Archive | Synthetic Biology

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Synthetic Biology Creates Smallest Bacteria

Posted on 12 April 2016 by Jerry

Craig Venter, a longtime leader in synthetic biology if not a founder, has continued to pursue creation of a life form with the smallest number of genes that can act as a living envelop for a created synthetic organism. Venter’s team has now announced a bacterial cell that Venter calls the “most simple of all organisms.”   It only has 473 genes.

An article published on March 24, 2016 by Science magazine describes the new organism as a “Tour de force” in a quote of George Church, a synthetic biologist at Harvard University. Also known as Syn 3.0, the living bacterium has been cut down to the bare essential genes to sustain life. It has the least known or smallest genome of a living organism to date.

The problem with this new development is that it can be described as creating more questions than it answers. In trying to eliminate genes that did not keep this most basic bacterium alive, the synthetic biologist team found 149 of the 473 genes whose purpose was unknown. These genes remained a mystery because no one on the team could identify what functions these particular genes had.

The March 25, 2016 issue of Science magazine has an article entitled Design and synthesis of a minimal bacterial genome, which was written by Venter’s own team. This article said in conclusion, “The minimal cell concept appears simple at first glance but becomes more complex upon close inspection. In addition to essential and nonessential genes, there are many quasi-essential genes, which are not absolutely critical for viability but are nevertheless required for robust growth….Unexpectedly, it also contains 149 genes with unknown biological functions, suggesting the presence of undiscovered functions that are essential for life.”

This represents a continuation of a trend that was last highlighted in an article in this blog entitled, “Troubling Progress for Synthetic Biology” see www.iamaguardian.com/category/protect/synthetic-biology/page/2/ . This May 2012 article shows that the same teams are making progress on their respective objectives. It also shows that this research team is taking the easiest path to a conclusion and the simplicity of their approach to research, simplicity that allows for 149 unknown genes. These bacteria represent the next chapter of the J. Craig Venter team. These bacteria grow and thrive in a laboratory environment.

We continue to call for regulation of Venter’s team’s experimental efforts. It is clear they are taking a very ‘ham-handed’ approach to finding the secret of life. What else will they fail to know about the microbes they create? What will they care? What will stop them from taking a shortcut to wealth when they find a path to an IPO or a new product rather than take the appropriate steps to be safety conscious? This again highlights that this area has no government regulator or regulatory regime to look over their shoulder and insure their efforts are in the public interest.

The announcements themselves seem to respond to funders thirst for progress, which must be threatening to not give them any more money. These numbers do not assuage the concerns of the public.

Would you announce proudly the fact that you have whittled down bacterial genes to 473 when you continue to not know what 149 or over 30% of these genes do? Why would you make sweeping public announcements about this accomplishment? We need regulation and oversight of this area now. We must slow these teams and their zeal to reach the next plateau in living out their founder’s dreams of great wealth and renown.

Use the following links to access more information or read the source documents used to prepare this article.

http://news.yahoo.com/stripped-down-synthetic-organism-sheds-light-nature-life-204848392–finance.html

http://www.sciencemag.org/news/2016/03/synthetic-microbe-lives-less-500-genes

http://www.sciencemag.org/news/2003/11/designer-genomes-pronto

http://www.bbc.com/news/science-environment-35895138

http://sciencemag.org/content/351/6280/aad6253

http://sciencemag.org/content/351/6280/1380

http://science.sciencemag.org/content/351/6280/aad6253.full

 

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Is Synthetic Biology Now Safe?

Posted on 06 December 2015 by Jerry

A couple of years ago a team led by George Church at Harvard Medical School, which included Farren Isaacs now a synthetic biologist at Yale University, made a strain of Escherichia coli that abandoned an old instruction to terminate protein synthesis and had a new instruction to make a synthetic amino acid within its proteins. It required this new strain of E-coli to look for the new amino acid or die as too reliant on the synthetic amino acid.

Now two teams independently have produced other genetically modified bacteria that are dependent upon amino acids that are not naturally occurring in the environment. Both bacteria will die if not nourished by the synthetic amino acids that of course only occur in a laboratory. This offers a protection should either bacteria escape the laboratory environment.

Dan Mandell, leader of the Harvard Medical School team (with George Church) is quoted in a January 22, 2015 article in Nature magazine as saying, “Our strains, to the extent that we can test them, won’t escape.” The article goes on to state, “The microbes also do not swap their engineered DNA with natural counterparts because they no longer speak life’s shared biochemical language.”

The article continued that the Mandell (and Church) team at Harvard started with protein structures “and added elements to help integrate and accommodate the artificial amino acids.” To the contrary, the Isaacs team from Yale began with genomic sequencing looking for sites in the proteins where microbes could use synthetic amino acids with no detrimental effect on the microbe.

“Establishing safety and security from the get-go will really enable broad and open use of engineered organisms,” stated Farren Isaacs, a Yale synthetic biologist. Farren Isaacs who led the second study was quoted from the same Nature magazine article.

In the original article from Yale that appeared online on Nature.com on January 21, 2015 the report says, “Here we describe the construction of a series of genomically recoded organisms (GROs) whose growth is restricted by the expression of multiple essential genes that depend on exogenously supplied synthetic amino acids (sAAs).” Farren Isaacs believes in this containment so much that he and Alexis J. Rovner applied for a provisional patent at the US Patent and Trademark Office. A “Corrigendum: Recoded organisms engineered to depend on synthetic amino acids” was filed in conjunction with this report. This filing also identifies Isaacs as a founder of enEvolv, Inc.

Isaacs was also quoted by BBC News on January 21, 2015 as saying “What we’re seeing here is an important proof of concept that re-coding genomes and engineering dependence on synthetic amino acids is technically feasible and in not just E coli but other micro-organisms and multicellular organisms such as plants.”

It would appear it is now possible to develop synthetically modified organisms that would be safer than today’s synthetic organisms. They are dependent on a continuous supply of synthetic amino acids for continued sustenance in all environments. Whether these developments are actually used by other researchers and companies in their products remains to be seen. It is safe to say we should applaud this research as a breakthrough that has the safety of the populous and its environments in mind.

We must increase and continue regulatory oversight over this synthetic biology area. We need caution from the government, private entrepreneurs and venture capitalists concerning synthetic biology experiments. But we should feel heartened that progress is being made and scientists are looking for ways to contain the resulting synthetic organisms.

Use the following links to obtain additional information or access the source articles used for this report.

http://www.nature.com/news/gm-microbes-created-that-can-t-escape-the-lab-1.16758?WT.ec_id=NATURE-20150122

http://www.nature.com/nature/journal/v518/n7537/full/nature14095.html

http://www.nature.com/nature/journal/v518/n7537/full/nature14121.html

http://www.nature.com/nature/journal/v527/n7577/full/nature15537.html

http://www.bbc.com/news/science-environment-30915785

http://www.sciencedaily.com/releases/2015/01/150121135617.htm

http://phys.org/news/2015-01-synthetic-amino-acid-enables-safe.html

http://news.yale.edu/2015/01/21/synthetic-amino-acid-enables-safe-new-biotechnology-solutions-global-problems

 

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We Need Worldwide Regulation of Synthetic Biology

Posted on 11 March 2015 by Jerry

Following the thought of the creation of new nucleotides, the x-y pair (see Synthetic Biology Advances With No Oversight, 7/15/14), synthetic biologists at Yale and a separate group at Harvard have constructed genetically altered organisms that require special synthetic amino acids to live.  Synthetic biologists reason this makes the synthetic organisms safer since they would die if released into the environment that lacks the amino acid.

This breakthrough would eventually allow synthetic organisms to be raised in laboratories for use in experimentation.  According to an article in the January 22, 2015 volume of Nature entitled Safety boost for GM organisms “The microbes also do not swap their engineered DNA with natural counterparts because they no longer speak life’s shared biochemical language.”  The article continued with a quote from a Yale synthetic biologist, Farren Isaacs who said, “Establishing safety and security from the get-go will really enable broad and open use of engineered organisms.”

While this does provide another layer of security to the development of synthetic organisms, it still begs the question of when there will be proper regulation of synthetic biology.  This is not to say there is no regulation today, for there is.  It is as if we have a bedspread that has been pulled in many different directions as we try to cover a synthetic biology spot by expanding existing coverage of a wide array of bureaucratic organizations each of which are designed to respond to other priorities.

This is like stating that in an environment where everyone is responsible, no one is.  The closest anyone comes to directly regulating this area is the National Institute of Health (NIH).  The law requires that any entity that receives money for research from the NIH must adhere to its guidelines that cover synthetic biology.  Everyone else is free to follow the guidelines or not, or worry about another governmental agency with a regulatory role that can be extended to synthetic biology.

The Environmental Protection Agency (EPA), the United States Department of Agriculture (USDA), the Food and Drug Administration (FDA), the Commerce Department and the Department of Health and Human Services (HHS) all have overlapping responsibility for Synthetic Biology.  It is doubtful that any of them has been given any additional budget to extend their regulation to include synthetic biology.  Let us reiterate that when all are responsible, no one is responsible.

There is a thorough description of the patchwork quilt of regulation of synthetic biology which can be found by accessing “synberc.org/safety-and-security-resources” and selecting the “The Regulation of Synthetic Biology: A Guide to U.S. & European Regulations, Rules & Guidelines.”

Synthetic biologists are working to solve humanity’s problems.  Today they are largely self-regulated.  This must change.  There must be regulation but it should be one regime that is worldwide (maybe from the U.N.) and assures that humans will not unleash a foreign organism into the world’s environment.

Use the following sites to gain additional information or access the original documents that were used to generate this article.

http://www.iamaguardian.com/category/protect/synthetic-biology/

http://www.nature.com/nature/journal/v518/n7537/full/nature14095.html

http://www.nature.com/nature/journal/v518/n7537/full/nature14121.html

Access “synberc.org/safety-and-security-resources” and select the “The Regulation of Synthetic Biology: A Guide to U.S. & European Regulations, Rules & Guidelines.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554958/

 

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Synthetic Biology Advances With No Oversight

Posted on 15 July 2014 by admin

Scientists have now created a self-replicating organism that can pass its uniqueness to subsequent generations.  All species of life on Earth from bacteria and viruses to human beings use the same genetic code.  This consists of four types of chemicals in DNA, A, C, G, and T.  The sequence of these chemicals, nucleotides or bases, determine which proteins each cell makes.

According to a New York Times article appearing on May 7, 2014 researchers have created two new nucleotides in addition to the original four, an X-Y pair.  They have put the new X-Y pair into a common bacterium, E. coli. In a unique way, “the bacteria were able to reproduce normally, through a bit more slowly than usual, replicating the X and Y along with the natural nucleotides.  In effect, the bacteria have a genetic code of six letters rather than four, perhaps allowing them to make novel proteins that could function in a completely different way from those created naturally.”

Each organism had only one X-Y pair and we don’t know if it would function with many of the new combinations.  We don’t know how long such a bacteria would survive retaining the foreign code.  In other words there is more we do not know than what we do know.

The uniqueness of this progress lies in the ability to get the X-Y pair to successfully duplicate as the E. coli cell splits.  Also, it is the ability of successive generations to copy the six-letter genetic code exactly.

This progress in synthetic biology may be why a recent conference attracted representatives from the Federal Bureau of Investigation and the Department of Homeland Security.  The Pentagon’s Defense Advanced Research Projects Agency (DARPA) recently created the Biological Technologies Office, with Dr. Alicia Jackson from MIT named as deputy director.

Dr. Neil Gershenfeld, a physicist from MIT was quoted in a New York Times article as saying, “The new abilities, he noted, raised ethical questions that are as yet unanswered.  When the ability to convert biology to data and data into biology becomes that cheap, that agile, that easy to do, what are the consequences?  The most exciting and frightening thing I saw this morning was a slide talking about designing and synthesizing genomes next to a slide describing a human being.”

This progress is attracting many of the same players who make genetically modified foodstuffs and drugs.  MIT announced its Synthetic Biology Center has just inked a three-year collaboration agreement with Pfizer to advance synthetic biology discovery and development.

There still is no governmental oversight or regulation of synthetic biology.  With incremental progress of synthetic biology’s efforts, the fear grows that there will ultimately be success.  In fact, the ultimate concern is that some alien life form will find itself loose in our environment.

A May 7,2014 New York Times article quotes Jim Thomas of the ETC Group, a Canadian advocacy organization as saying, “The arrival of this unprecedented ‘alien’  life form could in time have far reaching ethical, legal and regulatory implications.  While synthetic biologists invent new ways to monkey with the fundamentals of life, governments haven’t even been able to cobble together the basics of oversight, assessment or regulation for this surging field.”

Even with known procedures and strict security with known dangerous materials, mistakes will be made that will compromise our DNA.  An example is the recent admission that the Centers for Disease Control mislabeled and mishandled samples of deadly pathogens, including anthrax, smallpox, botulism bacteria, and a virulent bird flu virus.  These errors were committed in five occasions over the last decade.

These failures raise concerns that even the U.S. government, in its most closely watched environments, cannot safely store and transport dangerous microbes.  These include live samples of decades old vials of smallpox that killed hundreds of millions of people before being eradicated in the 1970s and 1980s.  A bioterrorist expert was most concerned about the distribution of a bird flu virus that was contaminated.  What should have been a safe strain of bird flu virus became a deadly H5N1 virus.

No one is advocating trying to put the genie back in the bottle.  Synthetic biology is here to stay.  In Beyond Animal, Ego and Time it was suggested synthetic biology should be taken out of the start-up stage of business where the profit motive is the reason venture capitalists are invested and returned to basic science.

In this case we would go backward from applied science to pure science by denying all patents on the grounds that life is the basis of these discoveries so there is insufficient novelty.  Denying patents would remove all economic incentive and return the field to scientists.

Now we must admit the moment has passed for this single step or for industry self-regulation.  On this basis there should be federal oversight established in four governmental departments; Centers for Disease Control, Environmental Protection Agency, the Federal Drug Administration and Homeland Security.   All of these departments should be engaged in drafting a law to be submitted by the Administration to Congress for action.

In addition, they should begin immediate oversight and regulation of the science consistent with their normal focus on our behalf.  This is an industry that is using the genetic code we all share for its own gains without thought to the continued integrity of our genetic code or to protection of the citizenry or environment we all share.   It has fought all efforts to seek self-regulation and now needs to be controlled.

Our government needs to stop looking at synthetic biology as a future opportunity for the U.S. to once again be a leader in a technology.  It needs to get serious about synthetic biology and recognize the threats it poses.

Use the following links to gain more information or access the source documents for this article.

http://www.nytimes.com/2014/05/08/business/researchers-report-breakthrough-in-creating-artificial-genetic-code.html?_r=o

http://www.nytimes.com/2014/05/09/science/a-synthetic-biology-conference-lures-an-intriguing-audience.html?_r=o

http://www.nytimes.com/2014/-5/08/business/researchers-report-breakthrough-in-creating-artificial-genetic-code.html?_r=0

http://newsoffice.mit.edu/2014/mits-synthetic-biology-center-collaborates-with-pfizer-to-advance-synthetic-biology-research-in-drug-discovery-and-development

http://news.yahoo.com/forgotten-vials-smallpox-found-storage-room-160303452.html

http://news.nationalgeographic.com/news/2014/03/140327-functional-designer-chromosome-synthetic-biology/

http://www.nature.com/nature/journal/v509/n7500/abs/nature13314.html

 

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Synthetic Biology: Potentially Useful, Weird or Creepy?

Posted on 22 June 2013 by Jerry

A lot of the language of synthetic biology is adopted from other fields, like engineering. This makes it difficult to understand.  It also masks from the rest of us what these experimenters are actually doing.  For instance, what are tunable mammalian oscillators, aptazyme-based riboswitches or double inversion recombination switches?

Rather than focus on developing new alien life forms, this article focuses on a different dimension of synthetic biology.  It deals with the development of predesigned genetic building blocks that use living cells to mimic existing functions that are performed today by common electronic components.  This assumes that someday scientists would be able to order synthetic genetic material from a catalogue for insertion, as a building block to create a new characteristic in a larger segment of genetic code or in a bacterium or another organism.

A report that originally appeared in the Oxford Journals in 2010 and was released by the National Institute of Health (NIH) hints at answers to the above raised questions.  “The challenges of informatics in synthetic biology: from biomolecular networks to artificial organisms” discusses the three challenges of synthetic biology in silico (in a computer), in vitro (in a test tube) and in vivo (as a part of a larger living organism).  See the link below.

Dissecting this phrase “tunable mammalian oscillators”, an oscillator is a familiar electronic device.  Wikipedia says it “is an electronic circuit that produces a repetitive, oscillating electronic signal, often a sine wave or a square wave.  Oscillators convert direct current (DC) from a power supply to an alternating current signal.”   Simple examples are a clock signal that regulates a computer and the sounds produced by electronic beepers.

In the animal kingdom a circadian clock (aka circadian oscillator) is just such a function.  Wikipedia says it “is a biological mechanism that oscillates with a period of 24 hours and is coordinated with the day-night cycle…. The clock is reset as the environment changes through an organism’s ability to sense external time cues of which the primary one is light.” In other words this is a function defined in the genes of a living cell or organism.

The synthetic biologist then seeks to transplant this capability via synthetic genetic material from one type of organism to another.  This could be a transfer to a new life form or figuring out how to devise a new tool that combines living tissue with inanimate components.

Imagine a future where once inanimate things now have living tissue; a personal computer that has living cells for its clock functions and that provide its memory?  How about asphalt streets that begin a self-healing function when a crack develops or a roof that contains living tissue that perspires when its temperature passes a certain point?  How about robots covered with synthetic tissue that look human (or cyborgs that are a self-regulating integration of artificial and natural systems known as Terminators)?

Beginning chimeric combinations such as these were described in an August 6, 2012 posting entitled “Chimeric Systems: Living and Non-Living Components”.  This article actually showed positive outcomes and hopeful research that could result from synthetic biology.

Do not misunderstand.  I do not oppose either genetic engineering or synthetic biology as potentially useful sciences.  I do think both areas copy that which was learned from observing the natural activities of bacteria and viruses.  I believe what was observed occurred in nature and consequently should not be patentable.

This would go a long way to slow the pace of both sciences by taking them out of the hands of entrepreneurs and putting them back in the hands of scientific researchers.  This would involve only a minor redefinition from what was unanimously defined in a recent Supreme Court ruling that a gene is not patentable. ( http://www.supremecourt.gov/opinions/slipopinions.aspx 6/13/13 Docket 12-398, Association for Molecular Pathology v. Myriad Genetics, Inc.)

I also take the position that both sciences are too dangerous to not have governmental oversight and regulatory restraints.  Today there is no one looking over either science’s shoulder to insure they are not endangering life.  I do not believe self-defined, voluntary industry rules governing experimentation protect us in either area.  Why do people wait until there is a disaster before taking steps to control that which is obviously dangerous?

Lest you think synthetic biology is some obscure science practiced by a few institutions, look at the following list of academic programs in synthetic biology across a whole spectrum of respected academic institutions in numerous countries.   See http://syntheticbiology.org/Graduate.html .

If you want an idea of who is heading these post-graduate programs or what they are working on, look at http://synbio.berkeley.edu/ or at http://bioengineering.rice.edu/Content.aspx?id=277 .  If you ask what is in it for them, see our previous posting of June 13, 2012 entitled “Genetic Engineering Influence Peddling and Profit”.  This article illustrates how moving from academic institutions to government and back can benefit and how setting up profit making organizations along side a non-profit lab can be profitable.

Previous posts about synthetic biology looked at its attempt to create new alien living organisms (see 5/17/12 – Troubling Progress for Synthetic Biology and 12/2/12 – Synthetic Biology Continued: Risks or Benefits?).

Use the following links to obtain more information:

http://www.ncbi.nlm.nih.gov/pubmed/19906839 (Select “Free PMC Article” in the middle of the page to access the entire report.)

http://www.wikipedia.org/wiki/electronic_oscillator

http://en.wikipedia.org/wiki/circadian_clock

http://www.cs.cmu.edu/~chongw/citeulike/docs/doc14956.html

http://www.supremecourt.gov/opinions/slipopinions.aspx See 6/13/13 Docket 12-398, Association for Molecular Pathology v. Myriad Genetics, Inc.)

http://www.nytimes.com/2013/06/14/us/supreme-court-rules-human-genes-may-not-be-patented.html

http://www.dailycal.org/2013/06/19/uc-professors-express-mixed-reactions-to-supreme-court-ruling-on-gene-patents/

http://syntheticbiology.org/Graduate.html

http://synbio.berkeley.edu/

http://bioengineering.rice.edu/Content.aspx?id=277

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