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

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

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.

Thanks for Listing to My Musings
The Teaching Cyborg