Synthetic Biology

The poet Joyce Kilmer wrote, "Poems are made by fools like me, / But only God can make a tree". New research by Craig Venter, one of the main scientists behind the human genome sequencing project, may change all that. His latest research, published in Science, has succeeded in making a new form of life in the laboratory. The hope is that this "synthetic life" will eventually lead to custom-made organisms engineered to tackle the world's woes.

Engineering living organisms isn't new. Scientists have been genetically modifying microbes, plants and animals for decades. GM crops are grown on more than 2bn acres of the world's surface. But this is a kind of genetic tinkering. What Venter and many other scientists envisage is far more revolutionary: engineering entirely new forms of life.

Synthetic life enthusiasts claim that we need new organisms to do the tasks that the existing ones are not so good at. For instance, farmers around the world are increasingly growing biofuel crops. But these crops take up land that would otherwise be used to grow food, which is at least partly why grain prices have soared. There are already efforts to exploit other resources, such as sewage or plant waste. But natural organisms have their own agenda: they want to produce descendants rather than ethanol, so aren't so efficient at making fuel.

Venter is a pioneer of genome mining: excavating organisms living in exotic environments for novel genes. Some of these genes may be perfectly evolved for synthetic biology applications, such as biofuel production. But useful genes are scattered across hundreds of species, some of which can't be grown in the laboratory. What Venter and other scientists want to do is bring these genes together in an easy-to-grow custom-engineered organism.

Several years ago Venter began this challenge by making a minimal cell to provide a kind of chassis capable of bolting on lots of different synthetic biology tools. His latest research has taken the genome of one bacterium, modified it inside a yeast cell and then inserted it into the cell of a related bacterium to create an entirely new organism. The next step will be to add genes and pathways to make biofuel or other products.

Biofuels aren't the only target of synthetic biology. Scientists at the University of Manchester are trying to engineer bacteria to make novel antibiotics. Scientists are also seeking to make anti-cancer drugs, degrade harmful pollutants or produce valuable nutrients. Other scientists envisage more blue-sky projects such as engineering microbes to remove carbon dioxide from the atmosphere or even to terraform Mars.

But why stop with microbes? It will soon be possible to make entirely novel forms of plants or animals (including man). New cereal crop plants might fix their own nitrogen, eliminating the need for costly fertiliser. Or, how about custom-made insects that seek out and kill locusts or malarial mosquitoes?

Of course, the prince of the realm and the anti-GM lobby will howl that we should not be playing God. Yet millions of tons of GM food are consumed each year without a single authenticated case of any harm. And although there have been justifiable concerns about the ecological impact of GM crops, research has tended to conclude they are more benign than conventional farming.

Mankind cannot stand still. Since the 19th century human longevity in the west has been increasing by about five hours every day. Most of our extra years have been bought with advances in science and technology. But much of the world has been left out. With people living longer, population growth, crop yields waning and global warming, we need to innovate. Synthetic biology provides new hope for a bright future.

Making cells like computers

Erik Parens

The Boston Globe, February 18 2008

http://www.boston.com/news/science/articles/2008/02/18/making_cells_like_computers/

CRAIG VENTER recently announced that his research institute had synthesized the genome of a bacterium. Upon hearing this, observers across the world anxiously suggested that he was on the verge of "synthesizing life."

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But Venter has not done what most people mean by "synthesizing life." It is true that he has helped to create a new field that is sometimes called "synthetic biology." Synthetic biologists, however, are far from creating the astonishingly complex systems we call life.

Strictly, what Venter did is stitch together segments of commercially produced copies of naturally occurring DNA to produce an almost exact replica of the genome of a bacterium. He hopes that by the end of the year, when he transplants that synthesized genome to a naturally occurring bacterial cell, it will take over the naturally occurring genome's role and direct the cell's activities.

His next step, which will be far more difficult, will be to create a stripped-down, "minimal" genome, which will exclude genes that he concludes are irrelevant for creating the gene products he wants.

The final step, which will be still more difficult, is to add a gene or genes to that minimal genome and then place it into a naturally occurring bacterial cell. Ultimately, he aims to get those new genes to "program" such a bacterial cell to produce things like malaria vaccines and cheap biofuels. Venter has no intention of trying to synthesize the marvelously complex bacterial cell membrane or cellular environment.

Essentially, "synthetic biologists" hope to make cells act more like computers and less like biological systems. To understand why they would want cells to act less like biological systems, it helps to understand some recent history of human genetics research.

Once upon a time, many geneticists believed that the human organism would work like a computer - at least in the sense that a given input (a gene) would reliably produce a predictable output (a protein). Based on early discoveries about the role of single-gene mutations in such rare disorders as Huntington's disease, many geneticists hoped that mutations in single genes might also have predictable effects on common traits like cancer.

Venter himself was one of the first geneticists to announce the demise of that hope.

In 2000, Venter's private company published its draft sequence of the human genome. But as he acknowledged shortly before that publication, knowing the sequence could only be a small step on the long road toward understanding how genes actually work in complex biological systems. In his colorful way, Venter said to a New Yorker writer, "We know shit about biology."

Geneticists today are exquisitely attuned to the staggering complexity of the processes that give rise to common traits and, more generally, to the organisms we are. Hardly a month goes by without a discovery that undermines the old-fashioned, simple story: from discovering that molecules that are not DNA play an important role in the expression of genes, to realizing that single genes can code for myriad proteins, to recognizing the significance of gene-gene and gene-environment interactions.

We are just beginning to understand that what just a few years ago we called "junk" DNA and "inefficient" repetitions of gene sequences both play important roles in cell functioning. As Francis Collins, the head of the National Human Genome Research Institute, recently said, we are in the midst of "a scientific revolution" in our understanding of what genes are and how they work.

Perhaps no one was more surprised by this complexity than researchers at the National Human Genome Research Institute. After all, the institute owes its existence to the promise made in 1990, that, if Congress would fund the project to sequence the human genome, cures for terrible diseases would be forthcoming. While progress has surely been made, we do not today use gene-transfer technology to reliably treat even one genetic disease. This is not for lack of intelligence, money or commitment. It is because of the extraordinary complexity of biological systems.

It would be a remarkable technical achievement if Venter were to get a bacterium to work more like a computer and less like a biological system. It is already a remarkable achievement to have synthesized a bacterial genome.

As we appreciate Venter's technical prowess, however, we also need to remember his scatological pronouncement of 2000. Conceivably, we are on the verge of installing synthetic genomes in bacterial cells to create products we want. But we are still a long, long way from doing what most people mean by "synthesizing life."

Erik Parens is a senior research scholar at The Hastings Center, a bioethics research institute in Garrison, N.Y. He is the first editor of "Wrestling with Behavioral Genetics: Science, Ethics, and Public Conversation."