Category: today i learned (til)

This article will be the first of a series of articles I hope to continue called Hidden Figures Beyond. The goal of this series is to go beyond the movie Hidden Figures, highlighting more scientists that are underrepresented minorities whose research and studies continue to make an impact on the discovery of knowledge today. The first scientist that I will be highlighting is the first African-American neurosurgeon in America, Alexa Canady. She is retired now, but I would like to discuss her history with neurosurgery and the research that she focused on and its impact.

To give a quick description of her early life, Alexa Canady was born in Lansing, Michigan to Elizabeth Hortense Canady and Clinton Canady Jr. Her mother was an educator and her father was a dentist, so she and her brother grew up in an education-based environment. Her family always emphasized the importance of education, especially as an African-American woman, which motivated her to graduate from her high school with honors and to attend the University of Michigan to earn. However, like most college students, she had her fair share of struggles as well. As a mathematics major, she had a ‘crisis of confidence’, questioning her place at the University of Michigan. When she learned about a minority scholarship for medicine, she felt an instant connection and decided to pursue it, thus switching her major to zoology and earning her bachelor’s degree in 1971, then graduating cum laude from medical school there in 1975. After graduating, she interned at Yale-New Haven Hospital for a year, where she still faced discrimination, being told on her first day, “You must be our new equal opportunity package.” Despite this, she continued to strive and be voted as one of the top interns by the physicians on her staff.

After her internship, she had her residency at the University of Minnesota from 1976 to 1981, when she started a fellowship at Children’s Hospital in Philidelphia. In 1982, she completed her fellowship and was soon hired onto the faculty of Detroit’s Henry Ford Hospital. She worked there until she was hired as the chief of pediatric neurosurgery at the Children’s Hospital of Michigan in 1987. Canady specialized and researched in life-threatening illnesses, congenital spinal abnormalities, and other brain injuries like hydrocephalus, trauma and brain tumors. She performed many life-saving treatments on thousands of patients, most of her patients being ten years or younger. During her time in Detroit, she researched at Wayne State University to improve neurosurgical technology with two other neuroscientists. This research led to the development of an antisiphon shunt that helps to treat hydrocephalus, an abnormal accumulation of fluid inside the brain. She continued this work until her partial retirement in 2001, retiring to Florida. During this time, she worked as a part-time surgeon until her complete retirement in 2012. Even though Canady is retired, she is still a full-time role model for African-Americans interested in STEM, and working on the issues of medical bias of African-American patients.

 

As I learned more and more about Alexa Canady and what an amazing scientist she is, I was also a little sad about the fact that she really isn’t very well known, even though she has done so much and has saved the lives of so many people. She’s stated that she doesn’t want the attention, but she is an inspirational role model and now that I know about her story, I don’t think I ever want to forget about her and her legacy. I’d like to leave this quote from a recent interview of hers when she was asked why young students should pursue neuroscience to perfectly define her life and legacy.

“It’s fun to make people better… It’s intellectually challenging, you get kind of a high when everybody says ‘Ah the neurosurgeon is here.’”
-Alexa Canady, 2017

CRISPR, an anacronym that stands for “clustered regularly interspaced short palindromic repeats,” is a concept becoming quite ubiquitous in most biology classes and rapidly gaining familiarity among experimental medicine and biology discussion circles not to mention scientific publications and health- or science-related news media. However, people who are not closely following these discussions or do not have a contemporary knowledge of genetics, understand very little about what exactly CRISPR could be or do. Even if one goes word by word for what each letter of the CRISPR anacronym stands for, it would be hard for the general public to have a workable idea of the science underlying this term. This article intends to provide an uncomplicate explanation of the concepts around CRISPR by resorting to a language that simplifies the ideas without decreasing the accuracy to the main concepts.

 Source: https://www.sciencenewsforstudents.org/article/crispr-enters-its-first-human-trials

CRISPR vs. CRISPR Technology

First, we may need to distinguish CRISPR, as a family of DNA sequences which is part of the immune system identified in bacteria cells, from CRISPR technology, as a tool to modify those DNA sequences in humans. Therefore, when scientists are talking about CRISPR and “trials in humans” they usually refer to a method used to modify the DNA genome in humans.

CRISPR has two components: the Cas9 which is a protein that can unwind and cut DNA sequences and the guide RNA (or gRNA) that recognizes the sequence of specific sequence of DNA to be edited.  In some literature the CRISPR technology is also known as CRISPR/Cas9 in reference to a specific cutting protein – we will return to this concept below.

At least, three important questions arise here: How well is our understanding of the DNA sequences in cells? How well developed and precise are the tools to manipulate those DNA sequences? Why do we need to modify any part of the DNA sequences? The first two questions are not only quite related, but also involve a lot of uncertainty even for scientist working everyday with CRISPR technology. The third question involves not only the diverse therapies and diagnostic purposes for which CRISPR technology is being used but also the dangers and ethical dilemmas involved in the use of this technology. We will mostly focus on the third question while bearing in mind and revisiting the first two questions.

Source: https://sciencehook.com/biology/crispr-cas9-and-gene-editing-explained-140

Understanding Gene Editing

CRISPR is a system mostly known for the modification of DNA sequences to correct or delete any mutations or defect within the sequence of spaced DNA palindrome. In a practical way, it could be seen as spellcheckers of misspelled sequences and a cut-and-paste tool for DNA editing.  CRISPR has been used in cancer patients, people with blood disorder and other possible diseases or defects that CRISPR could help to identify and correct.

To have a more precise idea lets return to the underlying concepts once more. The purpose of CRISPR technology is first to identify genes associated with CRISPR.  Particularly relevant are those genes that could produce enzymes or proteins named Cris9 which are able to unwind and cut DNA, which were identified in the laboratories of Jennifer Doudna and Emmanuelle Charpentier and for which they received the Nobel Prize in Medicine.

With Cris9 at hand, it could be used to unwind and cut out specific strands of DNA (mostly those parts of the human genome that were previously identified as the mutations that cause unwanted defects or health problems). At that point, a specific gRNA is created to match that stretch of the DNA sequence that was cut.  Next, after the gRNA is being attached to the DNA cutting enzyme Cas9, the complex formed by the Cas9 and gRNA is re-introduced to the targeted cell where the defect was detected.  In other words, the enzyme cuts the strands of DNA at the specific human genome so that whatever is deleted can be properly replaced by a corrected part. In this case, researchers would remove some cells that are susceptible to a bacteria or virus or cells that show some unwanted mutation, modify the DNA in those cells and then put the modified cells back to potentially decrease the likelihood of a disease or defect.

Hopes, Slow Progress and Concerns

In general, CRISPR has been associated with a scientific revolution happening in medicine that would soon help us to better fight diseases, cure cancer, diagnose diseases or maybe even create new humans. The increasing understanding of how CRISPR works has given some hope and enthusiasm to scientist.  Therefore, it is now frequent to find news about CRISPR being used in experiments.

However, we are in the early days of CRISPR and the progress is slow.  In spite of the hopes, CRISPR has been used solely in a limited number of well-known mutations that cause certain diseases. This is an important limitation for various reasons. The number of unknown mutations is still quite large compared to the few known ones.  Moreover, the mutations in the same place of the sequence of DNA of two individuals could be quite different and therefore the application of CRISPR to cut and correct such a mutation may work in some but not in all individuals. Even in the cases where the application of CRISPR in experiments with animals were relatively successful, for example the injection of corrected stem cells that let paralyzed rats walk again, when the same experiments were run in humans, they did not provide the same results.

The slow progress has not stopped the development of theoretical and laboratory models where CRISPR could be use beyond unwinding and cutting DNA, but also as a pointer and diagnostic tool. In the future, it is expected that CRISPR could be used in developing advanced patient therapies, customized medications and even cure life-long inherited diseases.

Ethical considerations

However, when CRISPR is associated with the “trials in humans,” a number of natural legitimate ethical concerns have been risen around the use of CRISPR.  For example, it has become accepted the use in CRISPR in somatic cells such as T-cells to treat diseases, but when CRISPR is used in embryo or stem cells, it becomes controversial, mainly because genome modifications are done at germline level with unknown of unintended consequences for patients and future generations.  In simple terms, the issue is the corrections at germline of a DNA sequence that could be passed to future generations by introducing heritable changes to sperm, eggs or embryos without full consideration of the risks or proper understanding of the participants.

Source: https://www.technologyreview.com/s/612997/the-crispr-twins-had-their-brains-altered/

This issue gained big relevance when a He Jiankui, a Chinese scientist, worked in the germline to modify the genes in twin kids (before birth), aimed to make the twins immune to HIV. This experiment was considered quite irresponsible and ethically questionable leading to a worldwide condemnation of the scientific community; the risks to the babies were higher than the benefits for a number of reasons: the parents provided consent without being properly informed, the CRISPR experiment was kept secret, He Jiankui ignored the ethical consensus against human germline genome editing. Due to this incident, regulations about when and how related research should be use in clinical treatment are being discussed and issued. Moreover, there have been even calls for a moratorium of clinical use of human germline editing.

Although still experimental, it is expected that one day CRISPR would arrive to the market. This creates another controversial set of issues. Who will have access to it? Would the cost be prohibitive for most people?  Would CRISPR be similar to many new cancer or other high-tech medications and therapies with quite expensive price tags? Would CRISPR be seen as a discrimination tool via the market? These are open questions with no simple answers.

Beyond the ethical concerns, people may tend, out of fear, to magnify some drawbacks and minimize important merits (or vice versa) and so, could be sensitive to rumors or unprecise information. That is the case of non-therapeutic uses of CRISPR. The idea that CRISPR could be used for frivolous ends (i.e., phenotype “corrections” like cosmetic surgery for aesthetics) is a frequent misconception about what CRISPR could do.  In general, it should be mentioned that the state of arts in genetics is not quite there yet to attempt any phenotype “correction.”  Simply put, science does not know exactly what the consequences are of changing some genes.

 

In conclusion, editing CRISPR genome allows scientists to quickly create cell, which can be used to accelerate research into diseases such as cancer and mental illness. Also, CRISPR is now being developed as a rapid diagnostic tool.  However, CRISPR is still in its early days of and there are still scientific and ethical limitations to take into consideration

 

Resources

• CRISPR definition: https://www.livescience.com/58790-crispr-explained.html
• CRISPR enters its first human clinical trials https://www.sciencenews.org/article/crispr-gene-editor-first-human-clinical-trials
• CRISPR Used in Human Trials for the First Time in the US https://singularityhub.com/2019/05/02/crispr-used-in-human-trials-for-the-first-time-in-the-us/
• China’s CRISPR twins might have had their brains inadvertently enhanced https://www.technologyreview.com/s/612997/the-crispr-twins-had-their-brains-altered/
• Zhan Y, Sastre D, Wang F (2018). CRISPR/Cas9 Genome Editing: A Promising Tool for Therapeutic Applications of Induced Pluripotent Stem Cells. Curr Stem Cell Res Ther. 2018;13(4):243-251. Available online at: https://www.ncbi.nlm.nih.gov/pubmed/29446747
• Zhang H McCarty N (2017). CRISPR Editing in Biological and Biomedical Investigation. J Cell Biochem. 2017 Dec;118(12):4152-4162. Available online at: https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.26111

 

 

 

What?

Sunscreens contain diverse active ingredients. Some use the inert inorganic mineral pigment, such as zinc oxide and titanium dioxide, primarily to reflect or scatter UV radiation. Others use organic chemicals or a mixture because chemicals can absorb UV rays. For instance, sunscreens also contain carbon-containing molecules that absorb light, such as oxybenzone, octinoxate, octisalate and avobenzone.

The Scientific Committee on Consumer Products (SCCP) has reviewed 27 UV filters approved for Cosmetic Directive, each processes a designation, by which they should be declared on product packaging.

Each sunscreen product has a sunscreen products factor (SPF). It is misleading to interpret SPF as the strength of protection. In fact, SPF refers to the time for the UVB rays to redden the skin with the product compared to that without product. For instance, 15 SPF means using this sunscreen will take 15 times longer for the skin to burn than without using it.

 

How?

Most sunscreen products work by blocking, absorbing, reflecting and scattering UV rays through physical and chemical approaches. Physical method uses particles like titanium dioxide or zinc oxide mentioned above to reflect UV rays away from skins. Meanwhile, many complicated ingredients have chemical reaction with radiation as they contact, absorbing the UV rays, prevent the radiation harming the skins.

Specifically, sunscreens can combat with two types of damaging UV rays: UVA and UVB. Recent researches show that both UVB and UVA radiation will cause sunburn and skin cancer, while UVA rays will also deeply penetrate the skins and cause faster aging, wrinkling and eye damaging.

However, most sunscreen products on the market only block UVB rays while overlook the damage caused by UVA rays. Focusing on efficient UVA protection has a significant prospect in the future.

 

Safety?

Besides SCCP inspections, ingredients used in sunscreen products also must be approved by the Food and Drug Administration (FDA). The FDA has reviewed 17 ingredients that can be used in UV products, including oxybenzone, titanium dioxide and zinc oxide mentioned before.

To guarantee the safety of ingredients, FDA conducts extensive inspections on the ingredients and moreover, regulates the safety and effectiveness of the ingredients until reaching the best performance. For instance, FDA has approved the use of zinc oxide in over-the-counter skin protectants and sunscreen products at concentrations up to 25 percent; active ingredients in sunscreen such as titanium dioxide protect our skin form the harmful UV rays.

 

Experiment!

Now let’s do something interesting using the nature print paper. The nature print paper will become very pale blue after exposure to the sunlight. We can use it to test the effectiveness of UV product by comparing the color.

Step 1: Take one piece of Nature print paper and put it on a piece of corrugated cardboard for support.

Step 2: Smear some sunscreen on part of the paper (the small circle). I used the Shiseido UV product with SPF 50, PF+++.

Step 3: Expose the paper under sunlight until the blue paper turns very pale blue.

Step 4: Check the resulted paper.

We can discover that the whole paper became light blue, except the circle with sunscreen barely changed after 2 hours of exposure. We can see that the sunscreen products do have intensive effect and we can surely believe that sunscreen products can protect our skins against the harmful UV light.

 

Binks, Bernard P., et al. “How the sun protection factor (SPF) of sunscreen films change during solar irradiation.” Journal of Photochemistry and Photobiology A: Chemistry 333 (2017): 186-199.

Holman, Dawn M., et al. “Patterns of sunscreen use on the face and other exposed skin among US adults.” Journal of the American Academy of Dermatology 73.1 (2015): 83-92.

Saini, Ritu, and Andrea Szemplinski. “How to choose the right sunscreen for your skin type.” (2016).

Wahie, S., J. J. Lloyd, and P. M. Farr. “Sunscreen ingredients and labelling: a survey of products available in the UK.” Clinical and Experimental Dermatology: Clinical dermatology 32.4 (2007): 359-364.

Gasparro, Francis P., Mark Mitchnick, and J. Frank Nash. “A review of sunscreen safety and efficacy.” Photochemistry and photobiology 68.3 (1998): 243-256.

Which came first, the chicken or the egg?

A classic philosophical conundrum, intentionally baffling and likely argument-provoking.

“You need a chicken to lay an egg, but chickens come from eggs, so you need an egg to get the chicken… to lay the egg, from which to get a chicken to lay an egg…”

This can (and often does) go on forever, an endlessly frustrating loop of logical fallacy.

I was pretty surprised  then, when the answer was suddenly provided in one of my classes, a course on evolutionary ornithology. We were discussing a phylogenetic tree,  when my professor casually pointed out an easy, glaringly logical, loophole in the age-old query.

So, scientifically speaking, which came first, the chicken or the egg?

Egg Timeline:

The amniotic egg, or cleodic egg as it is also sometimes called, is thought to have evolved between 340-370 million years ago, and is highly conserved across many classes and families, from mammals like us to crocodiles. The classification of amniotes includes all vertebrate animals with four limbs and amniotic eggs, so think all mammals (Synapsida), and reptiles/birds (Reptilia) (Sander 2012).

What exactly is so special about this egg?

The amniotic egg is characterized by its complex of inner membranes. The allantois, which is directly attached to the embryo, primarily holds the waste products, while the yolk sac contains all the nutrients the embryo will need for development. The embryo is bathed in a stable fluid environment, surrounded amniotic fluid and enclosed in amnion membrane. The outermost membrane, the chorion, provides close contact between the eggshell and its internal contents, allowing for the necessary gas exchanges of O₂ and CO₂, and holding the other structures together. Finally, there is the outer shell layer, which can be leathery (as can be seen in some turtle species) or calcified, like the hard eggshells of birds and crocodiles. This outer shell is semi-permeable, again to permit the gas exchanges needed for respiration, and to keep moisture in and harmful microorganisms out (Sander 2012).

Quick aside- yes, mammals generally don’t lay eggs (excepting the monotremes such as platypuses and echidnas). However, the eggs that develop in the uterus before live birth are still considered to be amniotic eggs, since the embryo is surrounded by necessary membranes to encase fluid. They simply lack the outer eggshell and remain inside the mother’s body.  It is also worth noting that while the placental organ does perform some of the functions internal membranes have in other animals, most noticeably the nourishing role of the yolk, mammal embryos still have a yolk sac in early stages of development, as well as the other characteristic structures of the amniotic egg.

This general structure of the amniotic egg is a major landmark in the evolutionary history of life. By providing a way to contain fluid, it eliminated the dependence of reproduction on bodies of water to lay and incubate in, and thus opened up a whole world for vertebrates to expand into. In fact, it’s considered the most defining development allowing for the evolution of life on land! And these eggs are quite old, evolving no later than 310 million years ago with the last common ancestor of mammals and birds. Most estimates place the appearance of the amniotic egg between 340 and 370 million years ago (Sues 2016).

Chicken Timeline:

Alright, now let’s consider the chicken. The modern common domestic fowl (Gallus gallus domesticus), what we know as chickens, have a long and storied evolution like all birds, stretching back into the age of dinosaurs, and more specifically, the therapods. Therapods are thought to have first appeared in the late Carnian age of the late Triassic period, somewhere around 232.4 million years ago, as a clade of saurischian dinosaur. They were a widely diverse group, but main features included hollow, light-weight bones, and bipedality, and they were generally carnivorous. Within the more specialized subsets, there are the Tetanurae, which are further subdivided into Megalosauroidea and the Avetheropoda. The Avetheropoda, contained Carnosauria and the Coelurosauria, from which birds are direct descendants!

If we jump ahead a few million millennia, we can track down the last relative from which our favorite bird diverged. Gallus gallus domesticus, is a subspecies of the junglefowl, Gallus gallus, of the order Galliformes, suborder Galli, and family Phasianidae. Galliformes are originally from Southeast Asia and have been around for an estimated 50 million years. Although there are other jungle fowl with whom the chicken may share genetics, including the gray jungle fowl, Gallus sonneratii, that likely contributed the trait of yellow skin on their feet,  it well accepted that the chicken diverged most directly from the red junglefowl (Potts 2012). In one study by Sawai et al (2010), an analysis of DNA from 19 birds (including red and green junglefowl and several breeds of chickens), found that that the domestic chicken diverged from the red junglefowl  58,000±16,000 years ago, which had in turn diverged from its last common ancestor with the green junglefowl around 3.6 million years ago. This places our oldest chicken between 42,000 and 74,000 years ago (Sawai et al 2010).

The Results are in…Eggs are way older

Compared to the egg’s minimum of 310 million years, the chicken is practically a baby in evolutionary terms, somewhere around a mere 58,000 years old.

When you set the comparison in these terms, it is an easy landslide. Of course, you may very well be thinking, “that’s great and all, but that’s not technically a chicken egg. Surely you need a chicken for the egg to be a chicken egg, right?”

And you are not wrong- there are specific enzymes and other proteins that only chickens have which play a crucial role in their eggshell formation, with most people citing ovocledidin-17 as the primary example of this.

When you think of an egg, a hard-shelled egg, the kind of egg  one might decorate at Eastertime, or buy by the dozen at the supermarket, however, the defining features are not of a chicken egg specifically. First and foremost, you are thinking of the massively distinct amniotic egg, which has existed before birds, much less chickens, were around to lay them.

Yes, the question is rigged. It is a false dichotomy, and not meant to have a clear solution. If you are like me, however, this is the most satisfying ending; a supportable conclusion and some great practice in phylogenetic problem-solving.

References:

Amniote Egg. (n.d.). Retrieved from http://www.biologyreference.com/A-Ar/Amniote-Egg.html.Emma.berthold@science.org.au. (2019, September 19). Which came first: the chicken or the egg? Retrieved from https://www.science.org.au/curious/earth-environment/which-came-first-chicken-or-egg.

Potts, A. (2012). Chicken. London: Reaktion.

Sander, P. M. (2012). Reproduction in Early Amniotes. Science, 337(6096), 806–808. doi: 10.1126/science.1224301

Sawai, H., Kim, H., Kuno, K., Suzuki, S., Gotoh, H., Takada, M., . . . Orban, L. (2010). The Origin and Genetic Variation of Domestic Chickens with Special Reference to Junglefowls Gallus g. gallus and G. varius (The Origin of Domestic Chicken). PLoS ONE, 5(5), E10639.

Sues, H.-D. (2016). Amniotes, Diversification of. Encyclopedia of Evolutionary Biology, 56–62. doi: 10.1016/b978-0-12-800049-6.00279-1