Endosymbiont Hypothesis and the Ironic Case for a Creator



i ·ro ·ny

The use of words to express something different from and often opposite to their literal meaning.
Incongruity between what might be expected and what actually occurs.

—The Free Dictionary

People often use irony in humor, rhetoric, and literature, but few would think it has a place in science. But wryly, this has become the case. Recent work in synthetic biology has created a real sense of irony among the scientific community—particularly for those who view life’s origin and design from an evolutionary framework.

Increasingly, life scientists are turning to synthetic biology to help them understand how life could have originated and evolved. But, they have achieved the opposite of what they intended. Instead of developing insights into key evolutionary transitions in life’s history, they have, ironically, demonstrated the central role intelligent agency must play in any scientific explanation for the origin, design, and history of life.

This paradoxical situation is nicely illustrated by recent work undertaken by researchers from Scripps Research (La Jolla, CA). Through genetic engineering, the scientific investigators created a non-natural version of the bacterium E. coli. This microbe is designed to take up permanent residence in yeast cells. (Cells that take up permanent residence within other cells are referred to as endosymbionts.) They hope that by studying these genetically engineered endosymbionts, they can gain a better understanding of how the first eukaryotic cells evolved. Along the way, they hope to find added support for the endosymbiont hypothesis.1

The Endosymbiont Hypothesis

Most biologists believe that the endosymbiont hypothesis (symbiogenesis) best explains one of the key transitions in life’s history; namely, the origin of complex cells from bacteria and archaea. Building on the ideas of Russian botanist Konstantin Mereschkowski, Lynn Margulis(1938–2011) advanced the endosymbiont hypothesis in the 1960s to explain the origin of eukaryotic cells.

Margulis’s work has become an integral part of the evolutionary paradigm. Many life scientists find the evidence for this idea compelling and consequently view it as providing broad support for an evolutionary explanation for the history and design of life.

According to this hypothesis, complex cells originated when symbiotic relationships formed among single-celled microbes after free-living bacterial and/or archaeal cells were engulfed by a “host” microbe. Presumably, organelles such as mitochondria were once endosymbionts. Evolutionary biologists believe that once engulfed by the host cell, the endosymbionts took up permanent residency, with the endosymbiont growing and dividing inside the host.

Over time, the endosymbionts and the host became mutually interdependent. Endosymbionts provided a metabolic benefit for the host cell—such as an added source of ATP—while the host cell provided nutrients to the endosymbionts. Presumably, the endosymbionts gradually evolved into organelles through a process referred to as genome reduction. This reduction resulted when genes from the endosymbionts’ genomes were transferred into the genome of the host organism.


Figure 1: Endosymbiont hypothesis. Image credit: Wikipedia.

Life scientists point to a number of similarities between mitochondria and alphaproteobacteria as evidence for the endosymbiont hypothesis. (For a description of the evidence, see the articles listed in the Resources section.) Nevertheless, they don’t understand how symbiogenesis actually occurred. To gain this insight, scientists from Scripps Research sought to experimentally replicate the earliest stages of mitochondrial evolution by engineering E. coli and brewer’s yeast (S. cerevisiae) to yield an endosymbiotic relationship.

Engineering Endosymbiosis

First, the research team generated a strain of E. coli that no longer has the capacity to produce the essential cofactor thiamin. They achieved this by disabling one of the genes involved in the biosynthesis of the compound. Without this metabolic capacity, this strain becomes dependent on an exogenous source of thiamin in order to survive. (Because the E. coli genome encodes for a transporter protein that can pump thiamin into the cell from the exterior environment, it can grow if an external supply of thiamin is available.) When incorporated into yeast cells, the thiamin in the yeast cytoplasm becomes the source of the exogenous thiamin, rendering E. coli dependent on the yeast cell’s metabolic processes.

Next, they transferred the gene that encodes a protein called ADP/ATP translocase into the E. coli strain. This gene was harbored on a plasmid (which is a small circular piece of DNA). Normally, the gene is found in the genome of an endosymbiotic bacterium that infects amoeba. This protein pumps ATP from the interior of the bacterial cell to the exterior environment.2

The team then exposed yeast cells (that were deficient in ATP production) to polyethylene glycol, which creates a passageway for E. coli cells to make their way into the yeast cells. In doing so, E. coli becomes established as endosymbionts within the yeast cells’ interior, with the E. coli providing ATP to the yeast cell and the yeast cell providing thiamin to the bacterial cell.

Researchers discovered that once taken up by the yeast cells, the E. coli did not persist inside the cell’s interior. They reasoned that the bacterial cells were being destroyed by the lysosomal degradation pathway. To prevent their destruction, the research team had to introduce three additional genes into the E. coli from three separate endosymbiotic bacteria. Each of these genes encodes proteins—called SNARE-like proteins—that interfere with the lysosomal destruction pathway.

Finally, to establish a mutualistic relationship between the genetically-engineered strain of E. coli and the yeast cell, the researchers used a yeast strain with defective mitochondria. This defect prevented the yeast cells from producing an adequate supply of ATP. Because of this limitation, the yeast cells grow slowly and would benefit from the E. coli endosymbionts, with the engineered capacity to transport ATP from their cellular interior to the exterior environment (the yeast cytoplasm.)

The researchers observed that the yeast cells with E. coli endosymbionts appeared to be stable for 40 rounds of cell doublings. To demonstrate the potential utility of this system to study symbiogenesis, the research team then began the process of genome reduction for the E. coli endosymbionts. They successively eliminated the capacity of the bacterial endosymbiont to make the key metabolic intermediate NAD and the amino acid serine. These triply-deficient E. coli strains survived in the yeast cells by taking up these nutrients from the yeast cytoplasm.

Evolution or Intentional Design?

The Scripps Research scientific team’s work is impressive, exemplifying science at its very best. They hope that their landmark accomplishment will lead to a better understanding of how eukaryotic cells appeared on Earth by providing the research community with a model system that allows them to probe the process of symbiogenesis. It will also allow them to test the various facets of the endosymbiont hypothesis.

In fact, I would argue that this study already has made important strides in explaining the genesis of eukaryotic cells. But ironically, instead of proffering support for an evolutionary origin of eukaryotic cells (even though the investigators operated within the confines of the evolutionary paradigm), their work points to the necessary role intelligent agency must have played in one of the most important events in life’s history.

This research was executed by some of the best minds in the world, who relied on a detailed and comprehensive understanding of biochemical and cellular systems. Such knowledge took a couple of centuries to accumulate. Furthermore, establishing mutualistic interactions between the two organisms required a significant amount of ingenuity—genius that is reflected in the experimental strategy and design of their study. And even at that point, execution of their experimental protocols necessitated the use of sophisticated laboratory techniques carried out under highly controlled, carefully orchestrated conditions. To sum it up: intelligent agency was required to establish the endosymbiotic relationship between the two microbes.


Figure 2: Lab researcher. Image credit: Shutterstock.

Or, to put it differently, the endosymbiotic relationship between these two organisms was intelligently designed. (All this work was necessary to recapitulate only the presumed first step in the process of symbiogenesis.) This conclusion gains added support given some of the significant problems confronting the endosymbiotic hypothesis. (For more details, see the Resources section.) By analogy, it seems reasonable to conclude that eukaryotic cells, too, must reflect the handiwork of a Divine Mind—a Creator.



  1. Angad P. Mehta et al., “Engineering Yeast Endosymbionts as a Step toward the Evolution of Mitochondria,” Proceedings of the National Academy of Sciences, USA 115 (November 13, 2018): doi:10.1073/pnas.1813143115.
  2. ATP is a biochemical that stores energy used to power the cell’s operation. Produced by mitochondria, ATP is one of the end products of energy harvesting pathways in the cell. The ATP produced in mitochondria is pumped into the cell’s cytoplasm from within the interior of this organelle by an ADP/ATP transporter.
Reprinted with permission by the author
Original article at:

A Genetically Engineered Case for a Creator



Since the 1960’s, the drug noscapine has been used in many parts of the world as a non-narcotic cough-suppressant. Recently, biomedical researchers have learned that that noscapine (and chemically-modified derivatives of this drug) has potential as a cancer drug. And that is nothing to sneeze at.

The use of the drug for nearly a half century as a cough suppressant means the safety of noscapine has already been established. In fact, pre-clinical studies indicate that noscapine has fewer side effects than many anti-cancer drugs.

Unfortunately, the source of noscapine is opium poppies. Even though tens of tons of noscapine is isolated each year from thousands of tons of raw plant material, biochemical engineers question if the agricultural supply line can meet the extra demand if noscapine finds use as an anti-cancer agent. Estimates indicate that the amounts of noscapine needed for cancer treatments would be about ten times the amount currently produced for its use as a cough suppressant. Complicating matters are the extensive regulations and bureaucratic red tape associated with growing poppy plants and extracting chemical materials from them.

It takes about 1 year to grow mature poppy plants. And once grown, the process of isolating pure noscapine is time intensive and expensive. This drug has to be separated from narcotics and other chemicals found in the opium extract, and then purified. Because poppy plants are an agricultural product, considerable batch-to-batch variation occurs for noscapine supplies.

Chemists have developed synthetic routes to make noscapine. But, these chemical routes are too complex and costly to scale up for large scale production of this drug.

But, researchers from Stanford University believe that they have come up with a solution to the noscapine supply problem. They have genetically engineered brewer’s yeast to produce large quantities of noscapine.1 This work demonstrates the power of synthetic biology to solve some of the world’s most pressing problems. But, the importance of this work extends beyond science and technology. This work has significant theological implications, as well. This work provides empirical proof that intelligent agency is necessary for the large-scale transformation of life forms.

Genetically Engineered Yeast

To modify brewer’s yeast to produce noscapine, the Stanford University research team had to: 1) first, construct a biosynthetic pathway that would convert simple carbon- and nitrogen-containing compounds into noscapine, and then, 2) add genes to the yeast’s genome that would produce the enzymes needed to carry out this transformation. Specifically, they added 25 genes from plants, bacteria, and mammals to this microbe’s genome. On top of the gene additions, they also had to modify 6 of genes in the yeast’s genome.

Biosynthetic pathways that yield complex molecules such as noscapine can be rather elaborate. Enzymes form these pathways. These protein machines bind molecules and convert them into new materials by facilitating chemical reactions. In biosynthetic pathways the starting molecule is modified by the first enzyme in the pathway and after its transformation is shuttled to the second enzyme in the pathway. This process continues until the original molecule is converted step-by-step into the final product.

Designing a biosynthetic route from scratch would be nearly impossible. Fortunately, the team from Stanford took advantage of previous work done by other life scientists who have characterized the metabolic reactions that produce noscapine in opium poppies. These pioneering researchers have identified a cluster of 10 genes that encode enzymes that work collaboratively to convert the compound scoulerine to noscapine.

The Stanford University researchers used these 10 poppy genes as the basis for the noscapine biosynthetic route they designed. They expanded this biosynthetic pathway by using genes that encode for the enzymes that convert glucose into reticuline. This compound is converted into scoulerine by the berberine bridge enzyme. They discovered that the conversion of glucose to reticuline is tricky, because one of the intermediary compounds in the pathway is dopamine. Life scientists don’t have a good understanding how this compound is made in poppies, so they used the genes that encode the enzymes to make dopamine from rats.

They discovered that when they added all of these genes into the yeast, these modified microbes produced noscapine, but at very low levels. At this point, the research team carried out a series of steps to optimize noscapine production, which included:

  • Genetically altering some of the enzymes in the noscapine biosynthetic pathway to improve their efficiency
  • Manipulating other metabolic pathways (by altering the expression of the genes that encode enzymes in these metabolic routes) to divert the maximum amounts of metabolic intermediates into the newly constructed noscapine pathway
  • Varying the media used to grow the yeast

These steps led to an 18,000-fold improvement in noscapine production.

With accomplishment, the scientific community is one step closer to have a commercially-viable source of noscapine.

Synthetic Biology and the Case for a Creator

Without question, the engineering of brewer’s yeast to produce noscapine is science at its very best. The level of ingenuity displayed by the research team from Stanford University is something to behold. And, it is for this reason, I maintain that this accomplishment (along with other work in synthetic biology) provides empirical evidence that a Creator must play a role in the origin, history, and design of life.

In short, these researchers demonstrated that intelligent agency is required to originate new metabolic capabilities in an organism. This work also illustrates the level of ingenuity required to optimize a metabolic pathway once it is in place.

Relying on hundreds of years of scientific knowledge, these researchers rationally designed the novel noscapine metabolic pathway. Then, they developed an elaborate experimental strategy to introduce this pathway in yeast. And then, it took highly educated and skilled molecular biologists to go in the lab to carry out the experimental strategy, under highly controlled conditions, using equipment that itself was designed. And, afterwards, the researchers employed rational design strategies to optimize the noscapine production.

Given the amount of insight, ingenuity, and skill it took to engineer and optimize the metabolic pathway for noscapine in yeast, is it reasonable to think that unguided, undirected, historically contingent evolutionary processes produced life’s metabolic processes?


Creating Life in the Lab: How New Discoveries in Synthetic Biology Make a Case for a Creatorby Fazale Rana (book)

New Discovery Fuels the Case for Intelligent Design” by Fazale Rana (article)

Fattening Up the Case for Intelligent Design” by Fazale Rana (article)

A Case for Intelligent Design, Part 1” by Fazale Rana (article)

A Case for Intelligent Design, Part 2” by Fazale Rana (article)

A Case for Intelligent Design, Part 3” by Fazale Rana (article)

A Case for Intelligent Design, Part 4” by Fazale Rana (article)

The Blueprint for an Artificial Cell” by Fazale Rana (article)

Do Self-Replicating Protocells Undermine the Evolutionary Theory” by Fazale Rana (article)

A Theology for Synthetic Biology, Part 1” by Fazale Rana (article)

A Theology for Synthetic Biology, Part 2” by Fazale Rana (article)


  1. Yanran Li et al., “Complete Biosynthesis of Noscapine and Halogenated Alkaloids in Yeast,” Proceedings of the National Academy of Sciences, USA(2018), doi: 10.1073/pnas.1721469115.
Reprinted with permission by the author
Original article at: