Monday, November 27, 2023

Charles Richard Drew: “Father of the Blood Bank”

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People don't often give a second thought to the process of donating blood or receiving it when needed. It's just always there in supply for routine and life-saving operations. But the history of blood transfusions and the nature of blood is a long one. And only 80 years ago did Dr. Charles Drew come up with a critical step in the storage of blood which has saved many lives.

From Wikipedia

William Harvey, an English doctor, discovered the circulatory system and published on it in 1628. Back then, the color of blood had been thought to indicate whether it was providing mere nutrients (purple blood) or some unique "vital factor", a life-giving principle from the lungs (red blood). Thirty years later, the Dutch scientist Jan Swammerdam looked at blood under a microscope and observed red blood cells for the first time. Nobody saw anything else until 1843, when Gabriel Andral, a French professor of medicine, and William Addison, an English doctor, separately noticed white blood cells. A year earlier, French physician Alfred Donné discovered platelets in blood, tinier than either red or white blood cells. These three made up the three solid components of blood as we know it today. The liquid part that carries these cells is called plasma.

Blood components after settling (Red Cross)

Charles Richard Drew was a Black American born on June 3, 1904 in Washington, D.C. It should be noted that he grew up in an interracial neighborhood in a middle-class family. At Dunbar High School, known as one of the best college prep schools in the country for blacks or whites, Drew was active in sports and earned letters in four of them. He joined the High School Cadet Corps there and became a captain. His goal at the time was not medicine but electrical engineering.

Drew's high school picture and description (Wikipedia)

He became interested in medicine at Amherst University, though, and graduated there in 1926. Drew decided to go teach biology and chemistry and be the football coach at Morgan University in Baltimore, Maryland for two years. That supplied him with enough money to attend medical school. For various reasons, he went to McGill University in Montreal instead of American schools. In 1933, he graduated second in his class while still playing sports there. As a resident then intern in 1933-1935 at Montréal General Hospital, Drew worked with bacteriology professor John Beattie, who studied exploring ways to treat shock with blood transfusions and other fluid replacement. 

Because places like the Mayo Clinic were not widely accepting Black physicians, he chose to work at Howard University College of Medicine (an all-Black institution) in Washington, DC in 1935. He was initially a pathology instructor, and then became a surgical instructor, and finally the chief surgical resident at its affiliated Freedmen's Hospital. The hospital was founded in 1862 and was known to be the first hospital to provide medical treatment to former slaves.

Drew teaching at Freedmen's Hospital (American Chemical Society)

From there, he gained surgical experience and moved to New York's Presbyterian Hospital, while simultaneously attending Columbia University beginning in 1938 for a doctorate in medical science. He was the first African American to earn such a degree there. At the hospital, he continued his interest in shock and transfusions. 

A short history is needed on transfusions in order to understand Drew's research and his later work.

  • 1665 The first recorded successful blood transfusion (England). Dogs to dogs.
  • 1667 More work on sheep, cows, dogs, horses, and goats. First transfusions from sheep to humans by Jean-Baptiste Denys (Denis). Because the lamb was a symbol of Jesus Christ and therefore would contain the purest blood, this was the reason it was chosen for humans. Initially a success, the patient then died, and a court case cleared Denys, but French and English governments put severe restrictions on transfusions after that for 150 years.
  • 1818 First successful transfusion of human blood (350 cc) by James Blundell to a patient.
  • 1873-1884 Americans attempt transfusing milk from cows, goats, and humans. Then they tried salt water (saline).
  • 1900-1905 Stitching together blood vessels for direct transfusions was perfected.

  • 1901 Austrian Karl Landsteiner discovers the first three human blood groups (A, B, O). Six years later, Ludvig Hektoen suggests that cross-matching blood between donors and patients would be safer, and Reuben Ottenberg and Albert Epstein perform the first blood transfusion using blood typing and cross-matching. Most physicians still thought that typing was not needed.
  • 1914 First indirect transfer of blood in a transfusion by Albert Hustin. Before this, patients and donors were connected directly. Indirect transfer means collecting the blood first into a container, then giving it to the patient.
Direct (left) and indirect (right) transfusion methods (indirect keeps blood warm in water bath)
  • 1915, 1916 Richard Weil and later Francis Rous and J.R.Turner add citrate or citrate-glucose to permits storage of blood for several days after collection.
  • 1932 First blood bank established (Leningrad) and in 1937 (Chicago)
  • 1936 John Elliot designed the first vacuum bottle for collecting blood
Elliot's vacuum bottle design (Transfusion, 2000)
  • 1939-1940 The Rh blood factor is discovered (you are either positive or negative).
  • 1940 Edwin Cohn developed a procedure to separate albumin, gamma globulin, and fibrinogen components from plasma.

Back to Charles Drew, with his newly minted doctoral degree awarded in 1940: "Banked Blood: A Study on Blood Preservation". What was it all about? Clearly, he had a lot of medical discoveries in recent years to fall back on.

Drew's dissertation mentions research from others in the 1920s suggesting how long blood could be kept under certain conditions that stabilized it (or "conserved" it). Those terms mean simply that care must be taken to ensure that during storage the red and white blood cells don't degenerate and that the blood doesn't clot. To quote from his dissertation:

p. 88 of Drew's dissertation

He looked into research on changes in blood's biochemistry and cell shape as well as immune properties, and he further spent 100 pages describing studies on preservation of blood, whether from placentas, cadavers, the aged, or freshly dead people. The blood chemistry changes during storage were explained in terms of illnesses that might benefit from transfusions. He even described the shape of containers and how they benefitted lengthy storage:

p. 198 of Drew's dissertation

He noted that the condition of blood was good up to 15 days at 3-5ºC (37-41ºF), compared to only 3 days at body temperature. Drew added that not only should blood be stored at that temperature, but that it should be chilled immediately after it was donated and kept "free from  mechanical shaking or movement" to reduce the risk of cellular damage. Ultimately, he determined that blood kept for 10 days under the physical and chemical conditions he outlined was as healthy as freshly drawn blood.

The final chapter in his dissertation described his proposal to establish a blood bank at his hospital. Survey results from four other hospitals in the U.S. (including Chicago) were used to incorporate valuable data in the creation of his own blood bank facility. His proposal was accepted. The result was a set of policies on administration, staff, blood drawing conditions of the hospital and patient, and sanitary conditions, and by the time he finished his dissertation, he had collected statistics (including health at blood drawing time and afterward) on the first 400 donors from August 9, 1939 to February 23, 1940!

Charles Drew, early 1940s

As mentioned already, blood is composed of liquid (plasma) with vital protein chemicals as well as the solid components of red and white cells and platelets. If they are together, it is called whole blood. Plasma was deemed more valuable than whole blood during wartime in many instances. Its loss from the body lowered blood pressure, and it was more important to restore that for the patient's stability than to provide red blood cells to boost oxygen-carrying capacity. Frozen plasma took 20 minutes to thaw, though, and it required special storage units. Freeze-dried plasma was more convenient in terms of storage and simply had to be reconstituted with sterile water before use.

British surgeons inspecting wartime blood, 1941 (American Chemical Society)

America was approached by Britain in World War II to help provide blood plasma for the expected casualties. In June 1940, Dr. Charles Drew was called upon to head up an effort to provide liquid plasma for British soldiers in the "Blood for Britain" campaign. With his guidance, the program scaled up his own hospital system to collect, process, and store plasma at nine hospitals. The first shipment went out in August. By the end in January 1941, Blood for Britain had collected 14,556 blood donations, and shipped over 5,000 liters of plasma with help from the American Red Cross. Drew was now considered the expert on blood donations and processing.

From February to April 1941, Drew worked again with the Red Cross to initiate a dried plasma program this time, which later became the National Blood Donor Service. 

Freeze-dried plasma (British Medical Journal, 1940)

It was Drew who introduced mobile collection units (later called "bloodmobiles.")

Drew's first bloodmobile, Feb. 1941 (American Chemical Society)

Despite his fame and success in assembling medical teams, the National Blood Donor Service became a sore point for Charles Drew. At the insistence of the Armed Forces, Blacks were not allowed to donate blood, and in retaliation, black news agents and the National Association for the Advancement of Colored People (NAACP) voiced their protests. A year later in 1942, the Red Cross changed its policy but insisted on separating blood from white populations. There was nothing scientific to suggest that Black blood was inferior or dangerous, but nothing could be done. A few months later, however, he resigned Drew himself, a light-skinned Black, was outraged and even mentioned this in 1944 in his acceptance speech for the Spingarn Medal, an honor from the NAACP for outstanding achievement:

"It is fundamentally wrong for any great nation to willfully discriminate against such a large group of its people. . . . One can say quite truthfully that on the battlefields nobody is very interested in where the plasma comes from when they are hurt. . . . It is unfortunate that such a worthwhile and scientific bit of work should have been hampered by such stupidity."

Charles Drew maintained a busy life thereafter. For example, he continued to serve as the chief surgeon at Freedmen's Hospital and as a professor at Howard University. He became the first African American examiner for the American Board of Surgery. He participated in Office of Civilian Defense (OCD) drills, created in 1941 by President Roosevelt. 

Practicing civilian defense in mock medical emergency for OCD, ~1942 (National Archives)

Drew dedicated himself to training and mentoring medical students and surgical residents, and raising standards in Black medical education. He was also an advocate against excluding Black physicians from local medical societies, medical specialty organizations, and the American Medical Association. Virginia State University and Amherst University both awarded him with honorary doctor of science degrees in 1945 and 1947. 

Tragically, at only 45 he died due to complication following a car accident on April 1, 1950 on his way to a medical conference in Alabama. An episode of the TV show M*A*S*H falsely depicted his death as being due to the hospital refusing to give him blood because of his race. This myth may have been included in the show because of the common (and sad) treatment many Blacks encountered with discrimination in hospitals at that time.

Drew's accolades are many, including have a Navy ship named after him, a national landmark, and a bridge. Thirty years after his death, the U.S. Post Office issued a stamp in his name.

Thursday, November 23, 2023

Four researchers on Earth are spending a year on ‘Mars’

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In the movie The Martian, Matt Damon plays an astronaut living on Mars with a small team of people. He gets left behind when the rest of the team leaves during an emergency. But the movie demonstrates how people set up a research base there, separate from their landing vehicle, to live and explore Mars for a month. They had to contend with a poisonous atmosphere, lighter gravity, and the time delay in sending and receiving messages to Earth. Damon's character had to contend with living far longer and needed to grow food there to survive until a rescue could come. But how do you train for any of that life on Mars? NASA is currently doing that right now here on Earth with a simulated habitat called Mars Dune Alpha.

Conceptual image of Mars Dune Alpha (Stir World)

Astronauts on the Apollo moon missions spent only a short time on the surface, living in a tiny lander. 

  • Apollo 11: 21 hr 36 minutes
  • Apollo 12: 7 hr 45 minutes 
  • Apollo 14: 9 hr 22 minutes
  • Apollo 15: 66 hr 54 minutes
  • Apollo 16: 71 hr 2 minutes
  • Apollo 17: 74 hr 54 minutes
Just imagine even a few hours in cramped quarters hundreds of thousands of miles from Earth!

Buzz Aldrin in lunar lander; diagrams of sleeping arrangements (helmets not needed)

Weeks-long or months-long space missions are a different story, and the Mars missions are different for a few reasons. One, although gravity is stronger there than on the Moon, it is still only one-third that of Earth. Two, the distance is much further to Mars, so returning is a much longer trip (about 7 months), and it will requires longer stays just so Earth is in the right position. See the positions of both planets and the time needed for the Perseverance spacecraft to get to Mars in 2020, below.

From mars.nasa.gov (TCM= trajectory correction maneuver)

To prepare for crewed trips to Mars, NASA has begun a series of three missions to simulate living there. The program is called CHAPEA (Crew Health and Performance Exploration Analog), and the first one is underway. Four volunteers were selected to spend more than a year living in the Mars Dune Alpha habitat, which is a 1,700-square foot structure that contains "crew quarters, a kitchen, and dedicated areas for medical, recreation, fitness, work, and crop growth activities, as well as a technical work area and two bathrooms". The missions are called analog because they are on Earth not Mars, but they give NASA the chance to collect data on how people live and work under Mars conditions.

Mars Dune Alpha is built at the Johnson Space Center in Houston, Texas using a 3D printer from the company ICON, which uses a proprietary material called Lavacrete. It took a month to build it. The video below explains some of the details and describes recruitment for the first CHAPEA mission, too. (The view you see in the video of the completed structure with sand dunes surrounding it and wind blowing is just a mock up, not the Houston facility.)

2021 video showing ICON building the Mars Dune Alpha

How will all of this simulate living and working on Mars? First of all, the volunteers will be completely isolated in Mars Dune Alpha. Outside will have an Earth atmosphere, but they will suit up for any extravehicular activities anyway. NASA will also not control the temperature outside of the shelter, unlike on Mars where it can be −10 to 62°F, or −20 to 17°C) in the daytime. Also, they won't be exposed to the radiation that gets through Mars' thin atmosphere. But, if they need to contact the outside world, there will be a delay in sending any messages just like the real conditions on Mars.

They will eat freeze-dried meals but will also have to grow their own food in special compartments. Leafy vegetables have already been shown to grow well aboard the International Space Station.

Food pods on Mars Dune Alpha; lettuce grown on the International Space Station

The whole Mars Dune Alpha facility will be surrounded by a "sandbox" of simulated Mars soil, and fake landscapes have been created to add to the realism. It looks like cameras on the dome will project the landscape. A harness and treadmill device will be used to give the feeling of walking long distances under one-third gravity.

Exterior simulation view and one-third gravity device (Yahoo)

Although the ICON 3D printing apparatus is too large to take aboard a spacecraft, some people still think using local Mars materials is likely the way to build structures there (and on the Moon). Keep in mind that every kilogram (2.2 pounds) of cargo on the Space Shuttle costs $54,000, too. But how will they perform the 3D construction? That has not yet been explained, and NASA has a couple of years to figure it out, but perhaps aerial drones might help, as shown below.

3D printing with drones (YouTube)

So, who are these four volunteers? 

  • Kelly Haston (52) is mission commander. Haston has a PhD in biomedicine.
  • Nathan Jones is an emergency medicine physician who will serve as the in-house doctor. 
  • Ross Brockwell is a structural engineer with a master’s degree in aeronautics.
  • Anca Selariu is a specialist in infectious diseases and an officer in the U.S. Navy.

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Anca Selariu, Nathan Jones, Kelly Haston, and Ross Brockwell entered the Mars Dune Alpha on June 25, 2023. For a 3-month update on the first CHAPEA mission, go to this link and watch the video from one of the volunteers.

This link shows how Ross Brockwell and the others trained for the mission, and some of his personal feelings toward the adventure.

Tour the mock Mars habitat where  NASA "analog astronauts" will spend the next year.

Saturday, November 18, 2023

Bizarre First: Viruses Seen 'Biting' Onto Other Viruses Like Tiny Vampires

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Viruses can't live on their own. They are hunks of DNA or RNA packaged in some kind of protein compartment just waiting to bump into cells that they can infect. Those can be human, animal, plant, or bacterial cells. After they attach, they insert their genetic material into the cell and use its machinery to make copies of the virus. Now, we have evidence of a virus attaching to another virus to help it spread its DNA/RNA, and some researchers are calling this a "vampire virus".

"Vampire virus" in purple attached to another virus in blue (UMBC website)

The word bacteriophage (or just phage) is used to describe a virus that infects bacteria. Small as bacteria are, viruses are even smaller, and they require the enzymes in bacteria to build copies of themselves. They come in various shapes, looking like a polygon, a filament, a blob, or a lemon, but the most commonly shown in news is the one that has a capsule-like head on top of a tail which has some leg-like fibers to help it attach to bacteria.

Various bacteriophage (Wikipedia)

The most complex one with the head (capsid) and tail will attach itself at the base of its tail to the bacterial cell, and like a syringe, it injects its genetic material.
Animation from YouTube

But there are some viruses that can't attach to cells and need another virus to help them do that and to enter a cell. They also need the DNA/RNA of the other virus to provide instructions on how to make its own protective capsid. They latch on to the "helper virus", give it its genetic material, and the helper virus does the rest when it infects a cell with both sets of DNA/RNA. These incomplete viruses dependent on others are called satellite viruses.

Researchers from the University of Maryland Baltimore County (UMBC) have just discovered a satellite virus that attaches to one type of bacteriophage, and even though the biological term for its attachment location is the tail of the phage, they described it as the neck. This led them to name the satellite virus a "vampire virus". After it broke free, the legs were still attached and resembled bite marks.

Vampire virus on bacteriophage (left); "bite marks", residual virus on bacteriophage (right) (Nature)

Undergraduate students were studying environmental samples as part of a routine project at UMBC. Streptomyces bacteria are very common in soil, and they knew there were likely some bacteriophage against it in their samples. Usually, they find bacteriophages from such samples, send them to another lab to analyze what the DNA or RNA sequence looks like (what genes the phage it has), and then study the results back at UMBC. 

Common soil Streptomyces bacteria (Science Photo Library)

They already knew the gene sequence for a phage that they suspected was in the soil sample, but the lab told them that it must have been contaminated because it had other genes in it, not just the ones from the phage. The students got a head teacher to prepare the samples next, but the lab got the same results, so everyone figured there had been no mistake, no contamination. Where did the unusual bits of DNA come from?

UMBC happens to have an imaging facility with very high-tech instruments. So, they sent their samples there to see (literally) what could be seen under an electron microscope. Normal microscopes have a magnification power around 1000x, but electron microscopes go much further, up to several millions of times.

Electron microscope at UMBC's imaging facility

The imaging facility assistant director Tagide deCarvalho was amazed at what she saw. About 80% of the helper phage had a satellite attached to its tail, just under the head-like capsid. Some of the phage that didn't have them showed fragments of the satellite virus attachment fibers clinging to it, and students describe them as the "bite mark" of this vampire satellite virus on the helper phage.

Hepatitis D virus is a satellite virus and can only infect human cells when hepatitis B virus is present. Together, they cause a "super-infection" that causes the liver to fail. Another real satellite virus is the one infecting tobacco, causing reduced crop yields, stunted growth, and plant death. Understanding more about vampire viruses might help our understanding of medical and agricultural conditions like this and how to treat or prevent them. How many other situations have given what people thought were contamination but instead were satellite viruses?

Sunday, November 12, 2023

Can humans reproduce in space? Mouse breakthrough on ISS a promising sign

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(Click on images to enlarge.)

If you think this article is about how humans can have sex in zero gravity, you will be disappointed. Humans are mentioned, but the topic revolves around studies on how well embryos from mammals will be able to deal with environmental issues in space. Those issues mainly include weightlessness and exposure to gamma rays. Since the heading mentions mice, be prepared for background material science has accumulated on that and other creatures, too. It all relates to the eventual goal of humans living and reproducing outside Earth as we make more steps toward colonizing the Moon and Mars.

Embryo blastocysts cultured at artificial gravity and microgravity on the International Space Station (iScience)

Interest in long-term living on the Moon or Mars is gaining ground. The Artemis program is aimed at setting up lunar base camps, and NASA has even set up a one-year CHAPEA habitat on Earth to simulate living on Mars. Astronauts have already spent months living on the International Space Station (ISS), with lots of physiological data collected on their exposure to isolation, microgravity, and radiation. But the safety of developing fetuses in space is part of the long list of unanswered questions on people's minds.

Artist's concept of Artemis camp (habit in rear); construction of Mars CHAPEA via 3D printing (right & middle)

In the early days of spaceflight, tests were being run on animal physiology to see what negative effects there might be when life met zero gravity and exposure to radiation. Beginning in 1948, dogs, monkeys, chimpanzees, birds, mice, rates, rabbits, turtles, wine flies, mealworms, turtles, insects, spiders, jellyfish, newts, frogs and frog eggs, fish, fungi, and bacteria were sent up for various types of tests. Some were performance tests (like how a spider would weave a web in zero gravity), but others were sent to test how they survived radiation, too. For example, NASA's Biocore Experiment sent five pocket mice along with the Apollo 17 astronauts and compared extensive biological examinations with mice on Earth.

Biocore pocket mouse and its container (NASA report)

Upon their return, they were examined thoroughly for many factors that might relate to damage caused by radiation, but virtually none were found. Because of the size of spacecraft (and the International Space Station), it's been difficult to test large numbers of animals in space.  The limited time of some experiments are due to using an orbiter or Space Shuttle, too, and that has an effect on what sort of exposure is being measured. For example:

TEXUS frog egg fertilization equipment (From Advances in Space Research, left and  ESA, right)

The statistics alone on such small numbers of animals make it difficult to assess accurately what changes may have occurred. And the animals in space did not breed there, nor did any mammal have birth in space. 

Japanese researchers at the Advanced Biotechnology Center, University of Yamanashi decided to send frozen mouse embryos to the ISS for a few days in 2021 to see what would happen as they developed. The goal was to observe any changes and try to relate them to the effects of microgravity.

Below, you can see part of the normal development process. After sperm and egg unite to create a one-celled zygote, it divides rapidly. At the 16-cell stage, there are basically two types of cells: the inner ones called the ICM (inner cell mass), and the outer layer. After one more cell division, the outer cells secrete fluid inward to create the liquid-filled cavity. This combination of cavity, inner, and outer cells is called a blastocyst (which means "sprout sac"). 

Mouse embryo development (Mihajlovic & Bruce, 2017)
ICM = inner cell mass, the precursor to the fetus

This process take place as the embryo travels to the uterus, as shown below. You can see that the blastocyst is upside down ready to implant into the wall of the uterus.

So, now we have a group of cells in a lopsided configuration. Is its formation (or its fate thereafter) affected by zero gravity (or microgravity)? 

What each cell in 2-cell, 4-cell, 8-cell, 16-cell, or 32-cell groupings does and where they end up in a blastocyst is not known. That can be important because the outer layer forms the placenta, and the ICM contributes to the formation of the fetus. The lopsided grouping of ICM cells inside the blastocyst made some scientists wonder if they grew together because gravity forced their them to. Also, when the blastocyst reaches the uterus, it must stick to it and be implanted to avoid it being washed out. The part of the blastocyst that makes contact is the outer membrane outside the ICM. Does attachment require gravity to make sure it touches properly, or is it just a biochemical difference in the outer membrane cells?

Mouse pregnancies are only 21 days long, and the time needed to reach the blastocyst stage is about 4 days after the zygote is formed (as you can see from the earlier diagram). Microgravity conditions have not been shown to adversely affect reproduction in sea urchins, fish, amphibians, and birds. But mammalian embryos develop a bit differently, and since humans are mammals, the Japanese experiment is a valid one. The Japanese sent up 2-celled embryos in frozen storage, and thawed them out in orbit.

Japanese thawing and culturing process.
RT= room temperature
SPB1 and CZB are nutrient solutions

Two-celled embryos were thawed and cultures in the same way on Earth, and differences were compared. They even grew embryos on the space station in regular microgravity conditions and under an artificially induced 1-g (normal Earth) gravity by rotating them in a special incubator to see whether something other than gravity off Earth would potentially have any effect. After 4 days, the blastocysts were preserved in a formaldehyde solution before returning to Earth.

Thawing cells on the ISS for the mouse embryo experiment (YouTube)

One result was clear: embryos grown in space produced about the same number of cells in the blastocysts as the embryos did on Earth with normal gravity. In the graph below, you can see the Earth control blastocysts compared to the two groups in space (one with artificial 1-g gravity, one with microgravity). The TE means the cells on the outside of the blastocyst. The photo shows the ones they harvested in space.

Graph from space.com; photo from PLoS ONE article

There were some noticeable differences:

  • on Earth, 60% of the 2-cell embryos developed into blastocysts, but in space 29.5% did for the artificial gravity test and 23.6% did at zero gravity.
  • the rate of DNA damage and gene expressions of blastocysts were no different in all three environments (this takes into effect gravity as well as radiation)
  • in three of the 12 blastocysts from the zero-gravity test, the ICM cells bunched together in two places, instead of the usual one place

Rats and mice sent into space earlier bred but didn't produce any offspring for unknown reasons. Because the space-bound embryos were preserved in formaldehyde, they couldn't be implanted into mice after they returned to Earth, so that step in this project was incomplete. But the Japanese researchers have two alternate plans.

We are planning to conduct an experiment on the ISS to create the same environment as the uterus to see if a blastocyst can be implanted there, and will observe the following development.

I would also like to conduct an experiment in which astronauts freeze blastocysts that have been cultured for four days on the ISS, bring them back to the ground, thaw them and implant them in female mice to see if they produce offspring.”

In an earlier experiment, the same researchers sent up frozen mouse sperm cells, which were stored on the ISS for 288 days. After they were returned to Earth, they were examined and used to fertilize mice. Some damage to the sperm's DNA was found, but the baby mice that grew did not appear any different from controls, and the rate of fertilization was also no different. The researchers felt that normal DNA-repair mechanisms in the mouse egg might have helped restore them to normal.

Blastocysts from Earth controls vs ISS sperm (from 2017 report)

The Japanese researchers have been studying mouse development for many years. This latest work simulated Earth gravity aboard the ISS, but earlier work simulated microgravity on Earth using unique 3D rotational devices called clinostats. 

All of the data is being compared, and Professor Wakayama of this research team put it best in 2009:

We are planning to perform similar experiments at different gravities, such as Moon gravity (1/6G) or Mars gravity (1/3G),” he says. “I want to know how much gravity is necessary to perform normal reproduction.

Saturday, November 4, 2023

How do we taste, and how many tastes are there?

(Click on figures to enlarge.)

How many tastes can the human tongue distinguish? Some people will say four: salt, sweet, sour, bitter. Some will claim five with a new-ish one in recent years hitting the limelight: umami (Japanese word for savory, and some would even say meaty is a part of it). But there may likely be six or seven, or even more. How does that figure? What do we know about these and about taste in general?

From Getty Images

Taste is one of the five traditional senses (followed by touch, hearing, sight, and smell). But humans have more than five senses, and no, the sixth sense is not an ESP perception. We have a sense of balance, a sense of movement and position of our limbs and muscles (proprioception), a sense of internal body needs (like hunger, thirst, or going to the toilet), etc. But let's stick with taste. 

Aristotle designated sweet, sour, bitter, and salty in the 4th century B.C. but also considered three others: astringent (slightly acidic or bitter), pungent, and harsh. Many other people created their own lists, as you can see below.

In more recent decades, we were taught incorrectly something about our ability to detect a handful of tastes. Yes, incorrectly. The following diagram you might be familiar with is wrong, yet it has been provided through the years to schoolchildren to show not only what we can taste, but where on the tongue the sensors are located. I repeat, this is incorrect information.

Widely used but inaccurate model of taste locations on the tongue

Many scientists in the 1700s ad 1800s were investigating the types of tastes we can detect and their locations on the tongue. In 1891, L.E. Shore published a mapping study he did ("A contribution to our knowledge of taste sensations") using the four accepted tastes with the following materials:

  • sweet (glycerine)
  • sour (sulfuric acid)
  • bitter (quinine)
  • salty (sodium chloride, table salt)
He determined the minimum amount of each one that could be detected and where.


Following that, in 1901, German scientist David P. Hänig published a paper, "On the Psychophysics of the Sense of Taste", in which he described similar locations on the human tongue and showed the data in graphical form. 

Results of Hänig's 1901 paper

 The differences in sensitivity seem really small for salt and sour, but he drew a map of where all four tastes were detected:

From Hänig, 1901

If you look at the drawing, you might be able to see the minute differences around the tongue's surface, where the dots representing tasting points are grouped closer together and therefore agree with the graph. In 1916, another German researcher Henning sketched a "taste tetrahedron" to show yet another view of the four recognized tastes (saline = salt). His picture meant to symbolize not just the four, but that along each edge and face of the shape, gradations of each taste could be found. Some of those gradations were listed as salt-bitter, salt-sour, salt-sweet, sour-sweet, sour-bitter, and sweet-bitter.


Almost three decades later, Harvard psychologist Edwin Boring compiled massive amounts of data and investigated on his own, ending up with a 644-page book in 1942, Sensation and Perception in the History of Experimental Psychology. It is stated by many people that Boring was the first to actually draw the incorrect taste map, probably based only on where the major locations were, but I cannot find any source that mentions the first tongue taste map.

If you look a your tongue, you can distinguish many bumps on its surface. These are called papillae (singular: papilla). There are 4 types, but only 3 contain groups of cells called taste buds. The buds consist of hair-like projections into the mouth, pores, and various types of gustatory (taste sensing) cells. These are the actual taste receptors that identify sweet, sour, salt, and bitter at different levels and send signals to the brain. 

Papilla, taste buds (cross section), and taste receptor cells (Chandrashekar et al., 2006, Nature)

To see the taste buds in better detail, the same authors as above provided the following colored version with various taste receptor cells. It's still not clear which of the three proposed models is accurate.

Model A: each taste bud receptor cell detects a separate taste and has its own nerve
Model B: each cell is "tuned" for different tastes but has its own nerve
Model C: each cell detects one taste but has nerve connections to the other cells for mixed taste potential

So, after decades of research, things were pinned down to four basic tastes, right? No. The above diagrams show five. Even though Boring seemed to indicate sweet, salt, bitter, and sour were definite distinct tastes, he wrote in 1942 that those may not be the only ones. Well, he was correct. Japanese researcher Kikunae Ikeda around 1908 had discovered a fifth taste from their diet: umami. He was searching for something to "make healthy, bland food more palatable" and essentially discovered MSG (monosodium glutamate) in sea kelp (konbu), which is used widely in broths in Japan. Other Japanese scientists found it dried bonito fish (1913) and in shiitake mushrooms (1957). It has since been associated with many savory foods like meats, cheeses, soy sauce, fish, yeast extract, mushrooms, tomatoes, and more. Umami comes from the Japanese casual word umai for delicious plus mi for taste.

Kikunae Ikeda (ajinomoto.com)

Ikeda got a patent for making umami (MSG) and shared it with Saburosuke Suzuki, who started the Suzuki Chemical Company and began manufacturing it in 1908 as "Aji-no-moto" (meaning "essence of taste"). But, popular as it was as a food ingredient in Asia, it wasn't until 1990 that umami was finally recognized as a separate taste at the International Symposium on Glutamate, which means it does not fit the "taste tetrahedron" from Henning. And the taste bud receptor for glutamate was located in only as early as 2006.

So, is that it, then? Five tastes plus whatever mixtures we can sense? No, again. In 2005, French researchers found that mice have a sense of tasting fatty foods. As for humans, we don't know. However, enzymes that break down fatty acids are found on the tip of the tongue, so Danish researcher Camilla Andersen tested types of milk on volunteers who were also hooked up to a monitor that measured brain activity. She determined that we can discriminate two milk fat extremes (0.1% and 38% fat).This sense of taste has not yet been fully confirmed.

Testing fatty acid taste from milk (Andersen et al., 2020)

The sense for umami on the tongue was first thought to be in the big blank area in the center where none of the other tastes had been detected. But like Shore's and Hänig's data from 1892 and 1901, it is widely accepted now that taste buds all over the tongue can detect all of the flavors we can describe; the sense is just stronger in certain parts of the tongue.

In addition to these tastes, scientists have also begun to feel we may have two senses for salt: high-salt and low-salt tastes. Salt itself helps regulate blood pressure and controls nerve impulse transmission. It may be that we have taste detectors which tell us that the amount in a food is acceptable ("just right") or unacceptable ("too salty"). The sodium in table salt seems to regulate our receptors' feeling for low salt acceptance, but recent research is emerging that suggests the chloride part of salt might be responsible for us rejecting foods that are too salty. All the data is not in yet, but wouldn't it be interesting to have two salt detector cells!

So, what is the most up to date tongue map that we should use? Perhaps the 2006 paper in Nature shows it best. In other words, we taste everything everywhere on the tongue.