Mars, Water, and Life

“Mars tugs at the human imagination like no other planet. With a force mightier than gravity, it attracts the eye to the shimmering red presence in the clear night sky.”
John Noble Wilford

It seems like everything associated with space has a Mars focus.  NASA’s plan to return to the moon has a Mars association. Scientists are receiving a nearly continuous string of data about Mars from orbiters, landers, and rovers. NASA is planning on sending astronauts to Mars for research, and SpaceX is planning to colonize the red planet.

When we think of Mars, we think of a dry radiation banked world.

This March 27, 2015, view from the Mast Camera (Mastcam) on NASA's Curiosity Mars rover shows a site with a network of prominent mineral veins below a cap rock ridge on lower Mount Sharp. https://www.nasa.gov/mission_pages/mars/images/index.html
This March 27, 2015, view from the Mast Camera (Mastcam) on NASA’s Curiosity Mars rover shows a site with a network of prominent mineral veins below a cap rock ridge on lower Mount Sharp. https://www.nasa.gov/mission_pages/mars/images/index.html

However, we know that Mars once looked very different. Exploration has shown that Mars was warmer with a thicker atmosphere and flowing water.  Martian rovers discovered much of this evidence.  Opportunity found hematite a mineral of iron that forms in water.  Opportunity also discovered gypsum, a calcium sulfate mineral usually created by the evaporation of water.  Opportunity also found evidence of clay minerals that form in water.

The rover Spirit found environments that suggest active hot springs and warm neutral (pH) water, environments that are highly conducive to life as we know it. The existence of these features and minerals tells us that water once flowed freely above and below the Martian surface.  (https://mars.nasa.gov/mer/mission/science/results/)

The scientific evidence shows that liquid water once flowed on the surface of Mars.  How does this tell us that the plant was warmer with a thicker atmosphere? Water can exist in three phases solid, liquid, and gas. Two physical properties affect the phases of water, temperature, and pressure.  We know that below specific pressures (about ten mbar), water can only exist as a solid and gas.

Additionally, above a specific pressure (about 100 kbar), water can only exist as a solid. Temperature has similar effects on water. Scientists mapped out the results of pressure and temperature water, producing a triple point diagram.

The triple point diagram tells us for there to have been flowing water on Mars. The plant had to be warmer with a higher pressure.  Higher pressure means a thicker atmosphere since the thickness of the atmosphere determines atmospheric pressure.  Therefore Mars was once a wet, warmer world with a thicker atmosphere.

All this scientific evidence means is that Mars once had all the ingredients necessary for life liquid water and energy either from the sun or from hot springs.  Hot springs are a great source of energy for life.  If you have ever been to an area rich geothermal activity, you have likely seen hot springs with multicolored patterns. Like the Grand Prismatic Spring in Yellowstone.

This picture shows the different colors of the Grand Prismatic Spring. A corner of Grand Prismatic Spring-1.jpg By Tigerzeng on 19 August 2017, 18:07:47. This file is licensed under the Creative Commons Attribution-Share Alike 4.0 International license.
This picture shows the different colors of the Grand Prismatic Spring. A corner of Grand Prismatic Spring-1.jpg By Tigerzeng on 19 August 2017, 18:07:47. This file is licensed under the Creative Commons Attribution-Share Alike 4.0 International license.

Microorganisms produce the colors. (The Science Behind Yellowstone’s Rainbow Hot Spring) Everyplace on earth where we have water and energy, we have found life. Therefore, we know that Mars once had all the ingredients to support life as we know it.  Additionally, we know that there are life forms like Tardigrades, also known as water bears, that can survive in extremely harsh environments.

Scanning electron micrograph of an adult tardigrade (water bear). By the Goldstein lab – tardigrades This image, which was originally posted to Flickr, was uploaded to Commons using Flickr upload bot on 28 September 2009, 13:40 by Tryphon. This file is licensed under the Creative Commons Attribution-Share Alike 2.0 Generic license.
Scanning electron micrograph of an adult tardigrade (water bear). By the Goldstein lab – tardigrades This image, which was originally posted to Flickr, was uploaded to Commons using Flickr upload bot on 28 September 2009, 13:40 by Tryphon. This file is licensed under the Creative Commons Attribution-Share Alike 2.0 Generic license.

In 2007, scientists exposed Tardigrades to the vacuum and radiation of space.  When the tardigrades returned to earth, many of them revived and reproduced. 

All of this might lead you to ask why NASA hasn’t looked directly for life on Mars.  NASA has looked for life on Mars. NASA’s first successful Martin landers Viking 1 and Viking 2 carried experiments to look for life on Mars.  These experiments incubate samples of Martian soil with organic nutrients and water.  The experiment then examined the containers holding the soil to see if they produced gas consist with life (Viking lander biological experiments).

At first, scientists thought they had uncovered proof of life on Mars. However, there were inconsistencies between different experiments. The scientific consensus was that the observations were the result of naturally occurring chemicals in the soil. However, Gilbert V. Levin principal scientist on the Viking lander Labeled Release experiment thinks they did find life.  In the Scientific America article I’m Convinced We Found Evidence of Life on Mars in the 1970s, he lays out the argument.

Whether or not NASA found life what is true as Dr. Levin said: “Inexplicably, over the 43 years since Viking, none of NASA’s subsequent Mars landers has carried a life-detection instrument to follow up on these exciting results.” that NASA has not sent any other direct life sensing experiments to Mars. Now I will freely admit I have a hard time understanding how life could exist on the Martian surface.  The environment on Mars is hostile to life in all ways.  However, even just a little way below the surface that starts to change.  After all, dirt is good at blocking radiation.

In the article Life on Mars? It’s pointed out that some scientists think Mars might still harbor life.  “At a February conference in the Netherlands, an audience of Mars experts was surveyed about Martian life. Some 75 percent of the scientists said they thought life once existed there, and of them, 25 percent think that Mars harbors life today.”

You might ask the question, “If there is or was life on Mars, let’s get there as fast as we can so we can study it.”  If there is still life on Mars, what we could learn from it is unknowable.  Studying the life on Mars might change our understanding of biology and medicine in ways we can’t imagine.

So, we want to get to Mars.  There is a distinctive difference between dedicated research and colonization.  Colonization will have a direct impact on the Martian environment.  We will have to create large areas for food productions and the mining of resources.  While much of the waste products produced will likely be recycled, some of it will get into the environment. Because of the waste products and modifications of the environment, the colony will disrupt possible Martian life, potentially leading to the loss of valuable information.  Lastly, it will be imposable to keep a living growing colony biologically sealed from Mars-based microorganisms.  Which could prove dangerous?

Long before we ever consider colonizing Mars, we need to know whether life existed or still exists on Mars. If life exists on Mars, we need to conduct research using carefully designed research outposts that protect both the astronauts and the Martian life.  We need to discuss and decide what conditions need to meet before colonization can happen. If we are not careful when it comes to Mars, we will end up doing things before we have decided if we should.

Lastly, why aren’t teams of students and professors proposing life find experiments to NASA? If enough teams think about and design experiments, we might come up with something that works.

Thanks for Listing to My Musings
The Teaching Cyborg

“The New Ph.D.” Again

“There are far, far better things ahead than any we leave behind.”
C.S. Lewis

A while ago, I wrote a blog post Re-Envisioning the PhD +13 Years.  While a graduate student, I was associated with the Woodrow Wilson Re-Envisioning the PhD project.  In that blog post, I reviewed my old notes to see if my opinion had changed. I concluded that the problem was not with a PhD degree but people trying to hijack the degree for other uses.

Today I came across an article in the Chronical of Higher Education, “The New Ph.D.: Momentum grows to rewrite the rules of graduate training.” While I am reluctant to dip back into the topic of changing the PhD, there is a lot going on, and I think we should give the Chronical article a look.  As Rear Admiral Grace Hopper said, “The most dangerous phrase in the language is: We’ve always done it this way.” (By the way, if you don’t know who Grace Hopper is, shame on you and educate yourself.)

The article starts with a story about Meg Berkobien, a graduate student in comparative literature.  Her dissertation was on 19th-century Catalan-language periodicals.  Meg was not motivated by her project and eventually decided to leave the program.  In a letter to her department chair, Meg wrote,

“Every time I sit down to write, I’m overwhelmed by a quiet despair — that our world is literally on fire and I’m not doing nearly enough to build a better world,” Berkobien wrote in an email to her department chair. “Pair these concerns with a downright awful job market, and I hope it’s clear why I think my best option is to leave.”

Instead of letting Berkobien leave the department let her “reimagine her dissertation as a series of essays focused largely on her public-facing work, which included building a translators’ collective that prints books and creating translation workshops for immigrant high schoolers learning English.” Beyond Berkobien’s story, the authors focused on a whole section of the Chronicle article on the dissertation.

One complaint is that the dissertation does not prepare students for jobs outside of academia. Since the bulk of Doctoral graduates will work outside of academia, maybe the dissertation should reflect that.  Sidonie Smith argues, “The one-size-fits-all proto-book structure shackles scholarship,” “It often yields bloated projects that don’t merit such long-form treatment.” While Earl Lewis says, “Lewis made a much-discussed suggestion that historians should consider allowing students to pursue co-authored dissertations. This, he says, would enable them to produce better answers to really big scholarly questions.”

The Chronical article lists several programs experimenting with alternative dissertations. It also contains several examples were alternative dissertation formats have been successful. However, the article never talks about the purpose of the dissertation.  Why is the dissertation part of the PhD?  Additionally, the dissertation is not that old.  According to DED: A Brief History of the Doctorate, a University awarded the first doctoral degree in the 12th century.  Universities awarded the first PhD in the 19th centaur, and Yale awarded the first US PhD in 1861.  Therefore, in the US, at most, the PhD dissertation is only 159 years.

What is the dissertation purpose? Why should the students write anything? The PhD is predominantly a research degree. If you do, a web search asking what a PhD is some were in the description will be a phrase like “original research” or “contribute new knowledge to your field.” The writing of a dissertation is how you show that your research answered the original research question.

I think the writers of the Chronical article are confusing several different problems. Let’s use Meg Berkobien as an example.  Meg was not engaged by her original research into 19-century Catalan-language periodicals.  As the article said, “What excited her was political organizing and mobilizing her translation expertise outside academe.” The department let her change her research topic to her translational working outside academia. They also changed the format of her dissertation.  Did the department have to do both?  Why couldn’t they have let Meg do a research project about her translational work outside academia while still writing a traditional dissertation?

Over the years, I have met many graduate students that have complained about their research projects.  There was an English lit major that wanted to study a 20th-century science fiction writer. The student’s advisors told the student no because science fiction wasn’t scholarly enough.  There was a biology student who wished to understand society’s comprehension of science. The student was told that it was not scientific enough.  I know an engineering student that wanted to understand how engineering impacted government policy; their advisor told them the department didn’t care.

In the end, these three students and many others left school.  In this case, the problem was not with the dissertation but with what was considered “scholarly” research.  However, it seems to me that almost any topic can be a research project, especially if we truly believe that all knowledge is worthwhile.  Do books have to be 100, 200, or 400 years old to be worthy of research. Isn’t it worthwhile to understand what the best way to communicate scientific information is?  The dissertation does not have to change to let in new and modern research questions.

The other reason given to change the dissertation is because it does not adequately prepare a student for work outside of academia.  While it is undoubtedly vital to train people so that they can be happy contributing members of society, we also need to train people for jobs in academia and research.  Part of the problem is overfilling in graduate programs, coupled with schools not being transparent about prospects.  I have had several faculty members tell me the only reason their departments enroll the number of graduate students is to fill the Graduate Teaching Positions, not because they need them.

While schools should be aware of student futures and provide their prospective students with realistic expectations, instead of changing the dissertation, why not allow a student to create additional projects or participate in internships to complement and enhance their graduate experiences.

The last issue brought up by Dr. Smith, and Dr. Lewis is that the current dissertation model inhibits the type of research and questions that students can ask. These are good questions concerning changes to the dissertation.  If a change to the structure of the dissertation improves the student’s ability to do research or open new kinds of research, then we should make changes.

While continuing to do something because we have always done it, that way is dumb.  It is equally foolish to change something because of problems with something else.  It is still worth looking for a better way to do things.  Just because something is not a perfect fit for everything doesn’t mean it should be changed.  After all, there are things for which a PhD is ideal.  As time and society change, schools will undoubtedly have to adapt to provide an educated society. However, as I have said before, perhaps the appropriate switch is to create a new degree not to edit the old degree out of existence.

Thanks for Listing to my Musings
The Teaching Cyborg

PS. In case you think rose-tinted glass biased my opinion, I hate my dissertation.  Not just because the company my school used to print and bind the digital files did such a horrible job.  The entire document looks like a bad copy produced off a low-quality copy machine. 

I suppose what gets me is that while I was worried about writing a document that large, I had a plan and was looking forward to creating the pseudo book.  I had a story to tell, present the background, which showed where there were holes in our knowledge.  Then develop the experimental methods to address the gaps.  Finally, I would get to show how my data added to the models and lead to new questions for future research.  Instead, my department wanted a catalog of every single experiment I did.  In the end, I felt like “my” dissertation belonged more to my committee, then it did to me.

But Will It Be a Mammoth?

“The dawn of the era of cloning is a little like splitting the atom, with enormous prospects for evil and enormous prospects for good.”
Glenn Bucher

Ice is central to the story of the Woolly Mammoth. The last ice age drove the evolution of Woolly Mammoths.  One of the driving factors in the extinction of Woolly Mammoths was the loss of ice at the end of the last ice age.  Finally, ice in the form of permafrost might let Woolly Mammoths walk the earth again. Permafrost “is a permanently frozen layer at variable depth below the surface in frigid regions of a planet (such as earth).”  Some permafrost dates to the last ice age. 

The Woolly Mammoth has become the poster child for the cloning of extinct animals. Most of the Woolly Mammoths became extinct around 11,000 years ago at the end of the last ice age. However, a group of Woolly Mammoths survived until about 4000 years ago on Wrangel Island in the arctic ocean.  Rising water separated Wrangle island from the rest of northern Russia around the time the rest of the Mammoths died out. (The Last Wooly Mammoths Died Isolated and Alone)

When some Wooly Mammoths died, they got frozen in the permafrost, which preserved the mammoths. In 2013 Scientists found a 10,000 years old Wooly Mammoth so well preserved it started to bleed when it thawed. (Preserved Woolly Mammoth with flowing blood found for first time, Russian scientists claim)

Preserved mammoth remains have led to scientists thinking that they might clone the Wooly Mammoth. The reason frozen mammoths might make cloning possible is DNA, more specifically the preservation of DNA.  Scientists hope that viable cells or DNA can be derived from the frozen mammoths and used to clone living mammoths.  Currently, scientists are researching three methods to clone the Wooly Mammoth. 

The first technique is nuclear transfer.  In this method, scientists would inject a mammoth nucleus into a host egg, which would give rise to a mammoth embryo.  Second, scientists are hoping to fertilize elephant eggs with mammoth sperm.  The fertilization would produce a half-mammoth half-elephant hybrid.  The hybrids would then be bread together over several generations to create a full mammoth. Lastly, scientists have sequenced the Woolly Mammoth genome.  With this information, scientists plan to use CRISPER to edit mammoth genes into elephant DNA. Scientists would then use the engineered cells to produce mammoths.

So, we have preserved mammoths, that scientists think they can use to clone the Wooly Mammoth. Why would we clone a Wooly Mammoth? There are two fundamental reasons to clone a Wooly Mammoth. One, we can get scientific information about mammoths from the clones. Two, we want to see Wooly Mammoths walking around. These two reasons are not mutually exclusive.

However, there are problems with cloning mammoths for scientific research.  Specifically, the only scientific reason to clone the mammoths is so we can learn something we can’t learn from the genomic sequence. Can any of the three cloning methods teach us how a real mammoth lived? The first method of nuclear transfer cloning doesn’t work. It turns out that mammoth nuclei from a 28,000-year-old mammoth named Yuka were injected into mouse eggs (Signs of biological activities of 28,000-year-old mammoth nuclei in mouse oocytes visualized by live-cell imaging).  Scientists hoped that the mouse eggs would activate the mammoth nuclei and repair the DNA.  The mammoth nuclei did activate, but the DNA repair failed. The scientists concluded, “the results presented here clearly show us again the de facto impossibility to clone the mammoth by current NT technology.”

The second method using mammoth sperm to fertilize an egg will have the same problems as nuclear transfer.  Essentially a sperm cell is simply a way to transfer a nucleus into an egg cell. Even if scientists could get nuclear transfer cloning or sperm fertilization to work, this will not produce a full mammoth. 

To understand why these cloning technics will not produce a full mammoth it’s necessary to understand some cell biology.  All multicellular animals are eukaryotes, and eukaryotic cells contain multiple membrane-bound organelles.  One organelle is the mitochondria, which have DNA and are inherited only from the mother.  Therefore, nuclear transfer or sperm fertilization will not produce mammoth mitochondria. Thus, with these two techniques, the “mammoth” will never have mammoth mitochondria.

That leaves CRISPR mediated genetic engineering.  Using CRISPR, scientists would take a cell and use CRISPR to engineer mammoth genes into the cell.  According to the Woolly Mammoth page on the Revives and Restore project site, the genome of the Woolly Mammoth is 99.96% identical to the Asian elephant.  Mammoth produced by genetic engineering, will be an engineered Asian elephant, there will always be some modern Asian elephant DNA.  While some modern DNA might not seem important, it will be imposable to rule out that modern DNA is affecting the mammoths’ biology.

There is one last problem with cloning a Wooly Mammoth for science.  Even if we clone a Wooly Mammoth, we will not have a prehistoric mammoth.  Mammoths like living elephant relatives were likely intelligent and social creatures.  Modern elephants learn how to be an elephant from the members of their herd.  Since we don’t have any living mammoths, we will produce a mammoth that acts like an elephant.

It is unlikely; we will ever produce a 100% biological mammoth.  Additionally, no matter what we do, we will never produce a mammoth that behaves like a prehistoric mammoth.  Therefore, the only real reason to create a Woolly Mammoth would be to see one walk around.  We should ask ourselves, “Is that a good reason to clone a mammoth?”  Additionally, the first few mammoth embryos would have to be gestated by Asian elephants, which is an endangered species.  Is it justifiable to use Asian elephants to produce mammoths when every Asian elephant birth is vital for their species?

There is a lot of information scientists can learn from the Woolly Mammoth.  I am not convinced scientists can learn anything from a “Woolly Mammoth” clone.  Maybe there is a question I am missing, if there is, I would love to hear it from one of the scientists.  I must admit if I had the opportunity to see a Woolly Mammoth walking around, I probably would.  However, is that a good enough reason to clone one? I can’t help but think a discussion about cloning the Woolly Mammoth would make an excellent addition to a scientific ethics course.

Thanks for Listing to My Musings
The Teaching Cyborg

Building Build, Thyself

“Good buildings come from good people, and all problems are solved by good design.”
Stephen Gardiner

Years ago, when I was in graduate school, an IT technician was repairing the lab internet. He asked me, “So when will we be able to grow cars?”  The first thing that popped into my mind was how complex a modern car is.  According to Toyota, a modern car is made up of 30,000 parts if you count down to the bolts.  Electric vehicles don’t have as many “parts” according to an article in Handelsblatt Today, an electric car has 200 parts while a gas or diesel car has more than a 1000 parts.  I answered, “It will be quite some time before we can grow a car.  There is still a lot of work to do.”

It might seem strange to ask “about growing cars”; however, writers fill science fiction with the unbelievable.  In the television show Earth: final conflict, the alien Taelons grew buildings. The Leviathans are living spaceships in the television series FarScape. While a science fiction show is not the best barometer for what is possible, it’s not a measure of the imposable either.  When the television show Star Trek debut in 1966, most of the technology seemed imposable.  However, a lot of “Star Trek” technology exists now.  Google translate, while not perfect, makes a passable universal translator.  We also have handheld communicators (cell phones) and tablet computers.  There is even a subset of 3D printers that focus on food (the replicator.)

Technology tends to make truth out of our imagination. That technology is often driven by challenging scientific endeavors.  One of the most complex scientific efforts currently being pursued is sending people to Mars.  One of the biggest problems is providing astronauts with safe housing.  Beyond the extremely thin atmosphere on Mars, the surface of the planet has two other significant issues, the temperature, and the surface radiation.  The average daily temperature of Mars is -81° F (-63° C).  While the average yearly surface radiation on Mars is eight rads, on earth, its 0.63 rads.

The surface of Mars is lethal to astronauts.  Currently, the “best” idea for providing protective habitats for astronauts is to bury the habitat under several feet of Martian soil.  The Martian soil would provide insulation and protect against radiation.   However, burying the habitats would require large equipment so that the astronauts can move large quantities of soil. Alternatively, we could send prebuilt habitats with walls that are highly insulated and resistant to radiation.  The exact thickness and weight of the habitats would depend on the material used.

The biggest problem with these ideas is the weight. Either the habitat or the equipment to build the habitat weighs a lot.  It is both expensive and difficult to transport heavy objects.  According to NASA, it currently costs $10,000 per pound to put an object into earth orbit.

So, what does science fiction technology, questions about growing cars, and visiting Mars have to do with each other?  Well, science is again working towards making science fiction reality.  NASA scientists are researching the possibility of using fungus (mushrooms) to grow buildings.  When we think of fungus, especially mushrooms, what you generally picture is just a small part of the whole organism, the fruiting body.  The fruiting body of the mushroom produces mushroom spores and allows the fungus to spread.

The bulk of the mushroom grows underground or inside a decaying log and is called the mycelium, which is a fibrous material composed of hyphae fibers.  The idea is that engineers will seed lightweight shells with spores and dried food.  Then when the structures reach their destination water, collected from the local environment would activate the spores, which grow filling the shell creating rigid, durable, and insulated buildings.

When the building is full-grown, withholding water and nutrients will stop the growth.  Later if the structure is damaged, astronauts can add water and nutrients, and the building will repair itself. Using biologicals materials like funguses to build buildings would have an additional advantage for places like Mars.  If you want to expand a building, add another shell filled with water and nutrients, the mycelium from the old structure will grow into and fill the new one.

The final advantage of biological buildings is that once they are no longer needed or reach the end of their life, they can be composted and used to either make new buildings or grow crops.  Reusing the fungus as nutrients will reduce the production of waste materials and make the site more efficient.

Additionally, using techniques like CRISPR, the Mycelium could be engineered to secret natural resins or rubbers, turning them into complex composite materials. It is even possible that eventually, we could engineer the fungus to grow into specific shapes.   Imagine a giant puffball mushroom engineered to grow into a hollow sphere 10-12 feet in diameter.

In addition to using fungus, other groups are exploring the use of other organisms to build buildings.  A group out of the University of Colorado at Boulder has developed a method using cyanobacterium.  The researchers’ mix cyanobacterium, gelatin, and sand together into a brick-shaped mold.  The bacteria grow into the gelatin, where it uses light and CO2 to produce calcium carbonate.  The result is a rigid cement-like brick after all calcium carbonate is one of the components of cement. 

Additionally, the bricks can heal themselves if cracked or even reproduce themselves if broken in half.   The researches cut bricks in half placed half back in the mold with more gelatin and sand, and the bacteria reformed the brick.

While I don’t expect to be living in a house, I grew myself anytime soon. It is starting to look like science will again make science fiction a reality.  While most of what scientists are developing is for use in resource-poor areas like the moon or Mars. We will see offshoots of this technology in use here on earth.  For instance, the bricks created by cyanobacterium absorb CO2 from the environment, unlike regular cement, which produces CO2.

Additionally, the company Basilisk out of the Netherlands is already selling self-healing concrete, which uses calcium carbonate producing bacteria.  For schools and universities, there is a tremendous research opportunity.  While researchers have established the basic idea behind biological building materials, there is still a lot to learn.  For example, there are large numbers of microorganisms that deposit minerals, which ones work best.  Does a mix of multiple microbes work better than one?  What is the most efficient sand size is it only one size or various sizes? This type of research that involves testing thousands of small permutations is perfect for undergraduate researchers and undergraduate classes.

I don’t know what effect all these biological materials will have on construction, but I’m sure it will be fascinating.  Maybe next time someone asks me, “when will we grow cars?” I will tell them, “I’m not sure, but I can grow your garage.”

Thanks for Listing to My Musings
The Teaching Cyborg

How Genetic Engineering Should Be Done

“As medical research continues and technology enables new breakthroughs, there will be a day when malaria and most all major deadly diseases are eradicated on Earth.”
Peter Diamandis

It seems that I have written about genetic engineering in humans a lot.  Most of the writing has focused on Dr. He Jiankui and his experiments to produce humans genetically resistant to HIV.  For a while, it was not even clear where Dr. Jiankui was, though he was said to be under house arrest. On January 3, 2020, Nature published a news article, “What CRISPR-baby prison sentences mean for research.” This article adds several pieces of information to the CRISPR-baby story.  First, China has confirmed that there was an additional birth.  Dr. Jiankui had previously stated that a second woman was pregnant.  However, the mother was in the earliest stages, so it was not clear whether the pregnancy would carry to term.  We now know that a third child was born.

Second, Chines news announced that Dr. Jiankui and two of his colleges were convicted.  The Chines court said, “in the pursuit of “fame and profit,” He and two colleagues had flouted regulations and research and medical ethics by altering genes in human embryos that were then implanted into two women.” Dr. Jiankui received the most severe sentence of three years in prison while his calibrators received shorter sentences.

While some scientist thinks this is a positive step. “Tang (a science-policy researcher at Fudan University in Shanghai) says the immediate disclosure of the court’s result demonstrates China’s commitment to research ethics. This is a big step forward in promoting responsible research and the ethical use of technology, she says.”  Lu You another scientist worries this could negatively impact other research into CRISPR mediated social health care. “If I were a newcomer, a researcher wishing to start gene-editing research and clinical trials, the case would be enough to alert me to the cost of such violations.”

I suspect that a lot of people will find it surprising that after the controversy over Dr. Jiankui’s use of CRISPR to engineer babies that there is any work going on using CRISPR and humans.  However, not only is their research into using CRISPR to treat human disease, some of this research has reached the stage of clinical trials.  Additionally, this use of CRISPR is a whole different animal from Dr. Jiankui’s work. Now that we have reached the end of Dr. Jiankui’s story, let’s talk about how to do human genetic engineering correctly.

First, when it comes to human genetic engineering, there are two general classifications, heritable and nonheritable. As the name implies heritable means, it can be passed on to children and released into the general population.  In nonheritable genetic engineering, parents cannot pass the genetic changes to their offspring.  In general, the difference between heritable and nonheritable genetic engineering is the cells that scientists genetically engineer.  The nonheritable engineering usually uses cells taken from an adult often adult stem cell.  In both cases, we will be discussing the use of CRISPR to modify adult blood stem cells.

Blood is composed of four components, red blood cells, white blood cells, platelets, and plasma.  The four types of blood cells have a finite lifetime, and the body continually replaces them.  The body uses stem cells to produce new blood cells.  For example, a red blood cell also known as an erythrocyte, develops from the common myeloid progenitor cell (Figure 1 B).  The common myeloid progenitor cell develops from the Hemocytoblast (Figure 1 A), which is a multipotent stem cell.  Hemocytoblasts are a stem cell because when it divides one of the daughter cells regenerates the Hemocytoblast while the other daughter develops into a mature cell type like an erythrocyte.  It is a multipotent stem cell because its progeny can develop into multiple types of cells (Figure 1 D1-10).

A basic diagram of hematopoiesis. Image modified from Hematopoiesis simple.png by Mikael Häggström. Creative Commons Attribution-Share Alike 3.0 Unported.
A basic diagram of hematopoiesis. Image modified from Hematopoiesis simple.png by Mikael Häggström. Creative Commons Attribution-Share Alike 3.0 Unported.

In addition to regenerating themselves and producing a differentiating daughter cell, hemocytoblasts can divide to produce two hemocytoblasts.  Since hemocytoblasts can produce two hemocytoblast stem cells, scientists can expand populations of hemocytoblasts.  The ability to expand the stem cells makes them particularly useful for genetic engineering.

Hemocytoblasts can be clonally grown in culture in a lab.  Growing cells clonally means that the population starts from a single cell. Therefore, all the cells are genetically identical.  The specifics of clonal cell culture are not essential to this article, but you can read the basics here. Clonal cell culture gives us the first advantage over embryotic genetic engineering.  When scientists genetically engineer an embryo, the only way to know if the change was successful in all the cells is to test all the cells, which will destroy the embryo.  With clonal cells, you can test as many of the cells as you want and grow more.  Additionally, since the cells are clonal, you know all the cells in the population are genetically the same. 

The other advantage of genetically engineered hemocytoblasts is that they can be transplanted into patients using the techniques for bone marrow transplantation, which brings us to the current generation of CRISPR mediated medical treatments.

The first clinical trial using CRISPR was carried out by oncologist Lu You at Sichuan University in Chengdu, China.  The plan was to use CRISPR to increase the immune system’s response to aggressive lung cancer.  The researchers removed cells from the patents and then disabled the PD-1 gene, which should enhance the immune response.  Dr. You is currently working on a manuscript describing the results of his work. This experiment is not a surprise; genetic engineering of immune cells for the treatment of cancer has a long history.  What CRISPR has added to the technique is a faster, more accurate way to change the cells.

In addition to the cancer work in China, the US has also approved CRISPR mediated medical treatment.  The treatment we know the most about involves Victoria Gray, who suffers from sickle cell anima.  Sickle cell anime is a painful, debilitating disease that causes red blood cells to become misshapen and sticky.  Victoria Gray volunteered to have her blood stem cells engineered so that the red blood cells express fetal hemoglobin which the doctors hope will compensate for the defective adult hemoglobin that causes sickle cell anima.  Victoria received the transfusion of genetically edited cells early this summer (2019) and the results are quite promising.  Doctors will follow Victoria’s progress for months perhaps even decades.  The researchers will also have to repeat the treatment with additional patients.  Using gene editing to treat sickle cell anime is by no means a done deal but for the first-time individuals that suffer from the illness might have a real permeant treatment.

Hopefully, people will be able to see how the work that scientists are doing to engineer adult cells for the treatment of diseases is different from what Dr. Jiankui did.  One of the most important things we need to get across is that there is nothing wrong with CRISPR or gene editing in general.  Gene editing is a powerful research tool with lots of benefits not only for general research but also for medical treatment.  Scientific techniques are not good or bad by themselves; they are only good or bad in how people use them.  After all, I bet Victoria Gray likes CRISPR.

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The Teaching Cyborg

Gene Editing in Humans Part Two

“The power to control our species’ genetic future is awesome and terrifying. Deciding how to handle it may be the biggest challenge we have ever faced.”
Jennifer A. Doudna

A year ago, He Jiankui announced that he had used CRISPR to create two gene engineered baby girls.  Since the initial announcement, there has been little new information released.  The government terminated Dr. Jiankui’s lab and research activities. “China’s Vice-Minister of Science and Technology Xu Nanping quickly shut down Dr He’s lab, ordering a full investigation and flagging some form of punishment for the researchers.”  It is also not clear where Dr. Jiankui is located “Hong Kong media reported that the university president, Chen Shiyi, personally flew to Hong Kong to collect and escort Dr He back to Shenzhen, where he was put “under house arrest”. The university denied Dr He was detained, telling the South China Morning Post “nobody’s information is accurate” on Dr He’s whereabouts, but refused to provide any details.

For about a year, this was the state of the information about the first two genetically engineered human beings.  Then early this month (Dec 2019), MIT Technology Review published a series of articles about Dr. Jiankui’s research.  It seems that He Jiankui wrote a 4699-word article titled “Birth of Twins After Genome Editing for HIV Resistance,” while the paper remains unpublished Dr. Jiankui submitted it to Nature and JAMA the Journal of the American Medical Association (China’s CRISPR babies: Read exclusive excerpts from the unseen original research.) Dr. Jiankui’s unpublished work answer several questions that were left unanswered last year.  However, the answers are perhaps more troubling than the speculation.

To understand what Dr. Jiankui was trying to accomplish, we need a little bit of history. Dr. Jiankui calms that he was trying to engineer humans to be resistant to HIV. The HIV-1 virus infects CD4 immune cells.  Over time an individual infected with HIV reaches a point where they cannot produce enough CD4 cells to mount a viable immune response. Leading to the collapse of the immune system and often death by disease.  Around 1996 a naturally occurring mutation in the CCR5 gene was discovered that rendered individuals resistant or possibly immune to infection by the HIV-1 virus.  The CCD5 mutation is a deletion of 32 base pairs (called Δ32) in the coding sequence of the CCR5 gene.  (Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection.)

The Δ32 mutation makes it so that the HIV-1 virus can’t bind to the CCR5 protein.  Since the HIV-1 virus uses the CCR5 receptor to enter cells, this mutation renders cells resistant or immune to infection by HIV-1.  According to his paper, Dr. Jiankui used the CRISPR technology to engineer the CCR5-Δ32 mutation into the in-vitro fertilized embryos of a couple where the husband was HIV positive, and the wife was HIV negative. The genetic change, in turn, would confer immunity to the children born from these embryos.

In the abstract, Dr. Jiankui says they were successful in editing the CCR5 gene.  “Genomic sequencing during pre-implantation genetic testing and after birth confirmed that the twins’ CCR5 genes were edited successfully and are thus expected to confer either complete or partial HIV resistance.” (China’s CRISPR babies: Read exclusive excerpts from the unseen original research) However, the actual data in the paper shows that one of the embryos has a frameshift mutation in the CCR5 gene, while the second embryo has a 15 bp delegation.  While both mutations cause changes in the CCR5 protein, they do not create the same disruption as the CCR5-Δ32 mutation.  It is not clear that these mutations will confer immunity to HIV since not every single mutation in CCR5 confers HIV immunity.  Beyond the question of the effectiveness of the created mutations, new research suggests that being homozygous for the CCR5-Δ32 mutation leads to a decrees in life expectancy (CCR5-∆32 is deleterious in the homozygous state in humans.)  Additionally, it appears that the cells in the embryos may not have all changed to the same extent leading to mosaics.

In addition to the potentially harmful nature of CCR5 mutations, there is a question about the type of genetic engineering.  If you are going to induce a mutation in a gene because of an observed effect, you need to create the same mutation that caused the original effect, not a similar mutation.  The reason is twofold one if you create a new mutation, you don’t know that the new mutation will have the same effect as the old one.  Two of the new mutation could cause a new and unintended consequence that the original mutation did not have.

Now at a first pass, Dr. Jiankui’s motives sound reasonable and altruistic.  He is trying to help a couple that is HIV positive have children.  Dr. Jiankui even states in his abstract, “Millions of children are born annually with inherited genetic diseases or infectious diseases acquired from parents.”  (China’s CRISPR babies: Read exclusive excerpts from the unseen original research) As stated by Rita Vassena, scientific director of the Eugin Group, there are well-established techniques to prevent transmission of HIV from parent to offspring. 

“It is worth remembering that HIV infection is not passed on through generations like a genetic disease; the embryo needs to “catch” the infection. For this reason, preventive measures such as controlling the viral load of the patient with appropriate drugs, and careful handling of the gametes during IVF, can avoid contagion very efficiently.” (China’s CRISPR babies: Read exclusive excerpts from the unseen original research

From a medical point of view, it is rarely if ever considered acceptable to use an experimental and potentially dangers technique when effective options already exist.

Beyond the question of whether the technology was ready, Dr. Jianjui’s foray into genetic engineering brings into sharp focus a question about the utilization of genetic engineering.  Dr. Jianhui attempted to create a new biological function in the twins.  He tried to engineer viral resistance.  What makes this especially troubling is that while we know that CCR5-Δ32 confers resistance to HIV-1 research into the normal biological functions of CCR5 is still ongoing.  The work showing that being homozygous for the CCR5-Δ32 can be harmful to the life span was published this year (2019). Instead of trying to create something “new,” why didn’t Dr. Jianjui try and fix a “broken” gene.

If Dr. Jianjui had at least tried to use genetic engineering to reverse a disease-causing mutation to the normal function, he would not have had to deal with the potential conquests of changing a gene function he would have restored it to normal function.  While this article should make it clear that gene-editing technology is not yet specific enough for reproductive genetic engineering, at the rate the technology is improving, it will not be long before we the technology can make specific changes in an embryo without producing additional defects.

A companion article also from the MIT Technology Review Opinion: We need to know what happened to CRISPR twins Lulu and Nana States that Dr. Jianjui’s papers need to be made public.  Specifically, Dr. Kiran Musunuru says, “Why must the information be public? It’s because He’s work reveals serious, unresolved safety concerns. It’s not clear that any effort to directly edit human embryos, even if done ethically and with full social approval, can reliably avoid these problems.”  While I think Dr. Musunuru’s interpretation is a little extreme.  I don’t believe Dr. Jianjui had a good enough grasp of what he was trying to do to use his research as a cornerstone of the technology limits.  After all, most of the information uncovered in his unpublished work is in aliment with the concerns and beliefs put forward by the scientist when human engineering was first made public.  I do agree that we need to discuss the uses and potentials of genetic engineering.

However, for people to have discussions about the ethics of genetic engineering, people need to understand the basics of genetics and genetic engineering.  Humans have been using genetic engineering since we planted our first crops and domesticated the first animals.  Our faithful companion, the dog, is the product of thousands of years of genetic engineering.  We are entering a point when we can change our ecosystem and ourselves at a rate faster than ever before. However, how much does the general public know about genetics?  Can we make a legitimate decision about genetic engineering if we don’t even understand the basics of what is going on?

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The Teaching Cyborg

Is it Dedication or Delusion?

“Delusion is the seed of dreams.”
Lailah Gifty Akita

Educational reform is a never-ending process, which is, in many ways, good.  The purpose of educational institutions is to provide the best education possible.  The individual teacher learns from experience and improves over time.  Research into learning and cognition lead to better understandings of how people learn and therefor better ways to teach.

However, even with our continually improving knowledge, changes in education seem painfully slow or to not occur at all.  A consistent problem is classroom size.  While just about anyone that has studied education will agree that the best way to teach someone is with a dedicated teacher in a one on one environment (feel free to disagree I would love to hear your reasons). However, in a society that wants education especially higher education available to everyone one on one education is not possible.

Don’t believe me look at the numbers.  According to the US census bureau, there are 76.4 million students in school K through University.  That means we would need 76.4 million teachers if we paid them an average living wage including overhead each teacher would make $41,923 – $46,953 (still a little low if you ask me)  this works out to 3.2 – 3.5 trillion dollars or 17-19% of the US Gross National Product.  As a comparison, the budget for the US national government was 21% of the GDP in 2015.  Also, 76.4 million students are 24.7% of the US population, three and older, if we also had 24.7% of the US population working as teachers, then almost half of the US population would be students or teachers. Remember we would still need all the support staff, and these are with current numbers, not what we would need for everyone eligible for school.

I don’t think any country can afford to devote that much of their population and resources to one thing and survive.  As someone that loves education, I would love it if some economist out there proves me wrong.  So, class size is a compromise between what we can afford to do and the best environment for our students.

However, outside of issues that are constrained by shall we call it a reality.  We have all seen programs and projects that we think can help students get canceled.  We have all seen programs developed by grants get canceled the second the grant ends.  The loss of these programs is not only that future students will not benefit, but also the loss of resources, including time, commitment, and motivation of staff.

I have been asked after several of my programs have been canceled “how many times are you going to keep building programs that just get canceled?” It’s an interesting question and one that is not easy to answer.  I was at the University of Colorado Boulder when Carl Wieman won the 2001 Noble prize for Physics.  After winning the Nobel prize, Wieman went on to advocate for the improvement of science education.  To the extent that he was appointed the White House’s Office of Science and Technology Policy Associate Director of Science in 2010.  In 2013 I remembered reading an article Crusader for Better Science Teaching Finds Colleges Slow to Change that was about Dr. Weiman and his frustrations with the slow changes in higher education “… Mr. Wieman is out of the White House. Frustrated by university lobbying and distracted by a diagnosis of multiple myeloma, an aggressive cancer of the circulatory system, he resigned last summer. … “I’m not sure what I can do beyond what I’ve already done,” Mr. Wieman says.”

You can’t help but think if someone with the prestige and influence of Carl Weiman can’t encourage change what hope does anyone else have.  The truth of the matter is that how much someone can take and when they have had enough is a personal question.  When thinking about how much is enough, I can’t help but think of a humorous little fable Nasreddin and the Sultan’s Horse.  I have encountered versions of this fable many times.  I think the first time was in the science fiction book The Mote in God’s Eye by Larry Niven and Jerry Pournelle.

Nasreddin and the Sultan’s Horse

One day, while Nasreddin was visiting the capital city, the Sultan took offense to a joke that was made at his expense. He had Nasreddin immediately arrested and imprisoned; accusing him of heresy and sedition. Nasreddin apologized to the Sultan for his joke and begged for his life; but the Sultan remained obstinate, and in his anger, sentenced Nasreddin to be beheaded the following day. When Nasreddin was brought out the next morning, he addressed the Sultan, saying “Oh Sultan, live forever! You know me to be a skilled teacher, the greatest in your kingdom. If you will but delay my sentence for one year, I will teach your favorite horse to sing.”

The Sultan did not believe that such a thing was possible, but his anger had cooled, and he was amused by the audacity of Nasreddin’s claim. “Very well,” replied the Sultan, “you will have a year. But if by the end of that year you have not taught my favorite horse to sing, then you will wish you had been beheaded today.”

That evening, Nasreddin’s friends could visit him in prison and found him in unexpected good spirits. “How can you be so happy?” they asked. “Do you really believe that you can teach the Sultan’s horse to sing?” “Of course not,” replied Nasreddin, “but I now have a year which I did not have yesterday, and much can happen in that time. The Sultan may come to repent of his anger and release me. He may die in battle or of illness, and it is traditional for a successor to pardon all prisoners upon taking office. He may be overthrown by another faction, and again, it is traditional for prisoners to be released at such a time. Or the horse may die, in which case the Sultan will be obliged to release me.”

“Finally,” said Nasreddin, “even if none of those things come to pass, perhaps the horse can sing.”

In 2017 I read an article from Inside Higher Ed Smarter Approach to Teaching Science.  The article talks about a book (Improving How Universities Teach Science: Lessons from the Science Education Initiative) written by Carl Weiman that documents the research and methods to improve science teaching in higher education.  It seems that Dr. Weiman did not give up after all, and he is back and still pushing.  Perhaps the truth is that people that try and change the monolith must be a little bit crazy if crazy is doing the same thing repeatedly and expecting a different outcome. Then again, maybe the horse will learn to sing.

Thanks for Listing to My Musings
The Teaching Cyborg