Tag Archives: Pamela Silver

Safety mechanisms needed before synthetic biology moves from the labs into the real world

A Sept. 17, 2015 news item on Nanotechnology Now makes note of an article where experts review the state of the synthetic biology field and discuss the need for safety as synthetic biology is poised to move from the laboratory into the real world,

Targeted cancer treatments, toxicity sensors and living factories: synthetic biology has the potential to revolutionize science and medicine. But before the technology is ready for real-world applications, more attention needs to be paid to its safety and stability, say experts in a review article published in Current Opinion in Chemical Biology.

Synthetic biology involves engineering microbes like bacteria to program them to behave in certain ways. For example, bacteria can be engineered to glow when they detect certain molecules, and can be turned into tiny factories to produce chemicals.

Synthetic biology has now reached a stage where it’s ready to move out of the lab and into the real world, to be used in patients and in the field. According to Professor Pamela Silver, one of the authors of the article from Harvard Medical School in the US, this move means researchers should increase focus on the safety of engineered microbes in biological systems like the human body.

A Sept. 16, 2015 Elsevier press release, which originated the news item, expands on the theme,

“Historically, molecular biologists engineered microbes as industrial organisms to produce different molecules,” said Professor Silver. “The more we discovered about microbes, the easier it was to program them. We’ve now reached a very exciting phase in synthetic biology where we’re ready to apply what we’ve developed in the real world, and this is where safety is vital.”

Microbes have an impact on health; the way they interact with animals is being ever more revealed by microbiome research – studies on all the microbes that live in the body – and this is making them easier and faster to engineer. Scientists are now able to synthesize whole genomes, making it technically possible to build a microbe from scratch.

“Ultimately, this is the future – this will be the way we program microbes and other cell types,” said Dr. Silver. “Microbes have small genomes, so they’re not too complex to build from scratch. That gives us huge opportunities to design them to do specific jobs, and we can also program in safety mechanisms.”

One of the big safety issues associated with engineering microbial genomes is the transfer of their genes to wild microbes. Microbes are able to transfer segments of their DNA during reproduction, which leads to genetic evolution. One key challenge associated with synthetic biology is preventing this transfer between the engineered genome and wild microbial genomes.

There are already several levels of safety infrastructure in place to ensure no unethical research is done, and the kinds of organisms that are allowed in laboratories. The focus now, according to Dr. Silver, is on technology to ensure safety. When scientists build synthetic microbes, they can program in mechanisms called kill switches that cause the microbes to self-destruct if their environment changes in certain ways.

Microbial sensors and drug delivery systems can be shown to work in the lab, but researchers are not yet sure how they will function in a human body or a large-scale bioreactor. Engineered organisms have huge potential, but they will only be useful if proven to be reliable, predictable, and cost effective. Today, engineered bacteria are already in clinical trials for cancer, and this is just the beginning, says Dr. Silver.

“The rate at which this field is moving forward is incredible. I don’t know what happened – maybe it’s the media coverage, maybe the charisma – but we’re on the verge of something very exciting. Once we’ve figured out how to make genomes more quickly and easily, synthetic biology will change the way we work as researchers, and even the way we treat diseases.”

Lucy Goodchild van Hilten has written a Sept. 16, 2015 article for Elsevier abut this paper,

In January, the UK government announced a funding injection of £40 million to boost synthetic biology research, adding three new Synthetic Biology Research Centres (SBRCs) in Manchester, Edinburgh and Warwick. The additional funding takes the UK’s total public spending on synthetic biology to £200 million – an investment that hints at the commercial potential of synthetic biology.

In fact, according to the authors of a new review published in Current Opinion in Chemical Biology, synthetic biology has the potential to revolutionize science and medicine. …

Here’s a link to and a citation for the paper,

Synthetic biology expands chemical control of microorganisms by Tyler J Ford, Pamela A Silver. Current Opinion in Chemical Biology Volume 28, October 2015, Pages 20–28  doi:10.1016/j.cbpa.2015.05.012

I believe this paper is open access until January 16, 2016.

As the paper has a nice introductory description of synthetic biology, I thought I’d include it here, as well as, the conclusion which is not as safety-oriented as I expected,

Synthetic biology allows scientists to re-program interactions between genes, proteins, and small molecules. One of the goals of synthetic biology is to produce organisms that predictably carry out desired functions and thereby perform as well-controlled so-called biological devices. Together, synthetic and chemical biology can provide increased control over biological systems by changing the ways these systems respond to and produce chemical stimuli. Sensors, which detect small molecules and direct later cellular function, provide the basis for chemical control over biological systems. The techniques of synthetic biology and metabolic engineering can link sensors to metabolic processes and proteins with many different activities. In this review we stratify the activities affected by sensors to three different levels: sensor-reporters that provide a simple read-out of small molecule levels, sensor-effectors that alter the behavior of single organisms in response to small molecules, and sensor effectors that coordinate the activities of multiple organisms in response to small molecules …

Conclusion

We have come to the point in synthetic biology where there are many lab-scale or proof-of-concept examples of chemically controlled systems useful to sense small molecules, treat disease, and produce commercially useful compounds. These systems have great potential, but more attention needs to be paid to their stability, efficacy, and safety. Being that the sensor-effectors discussed above function in living, evolving organisms, it is unclear how well they will retain function when distributed in a patient or in a large-scale bioreactor. Future efforts should focus on developing these sensor-effectors for real-world application. Engineered organisms will only be useful if we can prove that their functions are reliable, predictable, and cost effective.