Synthetic cell created in lab

“Scientists in the US have succeeded in developing the first living cell to be controlled entirely by synthetic DNA,” BBC News reported.

The research, which was fifteen years in the making, has proved that it is possible to transplant synthetic DNA into a bacterium cell, and that this cell acts like a normal cell by producing proteins and dividing.

This research has been described, perhaps rightly, as a “landmark” study. Further work is needed to assess the potential benefits of this technique over conventional genetic engineering methods and how such technological advancements should be regulated. Though some newspapers reported that this technique could have implications for health and be used in the manufacture of new drugs and vaccines, it is not likely to happen any time soon. Many technical issues would need to be overcome and ethical questions answered before this could become a reality.

Where did the story come from?

The study was carried out by J Craig Venter and colleagues from the J Craig Venter Institute. The work was funded by Synthetic Genomics Inc, and three of the authors and the institute itself hold stock in Synthetic Genomics Inc. The study was published in the peer-reviewed journal Science .

What kind of research was this?

This was a laboratory “proof of concept” study. The scientists copied the DNA sequence of a bacterium called Mycoplasma mycoides, then constructed a synthetic genome and transplanted it into a host bacterium cell called Mycoplasma capricolum, replacing this bacterium’s own DNA. They then assessed whether the cell could complete normal cell functions, such as producing proteins from the synthetic DNA and dividing or multiplying.

What did the research involve?

The researchers began by looking for a suitable bacterium to use as a template to make their synthetic DNA. Initially they chose Mycoplasma genitalium, which has the smallest number of genes of any known organism. They later switched to another “simple” bacterium, Mycoplasma mycoides, as this is a faster-dividing (growing) bacterium.

Creating synthetic DNA from a template is an established procedure, in which the four chemicals that make up DNA (adenine, thymine, cytosine and guanine) are put together in a defined order to make synthetic DNA. However, this technique can only produce small fragments of the DNA sequence at a time rather than the complete DNA sequence.

The researchers put extra “watermark” DNA into the Mycoplasma mycoides genetic sequence, which could be used to tell the difference between the synthetic DNA and natural DNA. Synthetic fragments of Mycoplasma mycoides DNA, including these watermarks, were then produced. Extra bits of DNA were added to the ends of the fragments so that they could be “stitched” together. Increasingly large sequences were stitched together and amplified (replicated) in yeast. As errors can sometimes be incorporated into the sequence, quality control steps were taken throughout.

Natural DNA in Mycoplasma mycoides is “methylated” with a chemical coating that stops the DNA from being digested by enzymes in the cell. However, when synthetic DNA is produced in yeast, it is not methylated. The researchers overcame this in two ways: by extracting the enzymes whose role it is to methylate DNA in the bacterium and adding this to the synthetic DNA so that it was methylated, and by disrupting the enzymes that digest unmethylated DNA.

The synthetic DNA was purified to remove any yeast DNA and transplanted into a different type of bacterium, called Mycoplasma capricolum, replacing its natural DNA with synthetic DNA. In one of the watermarking additions, the synthetic DNA was designed to produce a protein that would turn the cell blue when the researchers added a certain chemical to their cells. This protein is not found in natural cells. In this way, the researchers were able to screen which cells had successfully taken up the synthetic DNA and were capable of producing proteins based on the synthetic DNA sequence.

What were the basic results?

Using the “watermark” DNA sequence as a guide, the researchers identified the synthetic DNA from the natural DNA. They also segmented the synthetic DNA at specific genetic sequences and compared its size to that of natural DNA that had been segmented at the same sequences. The fragments of synthetic DNA were found to be the same size as natural DNA.

No DNA remained from the recipient Mycoplasma capricolum. Cells containing the synthetic DNA were capable of growth and produced almost identical proteins to natural Mycoplasma mycoides. However, there were minor differences between the synthetic cells and the natural Mycoplasma mycoides cells in that 14 genes were deleted or disrupted in the synthetic cell.

How did the researchers interpret the results?

The researchers said that “this work provides a proof of principle for producing cells based on genome sequences designed in the computer”, and it differs from other genetic engineering techniques that rely on modifying natural DNA. They say that this approach should be used in the synthesis and transplantation of more novel genomes as genome design progresses.

Conclusion

This research has demonstrated that it is possible to produce a synthetic genetic sequence and transplant it into a bacterial cell to produce a viable cell that is able to divide and produce proteins. The researchers made the DNA sequence based on the known sequence of a bacterium so, although the DNA was made synthetically, the proteins produced in the cell were the same.

The researchers mention that their work will raise philosophical and ethical discussions, and these have indeed been raised by the media and other commentators. This research has shown that this technique can work, but at present is very expensive. Further work is needed to assess the potential benefits of this technique over conventional genetic engineering methods and how such technological advancements should be regulated.

This research has been described, perhaps rightly, as a “landmark” study. Though some newspapers reported that this technique could have implications for health and be used in the manufacture of new drugs and vaccines, this is unlikely to happen any time soon.