The Pace of Scientific Advancement

The pace with which scientific and technological advances are happening is astounding. In 2014/2015, researchers had just begun to grasp the potential of the CRISPR/Cas9 system to edit genomes (see my previous blog here). The technology allows scientists to cut out pieces of DNA and replace the displaced DNA with a novel strand. This can be used to stop a gene from working or to correct its function. Now, researchers report that they have modified the CRISPR/Cas 9 and Cas 13 systems such that DNA is not cut but changed one base-pair at a time.

The principle in this case is that CRISPR systems can be used to guide other molecular enzymes to a location within the genome. Researchers can remove the cutting mechanism of CRISPR systems and add an enzyme that can convert the base-pair mutations one at a time. The technology is still not perfect, as the journals report that the efficiency of such systems may be only as much as 50% in the targeted areas. However, the procedure is seen as potentially safer than DNA cutting technologies that occasionally cut in the wrong place, potentially disrupting other genes.

CRISPR technology is our best hope yet for successful gene therapy. Although specificity and efficiency issues need to be resolved, this technology has the potential to repair cancer-causing mutations, correct single-base mutations that cause genetic diseases, seek out and disable HIV viruses lying dormant in human cells, repair mitochondria that have lost function due to a deletion or mutation, and many more beneficial effects. CRISPR could also be used to change such fundamental characteristics as eye-colour, skin-tone, propensity for a certain height or weight, and even some hard-wired behavioural traits. On the one hand, if possible, why would we not want to correct a propensity toward Autism, Alzheimers, or Huntingtons Chorea? On the other hand, how will we feel about genetic tinkering that allows one to choose whether or not a child will be born with an epicanthic fold, blond hair, or a small nose? How might we respond to research that created oversized or undersized humans or animals?  (Just imagine how many mini-humans you could fit on a West Jet economy flight; or the economic value of low-fat pigs for CRISPR bacon.) (Insert smile and groan here.) Such research is being conducted in animal models, once again proving that our scientific capabilities are exceeding our philosophical and ethical conversations on these subjects.

CRISPR technology is a contemporary “genie in a bottle” much like the atomic research of the previous century. It has been released from the bottle in which it was contained for many millennia. We cannot put it back; nor do we wish to put it back into the bottle. We must consider how we will use this precious gift of God’s science as we seek to live out God’s image in humanity on this fragile lifeboat planet.

Otters, Shells, and Genomes

Science News is asking questions about animal intelligence in an article about otters and tool use in a March 21, 2017 article. The article entitled, “Tool use in sea otters doesn't run in the family,” suggests that using rocks to crack open snails and other shells to get at the rich food inside, may truly be a learned behavior that each generation must discover.

Those who read this blog regularly will know that I am fascinated with the intelligence of animals. (You can read a quick summary here and find links to other articles on this subject in the same place.) Most of the writing and reading I have done on this subject has emphasized the learned aspect of such behaviour. There is a great deal of evidence to suggest that crows teach other crows the techniques related to breaking open mussel shells and staying away from strangers. So, it is not surprising that researchers are having a difficult time finding the gene responsible for tool use in otters. However, I would caution us that just because a gene carrying this propensity has not been found, does not mean that the gene does not exist. The author of the paper even admits this when she suggests that “sea otters may all be predisposed to using tools because their ancestors probably lived off mollusks, which required cracking open.” Could it be that all otters carry the gene for tool use and only use it when necessary?

I am thankful for authors who give us interesting summaries of research papers. At the very same time, I am cautious about how that data is characterized. I encourage us to read with great discernment, “wise as serpents and gentle as doves.”

JCVI-syn3.0

At a biological level, what is the minimal number of genes needed to sustain life in an organism? That is a question that is being asked by a group of scientists who have been engineering the genome of the bacteria known as Mycoplasma mycoides. For a few years, the team has been taking genes out and rearranging the order of the genome within this bacterium. In 2010, they engineered a strain called JCVI-syn1.0 which contained only 901 genes. That is a relatively small genome considering that a typical strain of Escherichia coli (E. coli) has approximately 5400 genes; but JCVI-syn1.0 was not yet minimal. A new strain, created in 2016, called JCVI-syn3.0 has been developed that contains only 473 genes. The bacteria continue to live, thrive, and reproduce with only these genes. This strain may be pointing to the basic building blocks of life and the minimum genes necessary to sustain life and reproduction.

It is an interesting philosophical question: “What is life?” What are the basic components necessary to make something alive versus inanimate? These 473 genes may define life. An interesting side-bar is that 65 of these genes are known to be necessary for life, but it is not known what they are doing in the cell. Further research into the function of these 65 genes will be a key area of future research.

Another fascinating aspect of this research is that the researchers have been organizing the genes into little modules and keeping genes of similar function together in the genome. Evolutionary change has put genes in a certain order, but these scientists have found that they can change that order and make it more convenient for their work without detrimental consequences to the bacteria. CRISPR technology has made the whole process simpler and led to the recent rapid developments.

This brings science a few steps closer to creating synthetic life. Of course, at this stage, researchers are simply reassembling the components supplied by the Creator to build a synthetic cell. How far might humans be able to go in building other cell structures beyond these artificial genomes? Whatever one thinks of such biological engineering, it is important to be aware of the directions in which science is moving. There are philosophical, theological, and ethical implications of such research. We must be ready to discuss and give guidance in these areas as technology continues to push boundaries. 

CRISPR

CRISPR is a relatively new term that describes new discoveries and new technology in the world of genetics. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats and refers to short repetitions of base pair sequences in bacterial genomes which naturally occur as part of bacterial genetic defence mechanisms against invading viruses. These CRISPR sequences are used by bacteria to store genetic memories of past viral invasions that might otherwise lead to the destruction of the bacterial cell. Next to a CRISPR sequence is a segment of DNA that represents part of a viral genome from a previous encounter with that virus. It is like the bacteria store a photo of all of the viruses that previously tried to kill them and then recognize that virus when it shows up again. Cas9 enzymes search through the cell for these potentially dangerous pieces of DNA and then make RNA copies that will guide the Cas9 enzyme to the dangerous viral DNA and cut it in two so that the virus is defeated. If a new virus shows up, Cas9 first makes a copy of the new viral genome and inserts it in between the CRISPR sequences so that it is ready for the next time this virus tries to invade.

This biological system within the cells of bacteria has been exploited and used by genetic scientists to create a tool that can be used to edit the genome of humans and other research subjects. So, you may also hear people refer to CRISPR technology as it is used for gene editing in medicine and research. Cas9 and other CRISPR enzymes recognize strings of DNA about 20 base-pairs in length and can therefore be engineered to be very specific and targeted. This has allowed researchers to load Cas9 with a specific sequence that can then target where they would like to cut out a piece of DNA, say to knock out a gene and determine what that gene does, knock out a rogue gene that is malfunctioning, or to cut out a defective gene and replace it with a properly functioning gene. Recently, scientists in China used this technology to engineer cells to potentially treat lung cancer. In this case, CRISPR technology was used on immune cells taken from the patients and a gene was disabled. The protein, PD-1, normally slows down or ends an immune response (something that is normally needed but exploited by cancer cells) and so researchers inactivated it so that the body might continue to mount an immune response against the cancer cells in the lungs. This represents the first time CRISPR technology has been used in such a way in human trials.

As one can readily see, this technology has vast implications and has the potential to solve many medical problems. CRISPR could repair the mutation that causes Cystic-Fibrosis in a family’s genetic makeup, or repair the gene that causes genetic forms of colon cancer such as Adenomatous Polyposis Coli (APC). It also brings with it the possibility of ethical challenges. It could be used to substitute the gene for blue eyes in place of the gene for brown eyes (or the opposite exchange); or it could be used to substitute a gene that codes for average height for a gene that codes for exceptional height (really handy if you are trying to build an Olympic basketball team). Taken to logical conclusions, CRISPR technology could be used to build a super-race of humans and even create genetic enhancements that cannot yet be imagined (think real life X-Men mutants). Scientists in China have already published data showing that they had successfully modified the DNA on nonviable human embryos. They could have just as easily been working on viable embryos.

In a future where diseases can be eradicated and enhancements can be made, what becomes of the average person with defects or no enhancements? Should we concern ourselves with this? A few years ago, the movie Gattaca attempted to engage audiences in questions related to such issues. Now, nearly 20 years later, genetic technology has advanced to nearly the point predicted in that movie. What will another 10 years of medical and technological advance look like in our world? How might we prepare now for the ethical questions yet to come?

For further explanation and discussion, read this article on the modification of DNA in nonviable human embryos.

Results of Tardigrade Paper Questioned

It only took a few days for the results of a new Tardigrade study to be called into question. No one questions the hardiness of Tardigrades, aka Water Bears; but are they the great scavengers of DNA that the Cambridge Researchers suggested? (See the paper by Eyres, et al.) A paper published by researchers at the University of Edinburgh and the University of Oxford concludes that the genomic research from Cambridge may have been contaminated by other genomes. (See also Science News here.) Of course the Cambridge team acknowledged this and worked hard to prevent such contamination; but the fact is, with incredibly sensitive PCR reactions and hardy sequencing of small amounts of DNA, contamination is always a possibility.

The Cambridge team will likely be working through the Christmas break to see if they can redeem the results of their previous study. But, with the suggested level of contamination, they might do well to move to another lab where they can start with a fresh supply of Tardigrades that will not be prone to the same sources of contamination. Perhaps the only thing hardier than a Tardigrade is cellular DNA. This lends a further significance to the concept of selfish genes. 

Science is Stranger than Screenplays

With Batman and Superman preparing to do battle in our movie theatres[1], perhaps you have wondered, "What is the most invulnerable creature on our planet?" The armadillo? The Blue Whale? Lions? Elephants? No, there is one creature that is much more durable than all of these. It can survive being boiled and frozen; in fact it can live in temperature ranges of −272 °C to 149 °C. It can tolerate the vacuum of space while being exposed to more ionizing radiation than any other creature. It can also survive without food or water for decades (some have been rehydrated after 120 years of desiccation).[2] No, it is not that fictional life form from the Alien[3] movies. Truth is sometimes stranger than our fictional screenplays.

The Tardigrade, or Water Bear, pictured here, wins the gold medal for invincibility. However, you would need a very small ribbon to hang the award around its neck; Water Bears are only visible with a microscope and measure approximately 1.5 mm across their longest dimension. They are certainly weird looking animals and would likely scare the wits out of any of us if they were more like half a meter in length. Fortunately, unless you go looking for them, you will never see one. They like to live on mossy surfaces where they thrive on microscopic drops of secreted liquid. They can also live in our water supply, the gutters of our city streets, and our cupboards.

Researchers (and yes there are those who study these tiny animals in the wild) have recently made a remarkable discovery about Tardigrades. They have the ability to scavenge and incorporate DNA from other living creatures. (Note well, the paper related to this research has been subsequently questioned and researchers are working to confirm or deny the results of this research.) In one recent study, it was found that "the Hypsibius dujardini tardigrade incorporated into their own DNA genes from more than 1,300 bacterial species, 40 archaea, 91 species of fungus, 45 plant species and six viruses."[4] When severely dehydrated, Water Bears, and other organisms around them, spill out DNA from broken cells. The unique thing about the Tardigrade is that when water returns to the environment, they can quickly sew their DNA back together and sometimes incorporate other free-floating DNA. It is likely this feature that has made them so invulnerable to extreme conditions. Move over Superman, there is a new god-like creature in town. Perhaps someone needs to turn this match-up into a movie.

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[1] Batman v Superman: Dawn of Justice (2016); IMDB; http://www.imdb.com/title/tt2975590/

[2] "Tardigrade," Wikipedia; https://en.wikipedia.org/wiki/Tardigrade#Ecology_and_life_history

[3] Alien (1979); IMDB; http://www.imdb.com/title/tt0078748/?ref_=nv_sr_2

[4] Science News; November 25, 2015, "Water Bears Are Genetic Mash-Ups;  https://www.sciencenews.org/article/water-bears-are-genetic-mash-ups The validity of this study has since been called into question. See the follow-up blog at http://bit.ly/1maOaCB.

Evolution and Christianity: to Kirk Durston

Today I would like to respond to a blog post written by Kirk Durston. I have never met Dr. Durston but I want to say I appreciate the post he has written even as I will disagree with points made within it. The post does a great service by pointing out many of the doctrines that would need to be examined and adjusted to fit an evolutionary understanding of creation. He notes, with Edwin Walhout, that “original sin,” “salvation,” and “God’s purpose in history” need to be re-examined. I will not take up any response to the issues of our understandings of “salvation” and “God’s purpose in history” for it seems to me that these two are more readily explainable and cause less of an issue than our concept of “original sin” and indeed it is this doctrine to which Durston refers throughout the rest of his post.

Our present understanding of original sin is highly linked to the understanding that historical persons named Adam and Eve lived in the literal Garden of Eden and made choices that were forever passed down to their descendents. Eve sinned first by eating fruit from the “Tree of Knowledge of Good and Evil” and then Adam joined her in this sin. There are several ways in which this rebellion against God is understood to be passed down from generation to generation but the key uniting factor in how this is viewed is that all of the physical descendents of this couple, in some fashion, receive this tendency toward rebellion or this sin into their lives at birth or shortly after. You can already see by my choice of words that there is a great deal of argument, confusion, and disagreement among theologians as to how precisely this occurs; but we will leave that out of things for now.

Durston points out the problem of accepting that humans were created by God through a process that involved ancestors who were more primitive hominids. He shows how this might require that we choose some couple within the evolutionary process to be the original Adam and Eve and make this couple the initial pair in God’s redemptive process for humanity. Yet, the problem with God simply choosing two humans and declaring them to be Adam and Eve, is that the same contemporary science which states that humans descended from other primitive hominids also states that the human population has never been less than a few thousand individuals.This means that we did not all descend from just two individual homo sapiens.

Up to this point, I agree with Durston’s post. It is here that we diverge in our hypotheses of how God began the redemptive process. I, along with such authors as Dennis Venema and Darrell Falk, would begin to disagree with certain statements in Durston’s next paragraphs. There are other ways to solve the difficulties of our present theology than the ones presented by Durston’s post. He rightly points out that the fact that the humans now on this earth descend from a few thousand original humans means that we could push the original chosen couple even further back in time and further back in evolutionary history such that the original Adam and Eve were one of the antecedent hominids. Adam and Eve may have been Neandertals (Homo neanderthalensis) or Denisovans (Denisova hominins) or a combination of the two. Of course this creates other questions with which our theology must wrestle but these are not insurmountable challenges, as Durston seems to suggest.

The other possibility to which Durston points is to suggest that there never was an historical couple named Adam and Eve. Although this may be a difficult concept to accept, again, it is possible to imagine that God speaks to us through Genesis in a fashion that was readily understandable to the people of the time in which it was written and must now be understood in a different fashion. Durston suggests that if we get rid of the concept of an historical Adam and Eve then the New Testament writers “were sincerely mistaken in their acceptance of Adam as a real historical figure” and that the Bible must be viewed as a document containing “divinely inspired misinformation.” I am tempted to take issue with Durston’s use of the words “mistaken” and “misinformation” because, to my mind, these words are too harsh and convey too much about the alleged character of our God, but I do not want to make this the main issue and so let us use the terms which Durston uses. Then we would say that the New Testament writers who refer to an historical Adam would be mistaken and that the New Testament would contain misinformation. Surely Mr. Durston is not unaware of other examples of mistaken ideas and misinformation in the Bible. Take for example the Old Testament commands regarding “clean” and “unclean” animals. Both Leviticus 11:3-6 and Deuteronomy 14:7 state that the hare chews a cud. This is clearly a mistaken concept based on Ancient Middle Eastern understandings. Hares or rabbits do not chew cuds and so this information in the Old Testament is technically wrong and “divinely inspired misinformation.” Despite this fact, we do not call into question the entire Bible or the entire Old Testament. What of Joshua 10:13 which speaks of the “sun standing still” to prolong the length of the day? Wouldn’t it be more accurate to speak of the earth standing still? What of Matthew 13:32 that refers to the Mustard seed as the smallest of all seeds? This is a mistake and represents a false understanding of the scientific world. We could go on with other examples.

Perhaps the New Testament writers were mistaken in their assessment that Adam was an historical figure. Is this an insurmountable theological problem? No. Is integrating an understanding of evolutionary creation going to require that we re-think some of the theology that has been created over the last two millennia? Yes. I respectfully submit that Kirk Durston is not willing to follow some of these possibilities to their theological ends; but they may indeed be workable and consistent with both divine inspiration and scientific discovery. Alternatives that reject an evolutionary understanding of creation have their own theological issues that must be explained. If God did not create humans using more primitive hominids, why do we find such ancient hominids in the fossil record? Why does our own DNA seem to contain DNA from ancient neandertals? Why does the earth and the universe appear to be extremely old?

Theology must work toward answers that are not yet seen. We need new hypotheses that may be tested to see how they work before moving on to seek to explain the next challenges that may come at our collective theologies. I pray that we might be able to live with uncertainty and hope until all uncertainty is banished and we see clearly the object of our hope. Of course, that time will only be when we see “all things with perfect clarity.”1



1 1 Corinthians 13:12 (New Living Translation)

Gene Therapy

Molecular biologists have been searching for years to find efficient and effective ways of accomplishing gene therapy. None of the attempts thus far have worked. One of the most promising in recent years is explained in an article published in the journal Science in February of 2013. The researchers suggest that using an RNA guiding system might be the way to achieve the desired repair. (RNA is a nucleic acid which binds to DNA and is the normal molecule that makes copies of our DNA so that proteins can be made from the RNA.)

This post will attempt to explain the procedure in simplified terms and point to the potential for valuable medicine in this method. First of all, gene therapy, if it is ever achieved, would be the ability to repair DNA mutations that lead to disease. For the purposes of this discussion we will use one of the most common mutations which causes Cystic Fibrosis (CF). CF is a disease which affects the lungs, pancreas, liver, and intestines because of excessively thick secretions in each of these organs. The most common genetic mutation is the delta-F508 mutation. If a person inherits one copy of this mutation from each of their parents, every cell in their body will carry two copies of this mutation and the person will be affected with the disorder. The disease is serious and results in a shortened life expectancy.

What this means at the DNA level is that where most of us have a stretch of DNA, at a spot marked as 507/508, that looks like this: TAGAAA. The person carrying the mutation has only TAA; the sequence GAA is missing. A slightly longer sequence in this region looks like this in the normal gene: TTATAGTAGAAACCA; and in the mutated form: TTATAGTAACCA.

In order for gene therapy to work in repairing this mutation, what is needed is an enzyme that disperses to every cell in our body (approximately 10 trillion cells), finds the appropriate TTATAGTAACCA (mutant, disease causing) string, cuts it out, and replaces it with TTATAGTAGAAACCA (the appropriate healthy string of DNA). That is quite the surgical procedure. The researchers who wrote in Science believe they may have come up with a way to do just this. They have created enzymes with short pieces of RNA attached. With appropriate RNA sequences, the enzymes will bind to specific DNA sequences so that the enzymes can do their repair work. It is a very interesting development. I will be watching this work to see how well it pans out. Many previous attempts at gene therapy have failed to live up to their original hype. This one, so far, shows great promise.

Works Cited:
"Top Scientific Discoveries of 2013;" Wired Science; December 18, 2013; http://www.wired.com/wiredscience/2013/12/top-scientific-discoveries-2013/#slideid-400731

Science 15 February 2013: Vol. 339, no. 6121, pp. 768-770, "New Tool for Genome Surgery," John van der Oost; http://www.sciencemag.org/content/339/6121/768.summary

Loving Truth

In 1999 I worked in a genetics lab in Calgary using the latest molecular DNA techniques to diagnose genetic disorders in the families that came into our clinics and other clinics across the country. Families relied on us and used the information we generated to make decisions about their own health and the health of their children. The techniques we used were developed in our lab using previously determined methods and we had a great deal of trust in the system. We were always aware of the possibility of building our systems upon inaccuracies of others but with peer reviewed papers and a healthy degree of checking each others work we generated data that was suitable for the needs of our patients.

In 1999 we were also very much aware of computer programs built upon other programs. Our lab data-base and our DNA analysis systems were built using other people's code and we did not always know the type of system previous programmers had used for labeling the dates on files. As the new millennium loomed before us we were concerned that someone might have used a calendar system that could not deal with the year 2000. Some systems would click over from 1999 to 2000 by going from 99 to 00 and programs might see this as an invalid date. This of course was the essence of the Y2K concerns of the late 1990s. Much time, energy, and money was expended on this issue to confirm that our databases, timers, and machines would survive into the new century.

Both the lab systems and the computer systems illustrate a problem that has implications for our scientific, philosophic, and theological systems. Any work we do presently is necessarily built upon the work of others and shares assumptions that we may not even comprehend as we build our work.

Blaise Pascal, the French mathematician, physicist, and philosopher looked into the philosophy of scientific discovery and found that the conclusions of one person were always dependent upon previous axioms;1 and that no one was able to completely investigate all previous assumptions, inferences, and "self-evident" truths. He concluded that, “Truth is so obscure in these times, and falsehood so established, that, unless we love the truth, we cannot know it.”2 Those are good words for all of us. Do we love truth enough to pursue it wherever it may take us? When we find truth in conflict with our previous beliefs can we examine how this truth may be incorrect because of a wrong assumption? Or, can we recognize that our previous belief may need some adjustment? Is my understanding of science or theology narrow and short-sighted because of flawed axioms built into my system of beliefs? What if we could all desire to love truth and live by it? What if it became natural to speak truth and seek it in all aspects of our lives? May our hearts long for and love all truth.


1 An axiom is 1: a maxim widely accepted on its intrinsic merit; 2: a statement accepted as true as the basis for argument or inference; or 3: an established rule or principle or a self-evident truth. – Merriam-Webster; http://www.merriam-webster.com/dictionary/axiom

2 Blaise Pascal (1623-1662, Thoughts, http://www.bartleby.com/48/1/14.html