Synthetic Biology: Creating New Forms of Life

by | 7.8.2011 at 1:39pm
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Photo credit by PhOtOnQuAnTiQuE

When leading genomic scientist, J. Craig Venter announced in May 2010 that he’d created the first self-replicating organism with a totally synthetic genome (the genetic material of an organism), it was the first time many people had heard of synthetic biology. Venter did not actually create a synthetic living organism—rather his research team created a synthetic copy of a bacterium’s DNA, which, when transplanted into an organism, took over its operation. Nonetheless it was a giant step for synthetic biology, a cutting-edge area of science that combines engineering with biology to construct living organisms from chemical ingredients, much like electrical engineers build computer chips.

Synthetic biology, or synbio, has the potential to fabricate pharmaceuticals, detect toxic chemicals, break down pollutants, fix defective genes, wipe out cancer cells, generate hydrogen for clean fuel, produce biofuels, and much more. In the process of trying to manufacture living systems, scientists can also learn a great deal about natural biological processes. But synbio’s great promise must be weighed against the potential risks it holds for our health and safety, and for the environment.

Synbio involves the insertion of synthesized genetic parts (synthesized DNA, RNA or ribosomes, where proteins are built) into living cells to program their inner workings. Over the past decade, advancements in reading DNA (DNA sequencing) and replicating DNA (DNA synthesis) have helped further the progress of synbio research. Unlike genetic engineering, which transplants genes from one living organism into another, synbio actually constructs the new genes or genomes it uses from short strands of synthesized DNA made in a DNA synthesizer from inert chemicals. Synbio can involve natural genes that have been redesigned to be more efficient, natural genes that are revamped to function in a new way or completely new artificial genes—some of which have no counterpart in nature.

A DNA synthesizer. Photo credit: Roguey000

According to biological weaponry experts Jonathan Tucker and Raymond Zilinskas, synbio has a number of different offshoots. Genome construction and design involves redesigning the genomes of microbes to make them more efficient or enable them to perform new tasks. One variation of this is the development of a simplified microbial genome into which new genes with specific functions can be transplanted to create synthesized organisms with new capabilities. Applied protein design includes modifying the genes that provide the genetic instructions for producing certain proteins—for example, redesigning enzymes to be more efficient, or to better tolerate heat or acidity. Completely new amino acids have been created and introduced into proteins to alter their properties. Microbes are also being engineered to synthesize natural products. Yeast cells have been redesigned to produce a compound called artemisinic acid, which is used to make artemisinin, a drug that treats malaria.

The Synthetic Biology Working Group has realized one of synbio’s main goals: the creation of a “toolkit” of standardized genetic parts with specific characteristics and functions. The Registry of Standard Biological Parts now contains over 15,000 genetic parts (these “BioBricks” consist of short strands of DNA) that can be mixed and matched like Legos to create new synthetic organisms or systems.

Icon for protein generators in the Registry of Standard Biological Parts

Catalogued by function, such as the production or degradation of chemicals, killing cells, sensing odors, or intercellular communication, the parts can be ordered from the site by almost anyone. In fact, each year the International Genetically Engineered Machine (iGEM) competition sends undergraduate students toolkits of BioBricks and invites them to submit their creations.

The Benefits

Enzyme companies are redesigning microbes to produce powerful enzymes capable of more easily breaking down the cellulose in plants that is fermented for biofuel. Synthetic microbes have been programmed to produce hydrocarbon fuels with the properties of gasoline; others have been programmed to produce synthetic rubber or pharmaceutical products. One iGEM student team engineered bacteria to enable them to transmit electricity. In Japan, scientists are developing synthetically altered soy plants and yeast that produce glycyrrhizen, a compound in licorice root that is 150 to 300 times sweeter than sugar. J. Craig Venter’s firm is using synthetic algae to produce a substitute for palm oil to use in food products, and developing a microbe that will facilitate a process to generate clean renewable hydrogen fuel. DuPont’s Sorona, a bioplastic made from corn, is already on the market, and Amyris Biotechnology’s No Compromise renewable diesel fuel will enter the market this year.

Synbio innovations could potentially help solve the world’s energy crisis, and provide life-saving medical therapies such as anti-cancer agents, gene therapies, stem-cell therapies, and live vaccines. Redesigned microbes could restore the environment by cleaning up the water, soil, and air; and developing substitutes for plant products such as palm oil might help conserve our land and water.

The Risks

But scientists don’t yet fully understand how living cells work so inserting synthesized DNA into live host cells can be unpredictable. According to a report by the ETC Group, scientists have found that synbio experiments that work perfectly on a computer, sometimes deliver erratic results when put to the test in living synthetic organisms. ETC cautions that DNA alone does not determine how a living cell develops; new research on epigenetics (the non-genetic aspects that affect development) has shown that environmental factors play an equally important role in determining development. Moreover genes comprise only 2% of our genomes—the rest, which scientists considered “junk DNA” until recently, most likely regulate gene expression.

Right now, scientists are transferring synthetic genetic material into known living host organisms, but eventually they hope to build completely new synthetic organisms which will have no place in ecosystems that evolved over millions of years. If synthetic organisms are accidently released, it’s impossible to predict what effect they might have on humans and the environment. If microbes programmed to break down cellulose or enhance photosynthesis were released, they could wipe out natural species, causing environmental disaster. Synthesized organisms engineered to clean up toxins would be used in the open environment. They too could conceivably destroy local species and ecosystems, and be impossible to eradicate.

Scientists say they will introduce kill switches or suicide genes into synthesized organisms to keep them from running amok, but since the organisms would be self-replicating, mutations could eventually disable those controls.

Bioterrorists might one day create pathogens or even more lethal biowarfare agents to use as weapons. Synbio scientists have already synthesized the Spanish influenza virus of 1918, which killed 20 to 50 million people. They have also constructed a live, infectious poliovirus from synthesized DNA ordered from a DNA synthesizer, using a map of the disease’s genome from the Internet. And although the 1972 Biological and Toxin Weapons Convention banned the development, production and stockpiling of biological agents and toxins, not every country has signed on.

ETC also warns that synbio—which aims to transform the world’s biomass (organic matter from plants and animals) into chemicals, fuels, plastics, pharmaceuticals and other valuable compounds—will put increased pressure on natural resources. Next generation biofuels, based on synbio, will utilize previously low-valued straw, leaves, and branches as feedstocks for chemical and energy companies. But this plant residue needs to be recycled back to earth to provide the nutrients that keep soil fertile, support biodiversity, and help prevent erosion.  And while the use of synthetic algae for biofuels does not require biomass feedstocks, scaling up algae-based biofuel production would consume enormous amounts of fertilizer and water, which are increasingly scarce.

Scientists and commercial companies involved in synbio are well aware of the challenges and risks their work poses. Many scientists are involved in finding ways to make synbio research and technology safe, and several commercial firms formed an international consortium to develop screening tools and reporting mechanisms for orders of potentially dangerous DNA sequences.

Rules and Regulations

In the US, synbio falls under the mantle of the National Institutes for Health Guidelines for Research involving Recombinant DNA Molecules. Regulators feel these guidelines can manage risks that might arise in the research stage of synbio, but more information will be needed to assess the risks inherent in containing completely synthetic organisms. Since synbio research is largely proprietary, there is concern that information related to risks might be withheld by companies claiming intellectual property rights. In 2010, the Department of Health and Human Services created guidelines to screen synthetic DNA sequences for any attempts to create dangerous toxins or biological weapons, but compliance by DNA synthesizing companies is voluntary. For planned releases, synbio organisms are subject to the same rules and regulations as genetically modified organisms, which are overseen by the Environmental Protection Agency, the Food and Drug Administration, and the Department of Agriculture. Should synbio organisms be subject to additional inspection because they use synthetic DNA?

After Venter’s announcement last year, President Obama charged a commission to examine the implications of synthetic biology. The commission’s report, issued in December 2010, analyzed the risks and benefits of synbio, and determined that new regulations were not needed. It recommended that synbio scientists regulate themselves, that the President’s office coordinate oversight by the relevant agencies, and that the agencies coordinate synbio risk assessment, allowing synthetic organisms to be released into the field only after a reasonable review.

58 environmental, public interest and religious groups from 22 countries denounced the commission’s recommendations because they “1) ignore the precautionary principle, 2) lack adequate concern for the environmental risks of synthetic biology, 3) rely on the use of ‘suicide genes’ and other technologies that provide no guarantee of environmental safety, and 4) rely on ‘self regulation,’ which means no real regulation or oversight of synthetic biology.” The groups called for a moratorium on the release and commercial use of synthetic organisms until a serious study of the potential environmental, health and socio-economic impacts has been conducted.

Meanwhile millions of dollars are being invested in synbio by corporations such as BASF, DuPont, Cargill, Weyerhaeuser, and Syngenta, and the oil companies BP, Shell, and ExxonMobil that are positioning themselves to control the future of fuel. The Gates Foundation invested $42.6 million into Amyris for research on artemisinin. Money is also pouring into synbio from the U.S. Department of Energy and the U.S. military, which invested $6 million in research on synthetic organisms that can live forever or be controlled with a kill switch. Just recently, the Defense Advanced Research Projects Agency (DARPA) committed $30 million to speed up the development of synbio by lowering costs and shortening the timelines of product development.

Outside the U.S., synbio research is ongoing in Europe, Israel, Japan, India and China; and synbio technology will soon be tested in countries like Brazil, Mexico, South Africa and Malaysia.

A poll of 1,000 Americans taken in September 2010 revealed that people are almost evenly split between those who believe the benefits of synbio will outweigh the risks and those who don’t; 32% are not sure. It appears that people are taking a wait-and-see attitude towards synbio, which is probably a good thing for now. But every day DNA sequencing and DNA synthesizing get cheaper and quicker— it’s crucial that we, the public, become properly informed about synthetic biology because it has the potential to radically alter our lives and our planet.

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