. Thankfully, one way by which water can indeed be obtained free of cost is by using sea water. But you need specific strains of algae (such as those belonging to the Nannochloropsis species) for marine water, and these strains might not necessarily have all the desired characteristics. What if highly desirable strains were genetically modified so they could thrive in marine water? Success in such an effort will go a long way in lowering the cost of cultivation, while at the same making large-scale algae cultivation that much more feasible.
But there is a limit to which biotechnology plays a role in influencing cultivation costs. Cultivation costs also to a significant extent depend on the cost of construction and maintenance of open ponds or photobioreactors, equipments used for mixing and aeration etc. These are areas where engineering technology, rather than biotechnology, plays an important role.
High cost of harvesting
In the case of Microalgae cultivation, harvesting can add to the costs significantly, as much as 20% of the total cost of production. Even if one were to use fairly simple belt filters for harvesting, the costs can be as high as $75-100 per T of dry algal biomass.
On the face of it, harvesting really looks like an engineering problem where Exxon’s skills will be more in need than SGI’s genetic engineering skills. But there are creative concepts that could indeed bring genetic engineering skills into play.
Let’s consider autoflocculation, a phenomenon in which algae clump together on their own to form a thick mass that can harvested easily, at much lower costs than otherwise. Even today, in nature, there are some algae that autoflocculate; however, these strains have little or no oil. What if genetic engineering methods are used to make high oil bearing algae to get the characteristic of autoflocculation? You get the idea…
High costs of drying
Drying appears to be such an innocent little thing, you wouldn’t think its cost could amount to anything. You couldn’t be more wrong. Based on the calculations done by the Oilgae team, drying alone could cost upwards of $2 per gallon of algae Biodiesel if we use the traditionally used dryers such as spray dryers. Admitted, it is likely that a more efficient drying system specifically adapted for making dry biomass for fuel could cost less, but even if one were to assume an 80% reduction, to $0.5 per gallon, the cost is still high!
Trust me, reducing the costs of drying could be a far more critical concern than what we all have assumed so far. Can genetic engineering play any role here?
Well, this was a toughie. I had almost given up trying to find a way where GM could play a role in more efficient drying when my colleague Parkavi Kumar pointed out to what OriginOil claims to be doing – bypassing the entire drying step (or for that matter, harvesting step), by extracting oil from the algae without killing the cells (http://www.originoil.com/technology/live-extraction.html ). Wouldn’t it be possible for genetic engineering to evolve algae that have cells less tough than normal so that such a “live extraction” becomes easier? Why not, I exclaimed, why not indeed – after all, we are talking about theoretical possibilities here!
Based on the research and brainstorming the Oilgae team did over the past one week on the impact of genetic engineering and Craig Venter’s recent breakthrough in “creating synthetic life”, it appears that Venter, with his expertise (and with a dose of imagination) could indeed influence algae fuel production by being able to address critical challenges along many points in the production value chain.
A related question is of course how quickly he could do it. Perhaps we will have some indications from him soon. Some statements jointly made by him and Exxon Mobil last year (at the time of their partnership agreement) suggested that it could take upwards of five years. Let’s hope his latest achievement shortens this.
That brings us to the end of what could be called an exercise in imagination. But you never know. These days, such imaginations have a way of becoming reality much faster than one can – imagine!