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Engineers of life

Synthetic biology is an extension of the spirit of genetic engineering that focuses on the development of biological systems with new, defined characteristics, assembled according to the principles of engineering. Synthetic biology has the potential to be used for a broad range of applications and has solutions in store for major problems of the future, including the sustainable supply of energy and the elimination of environmental damage. As the current debate on the creation of the first synthetic cell in the laboratory shows, synthetic biology also fuels fears that human beings are playing the role of creators and going beyond natural boundaries, with incalculable consequences for the future.

"Synthetic biology" © acatech

On 21st May 2010, the journal Science published a paper entitled "First self-replicating synthetic bacterial cell" in which researchers from the J. Craig Venter Institute (Rockville, Maryland, USA) describe the construction of a purely synthetic genome and its transplantation into a DNA-free bacterial cell. Subsequently, the "first synthetic cell that has ever been made" and the "first self-replicating cell on the planet whose parent is a computer" (J.C. Venter in a press conference held on 20th May 2010) started to synthesize proteins and replication based on the synthetic genome DNA transplanted into the cell. This news immediately hit the headlines worldwide.

J. Craig Venter - Prophet or Mephisto? © Florida State University

Many commentators believe that this spectacular success in the field of synthetic biology is an essential milestone for tackling the key problems related to the future of the human race: for example, artificial organisms that can convert carbon dioxide could be the solution for the world's energy requirements or they could be used to clean up after environmental disasters, such as the oil catastrophe in the Gulf of Mexico. Others believe that scientific progress of this kind brings us a step closer to the apocalypse caused by human hubris and for such people, Craig Venter is Mephistopheles incarnate. "A headline in the German newspaper "DIE ZEIT" of 27th May read: "Humans can now play creators", and the journalist concluded: "From now on anything and everything would seem to be possible."

The euphoria on the one side and the fears on the other mean that important facts need to be clarified. This special report is intended to shed light on synthetic biology, what it is and what can be expected from this rising new field of research.

What is synthetic biology?

This new field of research is an extension of conventional genetic engineering in which scientists assemble defined genetic modules into complex biological systems using engineering principles. Synthetic biology does not relate to the modification of individual genes or properties such as in transgenic organisms, but rather to the construction of new genome segments consisting of genes (from small to large quantities) or entire genomes and new organisms (see above) that have not naturally existed in this form before. Synthetic biology uses tried and proven technologies from molecular biology, recombinant genetic engineering, the chemical synthesis of biological constituents and nucleic acid synthesis amongst others. There is no clear separation between traditional genetic engineering and biotechnology and synthetic biology; the differences tend to be of a more quantitative nature. Synthetic biology is not a new revolutionary field, instead it can be best described on the basis of its strategic objectives and the approaches based on the modular design principle used in the engineering sciences. The assembly of synthetic genomes and cells requires a blueprint that is usually produced using computer-based systems biology approaches.

DNA double helix © acatech

There are two diametrically opposed opinions in the debate relating to the legal and ethical aspects of the progress in synthetic biology. One group holds that no additional safety problems arise with regard to already established techniques and that the existing regulatory tools (Genetic Engineering Law, Medical Device Act, etc.) are totally sufficient and need at most to be amended. The other group believes that humankind is about to cross another threshold towards a future with incalculable consequences for both human beings and the environment.

Applications of synthetic biology

The supporters of synthetic biology emphasise the broad range of applications of synthetic biology, ranging from the development of more effective and individualised drugs to specific biosensors, from novel biomaterials to the large-scale production of biofuels and the elimination of environmental damage. The German Academy of Science and Engineering (acatech), which supports the German government with technically qualified evaluations and forward-looking recommendations, attached particular importance to the following themes in its position paper on synthetic biology in 2009:

  

  1. The chemical-enzymatic synthesis of nucleic acids and complete genomes. The specific modification and optimisation of gene sequences has the potential to lead to gene therapy products and DNA vaccines.
  2. The construction of cells with a minimal genome. This genetic platform, which is reduced to the essential life functions, can be used as a "chassis" for establishing new functions.
  3. The synthesis of protocells, i.e. artificial systems constructed according to biological and physical principles, which can serve as models for living cells.
  4. The production of biomolecules using genetic engineering approaches to bring together complete metabolic reaction pathways according to a modular design principle.
  5. The design of regulatory circuits with sensitive sensory functions to control cellular and industrial process chains or networks.
  6. The use of modified cellular machines in orthogonal systems. This might enable the production of polymer compounds from chemical constituents according to the drawing-board principle. Orthogonality refers to the possibility of combining independent components and is an important construction principle in the technological and computer sciences.

At present the majority of applications are still visions for the future, and synthetic biology remains largely focused on basic research. However, this situation may soon change. The Mycoplasma mycoides cell created in the Venter lab is not yet a cell with a minimal genome and as such cannot yet be used as a chassis for certain syntheses. However, this possibility might not be that far off and many scientists are working hard to turn the vision into reality.

Glossary

  • Desoxyribonucleic acid (DNA) is a double-stranded, helical macromolecule encoding the genetic information of an organism.
  • A gene is a hereditary unit which has effects on the traits and thus on the phenotype of an organism. Part on the DNA which contains genetic information for the synthesis of a protein or functional RNA (e.g. tRNA).

Glossary

  • Desoxyribonucleic acid (DNA) is a double-stranded, helical macromolecule encoding the genetic information of an organism.
  • A gene is a hereditary unit which has effects on the traits and thus on the phenotype of an organism. Part on the DNA which contains genetic information for the synthesis of a protein or functional RNA (e.g. tRNA).
  • The genome is entire genetic material of an organism. Each cell of an organism contains the entire genetic material in its nucleus.
  • There are two definitions for the term organism: a) Any biological unit which is capable of reproduction and which is autonomous, i.e. that is able to exist without foreign help (microorganisms, fungi, plants, animals including humans). b) Definition from the Gentechnikgesetz (German Genetic Engineering Law): “Any biological unit which is capable of reproducing or transferring genetic material.“ This definition also includes viruses and viroids. In consequence, any genetic engineering work involving these kinds of particles is regulated by the Genetic Engineering Law.
  • Recombination is the process in which DNA is recombined. As a natural process, recombination takes place in sexual reproduction during meiosis. In vitro recombination involves the joining of DNA molecules of different origin using recombinant DNA technologies.
  • Replication is the biological term for the doubling of the DNA double helix.
  • Genetic sequences are successions of the bases adenine, thymine, guanine, and cytosine on the DNA (or uracil instead of thymine in the case of RNA).
  • The somatic gene therapy is used to compensate gene defects. Therefore, the correct form of the mutated gene is transferred into somatic cells.
  • Transgenic organisms are organisms (microorganisms, animals, plants), into which foreign material has been introduced using genetic engineering methods and which is inherited from one generation to the other. Transgenic organisms are thus genetically-modified organisms.
  • A vaccine is a preparation of dead or weakened pathogens (or of derived antigenic determinants) used to induce immunity against the pathogen.
  • The term metabolism includes the uptake, transport, biochemical conversion and excretion of substances within an organism. These processes are necessary to build up the body mass and to meet the energy demand of the body. The opposed processes of metabolism are called anabolism and catabolism. Effectiveness of several enzymes could be catabol and anabol. Within one biochemical pathway they cannot work in both directions at the same time.
  • Engrafting cells, tissue or organs from a donor into a recipient is called transplantation. There exist several types of transplantation which are classified in three categories: function, location and derivation. Engrafting an organ of a different species into a recipient is called xenogenic transplantation, whereas an allogenic transplantation describes the tranfer of grafts from a donor into a recipient being a member of the same species. If donor and recipient are the same individual, the transplantion is called autogenic. Furthermore there exists a syngenic transplantation which is characterized by grafts originating from the uniovular twin. Furthermore, engrafting artificial material is called alloplastic transplantation. To suppress the natural immune response being raised by the transplanted organs, recipients have to be administered immunosuppressants. Since 1997 in Germany the legitimacy of organ donation is regulated by the Transplantation Law. In the case of brain death, an organ donor card has to be available or relatives have to agree with the organ donation. Today, the most frequently transplanted organs are heart, liver, kidney and cornea.
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