Understanding Testing

The world of COVID-19 testing and our understanding of the virus has caused many of us to read science and health articles laden with new terminology that may be challenging to understand. One of the areas of knowledge that is difficult to understand is COVID-19 testing. Let’s take a closer look at some of the work presently being done.

When it comes to viruses and the diseases they cause, there are two basic types of testing. One, testing to see if the person being tested has virus in their system; and two, testing to see if the person has developed antibodies against the virus. We will look at each in turn with regard to the COVID-19 disease and the SARS-CoV-2 virus[1] which causes the disease.[2]

Virus testing in this first case, is done almost exclusively by reverse transcription polymerase chain reaction (RT-PCR). This is the recommended initial test to see if a person is carrying the SARS-CoV-2 virus in the deep parts of the nasal passages.[3] This test detects the rna of the actual virus by transcribing its rna into DNA and amplifying the DNA (making more of the DNA). This is a highly sensitive test and is capable of detecting as few as one virus particle. The test relies on the concept that if a virus particle is detected deep in the sinus cavity of the patient, the patient’s body is likely manufacturing the virus particles in the cells of their respiratory system[4] and shedding them out into the world around them through moisture in their breath.[5] This article will not assess the tests but rather describe the tests (some of the readers of this article may already be seeing the pros and cons of this testing method). Spartan Bioscience in Ottawa has just received approval to sell their rapid detection kit to the Canadian market.[6] It is exciting to see this new made-in-Canada solution to testing for SARS-CoV-2.

In the second type of testing, the clinicians initiating the test are looking for antibodies against the virus. Normally, when our bodies are introduced to a new virus in our cells, our immune system goes through a system of activation and biochemical cascades which result in the production of antibodies against the novel virus.[7] These antibodies are part of a healthy person’s biological response to a virus and the beginnings of how we fight off this new challenge to the integrity of our cells. We want our cells to exclusively make proteins for our own use and we do not want them making more viral rna or viral proteins. Therefore, our immune system must initiate its own biological warfare against the invading army of viruses. Antibody testing relies upon this ability of the body to make antibodies against a foreign particle in our system. If our body has experienced the new virus and has had sufficient time to mount a response, there will be antibodies in our blood to indicate that this has happened. Antibodies such as this may last for a matter of months or many years. Thus, one can test for specific antibodies against SARS-CoV-2 while the person is in an active COVID-19 disease state or even after they have recovered. This type of testing may be invaluable in determining who has survived the disease and may possibly be a source of antibodies that could potentially be transferred to another person to give them immunity to the disease.[8]

This second type of testing is more of a classical immunological test. A molecule capable of binding to the antibody, something that bears a resemblance to the binding portion of the viral particle, is bound onto a substrate (perhaps a paper inside a testing cassette) and then a blood sample is placed in contact with the detection molecule. After an appropriate wash, to cleanse the cassette of any unbound particles, the one performing the test looks for evidence of bound antibodies. This is most often a colour change on the substrate (think of how an early pregnancy detection stick works) to indicate the presence of the antibody against the virus. (Again, there are pros and cons of such a testing regime, but for now, we will forgo any assessments.) Tests such as this are in development in Canada as well. The test manufactured by BTNX is approved for sale in the US and UK but is not yet approved for the Canadian market.[9] This type of testing will be critical to further research and for such important tasks as testing donor blood at Canadian Blood Services. We can applaud such active and rapid research into both of these areas of testing.

Post a comment or send an email if this article has created further questions. I will do my best to research the questions and provide answers.

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[1] The virus itself is a simple little biological entity, less alive and more machine-like. It consists of only 30,000 base-pairs of rna and just a few proteins. Perhaps I will write more on that later.

[2] This virus is also sometimes referred to as “the coronavirus” (but of course it is simply one of many coronaviruses) or the 2019 novel coronavirus or 2019-nCoV.

[3] "Coronavirus Disease 2019 (COVID-19)." Centers for Disease Control and Prevention. 2020-03-21. Retrieved 28 March 2020.

[4] For that is what virus particles do, they get inside a host cell and use the cell’s machinery to make more virus particles.

[5] Notice I avoided saying, “by speaking moistly.” This is out of respect for our Prime Minister and the great job he is doing each day keeping the Canadian public informed. It is so easy to stumble over one’s words in such settings. We all need to give him a break.

[6] “Everyone wants them: Rapid COVID-19 test kits made in Canada approved for use,” CBC News, 2020-04-13, https://www.cbc.ca/news/canada/ottawa/spartan-covid19-test-kit-new-1.5530669.

[7] People who are immune-compromised for various reasons may not be fully capable of mounting such an immune response against the virus.

[8] I am intentionally using a number of conditional words and clauses here. The research has not yet shown whether or not it might be possible to transfer immunity via this method. But, it is a hopeful plan.

[9] “Health Canada says rapid blood test for COVID-19 remains under review,” CBC News, 2020-04-12, https://www.cbc.ca/news/health/health-canada-rapid-blood-tests-under-review-1.5529590

Chromosome 2

Human Chromosome 2 is an interesting example of evidence that suggests God used evolution to create humanity. Darrel Falk has made a series of YouTube videos that explain why he believes that Chromosome 2 is evidence for God using evolutionary processes.[1] Here I will explain the basic concepts and leave it to the reader to investigate further.

To understand this evidence, we must first understand a little bit about genetics, chromosomes, and DNA. Chromosomes are the structures that keep our DNA organized. In every cell of our bodies there are strings of 3 billion base pairs of DNA. DNA is a string of adenine (A), guanine (G), cytosine (C), and thymine (T) molecules strung together in a variety of combinations that can be represented like this:

(Click on images to enlarge)

Notice that the strings of molecules can be put together in many permutations and allow for an amazing amount of information to be stored in this format. The image shown above is a representation of one side of the DNA ladder. DNA pairs in such a way that A pairs with T and C pairs with G, so the two sides of a DNA double helix can be represented in the following way:

Chromosomes organize and constrain this DNA into discreet packages that allow the DNA to be copied, moved around, and accurately passed from one cell division to another and from one generation to the next. The ends of the chromosomes have distinct DNA structures called telomeres. In humans, the sequence of these telomeres is a number of repeats of TTAGGG and these telomeres prevent DNA from unraveling, much like the tips on the end of shoelaces prevent our shoelaces from fraying. Chromosomes have centromeric structures near the centre of the chromosomes where proteins look for specific conformations or shapes of DNA on the chromosome to grab the chromosomes and pull them in a specific direction when cell division such as mitosis or meiosis occurs (two forms of cell division in which the appropriate amount of DNA must be segregated into each cell).

Most humans have 23 pairs or a total of 46 chromosomes that look something like this when painted with fluorescent dyes:

Telomeric structures would be at the ends of each chromosome and centromeric structures would be at the darkened and pinched-in point generally toward the middle of the chromosome.

Different species of animals have different numbers of chromosomes. Here is a list of some animals and their chromosome number. I will continue to speak of the number of pairs of chromosomes in the typical animal, rather than the total number of chromosomes.

Mice have 20 pairs of chromosomes;

horses, 32 pairs;

donkeys, 31;

cows, 30;

tigers, 19;

lions, 19;

orangutans, 24;

gorillas, 24;

chimpanzees, 24;

and bonobos (pygmy chimpanzees), 24 pairs.

These last four entries represent the great apes and are especially interesting to the rest of this article and we will pursue this topic more in the next few paragraphs. But before we get there, let me remind the reader that plants also have distinct numbers of chromosomes and we could list some of those as well. The coffee plant has 22 pairs of chromosomes whereas the pineapple has 25 pairs. The number of pairs of chromosomes is one mechanism that acts as a boundary between species and prevents the crossing of one species with another. There are a few rare exceptions such as horses and donkeys in which cross-breeding is possible despite different chromosomal numbers, but for the most part, such crossings fail. This is sufficient background regarding our DNA and its packaging into chromosomes to remind us that our bodies are fearfully and wonderfully made and that there is still much to learn about how the mechanisms of genetics work.

Now we come to the interesting instance of human Chromosome 2. As noted above, humans have 23 pairs of chromosomes while the great apes have 24 pairs. If we look closely at and compare the chromosomes of humans and the great apes, a good deal of similarity is noted. G-banding patterns are a crude method of looking at the overall structure of chromosomes, but they are instructive in showing the similarities of chromosomes. Traditionally, this G-banding technique has been used to uniquely identify and arrange each of our 23 pairs of chromosomes.

Of particular note is the similarity between human chromosome 2 and ape chromosomes 12 and 13. The picture below shows the similarity in banding patterns of the human chromosome 2 compared to the banding patterns of two chimpanzee chromosomes.

What becomes immediately apparent at a crude structural level (and is further borne out in the actual DNA sequence of the chromosomes) is that human Chromosome 2 looks like a fusion of two chimp chromosomes. In fact, as we analyse the DNA sequence of human Chromosome 2, we find telomeric repetitive structures in the middle of Chromosome 2 (when they should only be at the ends of the chromosome) and a second, non-functional, centromeric structure where one would expect it would be if the chromosome resulted from a fusion event.

What this suggests is somewhere in the evolutionary development of humans, a fusion event occurred which resulted in the reduction of the number of chromosomes to 23 pairs for the humans and human-like species, while the great apes continue to have 24 pairs. The following diagram represents the phylogeny (or family-tree) with regard to this one feature (note, this diagram speaks of 46 and 48 chromosomes rather than 23 and 24 pairs). The question mark next to Neanderthals in the diagram represents the fact that, although the chromosomal number for humans and Denisovans has been experimentally confirmed, we do not presently have DNA of sufficient quality from Neanderthals to experimentally confirm that Neanderthals indeed had 23 pairs of chromosomes.[2]

[3]

Such evidence supports the idea that God used an evolutionary process to create species including the human species. It would indicate that we share a common ancestor with the great apes and that at a certain point in the evolutionary process our line diverged from the family tree of our ape cousins. It does not detract from God as creator and does offer insight into the mechanisms he used as he created.

A blog of this nature can only whet the reader’s appetite for further investigation into such topics. As previously stated, Darrel Falk’s YouTube videos may be the next place to turn for further understanding. The BioLogos website at biologos.org is always a great resource. Perhaps this blog might also open doors for respectful conversation, logical analysis, and a hunger and thirst for truth wherever it may be found. God is indeed the great creator and the mechanisms of biology are no surprise to him. We can continue to be confident that he is guiding the universe and guiding his revelation to those who seek him.

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[1] Darrel Falk series of YouTube videos regarding the human chromosome 2 fusion:

Part 1 - https://bit.ly/2JUIKeq

Part 2 - https://bit.ly/2HJbTEz

Part 3 - https://bit.ly/2HJsRCJ

[2] See “Denisovans, Humans and the Chromosome 2 Fusion” September 06, 2012, BioLogos Blog, Dennis Venema,  

https://biologos.org/blogs/dennis-venema-letters-to-the-duchess/denisovans-humans-and-the-chromosome-2-fusion

[3] The diagram is from “Denisovans, Humans and the Chromosome 2 Fusion” September 06, 2012, BioLogos Blog, Dennis Venema, https://biologos.org/blogs/dennis-venema-letters-to-the-duchess/denisovans-humans-and-the-chromosome-2-fusion

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.

Mysteries of the Human Genome

Many who read this blog regularly will know of my interest in human genetics and the evolutionary process by which God guided the creation of humans and imprinted the imago dei upon us. I have frequently written about various creation and evolutionary theories and I recognize that this is a controversial topic in some Christian circles and in discussions with humanistic evolutionary theorists. Some of the greatest evidence that God used evolution to create all life can be found in contemporary DNA studies. We now have the capability to analyze our entire human genome at detailed levels and compare it to ancient humanoid DNA and the genome of other animal species. This has led to remarkable findings as shown in the following quote.

Less than a decade ago, scientists discovered that human ancestors mixed with Neandertals. People outside of Africa still carry a small amount of Neandertal DNA, some of which may cause health problems (SN: 3/5/16, p. 18). Bohlender and colleagues calculate that Europeans and Chinese people carry a similar amount of Neandertal ancestry: about 2.8 percent. Europeans have no hint of Denisovan ancestry, and people in China have a tiny amount — 0.1 percent, according to Bohlender’s calculations. But 2.74 percent of the DNA in people in Papua New Guinea comes from Neandertals. And Bohlender estimates the amount of Denisovan DNA in Melanesians is about 1.11 percent, not the 3 to 6 percent estimated by other researchers.

While investigating the Denisovan discrepancy, Bohlender and colleagues came to the conclusion that a third group of hominids may have bred with the ancestors of Melanesians. “Human history is a lot more complicated than we thought it was,” Bohlender said.  (from Science News October 21, 2016)

 

My own theological paper regarding Denisovan DNA carried by some humans was written in 2010 and 2011 (as partial fulfillment of an MA in Theological Studies at Regent College) just a few months after ancient Denisovan DNA had been analyzed. The paper allowed me to wrestle with theological questions about the nature of the image of God and what makes us human. Such discussion, questioning, and research leads me to understand that my faith in the scientific process and my faith in Jesus, the Son of God, are both well-founded. Both the Bible and the biological world are ways in which God reveals himself to humans. Our theological understandings of both the natural world and the Bible are what must adapt so that we might have a greater perception of God's message for his people.

I encourage us to read widely and in a scholarly fashion. We need not fear what science discovers for it is God who gives us our minds and allows us to discover the insights of our universe. Let us read with the Bible in one hand and scientific writings in the other.

Links:

http://hungerandthirst4.blogspot.ca/2016/03/denisovan-dna.html

http://hungerandthirst4.blogspot.ca/2012/08/adam-and-genetics.html

https://www.sciencenews.org/article/neandertal-dna-may-raise-risk-some-modern-human-diseases
http://www.sciencenews.org/article/dna-data-offer-evidence-unknown-extinct-human-relative 
http://spasique.com/genes-of-this-tribe-carry-a-dna-of-a-third-unknown-human-species/ 

Thermophilic Bacteria as Great Wonders of the World

Lewis Thomas[1] was an award winning author and physician who had a way of explaining complex science in simple ways. In his essay, “Seven Wonders[2],” Lewis relates how he was once asked for his list of contemporary “Wonders of the World.” He is careful to say that he thinks it would be impossible to create a new list of the seven wonders of the world before giving a qualified list of naturally occurring wonders.

The “second” of his list (if you read the entire essay[3] you will understand why I put “second” in quotations) is a particular species of bacteria which thrives at extremely high temperatures. Prior to their discovery in the 1980s, many would have suggested that life as we knew it would not be possible in the severe environment of deep sea vents where temperatures exceed 250 degrees centigrade. Yet, these bacteria were found to be living and contributing to the ecosystem in just such a place. As Thomas says, it was thought that “Proteins and DNA would fall apart, enzymes would melt away, anything alive would die instantaneously.” On this basis, “the possibility of life on Venus . . .” and many other places was long ago ruled out.

Then came the discovery by B. J. A. Baross and J. W. Deming “of thriving colonies of bacteria in water fished directly from these deep-sea vents. . . . [that], when brought to the surface, encased in titanium syringes and sealed in pressurized chambers heated to 250 degrees centigrade, the bacteria not only survived” but reproduced themselves enthusiastically. They [could] be killed only by “chilling them down in boiling water. And yet they look just like ordinary bacteria. Under the electron microscope they have the same essential structure—cell walls, ribosomes, and all.”

I was later to learn of the great value of these bacteria in the work I would do in the Molecular Diagnostic Lab at the Alberta Children’s Hospital in Calgary. After this discovery by Baross and Deming, other researchers went on to isolate particular strains of bacteria from thermal vents. One species, Thermus aquaticus (abbreviated Taq), contained a DNA polymerase (an enzyme which makes more copies of a strand of DNA) that could be isolated and used in certain biochemical reactions to amplify regions of DNA. By the time I joined the lab in 1990, it was possible to use Taq DNA Polymerase for routine scientific investigation and molecular genetic testing of clinical disorders. The use of PCR (Polymerase Chain Reaction) greatly accelerated laboratory practices and led to the rapid development of clinical testing for molecular DNA mutations. I would echo Lewis Thomas in his recognition of these bacteria as one of the great wonders of the world.

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[1] “Lewis Thomas,” Wikipedia, https://en.wikipedia.org/wiki/Lewis_Thomas, accessed 2016-09-12.

[2] Late Night Thoughts on Listening to Mahler’s Ninth; Lewis Thomas, Viking Penguin, a division of Penguin Group (USA) Inc., 1983.

[3] http://hermiene.net/essays-trans/seven_wonders.html

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.